Science.gov

Sample records for adult human intervertebral

  1. High Glucose Accelerates Autophagy in Adult Rat Intervertebral Disc Cells

    PubMed Central

    Kong, Chae-Gwan; Kim, Man Soo; Park, Eun-Young

    2014-01-01

    Study Design In vitro cell culture. Purpose The purpose of this study was to investigate the effect of high glucose on autophagy in adult rat intervertebral disc cells. Overview of Literature Diabetes mellitus is considered to be an important etiologic factor for intervertebral disc degeneration, resulting in degenerative disc diseases. A glucose-mediated increase of autophagy is a major causative factor for the development of diseases associated with diabetes mellitus. However, no information is available for the effect of high glucose on autophagy in adult intervertebral disc cells. Methods Nucleus pulposus and annulus fibrosus cells were isolated from 24-week-old adult rats, cultured and placed in either 10% fetal bovine serum (normal control) or 10% fetal bovine serum plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days, respectively. The expressions of autophagy markers, such as beclin-1, light chain 3-I (LC3-I) and LC3-II, autophagy-related gene (Atg) 3, 5, 7 and 12, were identified and quantified. Results Two high glucoses significantly increased the expressions of beclin-1, LC3-II, Atg3, 5, 7, and 12 in adult rat nucleus pulposus and annulus fibrosus cells in a dose- and time-dependent manner. The ratio of LC3-II/LC3-I expression was also increased in a dose-respectively time-dependent manner. Conclusions The results suggest that autophagy of adult nucleus pulposus and annulus fibrosus cells might be a potential mechanism for the intervertebral disc degeneration in adult patients with diabetes mellitus. Thus, the prevention of autophagy in adult intervertebral disc cells might be considered as a novel therapeutic target to prevent or to delay the intervertebral disc degeneration in adult patients with diabetes mellitus. PMID:25346805

  2. Notochordal Cells in the Adult Intervertebral Disc: New Perspective on an Old Question

    PubMed Central

    Risbud, Makarand V.; Shapiro, Irving M.

    2011-01-01

    The intervertebral disc is a soft tissue, positioned between each of the vertebrae, that accommodates applied biomechanical forces to the spine. The central compartment of the disc contains the nucleus pulposus (NP), which is enclosed by the annulus fibrosus and the endplate cartilage. The NP is derived from the notochord, a rodlike structure of mesodermal origin. Development of the notochord is tightly regulated by interactive transcription factors and target genes. Since a number of these molecules are unique, they have been used for cell lineage and fate mapping studies of tissues of the intervertebral disc. These studies have shown that in a number of species including human, NP tissue retains notochordal cells throughout life. In the adult NP, there are present both large and small notochordal cells, as well as a progenitor cell population which can differentiate along the mesengenic pathway. Since tissue renewal in the intervertebral disc is dependent on the ability of these cells to commit to the NP lineage and undergo terminal differentiation, studies have been performed to assess which signaling pathways may regulate these activities. The notch signaling pathway is active in the intervertebral disc and is responsive to hypoxia, probably through HIF-1α. From a disease viewpoint, it is hypothesized that an oxemic shift, possibly mediated by alterations in the vascular supply to the tissues of the disc, would be expected to lead to a failure in notochordal progenitor cell activation and a decrease in the number of differentiated cells. In turn, this would lead to decrements in function and enhancement of the effect of agents that are known to promote disc degeneration. PMID:21967331

  3. [The three-dimensional culture of adult mesenchymal stem cells for intervertebral disc tissue engineering].

    PubMed

    Feng, Ganjun; Liu, Hao; Deng, Li; Chen, Xiaohe; Zhao, Xianfeng; Liang, Tao; Li, Xiuqiong

    2009-12-01

    Intervertebral disc (IVD) degeneration is one of the major causes of low back pain. As current clinical treatments are aimed at restoring biomechanical function and providing symptomatic relief, the methods focused on biological repair have aroused interest and several tissue engineering approaches using different cell types have been proposed. Owing to the unsuitable nature of degenerate cells for tissue engineering, attention has been given to the use of mesenchymal stem cells (MSCs). In this connection, we have made a study on the characteristics of MSCs derived from adult bone marrow and on the feasibility of constructing IVD tissue-engineering cell under a Three-Dimensional Pellet Culture System. The human bone marrow MSCs were isolated and purified with density gradient solution and attachment-independent culture system. MSCs isolated using this method are a homogeneous population as indicated by morphology and other criteria. They have the capacity for self-renewal and proliferation, and the multilineage potential to differentiate. PMID:20095491

  4. Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs

    PubMed Central

    Schaaf, Rainer; Wälchli, Beat; Boos, Norbert

    2006-01-01

    While there is consensus in the literature that blood vessels are confined to the outer anulus fibrosus of normal adult intervertebral disc, debate continues whether there is a vascular in-growths into inner parts of the intervertebral disc during degeneration. We therefore tested the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. The specific endothelial cell marker CD 31 (PECAM) was used to immunohistochemically investigate 42 paraffin-embedded complete mid-sagittal human intervertebral disc sections of various ages (0–86 years) and varying extent of histomorphological degeneration. Additionally, 20 surgical disc samples from individuals (26–69 years) were included in this study. In discs of fetal to infantile age, blood vessels perforated the cartilaginous end plate and extended into the inner and outer anulus fibrosus, but not into the nucleus pulposus. In adolescents and adults, no blood vessels were seen except for the outer zone of the anulus fibrosus adjacent to the insertion to ligaments. The cartilaginous end plate remained free of vessels, except for areas with circumscribed destruction of the end plate. In advanced disc degeneration, no vessels were observed except for those few cases with complete, scar-like disc destruction. However, some rim lesions and occasionally major clefts were surrounded by a small network of capillary blood vessels extending into deeper zones of the anulus fibrosus. A subsequent morphometric analysis, revealed slightly “deeper” blood vessel extension in juvenile/adolescent discs when compared to young, mature and senile adult individuals with significantly “deeper” extension in the posterior than anterior anulus. The analysis of the surgical specimens showed that only sparse capillary blood vessels which did not extend into the nucleus pulposus even in major disc disruption. Our results show that vascular invasion deeper than the periphery was not observed during disc

  5. Degenerated human intervertebral discs contain autoantibodies against extracellular matrix proteins.

    PubMed

    Capossela, S; Schläfli, P; Bertolo, A; Janner, T; Stadler, B M; Pötzel, T; Baur, M; Stoyanov, J V

    2014-01-01

    Degeneration of intervertebral discs (IVDs) is associated with back pain and elevated levels of inflammatory cells. It has been hypothesised that discogenic pain is a direct result of vascular and neural ingrowth along annulus fissures, which may expose the avascular nucleus pulposus (NP) to the systemic circulation and induce an autoimmune reaction. In this study, we confirmed our previous observation of antibodies in human degenerated and post-traumatic IVDs cultured in vitro. We hypothesised that the presence of antibodies was due to an autoimmune reaction against specific proteins of the disc. Furthermore we identified antigens which possibly trigger an autoimmune response in degenerative disc diseases. We demonstrated that degenerated and post-traumatic IVDs contain IgG antibodies against typical extracellular proteins of the disc, particularly proteins of the NP. We identified IgGs against collagen type II and aggrecan, confirming an autoimmune reaction against the normally immune privileged NP. We also found specific IgGs against collagens types I and V, but not against collagen type III. In conclusion, this study confirmed the association between disc degeneration and autoimmunity, and may open the avenue for future studies on developing prognostic, diagnostic and therapy-monitoring markers for degenerative disc diseases. PMID:24706108

  6. Excimer ablation of human intervertebral disc at 308 nanometers.

    PubMed

    Wolgin, M; Finkenberg, J; Papaioannou, T; Segil, C; Soma, C; Grundfest, W

    1989-01-01

    Excimer laser energy, which has been shown to photoablate tissue at a precisely controllable rate with minimal thermal damage, was applied to human intervertebral disc in an effort to develop a technique for percutaneous discectomy. Cadaveric samples of human disc were used. Excimer laser energy was produced by a XeCl, magnetically switched, long-pulse laser working at 308 nm, 20 Hz. Annulus tissue of approximately 1 mm thickness was placed in contact with the output tip of a 400 microns core diameter quartz fiber, and measurements of ablation rate were made at different radiant exposures. Ablation rates were found to vary linearly with radiant exposure, from 0.7 micron/pulse at 10 mJ/mm2 to 11.0 microns/pulse at 55 mJ/mm2, with a correlation coefficient of 0.984. Threshold radiant exposure, calculated by extrapolation, was found to be about 7 mJ/mm2. Histologic analysis showed a minimum of thermal damage in these specimens, and when ablated with modification to maintain constant fiber-tissue contact, thermal injury was nearly absent, as compared to samples ablated with Nd:YAG through a contact probe. Thermographic analysis, performed using the AGA 782 Digital Thermography system, showed increasing temperature with increasing radiant exposure, with a maximum temperature of 47.2 degrees C at 55 mJ/mm2. In that precise tissue ablation was demonstrated with minimal generated heat, and excimer energy at 308 nm is transmissible through fiber optics, excimer holds great promise for the development of a percutaneous discectomy technique. PMID:2716456

  7. Nonlinear dynamics of the human lumbar intervertebral disc.

    PubMed

    Marini, Giacomo; Huber, Gerd; Püschel, Klaus; Ferguson, Stephen J

    2015-02-01

    Systems with a quasi-static response similar to the axial response of the intervertebral disc (i.e. progressive stiffening) often present complex dynamics, characterized by peculiar nonlinearities in the frequency response. However, such characteristics have not been reported for the dynamic response of the disc. The accurate understanding of disc dynamics is essential to investigate the unclear correlation between whole body vibration and low back pain. The present study investigated the dynamic response of the disc, including its potential nonlinear response, over a range of loading conditions. Human lumbar discs were tested by applying a static preload to the top and a sinusoidal displacement at the bottom of the disc. The frequency of the stimuli was set to increase linearly from a low frequency to a high frequency limit and back down. In general, the response showed nonlinear and asymmetric characteristics. For each test, the disc had different response in the frequency-increasing compared to the frequency-decreasing sweep. In particular, the system presented abrupt changes of the oscillation amplitude at specific frequencies, which differed between the two sweeps. This behaviour indicates that the system oscillation has a different equilibrium condition depending on the path followed by the stimuli. Preload and amplitude of the oscillation directly influenced the disc response by changing the nonlinear dynamics and frequency of the jump-phenomenon. These results show that the characterization of the dynamic response of physiological systems should be readdressed to determine potential nonlinearities. Their direct effect on the system function should be further investigated. PMID:25573099

  8. Gene expression profile analysis of human intervertebral disc degeneration

    PubMed Central

    Chen, Kai; Wu, Dajiang; Zhu, Xiaodong; Ni, Haijian; Wei, Xianzhao; Mao, Ningfang; Xie, Yang; Niu, Yunfei; Li, Ming

    2013-01-01

    In this study, we used microarray analysis to investigate the biogenesis and progression of intervertebral disc degeneration. The gene expression profiles of 37 disc tissue samples obtained from patients with herniated discs and degenerative disc disease collected by the National Cancer Institute Cooperative Tissue Network were analyzed. Differentially expressed genes between more and less degenerated discs were identified by significant analysis of microarray. A total of 555 genes were significantly overexpressed in more degenerated discs with a false discovery rate of < 3%. Functional annotation showed that these genes were significantly associated with membrane-bound vesicles, calcium ion binding and extracellular matrix. Protein-protein interaction analysis showed that these genes, including previously reported genes such as fibronectin, COL2A1 and β-catenin, may play key roles in disc degeneration. Unsupervised clustering indicated that the widely used morphology-based Thompson grading system was only marginally associated with the molecular classification of intervertebral disc degeneration. These findings indicate that detailed, systematic gene analysis may be a useful way of studying the biology of intervertebral disc degeneration. PMID:24130454

  9. Fibronectin fragments and the cleaving enzyme ADAM-8 in the degenerative human intervertebral disc

    PubMed Central

    Ruel, Nancy; Markova, Dessislava Z.; Adams, Sherrill L.; Scanzello, Carla; Cs-Szabo, Gabriella; Gerard, David; Shi, Peng; Anderson, D. Greg; Zack, Marc; An, Howard S.; Chen, Di; Zhang, Yejia

    2014-01-01

    Study Design The presence fibronectin fragments (FN-fs) and the cleaving enzyme, A disintegrin and metalloproteinase domain-containing protein (ADAM)-8 were examined in human intervertebral disc (IVD) tissue in vitro. Objective To investigate the presence and pathophysiological concentration of FN-fs and their cleaving enzyme, ADAM-8, in the human IVD tissue. Summary of Background Data The 29kDa FN-f has been shown to result in extracellular matrix loss in rabbit IVDs. However, the concentration of this biologically active fragment in the degenerative human IVD tissue has previously not been determined. Further, it is critical to identify the enzyme(s) responsible for FN cleavage in the IVD. Methods Human degenerative IVD tissues were removed during spinal surgery. A normal appearing young adult and an infant human cadaveric sample were obtained as controls. Soluble proteins were extracted, and analyzed by Western blotting utilizing antibodies specific for the human FN neoepitope VRAA271. A purified 29 kDa FN-f was used to allow estimation of the concentration of FN-fs in the tissues. ADAM-8, a FN-cleaving enzyme, was analyzed by Western blotting and immunostaining. Results All adult IVD tissues contain many FN-f species, but these species were absent from the infant disc tissue. Moderately degenerative discs contained the highest amount of FN-fs; the concentration was estimated to be in the nanomolar range per gram of tissue. ADAM-8, known to cleave FN resulting in the VRAA271 neoepitope, was present in the human disc. ADAM-8 primarily localized in the pericellular matrix of the nucleus pulposus (NP) tissue, as determined by immunostaining. Conclusion This is the first report that N-terminal FN-fs are consistently present in IVD tissues from adult subjects. The pathophysiological concentration of these fragments is estimated to be at nanomolar range per gram of IVD tissue. Further, ADAM-8, known to cleave FN, is present at the pericellular matrix of disc cells

  10. Expression and functional roles of estrogen receptor GPR30 in human intervertebral disc.

    PubMed

    Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Yan, Feng; Chong, Beng H; Diwan, Ashish D

    2016-04-01

    Estrogen withdrawal, a characteristic of female aging, is associated with age-related intervertebral disc (IVD) degeneration. The function of estrogen is mediated by two classic nuclear receptors, estrogen receptor (ER)-α and -β, and a membrane bound G-protein-coupled receptor 30 (GPR30). To date, the expression and function of GPR30 in human spine is poorly understood. This study aimed to evaluate GPR30 expression in IVD, and its role in estrogen-related regulation of proliferation and apoptosis of disc nucleus pulposus (NP) cells. GPR30 expression was examined in 30 human adult NP and 9 fetal IVD. Results showed that GPR30 was expressed in NP cells at both mRNA and protein levels. In human fetal IVD, GPR30 protein was expressed in the NP at 12-14 weeks gestation, but was undetectable at 8-11 weeks. The effect of 17β-estradiol (E2) on GPR30-mediated proliferation and interleukin-1β (IL-1β)-induced apoptosis of NP cells was investigated. Cultured NP cells were treated with or without E2, GPR30 antagonist G36, and ER antagonist ICI 182,780. NP cell viability was tested by MTS assay. Apoptosis was determined by flow cytometry using fluorescence labeled annexin-V, TUNEL assay and immumnocytochemical staining of activated caspase-3. E2 enhanced cell proliferation and prevented IL-1β-induced cell death, but the effect was partially blocked by G36 and completely abrogated by a combination of ICI 182,780 and G36. This study demonstrates that GPR30 is expressed in human IVD to transmit signals triggering E2-induced NP cell proliferation and protecting against IL-1β-induced apoptosis. The effects of E2 on NP cells require both GPR30 and classic estrogen receptors. PMID:26815911

  11. Best paper NASS 2013: link-N can stimulate proteoglycan synthesis in the degenerated human intervertebral discs.

    PubMed

    Gawri, Rahul; Antoniou, John; Ouellet, Jean; Awwad, Waleed; Steffen, Thomas; Roughley, Peter; Haglund, Lisbet; Mwale, Fackson

    2013-01-01

    Intervertebral disc (IVD) degeneration is the most common cause of back pain. Presently there is no medical treatment, leaving surgery as the only offered option. Here we evaluate the potential of Link-N to promote extracellular matrix regeneration in human IVDs. Human disc cells cultured in alginate and intact human discs were exposed to a combination of Link-N and ³⁵SO₄ in the presence or absence of interleukin (IL)-1, and the effect on proteoglycan synthesis was evaluated. In addition, message levels of aggrecan, matrix metalloproteinase (MMP)-3, MMP-13, a Disintegrin And Metalloproteinase with Thrombospondin Motifs (ADAMTS)-4 and ADAMTS-5 were evaluated in alginate cultures. Human disc cells responded in a dose dependent manner with maximal proteoglycan synthesis at 1 µg/mL Link-N. Link-N treatment also induced proteoglycan synthesis in intact human discs, and a prolonged effect was found up to one week after Link-N treatment. Message levels of proteinases were decreased by Link-N in the presence of IL-1. Thus, Link-N can promote proteoglycan synthesis and deplete proteinase expression in adult human discs. Link-N could therefore be a promising candidate for biologically-induced disc repair, and could provide an alternative to surgical intervention for early stage disc degeneration. PMID:24027023

  12. Comparison of vertebral and intervertebral disc lesions in aging humans and rhesus monkeys

    PubMed Central

    Bailey, Jeannie F.; Fields, Aaron J.; Liebenberg, Ellen; Mattison, Julie A.; Lotz, Jeffrey C.; Kramer, Patricia A.

    2014-01-01

    Objective To compare gross and histologic patterns of age-related degeneration within the intervertebral disc and adjacent vertebra between rhesus monkeys and humans. Materials and methods We examined age-related patterns of disc degeneration from mid-sagittal sections of the intervertebral disc and adjacent vertebral bodies among six rhesus monkey thoracolumbar and seven human lumbar spines. Gross morphology and histopathology were assessed via the Thompson grading scheme and other degenerative features of the disc and adjacent bone. Results Thompson grades ranged from 3 through 5 for rhesus monkey discs (T9-L1) and 2 through 5 for the human discs (T12-S1). In both rhesus monkey and human discs, presence of distinct lesions were positively associated with Thompson grade of the overall segment. Degenerative patterns differed for radial tears, which were more prevalent with advanced disc degeneration in humans only. Additionally, compared to the more uniform anteroposterior disc degeneration patterns of humans, rhesus monkeys showed more severe osteophytosis and degeneration on the anterior border of the vertebral column. Conclusions Rhesus monkey spines evaluated in the present study appear to develop age-related patterns of disc degeneration similar to humans. One exception is the absence of an association between radial tears and disc degeneration, which could reflect species-specific differences in posture and spinal curvature. Considering rhesus monkeys demonstrate similar patterns of disc degeneration, and age at a faster rate than humans, these findings suggest longitudinal studies of rhesus monkeys may be a valuable model for better understanding the progression of human age-related spinal osteoarthritis and disc degeneration. PMID:24821664

  13. Nerve Growth Factor Is Regulated by Toll-Like Receptor 2 in Human Intervertebral Discs.

    PubMed

    Krock, Emerson; Currie, J Brooke; Weber, Michael H; Ouellet, Jean A; Stone, Laura S; Rosenzweig, Derek H; Haglund, Lisbet

    2016-02-12

    Nerve growth factor (NGF) contributes to the development of chronic pain associated with degenerative connective tissue pathologies, such as intervertebral disc degeneration and osteoarthritis. However, surprisingly little is known about the regulation of NGF in these conditions. Toll-like receptors (TLR) are pattern recognition receptors classically associated with innate immunity but more recently were found to be activated by endogenous alarmins such as fragmented extracellular matrix proteins found in degenerating discs or cartilage. In this study we investigated if TLR activation regulates NGF and which signaling mechanisms control this response in intervertebral discs. TLR2 agonists, TLR4 agonists, or IL-1β (control) treatment increased NGF, brain-derived neurotrophic factor (BDNF), and IL-1β gene expression in human disc cells isolated from healthy, pain-free organ donors. However, only TLR2 activation or IL-1β treatment increased NGF protein secretion. TLR2 activation increased p38, ERK1/2, and p65 activity and increased p65 translocation to the cell nucleus. JNK activity was not affected by TLR2 activation. Inhibition of NF-κB, and to a lesser extent p38, but not ERK1/2 activity, blocked TLR2-driven NGF up-regulation at both the transcript and protein levels. These results provide a novel mechanism of NGF regulation in the intervertebral disc and potentially other pathogenic connective tissues. TLR2 and NF-κB signaling are known to increase cytokines and proteases, which accelerate matrix degradation. Therefore, TLR2 or NF-κB inhibition may both attenuate chronic pain and slow the degenerative progress in vivo. PMID:26668319

  14. Effective modulus of the human intervertebral disc and its effect on vertebral bone stress.

    PubMed

    Yang, Haisheng; Jekir, Michael G; Davis, Maxwell W; Keaveny, Tony M

    2016-05-01

    The mechanism of vertebral wedge fractures remains unclear and may relate to typical variations in the mechanical behavior of the intervertebral disc. To gain insight, we tested 16 individual whole discs (between levels T8 and L5) from nine cadavers (mean±SD: 66±16 years), loaded in compression at different rates (0.05-20.0% strain/s), to measure a homogenized "effective" linear elastic modulus of the entire disc. The measured effective modulus, and average disc height, were then input and varied parametrically in micro-CT-based finite element models (60-μm element size, up to 80 million elements each) of six T9 human vertebrae that were virtually loaded to 3° of moderate forward-flexion via a homogenized disc. Across all specimens and loading rates, the measured effective modulus of the disc ranged from 5.8 to 42.7MPa and was significantly higher for higher rates of loading (p<0.002); average disc height ranged from 2.9 to 9.3mm. The parametric finite element analysis indicated that, as disc modulus increased and disc height decreased across these ranges, the vertebral bone stresses increased but their spatial distribution was largely unchanged: most of the highest stresses occurred in the central trabecular bone and endplates, and not anteriorly. Taken together with the literature, our findings suggest that the effective modulus of the human intervertebral disc should rarely exceed 100MPa and that typical variations in disc effective modulus (and less so, height) minimally influence the spatial distribution but can appreciably influence the magnitude of stress within the vertebral body. PMID:26949100

  15. Experimental observation of human bone marrow mesenchymal stem cell transplantation into rabbit intervertebral discs

    PubMed Central

    Tao, Hao; Lin, Yazhou; Zhang, Guoqing; Gu, Rui; Chen, Bohua

    2016-01-01

    Allogeneic bone marrow mesenchymal stem cell (BMSC) transplantation has been investigated worldwide. However, few reports have addressed the survival status of human BMSCs in the intervertebral discs (IVDs) in vivo following transplantation. The current study aimed to observe the survival status of human BMSCs in rabbit IVDs. The IVDs of 15 New Zealand white rabbits were divided into three groups: Punctured blank control group (L1-2); punctured physiological saline control group (L2-3); and punctured human BMSCs transfected with green fluorescent protein (GFP) group (L3-4, L4-5 and L5-6). One, 2, 4, 6 and 8 weeks after transplantation the IVDs were removed and a fluorescence microscope was used to observe the density of GFP-positive human BMSCs. The results indicated that in the sections of specimens removed at 1, 2, 4, 6 and 8 weeks post-transplantation, no GFP-positive cells were observed in the control groups, whereas GFP-positive cells were apparent in the nucleus pulposus at all periods in the GFP-labeled human BMSCs group, and the cell density at 6 and 8 weeks was significantly less than that at 1, 2 and 4 weeks post-transplantation (P<0.001). Thus, it was identified that human BMSCs were able to survive in the rabbit IVDs for 8 weeks. PMID:27588177

  16. Mechanical Characterization of the Human Lumbar Intervertebral Disc Subjected to Impact Loading Conditions

    NASA Astrophysics Data System (ADS)

    Jamison, David, IV

    Low back pain is a large and costly problem in the United States. Several working populations, such as miners, construction workers, forklift operators, and military personnel, have an increased risk and prevalence of low back pain compared to the general population. This is due to exposure to repeated, transient impact shocks, particularly while operating vehicles or other machinery. These shocks typically do not cause acute injury, but rather lead to pain and injury over time. The major focus in low back pain is often the intervertebral disc, due to its role as the major primary load-bearing component along the spinal column. The formation of a reliable standard for human lumbar disc exposure to repeated transient shock could potentially reduce injury risk for these working populations. The objective of this project, therefore, is to characterize the mechanical response of the lumbar intervertebral disc subjected to sub-traumatic impact loading conditions using both cadaveric and computational models, and to investigate the possible implications of this type of loading environment for low back pain. Axial, compressive impact loading events on Naval high speed boats were simulated in the laboratory and applied to human cadaveric specimen. Disc stiffness was higher and hysteresis was lower than quasi-static loading conditions. This indicates a shift in mechanical response when the disc is under impact loads and this behavior could be contributing to long-term back pain. Interstitial fluid loss and disc height changes were shown to affect disc impact mechanics in a creep study. Neutral zone increased, while energy dissipation and low-strain region stiffness decreased. This suggests that the disc has greater clinical instability during impact loading with progressive creep and fluid loss, indicating that time of day should be considered for working populations subjected to impact loads. A finite element model was developed and validated against cadaver specimen

  17. Human cartilage endplate permeability varies with degeneration and intervertebral disc site.

    PubMed

    DeLucca, John F; Cortes, Daniel H; Jacobs, Nathan T; Vresilovic, Edward J; Duncan, Randall L; Elliott, Dawn M

    2016-02-29

    Despite the critical functions the human cartilage endplate (CEP) plays in the intervertebral disc, little is known about its structural and mechanical properties and their changes with degeneration. Quantifying these changes with degeneration is important for understanding how the CEP contributes to the function and pathology of the disc. Therefore the objectives of this study were to quantify the effect of disc degeneration on human CEP mechanical properties, determine the influence of superior and inferior disc site on mechanics and composition, and simulate the role of collagen fibers in CEP and disc mechanics using a validated finite element model. Confined compression data and biochemical composition data were used in a biphasic-swelling model to calculate compressive extrafibrillar elastic and permeability properties. Tensile properties were obtained by applying published tensile test data to an ellipsoidal fiber distribution. Results showed that with degeneration CEP permeability decreased 50-60% suggesting that transport is inhibited in the degenerate disc. CEP fibers are organized parallel to the vertebrae and nucleus pulposus and may contribute to large shear strains (0.1-0.2) and delamination failure of the CEP commonly seen in herniated disc tissue. Fiber-reinforcement also reduces CEP axial strains thereby enhancing fluid flux by a factor of 1.8. Collectively, these results suggest that the structure and mechanics of the CEP may play critical roles in the solute transport and disc mechanics. PMID:26874969

  18. Temporal changes of mechanical signals and extracellular composition in human intervertebral disc during degenerative progression

    PubMed Central

    Zhu, Qiaoqiao; Gao, Xin; Gu, Weiyong

    2014-01-01

    In this study, a three-dimensional finite element model was used to investigate the changes in tissue composition and mechanical signals within human lumbar intervertebral disc during the degenerative progression. This model was developed based on the cell-activity coupled mechano-electrochemical mixture theory. The disc degeneration was simulated by lowering nutrition levels at disc boundaries, and the temporal and spatial distributions of the fixed charge density, water content, fluid pressure, Von Mises stress, and disc deformation were analyzed. Results showed that fixed charge density, fluid pressure, and water content decreased significantly in the nucleus pulposus (NP) and the inner to middle annulus fibrosus (AF) regions of the degenerative disc. It was found that, with degenerative progression, the Von Mises stress (relative to that at healthy state) increased within the disc, with a larger increase in the outer AF region. Both the disc volume and height decreased with the degenerative progression. The predicted results of fluid pressure change in the NP were consistent with experimental findings in the literature. The knowledge of the variations of temporal and spatial distributions of composition and mechanical signals within the human IVDs provide a better understanding of the progression of disc degeneration. PMID:25305690

  19. Down-Regulated CK8 Expression in Human Intervertebral Disc Degeneration

    PubMed Central

    Sun, Zhen; Wang, Hai-Qiang; Liu, Zhi-Heng; Chang, Le; Chen, Yu-Fei; Zhang, Yong-Zhao; Zhang, Wei-Lin; Gao, Yang; Wan, Zhong-Yuan; Che, Lu; Liu, Xu; Samartzis, Dino; Luo, Zhuo-Jing

    2013-01-01

    As an intermediate filament protein, cytokeratin 8 (CK8) exerts multiple cellular functions. Moreover, it has been identified as a marker of notochord cells, which play essential roles in human nucleus pulposus (NP). However, the distribution of CK8 positive cells in human NP and their relationship with intervertebral disc degeneration (IDD) have not been clarified until now. Here, we found the percentage of CK8 positive cells in IDD (25.7±4.14%) was significantly lower than that in normal and scoliosis NP (51.9±9.73% and 47.8±5.51%, respectively, p<0.05). Western blotting and qRT-PCR results confirmed the down-regulation of CK8 expression in IDD on both of protein and mRNA levels. Furthermore, approximately 37.4% of cell clusters were CK8 positive in IDD. Taken together, this is the first study to show a down-regulated CK8 expression and the percentage of CK8 positive cell clusters in IDD based upon multiple lines of evidence. Consequently, CK8 positive cells might be considered as a potential option in the development of cellular treatment strategies for NP repair. PMID:23801880

  20. Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

    PubMed Central

    Gantenbein, Benjamin; Illien-Jünger, Svenja; Chan, Samantha CW; Walser, Jochen; Haglund, Lisbet; Ferguson, Stephen J; Iatridis, James C; Grad, Sibylle

    2015-01-01

    In recent decades the application of bioreactors has revolutionized the concept of culturing tissues and organs that require mechanical loading. In intervertebral disc (IVD) research, collaborative efforts of biomedical engineering, biology and mechatronics have led to the innovation of new loading devices that can maintain viable IVD organ explants from large animals and human cadavers in precisely defined nutritional and mechanical environments over extended culture periods. Particularly in spine and IVD research, these organ culture models offer appealing alternatives, as large bipedal animal models with naturally occurring IVD degeneration and a genetic background similar to the human condition do not exist. Latest research has demonstrated important concepts including the potential of homing of mesenchymal stem cells to nutritionally or mechanically stressed IVDs, and the regenerative potential of “smart” biomaterials for nucleus pulposus or annulus fibrosus repair. In this review, we summarize the current knowledge about cell therapy, injection of cytokines and short peptides to rescue the degenerating IVD. We further stress that most bioreactor systems simplify the real in vivo conditions providing a useful proof of concept. Limitations are that certain aspects of the immune host response and pain assessments cannot be addressed with ex vivo systems. Coccygeal animal disc models are commonly used because of their availability and similarity to human IVDs. Although in vitro loading environments are not identical to the human in vivo situation, 3D ex vivo organ culture models of large animal coccygeal and human lumbar IVDs should be seen as valid alternatives for screening and feasibility testing to augment existing small animal, large animal, and human clinical trial experiments. PMID:25764196

  1. The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration

    PubMed Central

    Le Maitre, Christine Lyn; Freemont, Anthony J; Hoyland, Judith Alison

    2005-01-01

    In this study, we investigated the hypotheses that in human intervertebral disc (IVD) degeneration there is local production of the cytokine IL-1, and that this locally produced cytokine can induce the cellular and matrix changes of IVD degeneration. Immunohistochemistry was used to localize five members of the IL-1 family (IL-1α, IL-1β, IL-1Ra (IL-1 receptor antagonist), IL-1RI (IL-1 receptor, type I), and ICE (IL-1β-converting enzyme)) in non-degenerate and degenerate human IVDs. In addition, cells derived from non-degenerate and degenerate human IVDs were challenged with IL-1 agonists and the response was investigated using real-time PCR for a number of matrix-degrading enzymes, matrix proteins, and members of the IL-1 family. This study has shown that native disc cells from non-degenerate and degenerate discs produced the IL-1 agonists, antagonist, the active receptor, and IL-1β-converting enzyme. In addition, immunopositivity for these proteins, with the exception of IL-1Ra, increased with severity of degeneration. We have also shown that IL-1 treatment of human IVD cells resulted in increased gene expression for the matrix-degrading enzymes (MMP 3 (matrix metalloproteinase 3), MMP 13 (matrix metalloproteinase 13), and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs)) and a decrease in the gene expression for matrix genes (aggrecan, collagen II, collagen I, and SOX6). In conclusion we have shown that IL-1 is produced in the degenerate IVD. It is synthesized by native disc cells, and treatment of human disc cells with IL-1 induces an imbalance between catabolic and anabolic events, responses that represent the changes seen during disc degeneration. Therefore, inhibiting IL-1 could be an important therapeutic target for preventing and reversing disc degeneration. PMID:15987475

  2. Laser radiation at various wavelengths for decompression of intervertebral disk. Experimental observations on human autopsy specimens.

    PubMed

    Choy, D S; Altman, P A; Case, R B; Trokel, S L

    1991-06-01

    The interaction of laser radiation with the nucleus pulposus from autopsy specimens of human intervertebral disks was evaluated at different wavelengths (193 nm, 488 nm & 514 nm, 1064 nm, 1318 nm, 2150 nm, 2940 nm, and 10600 nm). A significant correlation of linear least squares fit of the mass ablated as a function of incident energy was found for all lasers used except the Excimer at 193 nm. The 2940-nm Erbium:YAG laser was most efficient in terms of mass of disk ablated per joule in the limited lower range where this wavelength was observed. At higher energy levels, the CO2 laser in the pulsed mode was most efficient. However, the Nd:YAG 1064-nm and 1318-nm lasers are currently best suited for percutaneous laser disk decompression because of the availability of usable waveguides. Carbonization of tissue with the more penetrating Nd:YAG 1064-nm laser increases the efficiency of tissue ablation and makes it comparable to the Nd:YAG 1318-nm laser. PMID:1904334

  3. Noncoding RNAs in human intervertebral disc degeneration: An integrated microarray study

    PubMed Central

    Liu, Xu; Che, Lu; Xie, Yan-Ke; Hu, Qing-Jie; Ma, Chi-Jiao; Pei, Yan-Jun; Wu, Zhi-Gang; Liu, Zhi-Heng; Fan, Li-Ying; Wang, Hai-Qiang

    2015-01-01

    Accumulating evidence indicates that noncoding RNAs play important roles in a multitude of biological processes. The striking findings of miRNAs (microRNAs) and lncRNAs (long noncoding RNAs) as members of noncoding RNAs open up an exciting era in the studies of gene regulation. More recently, the reports of circRNAs (circular RNAs) add fuel to the noncoding RNAs research. Human intervertebral disc degeneration (IDD) is a main cause of low back pain as a disabling spinal disease. We have addressed the expression profiles if miRNAs, lncRNAs and mRNAs in IDD (Wang et al., J Pathology, 2011 and Wan et al., Arthritis Res Ther, 2014). Furthermore, we thoroughly analysed noncoding RNAs, including miRNAs, lncRNAs and circRNAs in IDD using the very same samples. Here we delineate in detail the contents of the aforementioned microarray analyses. Microarray and sample annotation data were deposited in GEO under accession number GSE67567 as SuperSeries. The integrated analyses of these noncoding RNAs will shed a novel light on coding-noncoding regulatory machinery. PMID:26484230

  4. Noncoding RNAs in human intervertebral disc degeneration: An integrated microarray study.

    PubMed

    Liu, Xu; Che, Lu; Xie, Yan-Ke; Hu, Qing-Jie; Ma, Chi-Jiao; Pei, Yan-Jun; Wu, Zhi-Gang; Liu, Zhi-Heng; Fan, Li-Ying; Wang, Hai-Qiang

    2015-09-01

    Accumulating evidence indicates that noncoding RNAs play important roles in a multitude of biological processes. The striking findings of miRNAs (microRNAs) and lncRNAs (long noncoding RNAs) as members of noncoding RNAs open up an exciting era in the studies of gene regulation. More recently, the reports of circRNAs (circular RNAs) add fuel to the noncoding RNAs research. Human intervertebral disc degeneration (IDD) is a main cause of low back pain as a disabling spinal disease. We have addressed the expression profiles if miRNAs, lncRNAs and mRNAs in IDD (Wang et al., J Pathology, 2011 and Wan et al., Arthritis Res Ther, 2014). Furthermore, we thoroughly analysed noncoding RNAs, including miRNAs, lncRNAs and circRNAs in IDD using the very same samples. Here we delineate in detail the contents of the aforementioned microarray analyses. Microarray and sample annotation data were deposited in GEO under accession number GSE67567 as SuperSeries. The integrated analyses of these noncoding RNAs will shed a novel light on coding-noncoding regulatory machinery. PMID:26484230

  5. Dynamic loading, matrix maintenance and cell injection therapy of human intervertebral discs cultured in a bioreactor.

    PubMed

    Rosenzweig, D H; Gawri, R; Moir, J; Beckman, L; Eglin, D; Steffen, T; Roughley, P J; Ouellet, J A; Haglund, L

    2016-01-01

    Low back pain originating from intervertebral disc (IVD) degeneration affects the quality of life for millions of people, and it is a major contributor to global healthcare costs. Long-term culture of intact IVDs is necessary to develop ex vivo models of human IVD degeneration and repair, where the relationship between mechanobiology, disc matrix composition and metabolism can be better understood. A bioreactor was developed that facilitates culture of intact human IVDs in a controlled, dynamically loaded environment. Tissue integrity and cell viability was evaluated under 3 different loading conditions: low 0.1-0.3, medium 0.1-0.3 and high 0.1-1.2 MPa. Cell viability was maintained > 80 % throughout the disc at low and medium loads, whereas it dropped to approximately 70 % (NP) and 50 % (AF) under high loads. Although cell viability was affected at high loads, there was no evidence of sGAG loss, changes in newly synthesised collagen type II or chondroadherin fragmentation. Sulphated GAG content remained at a stable level of approximately 50 µg sGAG/mg tissue in all loading protocols. To evaluate the feasibility of tissue repair strategies with cell supplementation, human NP cells were transplanted into discs within a thermoreversible hyaluronan hydrogel. The discs were loaded under medium loads, and the injected cells remained largely localised to the NP region. This study demonstrates the feasibility of culturing human IVDs for 14 days under cyclic dynamic loading conditions. The system allows the determination a safe range-of-loading and presents a platform to evaluate cell therapies and help to elucidate the effect of load following cell-based therapies. PMID:26728497

  6. Acid-sensing ion channels in healthy and degenerated human intervertebral disc.

    PubMed

    Cuesta, Antonio; Del Valle, Miguel E; García-Suárez, Olivia; Viña, Eliseo; Cabo, Roberto; Vázquez, Gorka; Cobo, Juan L; Murcia, Antonio; Alvarez-Vega, Marco; García-Cosamalón, José; Vega, José A

    2014-06-01

    Acid-sensing ion channels (ASICs) are a family of H(+)-gated voltage-insensitive ion channels that respond to extracellular acidification by regulating transmembrane Ca(2+) flux. Moreover, ASICs can also be gated by mechanical forces and may function as mechanosensors. The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. Changes in the pH and osmolarity determine the viability of IVD cells and the composition of the extracellular matrix, and both are the basis of IVD degeneration. In this study, the expression of ASICs (ASIC1, ASIC2, ASIC3 and ASIC4) mRNAs and proteins in human healthy and degenerated IVD was evaluated by quantitative reverse transcription-quantitative polymerase chain reaction and Western blot. The distribution of ASIC proteins was determined by immunohistochemistry. The mRNAs for all ASICs were detected in normal human IVD, and significantly increased levels were found in degenerated IVD. Western blots demonstrated the presence of proteins with estimated molecular weights of approximately 68-72 kDa. In both the annulus fibrosus (AF) and nucleus pulposus (NP) of normal IVD, ASIC2 is the most frequently expressed ASIC followed by ASIC3, ASIC1 and ASIC4. In the AF of degenerated IVD, there was a significant increase in the number of ASIC1 and ASIC4 positive cells, whereas in the NP, we found significant increase of expression of ASIC1, ASIC2 and ASIC3. These results describe the occurrence and localization of different ASICs in human healthy IVD, and their increased expression in degenerated IVD, thus suggesting that ASICs may be involved in IVD degeneration. PMID:24432912

  7. Axial Creep Loading and Unloaded Recovery of the Human Intervertebral Disc and the Effect of Degeneration

    PubMed Central

    O'Connell, Grace D.; Jacobs, Nathan T.; Sen, Sounok; Vresilovic, Edward J.; Elliott, Dawn M.

    2011-01-01

    The intervertebral disc maintains a balance between externally applied loads and internal osmotic pressure. Fluid flow plays a key role in this process, causing fluctuations in disc hydration and height. The objectives of this study were to quantify and model the axial creep and recovery responses of nondegenerate and degenerate human lumbar discs. Two experiments were performed. First, a slow compressive ramp was applied to 2000 N, unloaded to allow recovery for up to 24 hours, and re-applied. The linear-region stiffness and disc height were within 5% of the initial condition for recovery times greater than 8 hours. In the second experiment, a 1000 N creep load was applied for four hours, unloaded recovery monitored for 24 hours, and the creep load repeated. A viscoelastic model comprised of a “fast” and “slow” exponential response was used to describe the creep and recovery, where the fast response is associated with flow in the nucleus pulposus (NP) and endplate, while the slow response is associated with the annulus fibrosus (AF). The study demonstrated that recovery is 3-4X slower than loading. The fast response was correlated with degeneration, suggesting larger changes in the NP with degeneration compared to the AF. However, the fast response comprised only 10-15% of the total equilibrium displacement, with the AF-dominated slow response comprising 40-70%. Finally, the physiological loads and deformations and their associated long equilibrium times confirm that diurnal loading does not represent “equilibrium” in the disc, but that over time the disc is in steady-state. PMID:21783103

  8. Role of microRNA-210 in human intervertebral disc degeneration

    PubMed Central

    ZHANG, DA-YING; WANG, ZHI-JIAN; YU, YAN-BO; ZHANG, YONG; ZHANG, XUE-XUE

    2016-01-01

    The present study aimed to investigate the role of microRNA (miR)-210 in the development of intervertebral disc degeneration (IDD). Human nucleus pulposus (NP) samples were collected from patients with scoliosis and IDD (n=12 each) as the scoliosis control and IDD groups, respectively. The expression levels of miR-210 were detected using reverse-transcription quantitative polymerase chain reaction. In vitro overexpression and knockdown of miR-210 in human NP cells were achieved by transfection of NP cells with lentiviral pre-miR-210 and antagomiR-210, respectively. The protein expression levels of homeobox A9 (HOXA9) were then detected in NP cells with modulated miR-210 using western blot analysis. Flow cytometry with allophycocyanin-Annexin V/7 and 7-aminoactinomycin D staining was also used to detect the proportion of NP cells with modulated miR-210 undergoing apoptosis. The current study revealed that the miR-210 expression was decreased in patients with IDD compared with that of the scoliosis control group (P<0.05). Furthermore, the upregulation of miR-210 with pre-miR-210 led to the repression of HOXA9. The HOXA9 level was significantly lower in these cells compared with that of NP cells treated with a corresponding negative sequence (P<0.05). Knockdown of miR-210 with antagomiR-210 resulted in upregulation of HOXA9 in NP cells, determined as the level of HOXA9 was significantly higher than that of NP cells treated with a negative sequence (P<0.05). The proportion of apoptotic NP cells also significantly decreased following treatment with pre-miR-210 compared with the scoliosis control group (12.1±1.43 vs. 23.8±1.22%, respectively; P<0.05). In conclusion, downregulation of miR-210 may promote Fas-mediated apoptosis in human IDD by regulating the expression of HOXA9. This indicates that miR-210 may be closely associated with the development of IDD and may act as a novel target in IDD treatment. PMID:27284319

  9. A forward dynamics simulation of human lumbar spine flexion predicting the load sharing of intervertebral discs, ligaments, and muscles.

    PubMed

    Rupp, T K; Ehlers, W; Karajan, N; Günther, M; Schmitt, S

    2015-10-01

    Determining the internal dynamics of the human spine's biological structure is one essential step that allows enhanced understanding of spinal degeneration processes. The unavailability of internal load figures in other methods highlights the importance of the forward dynamics approach as the most powerful approach to examine the internal degeneration of spinal structures. Consequently, a forward dynamics full-body model of the human body with a detailed lumbar spine is introduced. The aim was to determine the internal dynamics and the contribution of different spinal structures to loading. The multi-body model consists of the lower extremities, two feet, shanks and thighs, the pelvis, five lumbar vertebrae, and a lumped upper body including the head and both arms. All segments are modelled as rigid bodies. 202 muscles (legs, back, abdomen) are included as Hill-type elements. 58 nonlinear force elements are included to represent all spinal ligaments. The lumbar intervertebral discs were modelled nonlinearly. As results, internal kinematics, muscle forces, and internal loads for each biological structure are presented. A comparison between the nonlinear (new, enhanced modelling approach) and linear (standard modelling approach, bushing) modelling approaches of the intervertebral disc is presented. The model is available to all researchers as ready-to-use C/C++ code within our in-house multi-body simulation code demoa with all relevant binaries included. PMID:25653134

  10. Elastic, Permeability and Swelling Properties of Human Intervertebral Disc Tissues: A Benchmark for Tissue engineering

    PubMed Central

    Cortes, Daniel H.; Jacobs, Nathan T.; DeLucca, John F.; Elliott, Dawn M.

    2014-01-01

    SUMMARY The aim of functional tissue engineering is to repair and replace tissues that have a biomechanical function, i.e., connective orthopaedic tissues. To do this, it is necessary to have accurate benchmarks for the elastic, permeability, and swelling (i.e., biphasic-swelling) properties of native tissues. However, in the case of the intervertebral disc, the biphasic-swelling properties of individual tissues reported in the literature exhibit great variation and even span several orders of magnitude. This variation is probably caused by differences in the testing protocols and the constitutive models used to analyze the data. Therefore, the objective of this study was to measure the human lumbar disc annulus fibrosus (AF), nucleus pulposus (NP), and cartilaginous endplates (CEP) biphasic-swelling properties using a consistent experimental protocol and analyses. The testing protocol was composed of a swelling period followed by multiple confined compression ramps. To analyze the confined compression data, the tissues were modeled using a biphasic-swelling model, which augments the standard biphasic model through the addition of a deformation-dependent osmotic pressure term. This model allows considering the swelling deformations and the contribution of osmotic pressure in the analysis of the experimental data. The swelling stretch was not different between the disc regions (AF: 1.28±0.16; NP: 1.73±0.74; CEP: 1.29±0.26), with a total average of 1.42. The aggregate modulus (Ha) of the matrix was higher in the CEP (390 kPa) compared to the NP (100 kPA) or AF (30 kPa). The permeability was very different across tissues regions, with the AF permeability (80 E−4 mm4/Ns) higher than the NP and CEP (6-7 E−16 m4/Ns). Additionally, a normalized time-constant (3000 sec) for the stress relaxation was similar for all the disc tissues. The properties measured in this study are important as benchmarks for tissue engineering and for modeling the disc's mechanical

  11. The Changes in the Expression of NF-KB in a Degenerative Human Intervertebral Disc model.

    PubMed

    Sun, Zhongyi; Yin, Zhanmin; Liu, Chao; Tian, Jiwei

    2015-05-01

    We aim at determining the changes in the expression of NF-kB signaling pathway in degenerative intervertebral discs. We collected normal and degenerated intervertebral discs tissues. The normal and degenerated cells were cultivated and their histopathology and immunofluoresence studies were used to observe the position of NF-kB p65 in the cell. We also treated the nucleus pulposus cells with inflammatory factors and inhibitors. Western blot was used to analyze the expression of different proteins. Real time fluorescence-based quantitative PCR was used for observation of NF-kB regulation of change in gene expression. Immunofluorescence showed that in the non-degenerative group the p65 was found in the cytoplasm of the nucleus pulposus cell while in the degenerated cell group the p65 protein was found in the nucleus of the cell. The expression of p65 increased with increase in the degree of degenerative change of the nucleus pulposus cell. RT-PCR showed that the expression of matrix metalloproteinases, aggrecanases and IL-6 was higher in the degenerative group. The amount of aggrecan and type II collagen was significantly decreased in the degenerative group. IL-1β was able to upregulate the activation of NF-kB and the expression of MMP-13 and ADAMTS-4 was also significantly increased. The effect of these proteins can be inhibited by the NF-kB inhibitor, BAY11-7082. The activation of the NK-kB signaling pathway in a degenerative intervertebral disc is gradually increased, regulating the over-expression of matrix-degrading enzymes. It plays an important role in the degradation of extracellular matrix. PMID:25433723

  12. The Effects of TWEAK, Fn14, and TGF-β1 on Degeneration of Human Intervertebral Disc

    PubMed Central

    Huh, Hoon; Kim, Jung-Hee; Kong, Min-Ho; Song, Kwan-Young; Choi, Gun

    2010-01-01

    Objective The purpose of this study is to explain the effect and reciprocal action among tumor necrosis factor (TNF) like weak inducer of apoptosis (TWEAK), fibroblast growth factor-inducible 14 (Fn14), and transforming growth factor-β1 (TGF-β1) on degeneration of human intervertebral disc (IVD). Methods Human intervertebral disc tissues and cells were cultured with Dulbecco's Modified Eagle's Medium/Nutrient F-12 Ham (DMEM/F-12) media in 37℃, 5% CO2 incubator. When IVD tissues were cultured with TWEAK, Fn14 that is an antagonistic receptor for TWEAK and TGF-β1, the level of sulfated glycosaminoglycan (sGAG) was estimated by dimethyl methyleneblue (DMMB) assay and sex determining region Y (SRY)-box 9 (Sox9) and versican messenger ribonucleic acid (mRNA) levels were estimated by reverse transcriptase polymerase chain reaction (RT-PCR). Results When human IVD tissue was cultured for nine days, the sGAG content was elevated in proportion to culture duration. The sGAG was decreased significantly by TWEAK 100 ng/mL, however, Fn14 500 ng/mL did not change the sGAG production of IVD tissue. The Fn14 increased versican and Sox9 mRNA levels decreased with TWEAK in IVD tissue TGF-β1 20 ng/mL elevated the sGAG concentration 40% more than control. The sGAG amount decreased with TWEAK was increased with Fn14 or TGF-β1 but the result was insignificant statistically. TGF-β1 increased the Sox9 mRNA expression to 180% compared to control group in IVD tissue. Sox9 and versican mRNA levels decreased by TWEAK were increased with TGF-β1 in primary cultured IVD cells, however, Fn14 did not show increasing effect on Sox9 and versican. Conclusion This study suggests that TWEAK would act a role in intervertebral disc degeneration through decreasing sGAG and the mRNA level of versican and Sox9. PMID:20157375

  13. Human L3L4 intervertebral disc mean 3D shape, modes of variation, and their relationship to degeneration

    PubMed Central

    Peloquin, John M.; Yoder, Jonathon H.; Jacobs, Nathan T.; Moon, Sung M.; Wright, Alexander C.; Vresilovic, Edward J.; Elliott, Dawn M.

    2014-01-01

    Intervertebral disc mechanics are affected by both disc shape and disc degeneration, which in turn each affect the other; disc mechanics additionally have a role in the etiology of disc degeneration. Finite element analysis (FEA) is a favored tool to investigate these relationships, but limited data for intervertebral disc 3D shape has forced the use of simplified or single-subject geometries, with the effect of inter-individual shape variation investigated only in specialized studies. Similarly, most data on disc shape variation with degeneration is based on 2D mid-sagittal images, which incompletely define 3D shape changes. Therefore, the objective of this study was to quantify inter-individual disc shape variation in 3D, classify this variation into independently-occurring modes using a statistical shape model, and identify correlations between disc shape and degeneration. Three-dimensional disc shapes were obtained from MRI of 13 human male cadaver L3L4 discs. An average disc shape and four major modes of shape variation (representing 90% of the variance) were identified. The first mode represented disc axial area and was significantly correlated to degeneration (R2 = 0.44), indicating larger axial area in degenerate discs. Disc height variation occurred in three distinct modes, each also involving non-height variation. The statistical shape model provides an average L3L4 disc shape for FEA that is fully defined in 3D, and makes it convenient to generate a set of shapes with which to represent aggregate inter-individual variation. Degeneration grade-specific shapes can also be generated. To facilitate application, the model is included in this paper’s supplemental content. PMID:24792581

  14. Human metapneumovirus in adults.

    PubMed

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

    2013-01-01

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

  15. Human Metapneumovirus in Adults

    PubMed Central

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

    2013-01-01

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

  16. Tissue engineering strategies applied in the regeneration of the human intervertebral disk.

    PubMed

    Silva-Correia, Joana; Correia, Sandra I; Oliveira, Joaquim M; Reis, Rui L

    2013-12-01

    Low back pain (LBP) is one of the most common painful conditions that lead to work absenteeism, medical visits, and hospitalization. The majority of cases showing signs of LBP are due to age-related degenerative changes in the intervertebral disk (IVD), which are, in fact, associated with multiple spine pathologies. Traditional and more conservative procedures/clinical approaches only treat the symptoms of disease and not the underlying pathology, thus limiting their long-term efficiency. In the last few years, research and development of new approaches aiming to substitute the nucleus pulposus and annulus fibrosus tissue and stimulate its regeneration has been conducted. Regeneration of the damaged IVD using tissue engineering strategies appears particularly promising in pre-clinical studies. Meanwhile, surgical techniques must be adapted to this new approach in order to be as minimally invasive as possible, reducing recovering time and side effects associated to traditional surgeries. In this review, the current knowledge on IVD, its associated pathologies and current surgical procedures are summarized. Furthermore, it also provides a succinct and up-to-date overview on regenerative medicine research, especially on the newest tissue engineering strategies for IVD regeneration. PMID:23911974

  17. Morphological similarities after compression trauma of bovine and human intervertebral discs: Do disc cells have a chance of surviving?

    PubMed

    Sitte, Ingrid; Kathrein, Anton; Klosterhuber, Miranda; Lindtner, Richard Andreas; Neururer, Sabrina Barbara; Rauch, Stefan; Kuhn, Volker; Schmoelz, Werner

    2014-09-01

    To study the behavior of bovine disc cells and changes in disc matrix following in vitro compression tests; to compare the findings to investigations on human intervertebral discs (IVD) after burst fracture of the cervical spine. Healthy IVDs (n = 21) from three bovine tails were studied at 6 and 12 h post-mortem, with 16 IVDs subjected to impact loading and five as unloaded controls. IVDs (n = 8) from patients with burst fractures were compared to the bovine compression group. Specimens were studied macroscopically, histologically, and ultrastructurally for healthy cells, balloon cells, and disc cell death (DCD). Annulus ruptures were seen in both post-trauma groups, with radial ruptures being present histologically in all loaded bovine discs. Balloon cells were found in some human IVDs and were induced in vitro in bovine loaded discs within a distinct range of absorbed energy. There was a positive correlation between DCD and absorbed energy in all compartments of bovine discs. Both species showed similar patterns of DCD in the different compartments. This study was able to show similarities between both species in cell morphologies and matrix damage. The survival of the disc after substantial compression trauma thus seems to remain highly questionable. PMID:24888549

  18. Low level light therapy modulates inflammatory mediators secreted by human annulus fibrosus cells during intervertebral disc degeneration in vitro.

    PubMed

    Hwang, Min Ho; Shin, Jae Hee; Kim, Kyoung Soo; Yoo, Chang Min; Jo, Ga Eun; Kim, Joo Han; Choi, Hyuk

    2015-01-01

    Intervertebral disc degeneration (IVD) is one of the important causes of low back pain and is associated with inflammation induced by interaction between macrophages and the human annulus fibrosus (AF) cells. Low-level light therapy (LLLT) has been widely known to regulate inflammatory reaction. However, the effect of LLLT on macrophage-mediated inflammation in the AF cells has not been studied till date. The aim of this study is to mimic the inflammatory microenvironment and to investigate the anti-inflammatory effect of LLLT at a range of wavelengths (405, 532 and 650 nm) on the AF treated with macrophage-like THP-1 cells conditioned medium (MCM) containing proinflammatory cytokines and chemokines (interleukin-1beta, tumor necrosis factor-alpha, interleukin-6 and 8). We observed that AF cells exposed to MCM secrete significantly higher concentrations of IL-6, IL-8, IL-1β and TNF-α. LLLT markedly inhibited secretion of IL-6 at 405 nm in a time-dependent manner. Level of IL-8 was significantly decreased at all wavelengths in a time-dependent manner. We showed that MCM can induce the inflammatory microenvironment in AF cells and LLLT selectively suppressed IL-6 and 8 levels. The results indicate that LLLT is a potential method of IVD treatment and provide insights into further investigation of its anti-inflammation effect on IVD. PMID:25557915

  19. Calibration of hyperelastic material properties of the human lumbar intervertebral disc under fast dynamic compressive loads.

    PubMed

    Wagnac, Eric; Arnoux, Pierre-Jean; Garo, Anaïs; El-Rich, Marwan; Aubin, Carl-Eric

    2011-10-01

    Under fast dynamic loading conditions (e.g. high-energy impact), the load rate dependency of the intervertebral disc (IVD) material properties may play a crucial role in the biomechanics of spinal trauma. However, most finite element models (FEM) of dynamic spinal trauma uses material properties derived from quasi-static experiments, thus neglecting this load rate dependency. The aim of this study was to identify hyperelastic material properties that ensure a more biofidelic simulation of the IVD under a fast dynamic compressive load. A hyperelastic material law based on a first-order Mooney-Rivlin formulation was implemented in a detailed FEM of a L2-L3 functional spinal unit (FSU) to represent the mechanical behavior of the IVD. Bony structures were modeled using an elasto-plastic Johnson-Cook material law that simulates bone fracture while ligaments were governed by a viscoelastic material law. To mimic experimental studies performed in fast dynamic compression, a compressive loading velocity of 1 m/s was applied to the superior half of L2, while the inferior half of L3 was fixed. An exploratory technique was used to simulate dynamic compression of the FSU using 34 sets of hyperelastic material constants randomly selected using an optimal Latin hypercube algorithm and a set of material constants derived from quasi-static experiments. Selection or rejection of the sets of material constants was based on compressive stiffness and failure parameters criteria measured experimentally. The two simulations performed with calibrated hyperelastic constants resulted in nonlinear load-displacement curves with compressive stiffness (7335 and 7079 N/mm), load (12,488 and 12,473 N), displacement (1.95 and 2.09 mm) and energy at failure (13.5 and 14.7 J) in agreement with experimental results (6551 ± 2017 N/mm, 12,411 ± 829 N, 2.1 ± 0.2 mm and 13.0 ± 1.5 J respectively). The fracture pattern and location also agreed with experimental results. The simulation performed with

  20. Regenerative and Immunogenic Characteristics of Cultured Nucleus Pulposus Cells from Human Cervical Intervertebral Discs

    PubMed Central

    Stich, Stefan; Stolk, Meaghan; Girod, Pierre Pascal; Thomé, Claudius; Sittinger, Michael; Ringe, Jochen; Seifert, Martina; Hegewald, Aldemar Andres

    2015-01-01

    Cell-based regenerative approaches have been suggested as primary or adjuvant procedures for the treatment of degenerated intervertebral disc (IVD) diseases. Our aim was to evaluate the regenerative and immunogenic properties of mildly and severely degenerated cervical nucleus pulposus (NP) cells with regard to cell isolation, proliferation and differentiation, as well as to cell surface markers and co-cultures with autologous or allogeneic peripheral blood mononuclear cells (PBMC) including changes in their immunogenic properties after 3-dimensional (3D)-culture. Tissue from the NP compartment of 10 patients with mild or severe grades of IVD degeneration was collected. Cells were isolated, expanded with and without basic fibroblast growth factor and cultured in 3D fibrin/poly (lactic-co-glycolic) acid transplants for 21 days. Real-time reverse-transcription polymerase chain reaction (RT-PCR) showed the expression of characteristic NP markers ACAN, COL1A1 and COL2A1 in 2D- and 3D-culture with degeneration- and culture-dependent differences. In a 5,6-carboxyfluorescein diacetate N-succinimidyl ester-based proliferation assay, NP cells in monolayer, regardless of their grade of degeneration, did not provoke a significant proliferation response in T cells, natural killer (NK) cells or B cells, not only with donor PBMC, but also with allogeneic PBMC. In conjunction with low inflammatory cytokine expression, analyzed by Cytometric Bead Array and fluorescence-activated cell sorting (FACS), a low immunogenicity can be assumed, facilitating possible therapeutic approaches. In 3D-culture, however, we found elevated immune cell proliferation levels, and there was a general trend to higher responses for NP cells from severely degenerated IVD tissue. This emphasizes the importance of considering the specific immunological alterations when including biomaterials in a therapeutic concept. The overall expression of Fas receptor, found on cultured NP cells, could have

  1. The chemical morphology of age-related changes in human intervertebral disc glycosaminoglycans from cervical, thoracic and lumbar nucleus pulposus and annulus fibrosus.

    PubMed Central

    Scott, J E; Bosworth, T R; Cribb, A M; Taylor, J R

    1994-01-01

    Hyaluronan (HA), chondroitin and keratan sulphates (CS, KS), collagen and dry weights were measured in the annulus fibrosus and nucleus pulposus of human cervical, thoracic and lumbar intervertebral discs aged 36-79 y. Alcian blue-critical electrolyte concentration (CEC) staining of sections extended the results. The collagen, total polyanion, HA, CS and KS contents of the nucleus pulposus and annulus fibrosus were plotted for all 3 regions against age. Regional differences and age-related trends were found. For regional differences, the collagen content of the nucleus pulposus was highest in cervical discs and lowest in lumbar discs. In contrast, the total polyanion content of the nucleus pulposus was highest in lumbar discs and lowest in cervical discs. These differences were seen in fetal and adult discs. With respect to age-related trends, the collagen content of the annulus fibrosus was higher in adults and children than in neonates and infants. The collagen content of the nucleus pulposus increased with age in thoracic and lumbar discs, but it was consistently high in cervical discs. There was generally a downward trend of total polyanion and CS with increase in age. This was quite consistent for the annulus fibrosus in all regions and there were dramatic decreases in the lumbar nucleus pulposus in all adults compared with infants and children. These trends were least evident in the cervical nucleus pulposus where infant values were low. CS changes correlated with water content. HA and KS increased in all discs with increasing maturity. Oversulphated KS, absent from fetal discs, reached mature levels by 10 y. Many of the changes occurred before maturity. Glycosaminoglycan (GAG) levels correlated with increasing compressive loads. Higher collagen levels in the cervical nucleus pulposus correlated with greater ranges of torsional and shearing strains in cervical discs. High GAG levels in cervical annulus fibrosus probably facilitate lamellar movements during

  2. Regenerative Potential of TGFβ3 + Dex and Notochordal Cell Conditioned Media on Degenerated Human Intervertebral Disc Cells

    PubMed Central

    Abbott, Rosalyn Delia; Purmessur, Devina; Monsey, Robert Daniel; Iatridis, James Christopher

    2011-01-01

    Injection of soluble cell signaling factors into degenerated intervertebral discs (IVDs) offers a minimally invasive treatment that could limit the processes of degeneration by stimulating native matrix repair. This study evaluated the regenerative capacity of degenerated nucleus pulposus (NP) cells obtained from patients undergoing anterior interbody fusions by measuring metabolic activity, DNA content, glycosaminoglycan (GAG) content, and cellular phenotype using qRT-PCR profiling with a custom array of 42 genes. NP cells were cultured in alginate for 7 days with 4 treatment groups: transforming growth factor beta 3 (TGFβ3) + dexamethasone (Dex), soluble factors released from notochordal cells (NCs) cultured in alginate (NCA), soluble factors released from NCs in their native tissue environment (NCT), and basal media. TGFβ3 + Dex stimulated degenerated human NP cells to proliferate and exhibit an anti-catabolic gene expression profile (with a decrease in ADAMTS5 and MMP1 compared to basal, and an increase in SOX9, decrease in ADAMTS5, MMP1, collagen I and collagen III compared to day 0), while NCA stimulated the greatest GAG per cell. We conclude that degenerated human NP cells exhibit regenerative potential, and that an optimal treatment will likely require treatments, such as TGFβ3 + Dex, which were able to increase cell metabolism and reduce catabolism, as well as treatments with factors found in NC conditioned medium, that were able to produce high amounts of GAG per cell. Additional studies to optimize NC culture conditions are required to determine if NC conditioned medium can be made with the capacity to enhance NP cell proliferation and metabolism. PMID:21866573

  3. Injectable microcarriers as human mesenchymal stem cell support and their application for cartilage and degenerated intervertebral disc repair.

    PubMed

    Bertolo, A; Häfner, S; Taddei, A R; Baur, M; Pötzel, T; Steffen, F; Stoyanov, J

    2015-01-01

    Degeneration of the intervertebral disc (IVD) is a progressive and chronic process, and the high incidence of discogenic disorders calls for new therapeutic approaches, such as cell-based therapies using three dimensional cultures and mesenchymal stem cells (MSC), which can differentiate to chondrogenic- and IVD-lineages. Here, we investigated the growth and differentiation of human MSC culture on biodegradable collagen scaffolds in order to obtain an injectable suspension. Commercially available wound dressings were downsized to dimensions between 100 and 1500 μm and seeded with freshly isolated or early passages MSC. Proliferation rate and chondrogenic differentiation potential was tested at oxygenation levels of 2%, 5%, 10% and 21% in static and dynamic cultures. Evaluation methods included cell viability test, disc marker genes expression (aggrecan, collagen type I and type II), histological detection of proteoglycans and immunohistochemical analysis. On microcarriers, freshly isolated MSC had lower proliferation rate and chondrogenic differentiation potential compared with early passages MSC. Proliferation of MSC was significantly increased 1.7-fold at 5% oxygen level and in combination with dynamic culture was further increased to 2.3-fold, with respect to normoxia. Chondrogenesis was positively affected by 2% and 5% hypoxia, as shown by increased transcription levels and protein expression of collagen type II and proteoglycan accumulation in static cultures, while it was inhibited in dynamic cultures. Collagen type I and aggrecan expression were not affected by hypoxia. In conclusion, collagen based microcarriers are a suitable support for in vitro MSC growth and chondrogenesis especially when cultured at 5% oxygen level. PMID:25579755

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

    PubMed

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

    2016-01-01

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

  5. Pamidronate Down-regulates Tumor Necrosis Factor-alpha Induced Matrix Metalloproteinases Expression in Human Intervertebral Disc Cells

    PubMed Central

    Kang, Young-Mi; Hong, Seong-Hwan; Yang, Jae-Ho; Oh, Jin-Cheol; Park, Jin-Oh; Lee, Byung Ho; Lee, Sang-Yoon; Kim, Hak-Sun; Lee, Hwan-Mo

    2016-01-01

    Background N-containing bisphosphonates (BPs), such as pamidronate and risedronate, can inhibit osteoclastic function and reduce osteoclast number by inducing apoptotic cell death in osteoclasts. The aim of this study is to demonstrate the effect of pamidronate, second generation nitrogen-containing BPs and to elucidate matrix metallo-proteinases (MMPs) mRNA expression under serum starvation and/or tumor necrosis factor alpha (TNF-α) stimulation on metabolism of intervertebral disc (IVD) cells in vitro. Methods Firstly, to test the effect of pamidronate on IVD cells in vitro, various concentrations (10-12, 10-10, 10-8, and 10-6 M) of pamidronate were administered to IVD cells. Then DNA and proteoglycan synthesis were measured and messenger RNA (mRNA) expressions of type I collagen, type II collagen, and aggrecan were analyzed. Secondly, to elucidate the expression of MMPs mRNA in human IVD cells under the lower serum status, IVD cells were cultivated in full serum or 1% serum. Thirdly, to elucidate the expression of MMPs mRNA in IVD cells under the stimulation of 1% serum and TNF-α (10 ng/mL) In this study, IVD cells were cultivated in three dimensional alginate bead. Results Under the lower serum culture, IVD cells in alginate beads showed upregulation of MMP 2, 3, 9, 13 mRNA. The cells in lower serum and TNF-α also demonstrated upregulation of MMP-2, 3, 9, and 13 mRNA. The cells with various doses of pamidronate and lower serum and TNF-α were reveled partial down-regulation of MMPs. Conclusions Pamidronate, N-containing second generation BPs, was safe in metabolism of IVD in vitro maintaining chondrogenic phenotype and matrix synthesis, and down-regulated TNF-α induced MMPs expression. PMID:27622181

  6. Chondroadherin Fragmentation Mediated by the Protease HTRA1 Distinguishes Human Intervertebral Disc Degeneration from Normal Aging*

    PubMed Central

    Akhatib, Bashar; Önnerfjord, Patrik; Gawri, Rahul; Ouellet, Jean; Jarzem, Peter; Heinegård, Dick; Mort, John; Roughley, Peter; Haglund, Lisbet

    2013-01-01

    Chondroadherin, a member of the leucine-rich repeat family, has previously been demonstrated to be fragmented in some juveniles with idiopathic scoliosis. This observation led us to investigate adults with disc degeneration. Immunoblotting analysis demonstrated that non-degenerate discs from three different age groups show no chondroadherin fragmentation. Furthermore, the chondroadherin fragments in adult degenerate disc and the juvenile scoliotic disc were compared via immunoblot analysis and appeared to have a similar size. We then investigated whether or not chondroadherin fragmentation increases with the severity of disc degeneration. Three different samples with different severities were chosen from the same disc, and chondroadherin fragmentation was found to be more abundant with increasing severity of degeneration. This observation led us to the creation of a neoepitope antibody to the cleavage site observed. We then observed that the cleavage site in adult degenerate discs and juvenile scoliotic discs was identical as confirmed by the neoepitope antibody. Consequently, investigation of the protease capable of cleaving chondroadherin at this site was necessary. In vitro digests of disc tissue demonstrated that ADAMTS-4 and -5; cathepsins K, B, and L; and MMP-3, -7, -12, and -13 were incapable of cleavage of chondroadherin at this site and that HTRA1 was indeed the only protease capable. Furthermore, increased protein levels of the processed form of HTRA1 were demonstrated in degenerate disc tissues via immunoblotting. The results suggest that chondroadherin fragmentation can be used as a biomarker to distinguish the processes of disc degeneration from normal aging. PMID:23673665

  7. Age-related accumulation of pentosidine in aggrecan and collagen from normal and degenerate human intervertebral discs

    PubMed Central

    Sivan, Sarit Sara; Tsitron, Eve; Wachtel, Ellen; Roughley, Peter; Sakkee, Nico; van der Ham, Frits; Degroot, Jeroen; Maroudas, Alice

    2006-01-01

    During aging and degeneration, many changes occur in the structure and composition of human cartilaginous tissues, which include the accumulation of the AGE (advanced glycation end-product), pentosidine, in long-lived proteins. In the present study, we investigated the accumulation of pentosidine in constituents of the human IVD (intervertebral disc), i.e. collagen, aggrecan-derived PG (proteoglycan) (A1) and its fractions (A1D1–A1D6) in health and pathology. We found that, after maturity, pentosidine accumulates with age. Over the age range studied, a linear 6-fold increase was observed in pentosidine accumulation for A1 and collagen with respective rates of 0.12 and 0.66 nmol·(g of protein)−1·year−1. Using previously reported protein turnover rate constants (kT) obtained from measurements of the D-isomer of aspartic residue in collagen and aggrecan of human IVD, we could calculate the pentosidine formation rate constants (kF) for these constituents [Sivan, Tsitron, Wachtel, Roughley, Sakkee, van der Ham, DeGroot, Roberts and Maroudas (2006) J. Biol. Chem. 281, 13009–13014; Tsitron (2006) MSc Thesis, Technion-Israel Institute of Technology, Haifa, Israel]. In spite of the comparable formation rate constants obtained for A1D1 and collagen [1.81±0.25 compared with 3.71±0.26 μmol of pentosidine·(mol of lysine)−1·year−1 respectively], the higher pentosidine accumulation in collagen is consistent with its slower turnover (0.005 year−1 compared with 0.134 year−1 for A1D1). Pentosidine accumulation increased with decreasing buoyant density and decreasing turnover of the proteins from the most glycosaminoglycan-rich PG components (A1D1) to the least (A1D6), with respective kF values of 1.81±0.25 and 3.18±0.37 μmol of pentosidine·(mol of lysine)−1·year−1. We concluded that protein turnover is an important determinant of pentosidine accumulation in aggrecan and collagen of human IVD, as was found for articular cartilage. Correlation of

  8. Intervertebral disc disease.

    PubMed

    Simpson, S T

    1992-07-01

    This article describes the functional anatomy of intervertebral discs and their relationship to the vertebrae and spinal cord. The pathologic events and clinical complications of intervertebral disc disease are described. A discussion of proper staging of disc disease and appropriate conservative management of degenerative disc disease is included. PMID:1641922

  9. 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…

  10. Human mesenchymal stem cell co-culture modulates the immunological properties of human intervertebral disc tissue fragments in vitro.

    PubMed

    Bertolo, Alessandro; Thiede, Thomas; Aebli, Niklaus; Baur, Martin; Ferguson, Stephen J; Stoyanov, Jivko V

    2011-04-01

    The capacity of mesenchymal stem cells (MSCs) to differentiate into intervertebral disc (IVD)-like cells has been well described, but their ability to modulate the inflammatory processes in the IVD remains unclear. We found that tissue obtained by discectomy of degenerated and post-traumatic IVD contains significant amounts of IgG antibodies, a sign of lymphocyte infiltration. Further we investigated whether MSCs in vitro, which were characterized for their multilineage differentiation potential and may have immunomodulatory effects on IVD fragments. IVD fragments were co-cultured in contact with peripheral blood lymphocytes (PBLs) and MSCs, and as functional controls we used contact co-cultures of PBLs stimulated with pokeweed mitogen (2.5 μg/mL) and MSCs. The time course of lymphocyte proliferation (Alamar Blue), IgG (ELISA) and gene expression (RT-PCR) of anti-inflammatory cytokines (TGF-β1, IL-10) by MSCs and pro-inflammatory molecules (IL-1α, IL-1β and TNF-α) by the IVD fragments were analyzed. Depending on the response to the presence of MSCs, the IVD fragments (n = 13) were divided in two groups: responders (n = 9), where inflammation was inhibited by MSCs and non-responders (n = 4), where MSCs did not decrease inflammation. At 1 week in co-culture, MSCs reduced significantly the IgG production in the IVD responders group to 69% and PBLs proliferation to 57% of the control. MSCs expression of the anti-inflammatory TGF-β1 increased with time, while IL-10 was expressed only at day 1. IVD gene expression of TNF-α decreased constantly, whereas IL-1α and IL-1β expression increased. In conclusion, these data suggest that MSCs may modulate disc-specific inflammatory and pain status and aid regeneration of the host tissue. PMID:21181480

  11. Mechanical behavior of the human lumbar intervertebral disc with polymeric hydrogel nucleus implant: An experimental and finite element study

    NASA Astrophysics Data System (ADS)

    Joshi, Abhijeet Bhaskar

    The origin of the lower back pain is often the degenerated lumbar intervertebral disc (IVD). We are proposing replacement of the degenerated nucleus by a PVA/PVP polymeric hydrogel implant. We hypothesize that a polymeric hydrogel nucleus implant can restore the normal biomechanics of the denucleated IVD by mimicking the natural load transfer phenomenon as in case of the intact IVD. Lumbar IVDs (n = 15) were harvested from human cadavers. In the first part, specimens were tested in four different conditions for compression: Intact, bone in plug, denucleated and Implanted. Hydrogel nucleus implants were chosen to have line-to-line fit in the created nuclear cavity. In the second part, nucleus implant material (modulus) and geometric (height and diameter) parameters were varied and specimens (n = 9) were tested. Nucleus implants with line-to-line fit significantly restored (88%) the compressive stiffness of the denucleated IVD. The synergistic effect between the implant and the intact annulus resulted in the nonlinear increase in implanted IVD stiffness, where Poisson effect of the hydrogel played major role. Nucleus implant parameters were observed to have a significant effect on the compressive stiffness. All implants with modulus in the tested range restored the compressive stiffness. The undersize implants resulted in incomplete restoration while oversize implants resulted in complete restoration compared to the BI condition. Finite element models (FEM) were developed to simulate the actual test conditions and validated against the experimental results for all conditions. The annulus (defined as hyperelastic, isotropic) mainly determined the nonlinear response of the IVD. Validated FEMs predicted 120--3000 kPa as a feasible range for nucleus implant modulus. FEMs also predicted that overdiameter implant would be more effective than overheight implant in terms of stiffness restoration. Underdiameter implants, initially allowed inward deformation of the annulus and

  12. Variations in aggrecan localization and gene expression patterns characterize increasing stages of human intervertebral disk degeneration.

    PubMed

    Gruber, Helen E; Hoelscher, Gretchen L; Ingram, Jane A; Bethea, Synthia; Zinchenko, Natalia; Hanley, Edward N

    2011-10-01

    During disk degeneration, annulus dehydration and matrix fraying culminate in the formation of tears through which nucleus and annulus disk material may rupture, causing radicular pain. Annular tears are present in more than half of the patients in early adulthood and are almost always present in the elderly. Aggrecan, which provides the disk with a shock absorber function under loading, is a key disk extracellular matrix (ECM) component. The objective of the present study was to assess the immunolocalization of aggrecan in the annulus, and to assess molecular gene expression patterns in the annulus ECM utilizing microarray analysis. Immunohistochemistry was performed on 45 specimens using an anti-human aggrecan antibody. Affymetrix microarray gene expression studies used the extracellular matrix ontology approach to evaluate an additional 6 grade I-II, 9 grade III, and 4 grade IV disks. Grade III/IV disks were compared to healthier grade I/II disks. Healthy and less degenerated disks showed a general uniform aggrecan immunolocalization; more degenerated disks contained regions with little or no identifiable aggrecan localization. In degenerated disks, molecular studies showed a significant downregulation of aggrecan, ADAMTS-like 3, and ADAMTS10. Collagen types III and VIII, fibronectin, decorin, connective tissue growth factor, TIMP-3, latent TGF-β binding protein 2 and TGF-β1 were significantly upregulated with fold changes ranging from 2.4 to 9.8. Findings here help us better understand changes in the immunohistochemical distribution of a key proteoglycan during disk aging. Such information may have application as we work towards biologic therapies to improve the aging/degenerating disk matrix. PMID:21689646

  13. Quantitative T2 Magnetic Resonance Imaging Compared to Morphological Grading of the Early Cervical Intervertebral Disc Degeneration: An Evaluation Approach in Asymptomatic Young Adults

    PubMed Central

    Han, Zhihua; Shao, Lixin; Xie, Yan; Wu, Jianhong; Zhang, Yan; Xin, Hongkui; Ren, Aijun; Guo, Yong; Wang, Deli; He, Qing; Ruan, Dike

    2014-01-01

    Objective The objective of this study was to evaluate the efficacy of quantitative T2 magnetic resonance imaging (MRI) for quantifying early cervical intervertebral disc (IVD) degeneration in asymptomatic young adults by correlating the T2 value with Pfirrmann grade, sex, and anatomic level. Methods Seventy asymptomatic young subjects (34 men and 36 women; mean age, 22.80±2.11 yr; range, 18–25 years) underwent 3.0-T MRI to obtain morphological data (one T1-fast spin echo (FSE) and three-plane T2-FSE, used to assign a Pfirrmann grade (I–V)) and for T2 mapping (multi-echo spin echo). T2 values in the nucleus pulposus (NP, n = 350) and anulus fibrosus (AF, n = 700) were obtained. Differences in T2 values between sexes and anatomic level were evaluated, and linear correlation analysis of T2 values versus degenerative grade was conducted. Findings Cervical IVDs of healthy young adults were commonly determined to be at Pfirrmann grades I and II. T2 values of NPs were significantly higher than those of AF at all anatomic levels (P<0.000). The NP, anterior AF and posterior AF values did not differ significantly between genders at the same anatomic level (P>0.05). T2 values decreased linearly with degenerative grade. Linear correlation analysis revealed a strong negative association between the Pfirrmann grade and the T2 values of the NP (P = 0.000) but not the T2 values of the AF (P = 0.854). However, non-degenerated discs (Pfirrmann grades I and II) showed a wide range of T2 relaxation time. T2 values according to disc degeneration level classification were as follows: grade I (>62.03 ms), grade II (54.60–62.03 ms), grade III (<54.60 ms). Conclusions T2 quantitation provides a more sensitive and robust approach for detecting and characterizing the early stage of cervical IVD degeneration and to create a reliable quantitative in healthy young adults. PMID:24498384

  14. Intervertebral Disc Degeneration

    PubMed Central

    Rannou, François; Lee, Tzong-Shyuan; Zhou, Rui-Hai; Chin, Jennie; Lotz, Jeffrey C.; Mayoux-Benhamou, Marie-Anne; Barbet, Jacques Patrick; Chevrot, Alain; Shyy, John Y.-J.

    2004-01-01

    Degeneration of the intervertebral disk (IVD) is a major pathological process implicated in low back pain and is a prerequisite to disk herniation. Although mechanical stress is an important modulator of the degeneration, the underlying molecular mechanism remains unclear. The association of human IVD degeneration, assessed by magnetic resonance imaging, with annulus fibrosus cell apoptosis and anti-cytochrome c staining revealed that the activation of the mitochondria-dependent apoptosome was a major event in the degeneration process. Mouse models of IVD degeneration were used to investigate the role of the mechanical stress in this process. The application of mechanical overload (1.3 MPa) for 24 hours induced annulus fibrosus cell apoptosis and led to severe degeneration of the mouse disks. Immunostaining revealed cytochrome c release but not Fas-L generation. The role of the caspase-9-dependent mitochondrial pathway in annulus fibrosus cell apoptosis induced by overload was investigated further with the use of cultured rabbit IVD cells in a stretch device. Mechanical overload (15% area change) induced apoptosis with increased caspase-9 activity and decreased mitochondrial membrane potential. Furthermore, Z-LEHD-FMK, a caspase-9 inhibitor, but not Z-IETD-FMK, a caspase-8 inhibitor, attenuated the overload-induced apoptosis. Our results from human samples, mouse models, and annulus fibrosus culture experiments demonstrate that the mechanical overload-induced IVD degeneration is mediated through the mitochondrial apoptotic pathway in IVD cells. PMID:14982845

  15. Development and Validation of a Bioreactor System for Dynamic Loading and Mechanical Characterization of Whole Human Intervertebral Discs in Organ Culture

    PubMed Central

    Walter, BA; Illien-Junger, S; Nasser, P; Hecht, AC; Iatridis, JC

    2014-01-01

    Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48 hours of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error <2.5N and total harmonic distortion <2.45%), and precisely evaluated mechanical behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical behavior and retained >85% viable cells throughout the 3 week culture period. This organ culture loading system can closely mimic physiological conditions and be used to investigate response of living human and bovine IVDs to mechanical and chemical challenges and to screen therapeutic repair techniques. PMID:24725441

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

    PubMed Central

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

    2011-01-01

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

  17. A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic

    PubMed Central

    Ghosh, Peter

    2016-01-01

    Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored. PMID:27314030

  18. A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic.

    PubMed

    Daly, Chris; Ghosh, Peter; Jenkin, Graham; Oehme, David; Goldschlager, Tony

    2016-01-01

    Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored. PMID:27314030

  19. FasL Expression on Human Nucleus Pulposus Cells Contributes to the Immune Privilege of Intervertebral Disc by Interacting with Immunocytes

    PubMed Central

    Liu, Zhi-Heng; Sun, Zhen; Wang, Hai-Qiang; Ge, Jun; Jiang, Ting-Shuai; Chen, Yu-Fei; Ma, Ying; Wang, Chen; Hu, Sheng; Samartzis, Dino; Luo, Zhuo-Jing

    2013-01-01

    The mechanisms of immune privilege in human nucleus pulposus (NP) remain unclear. Accumulating evidence indicates that Fas ligand (FasL) might play an important role in the immune privilege of the disc. We aimed for addressing the role of FasL expression in human intervertebral disc degeneration (IDD) and immune privilege in terms of the interaction between NP cells and immunocytes via the FasL-Fas machinery. We collected NP specimens from 20 patients with IDD as degenerative group and 8 normal cadaveric donors as control. FasL expression was detected by qRT-PCR, western blotting and flow cytometry (FCM). We also collected macrophages and CD8+ T cells from the peripheral blood of patients with IDD for co-cultures with NP cells. And macrophages and CD8+ T cells were harvested for apoptosis analysis by FCM after 2 days of co-cultures. We found that FasL expression in mRNA, protein and cellular resolutions demonstrated a significant decrease in degenerative group compared with normal control (p<0.05). FCM analysis found that human NP cells with increased FasL expression resulted in significantly increased apoptosis ratio of macrophages and CD8+ T cells. Our study demonstrated that FasL expression tends to decrease in degenerated discs and FasL plays an important role in human disc immune privilege, which might provide a novel target for the treatment strategies for IDD. PMID:23801893

  20. Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: Novel HIF-1-mediated regulation of aquaporins in NP cells.

    PubMed

    Johnson, Zariel I; Gogate, Shilpa S; Day, Rebecca; Binch, Abbie; Markova, Dessislava Z; Chiverton, Neil; Cole, Ashley; Conner, Matt; Shapiro, Irving M; Le Maitre, Christine L; Risbud, Makarand V

    2015-05-20

    Objectives of this study were to investigate whether AQP1 and AQP5 expression is altered during intervertebral disc degeneration and if hypoxia and HIF-1 regulate their expression in NP cells. AQP expression was measured in human tissues from different degenerative grades; regulation by hypoxia and HIF-1 was studied using promoter analysis and gain- and loss-of-function experiments. We show that both AQPs are expressed in the disc and that mRNA and protein levels decline with human disease severity. Bioinformatic analyses of AQP promoters showed multiple evolutionarily conserved HREs. Surprisingly, hypoxia failed to induce promoter activity or expression of either AQP. While genomic chromatin immunoprecipitation showed limited binding of HIF-1α to conserved HREs, their mutation did not suppress promoter activities. Stable HIF-1α suppression significantly decreased mRNA and protein levels of both AQPs, but HIF-1α failed to induce AQP levels following accumulation. Together, our results demonstrate that AQP1 and AQP5 expression is sensitive to human disc degeneration and that HIF-1α uniquely maintains basal expression of both AQPs in NP cells, independent of oxemic tension and HIF-1 binding to promoter HREs. Diminished HIF-1 activity during degeneration may suppress AQP levels in NP cells, compromising their ability to respond to extracellular osmolarity changes. PMID:25844601

  1. Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: novel HIF-1-mediated regulation of aquaporins in NP cells

    PubMed Central

    Day, Rebecca; Binch, Abbie; Markova, Dessislava Z.; Chiverton, Neil; Cole, Ashley; Conner, Matt; Shapiro, Irving M.; Le Maitre, Christine L.; Risbud, Makarand V.

    2015-01-01

    Objectives of this study were to investigate whether AQP1 and AQP5 expression is altered during intervertebral disc degeneration and if hypoxia and HIF-1 regulate their expression in NP cells. AQP expression was measured in human tissues from different degenerative grades; regulation by hypoxia and HIF-1 was studied using promoter analysis and gain- and loss-of-function experiments. We show that both AQPs are expressed in the disc and that mRNA and protein levels decline with human disease severity. Bioinformatic analyses of AQP promoters showed multiple evolutionarily conserved HREs. Surprisingly, hypoxia failed to induce promoter activity or expression of either AQP. While genomic chromatin immunoprecipitation showed limited binding of HIF-1α to conserved HREs, their mutation did not suppress promoter activities. Stable HIF-1α suppression significantly decreased mRNA and protein levels of both AQPs, but HIF-1α failed to induce AQP levels following accumulation. Together, our results demonstrate that AQP1 and AQP5 expression is sensitive to human disc degeneration and that HIF-1α uniquely maintains basal expression of both AQPs in NP cells, independent of oxemic tension and HIF-1 binding to promoter HREs. Diminished HIF-1 activity during degeneration may suppress AQP levels in NP cells, compromising their ability to respond to extracellular osmolarity changes. PMID:25844601

  2. Interleukin-1 receptor antagonist delivered directly and by gene therapy inhibits matrix degradation in the intact degenerate human intervertebral disc: an in situ zymographic and gene therapy study

    PubMed Central

    Le Maitre, Christine L; Hoyland, Judith A; Freemont, Anthony J

    2007-01-01

    Data implicate IL-1 in the altered matrix biology that characterizes human intervertebral disc (IVD) degeneration. In the current study we investigated the enzymic mechanism by which IL-1 induces matrix degradation in degeneration of the human IVD, and whether the IL-1 inhibitor IL-1 receptor antagonist (IL-1Ra) will inhibit degradation. A combination of in situ zymography (ISZ) and immunohistochemistry was used to examine the effects of IL-1 and IL-1Ra on matrix degradation and metal-dependent protease (MDP) expression in explants of non-degenerate and degenerate human IVDs. ISZ employed three substrates (gelatin, collagen, casein) and different challenges (IL-1β, IL-1Ra and enzyme inhibitors). Immunohistochemistry was undertaken for MDPs. In addition, IL-1Ra was introduced into degenerate IVD explants using genetically engineered constructs. The novel findings from this study are: IL-1Ra delivered directly onto explants of degenerate IVDs eliminates matrix degradation as assessed by multi-substrate ISZ; there is a direct relationship between matrix degradation assessed by ISZ and MDP expression defined by immunohistochemistry; single injections of IVD cells engineered to over-express IL-1Ra significantly inhibit MDP expression for two weeks. Our findings show that IL-1 is a key cytokine driving matrix degradation in the degenerate IVD. Furthermore, IL-1Ra delivered directly or by gene therapy inhibits IVD matrix degradation. IL-1Ra could be used therapeutically to inhibit degeneration of the IVD. PMID:17760968

  3. SIRT1 alleviates senescence of degenerative human intervertebral disc cartilage endo-plate cells via the p53/p21 pathway.

    PubMed

    Zhou, Nian; Lin, Xin; Dong, Wen; Huang, Wei; Jiang, Wei; Lin, Liangbo; Qiu, Quanhe; Zhang, Xiaojun; Shen, Jieliang; Song, Zhaojun; Liang, Xi; Hao, Jie; Wang, Dawu; Hu, Zhenming

    2016-01-01

    Cartilage end plates (CEP) degeneration plays an integral role in intervertebral disc (IVD) degeneration resulting from nutrient diffusion disorders. Although cell senescence resulting from oxidative stress is known to contribute to degeneration, no studies concerning the role of senescence in CEP degeneration have been conducted. SIRT1 is a longevity gene that plays a pivotal role in many cellular functions, including cell senescence. Therefore, the aim of this study was to investigate whether senescence is more prominent in human degenerative CEP and whether SIRT1-regulated CEP cells senescence in degenerative IVD as well as identify the signaling pathways that control that cell fate decision. In this study, the cell senescence phenotype was found to be more prominent in the CEP cells obtained from disc degenerative disease (DDD) patients than in the CEP cells obtained from age-matched lumbar vertebral fractures (LVF) patients. In addition, the results indicated that p53/p21 pathway plays an important role in the senescence of CEP cells in vivo and vitro. Furthermore, SIRT1 was found to be capable of alleviating the oxidative stress-induced senescence of CEP cells in humans via p53/p21 pathway. Thus, the information presented in this study could be used to further investigate the underlying mechanisms of CEP. PMID:26940203

  4. Expression of acid-sensing ion channels in nucleus pulposus cells of the human intervertebral disk is regulated by non-steroid anti-inflammatory drugs.

    PubMed

    Sun, Xue; Jin, Jun; Zhang, Ji-Gang; Qi, Lin; Braun, Frank Karl; Zhang, Xing-Ding; Xu, Feng

    2014-09-01

    Non-steroid anti-inflammatory drugs (NSAIDs) are generally used in the treatment of inflammation and pain through cyclooxygenase (COX) inhibition. Mounting evidence has indicated additional COX-independent targets for NSAIDs including acid-sensing ion channels (ASICs) 1a and 3. However, detailed function and mechanism of ASICs still remain largely elusive. In this study, the impact of NSAIDs on ASICs in nucleus pulposus cells of the human intervertebral disk was investigated. Nucleus pulposus cells were isolated and cultured from protruded disk tissues of 40 patients. It was shown that ASIC1a and ASIC3 were expressed and functional in these cells by analyzing proton-gated currents after ASIC inhibition. We further investigated the neuroprotective capacity of ibuprofen (a COX inhibitor), psalmotoxin-1 (PcTX1, a tarantula toxin specific for homomeric ASIC1a), and amiloride (a classic inhibitor of the epithelial sodium channel ENaC/DEG family to which ASICs belong). PcTX1-containing venom has been shown to be comparable with amiloride in its neuroprotective features in rodent models of ischemia. Taken together, our data showed that amiloride, PcTX1, and ibuprofen decreased ASIC protein expression and thereby exerted protective effects from ASIC inhibition-mediated cell damage. PMID:25079679

  5. Expression of acid-sensing ion channels in nucleus pulposus cells of the human intervertebral disk is regulated by non-steroid anti-inflammatory drugs

    PubMed Central

    Sun, Xue; Jin, Jun; Zhang, Ji-Gang; Qi, Lin; Braun, Frank Karl; Zhang, Xing-Ding; Xu, Feng

    2014-01-01

    Non-steroid anti-inflammatory drugs (NSAIDs) are generally used in the treatment of inflammation and pain through cyclooxygenase (COX) inhibition. Mounting evidence has indicated additional COX-independent targets for NSAIDs including acid-sensing ion channels (ASICs) 1a and 3. However, detailed function and mechanism of ASICs still remain largely elusive. In this study, the impact of NSAIDs on ASICs in nucleus pulposus cells of the human intervertebral disk was investigated. Nucleus pulposus cells were isolated and cultured from protruded disk tissues of 40 patients. It was shown that ASIC1a and ASIC3 were expressed and functional in these cells by analyzing proton-gated currents after ASIC inhibition. We further investigated the neuroprotective capacity of ibuprofen (a COX inhibitor), psalmotoxin-1 (PcTX1, a tarantula toxin specific for homomeric ASIC1a), and amiloride (a classic inhibitor of the epithelial sodium channel ENaC/DEG family to which ASICs belong). PcTX1-containing venom has been shown to be comparable with amiloride in its neuroprotective features in rodent models of ischemia. Taken together, our data showed that amiloride, PcTX1, and ibuprofen decreased ASIC protein expression and thereby exerted protective effects from ASIC inhibition-mediated cell damage. PMID:25079679

  6. Establishment of a Cytocompatible Cell-Free Intervertebral Disc Matrix for Chondrogenesis with Human Bone Marrow-Derived Mesenchymal Stromal Cells.

    PubMed

    Huang, Zhao; Kohl, Benjamin; Kokozidou, Maria; Arens, Stephan; Schulze-Tanzil, Gundula

    2016-01-01

    Tissue-engineered intervertebral discs (IVDs) utilizing decellularized extracellular matrix (ECM) could be an option for the reconstruction of impaired IVDs due to degeneration or injury. The objective of this study was to prepare a cell-free decellularized human IVD scaffold and to compare neotissue formation in response to recellularization with human IVD cells (hIVDCs) or human bone marrow-derived (hBM) mesenchymal stromal cells (MSCs). IVDs were decellularized via freeze-thaw cycles, detergents and trypsin. Histological staining was performed to monitor cell removal and glycosaminoglycan (GAG) removal. The decellularized IVD was preconditioned using bovine serum albumin and fetal bovine serum before its cytocompatibility for dynamically cultured hBM-MSCs (chondrogenically induced or not) and hIVDCs was compared after 14 days. In addition, DNA, total collagen and GAG contents were assessed. The decellularization protocol achieved maximal cell removal, with only few remaining cell nuclei compared with native tissue, and low toxicity. The DNA content was significantly higher in scaffolds seeded with hIVDCs compared with native IVDs, cell-free and hBM-MSC-seeded scaffolds (p < 0.01). The GAG content in the native tissue was significantly higher compared to the others groups except for the scaffolds reseeded with chondrogenically induced hBM-MSCs (p < 0.05). In addition, there was a significantly increased total collagen content in the chondrogenically induced hBM-MSCs group (p < 0.01) compared with the native IVDs, cell-free and hIVDC-seeded scaffolds (p < 0.01); both recolonizing cell types were more evenly distributed on the scaffold surface, but only few cells penetrated the scaffold. The resulting decellularized ECM was cytocompatible and allowed hBM-MSCs/hIVDCs survival and ECM production. PMID:27160711

  7. Stem cells sources for intervertebral disc regeneration

    PubMed Central

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-01-01

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  8. Stem cells sources for intervertebral disc regeneration.

    PubMed

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-05-26

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  9. Hyaluronic acid fragments enhance the inflammatory and catabolic response in human intervertebral disc cells through modulation of toll-like receptor 2 signalling pathways

    PubMed Central

    2013-01-01

    Introduction Intervertebral disc (IVD) degeneration is characterized by extracellular matrix breakdown and is considered to be a primary cause of discogenic back pain. Although increases in pro-inflammatory cytokine levels within degenerating discs are associated with discogenic back pain, the mechanisms leading to their overproduction have not yet been elucidated. As fragmentation of matrix components occurs during IVD degeneration, we assessed the potential involvement of hyaluronic acid fragments (fHAs) in the induction of inflammatory and catabolic mediators. Methods Human IVD cells isolated from patient biopsies were stimulated with fHAs (6 to 12 disaccharides) and their effect on cytokine and matrix degrading enzyme production was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The involvement of specific cell surface receptors and signal transduction pathways in mediating the effects of fHAs was tested using small interfering RNA (siRNA) approaches and kinase inhibition assays. Results Treatment of IVD cells with fHAs significantly increased mRNA expression levels of interleukin (IL)-1β, IL-6, IL-8, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-1 and -13. The stimulatory effects of fHAs on IL-6 protein production were significantly impaired when added to IVD cells in combination with either Toll-like receptor (TLR)-2 siRNA or a TLR2 neutralizing antibody. Furthermore, the ability of fHAs to enhance IL-6 and MMP-3 protein production was found to be dependent on the mitogen-activated protein (MAP) kinase signaling pathway. Conclusions These findings suggest that fHAs may have the potential to mediate IVD degeneration and discogenic back pain through activation of the TLR2 signaling pathway in resident IVD cells. PMID:23968377

  10. Effects of TGF-β1 and IL-1β on expression of ADAMTS enzymes and TIMP-3 in human intervertebral disc degeneration

    PubMed Central

    WANG, SHI-LONG; YU, YONG-LIN; TANG, CHAO-LIANG; LV, FEI-ZHOU

    2013-01-01

    The aim of this study was to investigate the effects of transforming growth factor-β1 (TGF-β1) and interleukin-1β (IL-1β) on the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) enzymes and their inhibitor, tissue inhibitor of metalloproteinase 3 (TIMP-3), in human intervertebral disc (IVD) degeneration. Cells from patients with IVD degeneration were cultured with Dulbecco’s modified Eagle’s medium with Ham’s F12 nutrient mixture (DMEM/F12) medium at 37°C in a 5% CO2 incubator. Cell proliferation was measured by cell counting kit-8 assays with varying concentrations of TGF-β1 and IL-1β in a time-response experiment. The mRNA and protein expression levels of ADAMTS-4, ADAMTS-5 and TIMP-3 were detected with qPCR and western blot analysis, respectively. The present study demonstrated that TGF-β1 promoted nucleus pulposus (NP) cell proliferation, decreased the expression of ADAMTS-4 and -5 and increased the expression of TIMP-3. By contrast, the IL-1β treatment inhibited NP cell proliferation and significantly increased the expression of ADAMTS-4 and -5. However, IL-1β appeared to have no marked effect on the expression of TIMP-3. This study suggests that TGF-β1 and IL-1β are involved in the synthesis and degradation of the extracellular matrix and may act as potential therapeutic targets for the prevention or reversal of IVD degeneration. PMID:24250727

  11. Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3.

    PubMed

    Wang, Hai-Qiang; Yu, Xiao-Dong; Liu, Zhi-Heng; Cheng, Xin; Samartzis, Dino; Jia, Lin-Tao; Wu, Sheng-Xi; Huang, Jing; Chen, Jing; Luo, Zhuo-Jing

    2011-10-01

    The role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains enigmatic. Accumulating evidence has shown that the apoptotic machinery is regulated by miRNAs. We hypothesized that miRNAs might contribute to apoptosis in IDD. We have found that 29 miRNAs were differentially expressed and miR-155 was down-regulated in degenerative nucleus pulposus (NP). The deregulation of miR-155 was further verified using real-time PCR (0.56 fold, p < 0.05). Bioinformatics target prediction identified FADD and caspase-3 as putative targets of miR-155. Furthermore, miR-155 inhibited FADD and caspase-3 expression by directly targeting their 3'-UTRs, which was abolished by mutation of the miR-155 binding sites. In vitro up-regulation of miR-155 in human NP cells by transfection with lentiviral pre-miR-155 resulted in repression of FADD and caspase-3; whereas knockdown of miR-155 with lentiviral antigomiR-155 led to over-expression of FADD and caspase-3. Also, Fas-mediated apoptosis was increased when antagonizing miR-155 and decreased when using pre-miR-155 in human NP cells. In addition, we presented direct evidence of NP cells undergoing apoptosis in IDD tissues using transmission electron microscopy analysis. Moreover, a combination of in situ hybridization (ISH) and immunohistochemistry (IHC) revealed that miR-155 expressed in the cytoplasm of human NP cells with reverse correlation with FADD and caspase-3. In summary, this is the first study addressing the underlying mechanisms of IDD in terms of apoptosis and miRNAs. Furthermore, caspase-3 is identified as a novel target of miR-155. Our results suggest that deregulated miR-155 promotes Fas-mediated apoptosis in human IDD by targeting FADD and caspase-3, implicating an aetiological and therapeutic role of miR-155 in IDD. PMID:21706480

  12. Injection of human umbilical tissue–derived cells into the nucleus pulposus alters the course of intervertebral disc degeneration in vivo

    PubMed Central

    Leckie, Steven K.; Sowa, Gwendolyn A.; Bechara, Bernard P.; Hartman, Robert A.; Coelho, Joao Paulo; Witt, William T.; Dong, Qing D.; Bowman, Brent W.; Bell, Kevin M.; Vo, Nam V.; Kramer, Brian C.; Kang, James D.

    2016-01-01

    Background context Patients often present to spine clinic with evidence of intervertebral disc degeneration (IDD). If conservative management fails, a safe and effective injection directly into the disc might be preferable to the risks and morbidity of surgery. Purpose To determine whether injecting human umbilical tissue–derived cells (hUTC) into the nucleus pulposus (NP) might improve the course of IDD. Design Prospective, randomized, blinded placebo–controlled in vivo study. Patient sample Skeletally mature New Zealand white rabbits. Outcome measures Degree of IDD based on magnetic resonance imaging (MRI), biomechanics, and histology. Methods Thirty skeletally mature New Zealand white rabbits were used in a previously validated rabbit annulotomy model for IDD. Discs L2–L3, L3–L4, and L4–L5 were surgically exposed and punctured to induce degeneration and then 3 weeks later the same discs were injected with hUTC with or without a hydrogel carrier. Serial MRIs obtained at 0, 3, 6, and 12 weeks were analyzed for evidence of degeneration qualitatively and quantitatively via NP area and MRI Index. The rabbits were sacrificed at 12 weeks and discs L4–L5 were analyzed histologically. The L3–L4 discs were fixed to a robotic arm and subjected to uniaxial compression, and viscoelastic displacement curves were generated. Results Qualitatively, the MRIs demonstrated no evidence of degeneration in the control group over the course of 12 weeks. The punctured group yielded MRIs with the evidence of disc height loss and darkening, suggestive of degeneration. The three treatment groups (cells alone, carrier alone, or cells+carrier) generated MRIs with less qualitative evidence of degeneration than the punctured group. MRI Index and area for the cell and the cell+carrier groups were significantly distinct from the punctured group at 12 weeks. The carrier group generated MRI data that fell between control and punctured values but failed to reach a statistically

  13. Mechanotransduction in intervertebral discs

    PubMed Central

    Tsai, Tsung-Ting; Cheng, Chao-Min; Chen, Chien-Fu; Lai, Po-Liang

    2014-01-01

    Mechanotransduction plays a critical role in intracellular functioning—it allows cells to translate external physical forces into internal biochemical activities, thereby affecting processes ranging from proliferation and apoptosis to gene expression and protein synthesis in a complex web of interactions and reactions. Accordingly, aberrant mechanotransduction can either lead to, or be a result of, a variety of diseases or degenerative states. In this review, we provide an overview of mechanotransduction in the context of intervertebral discs, with a focus on the latest methods of investigating mechanotransduction and the most recent findings regarding the means and effects of mechanotransduction in healthy and degenerative discs. We also provide some discussion of potential directions for future research and treatments. PMID:25267492

  14. In Vivo Mouse Intervertebral Disc Degeneration Model Based on a New Histological Classification

    PubMed Central

    Ohnishi, Takashi; Sudo, Hideki; Iwasaki, Koji; Tsujimoto, Takeru; Ito, Yoichi M.; Iwasaki, Norimasa

    2016-01-01

    Although human intervertebral disc degeneration can lead to several spinal diseases, its pathogenesis remains unclear. This study aimed to create a new histological classification applicable to an in vivo mouse intervertebral disc degeneration model induced by needle puncture. One hundred six mice were operated and the L4/5 intervertebral disc was punctured with a 35- or 33-gauge needle. Micro-computed tomography scanning was performed, and the punctured region was confirmed. Evaluation was performed by using magnetic resonance imaging and histology by employing our classification scoring system. Our histological classification scores correlated well with the findings of magnetic resonance imaging and could detect degenerative progression, irrespective of the punctured region. However, the magnetic resonance imaging analysis revealed that there was no significant degenerative intervertebral disc change between the ventrally punctured and non-punctured control groups. To induce significant degeneration in the lumbar intervertebral discs, the central or dorsal region should be punctured instead of the ventral region. PMID:27482708

  15. MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine.

    PubMed

    Stolworthy, Dean K; Bowden, Anton E; Roeder, Beverly L; Robinson, Todd F; Holland, Jacob G; Christensen, S Loyd; Beatty, Amanda M; Bridgewater, Laura C; Eggett, Dennis L; Wendel, John D; Stieger-Vanegas, Susanne M; Taylor, Meredith D

    2015-12-01

    Animal models have historically provided an appropriate benchmark for understanding human pathology, treatment, and healing, but few animals are known to naturally develop intervertebral disc degeneration. The study of degenerative disc disease and its treatment would greatly benefit from a more comprehensive, and comparable animal model. Alpacas have recently been presented as a potential large animal model of intervertebral disc degeneration due to similarities in spinal posture, disc size, biomechanical flexibility, and natural disc pathology. This research further investigated alpacas by determining the prevalence of intervertebral disc degeneration among an aging alpaca population. Twenty healthy female alpacas comprised two age subgroups (5 young: 2-6 years; and 15 older: 10+ years) and were rated according to the Pfirrmann-grade for degeneration of the cervical intervertebral discs. Incidence rates of degeneration showed strong correlations with age and spinal level: younger alpacas were nearly immune to developing disc degeneration, and in older animals, disc degeneration had an increased incidence rate and severity at lower cervical levels. Advanced disc degeneration was present in at least one of the cervical intervertebral discs of 47% of the older alpacas, and it was most common at the two lowest cervical intervertebral discs. The prevalence of intervertebral disc degeneration encourages further investigation and application of the lower cervical spine of alpacas and similar camelids as a large animal model of intervertebral disc degeneration. PMID:26135031

  16. [Laser ablation of intervertebral disc: animal experiment].

    PubMed

    Qi, Q; Dang, G D; Cai, Q L

    1994-03-01

    The lumbar intervertebral discs (L3-6) were ablated through a transperitoneal approach in 12 adult dogs by using Nd: YAG laser (1.06 microns) with a 600 microns quartz fiber. The status of limbs motion and sphincter (bladder, bowel) was observed for evaluating the safety of laser irradiation. After irradiation, the animals were sacrificed at prescribed intervals of up to 40 weeks (2, 4, 8, 12 and 40 weeks after operation). The lumbar intervertebral discs were harvested and subjected to light microscopic observation. No dog had suffered from neurogenic dysfunction of limb motion and sphincter. Histological findings immediately after the irradiation showed the disc was vaporized and a cavity was made. After 2 and 4 weeks, fibrous tissues began to proliferate, but cartilaginous tissues replaced the fibrous tissues 12 weeks after the laser irradiation. No new bone formation was found within 40 weeks after operation. On the basis of this study and our previous cadaveric study, percutaneous laser disc decompression (PLDD) was applied in clinical practice in march of 1993. 10 patients underwent PLDD utilizing the same laser equipment. The average follow-up was 3 months. According to the Macnab's criteria, there was an excellent response in 7 patients and a good response in 3. PMID:7842915

  17. A diffusion and T2 relaxation MRI study of the ovine lumbar intervertebral disc under compression in vitro

    NASA Astrophysics Data System (ADS)

    Drew, Simon C.; Silva, Pujitha; Crozier, Stuart; Pearcy, Mark J.

    2004-08-01

    The ovine lumbar intervertebral disc is a useful model for the human lumbar disc. We present preliminary estimates of diffusion coefficients and T2 relaxation times in a pilot MRI study of the ovine lumbar intervertebral disc during uniaxial compression in vitro, and identify factors that hamper the ability to accurately monitor the temporal evolution of the effective diffusion tensor at high spatial resolution.

  18. 21 CFR 888.3080 - Intervertebral body fusion device.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3080 Intervertebral body fusion device. (a) Identification. An intervertebral body fusion device is an implanted single or...

  19. MicroRNA in intervertebral disc degeneration.

    PubMed

    Li, Zheng; Yu, Xin; Shen, Jianxiong; Chan, Matthew T V; Wu, William Ka Kei

    2015-06-01

    Aetiology of intervertebral disc degeneration (IDD) is complex, with genetic, developmental, biochemical and biomechanical factors contributing to the disease process. It is becoming obvious that epigenetic processes influence evolution of IDD as strongly as the genetic background. Deregulated phenotypes of nucleus pulposus cells, including differentiation, migration, proliferation and apoptosis, are involved in all stages of progression of human IDD. Non-coding RNAs, including microRNAs, have recently been recognized as important regulators of gene expression. Research into roles of microRNAs in IDD has been very active over the past 5 years. Our review summarizes current research enlightenment towards understanding roles of microRNAs in regulating nucleus pulposus cell functions in IDD. These exciting findings support the notion that specific modulation of microRNAs may represent an attractive approach for management of IDD. PMID:25736871

  20. 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,…

  1. Analysis of compressive creep behavior of the vertebral unit subjected to a uniform axial loading using exact parametric solution equations of Kelvin-solid models--Part I. Human intervertebral joints.

    PubMed

    Burns, M L; Kaleps, I; Kazarian, L E

    1984-01-01

    The creep response phenomena observed on 47 human intervertebral discs subjected to a constant axial compressive stress was analytically studied by two-, three- and four-parameter-solid models employing the Burns- Kaleps 'exact analysis scheme'. The mechanical properties (Young's moduli and viscosity coefficients) associated with each model were calculated for each of the 47 disks, with superior results obtained for the latter two models. Results for the two-parameter-solid model suggest its possible usefulness in simulating creep response that is characteristic of disk degeneration. Results for the three- and four-parameter-solid models were excellent, with an average error for the model predicted strain, epsilon(ti)cal, values from the experimentally measured, epsilon(ti)exp, values of 2.314% for the former model and 4.446% for the latter model on the 47 human spinal segments analyzed. The three-parameter-solid model was most sensitive in its predictability of strain behavior for ti greater than 1 min; whereas the four-parameter-solid model demonstrated greater simulation sensitivity in the 0 less than ti less than or equal to 1 min range. PMID:6725291

  2. PSOCT studies of intervertebral disk

    NASA Astrophysics Data System (ADS)

    Matcher, Stephen J.; Winlove, Peter C.; Gangnus, Sergey V.

    2004-07-01

    Polarization-sensitive optical coherence tomography (PSOCT) is an emerging optical imaging technique that is sensitive to the birefringence properties of tissues. It thus has applications in studying the large-scale ordering of collagen fibers within connective tissues. This ordering not only provides useful insights into the relationship between structure and function for various anatomical structures but also is an indicator of pathology. Intervertebral disk is an elastic tissue of the spine and possesses a 3-D collagen structure well suited to study using PSOCT. Since the outer layer of the disk has a lamellar structure with collagen fibers oriented in a trellis-like arrangement between lamellae, the birefringence fast-axis shows pronounced variations with depth, on a spatial scale of about 100 μm. The lamellar thickness varies with age and possibly with disease. We have used a polarisation-sensitive optical coherence tomography system to measure the birefringence properties of freshly excised, hydrated bovine caudal intervertebral disk and compared this with equine flexor tendon. Our results clearly demonstrate the ability of PSOCT to detect the outer three lamellae, down to a depth of at least 700 μm, via discontinuities in the depth-resolved retardance. We have applied a simple semi-empirical model based on Jones calculus to quantify the variation in the fast-axis orientation with depth. Our data and modeling is in broad agreement with previous studies using x-ray diffraction and polarization microscopy applied to histological sections of dehydrated disk. Our results imply that PSOCT may prove a useful tool to study collagen organisation within intervertebral disk in vitro and possibly in vivo and its variation with age and disease.

  3. 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.

  4. On the Relative Relevance of Subject-Specific Geometries and Degeneration-Specific Mechanical Properties for the Study of Cell Death in Human Intervertebral Disk Models

    PubMed Central

    Malandrino, Andrea; Pozo, José M.; Castro-Mateos, Isaac; Frangi, Alejandro F.; van Rijsbergen, Marc M.; Ito, Keita; Wilke, Hans-Joachim; Dao, Tien Tuan; Ho Ba Tho, Marie-Christine; Noailly, Jérôme

    2015-01-01

    Capturing patient- or condition-specific intervertebral disk (IVD) properties in finite element models is outmost important in order to explore how biomechanical and biophysical processes may interact in spine diseases. However, disk degenerative changes are often modeled through equations similar to those employed for healthy organs, which might not be valid. As for the simulated effects of degenerative changes, they likely depend on specific disk geometries. Accordingly, we explored the ability of continuum tissue models to simulate disk degenerative changes. We further used the results in order to assess the interplay between these simulated changes and particular IVD morphologies, in relation to disk cell nutrition, a potentially important factor in disk tissue regulation. A protocol to derive patient-specific computational models from clinical images was applied to different spine specimens. In vitro, IVD creep tests were used to optimize poro-hyperelastic input material parameters in these models, in function of the IVD degeneration grade. The use of condition-specific tissue model parameters in the specimen-specific geometrical models was validated against independent kinematic measurements in vitro. Then, models were coupled to a transport-cell viability model in order to assess the respective effects of tissue degeneration and disk geometry on cell viability. While classic disk poro-mechanical models failed in representing known degenerative changes, additional simulation of tissue damage allowed model validation and gave degeneration-dependent material properties related to osmotic pressure and water loss, and to increased fibrosis. Surprisingly, nutrition-induced cell death was independent of the grade-dependent material properties, but was favored by increased diffusion distances in large IVDs. Our results suggest that in situ geometrical screening of IVD morphology might help to anticipate particular mechanisms of disk degeneration. PMID:25717471

  5. On the relative relevance of subject-specific geometries and degeneration-specific mechanical properties for the study of cell death in human intervertebral disk models.

    PubMed

    Malandrino, Andrea; Pozo, José M; Castro-Mateos, Isaac; Frangi, Alejandro F; van Rijsbergen, Marc M; Ito, Keita; Wilke, Hans-Joachim; Dao, Tien Tuan; Ho Ba Tho, Marie-Christine; Noailly, Jérôme

    2015-01-01

    Capturing patient- or condition-specific intervertebral disk (IVD) properties in finite element models is outmost important in order to explore how biomechanical and biophysical processes may interact in spine diseases. However, disk degenerative changes are often modeled through equations similar to those employed for healthy organs, which might not be valid. As for the simulated effects of degenerative changes, they likely depend on specific disk geometries. Accordingly, we explored the ability of continuum tissue models to simulate disk degenerative changes. We further used the results in order to assess the interplay between these simulated changes and particular IVD morphologies, in relation to disk cell nutrition, a potentially important factor in disk tissue regulation. A protocol to derive patient-specific computational models from clinical images was applied to different spine specimens. In vitro, IVD creep tests were used to optimize poro-hyperelastic input material parameters in these models, in function of the IVD degeneration grade. The use of condition-specific tissue model parameters in the specimen-specific geometrical models was validated against independent kinematic measurements in vitro. Then, models were coupled to a transport-cell viability model in order to assess the respective effects of tissue degeneration and disk geometry on cell viability. While classic disk poro-mechanical models failed in representing known degenerative changes, additional simulation of tissue damage allowed model validation and gave degeneration-dependent material properties related to osmotic pressure and water loss, and to increased fibrosis. Surprisingly, nutrition-induced cell death was independent of the grade-dependent material properties, but was favored by increased diffusion distances in large IVDs. Our results suggest that in situ geometrical screening of IVD morphology might help to anticipate particular mechanisms of disk degeneration. PMID:25717471

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

    ERIC Educational Resources Information Center

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

    1998-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  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. Primary Bovine Intervertebral Disc Cells Transduced with Adenovirus Overexpressing 12 BMPs and Sox9 Maintain Appropriate Phenotype

    PubMed Central

    Zhang, Yejia; Markova, Dessislava; Im, Hee-Jeong; Hu, Wenyang; Thonar, Eugene J.-M.A.; He, Tong-Chuan; An, Howard S.; Phillips, Frank M.; Anderson, D. Greg

    2010-01-01

    Objective To confirm that primary intervertebral disc cells cultured in monolayer transduced with adenovirus maintained their phenotype, hence is an appropriate system to test gene therapy agents. Design Adult bovine nucleus pulposus and anulus fibrosus cells cultured in monolayer were transduced with adenoviruses expressing human bone morphogenetic proteins (AdBMPs) or Sox9 (AdSox9), or green fluorescence protein (AdGFP, as control). Chondrocyte phenotypic markers (e.g., type II collagen and aggrecan) and the chondrocyte hypertrophy marker (type X collagen) were measured 6 days after viral transduction by reverse-transcription polymerase chain reaction. Results Primary nucleus pulposus and anulus fibrosus cells transduced with AdBMPs, AdSox9, or adenovirus-expressing green fluorescence protein only (AdGFP, as control) continue to express healthy chondrocyte phenotypic markers and showed no evidence of the expression of the chondrocyte hypertrophy marker (type X collagen gene). Thus, we have shown that bovine nucleus pulposus and anulus fibrosus cells transduced with adenovirus overexpressing 12 different bone morphogenetic proteins or Sox9 maintain their phenotype in short-term culture. Conclusions In this study, primary bovine intervertebral disc cells transduced with adenovirus overexpressing 12 bone morphogenetic proteins or Sox9 preserved their phenotype in short-term culture. These cells did not express the type X collagen gene, an undesirable chondrocyte hypertrophic gene that could lead to ossification. Therefore, low-passage intervertebral disc cells cultured in monolayer is an appropriate culture system to test therapeutic genes. We further suggest that these cells may also be appropriate for engineering tissues or for cell therapy for degenerative disc diseases. PMID:19454853

  10. Dysregulated miR-98 Contributes to Extracellular Matrix Degradation by Targeting IL-6/STAT3 Signaling Pathway in Human Intervertebral Disc Degeneration.

    PubMed

    Ji, Ming-Liang; Lu, Jun; Shi, Pei-Liang; Zhang, Xue-Jun; Wang, Shan-Zheng; Chang, Qing; Chen, Hui; Wang, Chen

    2016-04-01

    Intervertebral disc degeneration (IDD) is associated with dysregulated expression of microRNAs (miRNAs). However, the precise molecular mechanisms underlying this disorder remain unclear. Therefore, we tested the hypothesis that miRNAs modulate IDD through effects on the IL-6/STAT3 signaling pathway, a potential regulator of IDD. The miRNA expression profile was determined in nucleus pulposus (NP) tissues from patients with IDD and controls, employing miRNA microarray and quantitative real-time PCR (RT-qPCR). Biological functions of differential expression miRNAs were further investigated using immunofluorescent staining. Luciferase reporter assays and Western blotting were performed to determine miRNA targets. We identified 41 miRNAs that were differentially expressed in patients compared with controls. Following RT-qPCR confirmation, miR-98 was significantly downregulated in degenerative NP tissues. Moreover, its level was inversely correlated with grade of disc degeneration. Through gain-of-function and loss-of-function studies, miR-98 was shown to significantly promote type II collagen expression in NP cells. Interleukin-6 (IL-6) was identified as a target of miR-98. Knockdown of IL-6 induced effects on NP cells similar to those induced by miR-98. In contrast, IL-6 treatment abrogated the effects induced by miR-98 upregulation. Moreover, miR-98 dramatically suppressed expression of STAT3 target gene, MMP2. IL-6 treatment antagonized this effect, whereas knockdown of IL-6 by IL-6 short hairpin RNA (shIL-6) induced inhibitory effects on the expression of p-STAT3 and its main target genes, similar to miR-98. The mRNA level of IL-6 was inversely correlated with that of miR-98 in degenerative NP tissues. These results suggest the downregulation of miR-98 could promote IDD through the IL-6/STAT3 signaling pathway. Our findings also highlight miR-98 as a novel hopeful therapeutic target for IDD. © 2015 American Society for Bone and Mineral Research. PMID:26587789

  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. Intervertebral disc extrusion in six cats.

    PubMed

    Knipe, M F; Vernau, K M; Hornof, W J; LeCouteur, R A

    2001-09-01

    Existing reports concerning intervertebral disc disease (IVDD) have focused almost exclusively on dogs, although a small number of individual case reports of IVDD of cats has been published. The medical records of six cats with IVDD were reviewed. Radiographic studies confirmed narrowed intervertebral disc spaces, mineralised intervertebral discs, and one or more extradural compressive lesions of the spinal cord in each cat. All disc extrusions were located in the thoracolumbar region. Surgical decompression of the spinal cord was achieved in all cats by means of hemilaminectomy and removal of compressive extradural material confirmed to be degenerative disc material. Good to excellent neurological recovery was noted in five of the six cats included in this report. Based on this review, it appears that IVDD of cats has many similarities to IVDD of dogs, and that healthy cats with acute intervertebral disc extrusion(s) respond favourably to surgical decompression of the spinal cord. PMID:11876633

  13. 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

  14. [Innervation of the intervertebral disc].

    PubMed

    García-Cosamalón, José; Fernández-Fernández, Javier; González-Martínez, Emilio; Ibáñez-Plágaro, Javier; Robla Costales, Javier; Martínez-Madrigal, Milton; López Muñíz, Alfonso; del Valle, Miguel Enrique; Vega, José Antonio

    2013-01-01

    Until very recently, intervertebral disc innervation was a subject of considerable debate. Nowadays, the introduction of inmunohistochemical techniques associated to specific antibodies and studies with retrograde tracers in nerves have allowed greater understanding of disc innervation in physiological and pathological conditions and also endings characteristics and their patterns of distribution in both situations. The existing controversies regarding structural basis of discogenic pain, have raised the interest of knowing the influence of innervation in back pain from discal origin and its characteristics. Today, we know that pathologic neoinnervation accompanying radial fissures is an important factor in the genesis of discogenic pain; within a complex mechanism in which other neurobiomechemical, inflammatory and biomechanical factors are involved. PMID:23582224

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

    ERIC Educational Resources Information Center

    Burton, Lynn Elen, Ed.

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

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

    ERIC Educational Resources Information Center

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

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

  17. 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…

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

    ERIC Educational Resources Information Center

    Hilton, Ronald

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

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

    ERIC Educational Resources Information Center

    Rodriquez, Frank G.; Nash, Susan Smith

    2004-01-01

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

  20. Spectroscopic Parameters of Lumbar Intervertebral Disc Material

    NASA Astrophysics Data System (ADS)

    Terbetas, G.; Kozlovskaja, A.; Varanius, D.; Graziene, V.; Vaitkus, J.; Vaitkuviene, A.

    2009-06-01

    There are numerous methods of investigating intervertebral disc. Visualization methods are widely used in clinical practice. Histological, imunohistochemical and biochemical methods are more used in scientific research. We propose that a new spectroscopic investigation would be useful in determining intervertebral disc material, especially when no histological specimens are available. Purpose: to determine spectroscopic parameters of intervertebral disc material; to determine emission spectra common for all intervertebral discs; to create a background for further spectroscopic investigation where no histological specimen will be available. Material and Methods: 20 patients, 68 frozen sections of 20 μm thickness from operatively removed intervertebral disc hernia were excited by Nd:YAG microlaser STA-01-TH third harmonic 355 nm light throw 0, 1 mm fiber. Spectrophotometer OceanOptics USB2000 was used for spectra collection. Mathematical analysis of spectra was performed by ORIGIN multiple Gaussian peaks analysis. Results: In each specimen of disc hernia were found distinct maximal spectral peaks of 4 types supporting the histological evaluation of mixture content of the hernia. Fluorescence in the spectral regions 370-700 nm was detected in the disc hernias. The main spectral component was at 494 nm and the contribution of the components with the peak wavelength values at 388 nm, 412 nm and 435±5 nm were varying in the different groups of samples. In comparison to average spectrum of all cases, there are 4 groups of different spectral signatures in the region 400-500 nm in the patient groups, supporting a clinical data on different clinical features of the patients. Discussion and Conclusion: besides the classical open discectomy, new minimally invasive techniques of treating intervertebral disc emerge (PLDD). Intervertebral disc in these techniques is assessed by needle, no histological specimen is taken. Spectroscopic investigation via fiber optics through the

  1. 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

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

    PubMed

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

    2016-01-01

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

  3. 21 CFR 888.3080 - Intervertebral body fusion device.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Intervertebral body fusion device. 888.3080... (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3080 Intervertebral body fusion device. (a) Identification. An intervertebral body fusion device is an implanted single or...

  4. 21 CFR 888.3080 - Intervertebral body fusion device.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Intervertebral body fusion device. 888.3080... (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3080 Intervertebral body fusion device. (a) Identification. An intervertebral body fusion device is an implanted single or...

  5. 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…

  6. Proteomic Signature of the Murine Intervertebral Disc

    PubMed Central

    McCann, Matthew R.; Patel, Priya; Frimpong, Agya; Xiao, Yizhi; Siqueira, Walter L.; Séguin, Cheryle A.

    2015-01-01

    Low back pain is the most common musculoskeletal problem and the single most common cause of disability, often attributed to degeneration of the intervertebral disc. Lack of effective treatment is directly related to our limited understanding of the pathways responsible for maintaining disc health. While transcriptional analysis has permitted initial insights into the biology of the intervertebral disc, complete proteomic characterization is required. We therefore employed liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) protein/peptide separation and mass spectrometric analyses to characterize the protein content of intervertebral discs from skeletally mature wild-type mice. A total of 1360 proteins were identified and categorized using PANTHER. Identified proteins were primarily intracellular/plasma membrane (35%), organelle (30%), macromolecular complex (10%), extracellular region (9%). Molecular function categorization resulted in three distinct categories: catalytic activity (33%), binding (molecule interactions) (29%), and structural activity (13%). To validate our list, we confirmed the presence of 14 of 20 previously identified IVD-associated markers, including matrix proteins, transcriptional regulators, and secreted proteins. Immunohistochemical analysis confirmed distinct localization patterns of select protein with the intervertebral disc. Characterization of the protein composition of healthy intervertebral disc tissue is an important first step in identifying cellular processes and pathways disrupted during aging or disease progression. PMID:25689066

  7. Action of fibroblast growth factor-2 on the intervertebral disc

    PubMed Central

    Li, Xin; An, Howard S; Ellman, Michael; Phillips, Frank; Thonar, Eugene J; Park, Daniel K; Udayakumar, Ranjith K; Im, Hee-Jeong

    2008-01-01

    Introduction Fibroblast growth factor 2 (FGF2) is a growth factor that is immediately released after cartilage injury and plays a pivotal role in cartilage homeostasis. In human adult articular cartilage, FGF2 mediates anti-anabolic and potentially catabolic effects via the suppression of proteoglycan (PG) production along with the upregulation of matrix-degrading enzyme activity. The aim of the present study was to determine the biological effects of FGF2 in spine disc cells and to elucidate the complex biochemical pathways utilized by FGF2 in bovine intervertebral disc (IVD) cells in an attempt to further understand the pathophysiologic processes involved in disc degeneration. Methods We studied the effect of FGF2 on IVD tissue homeostasis by assessing MMP-13 expression (potent matrix-degrading enzyme), PG accumulation, and PG synthesis in the bovine spine IVD, as well as evaluating whether FGF2 counteracts known anabolic factors such as BMP7. To understand the molecular mechanisms by which FGF2 antagonizes BMP7 activity, we also investigated the signaling pathways utilized by FGF2 in bovine disc tissue. Results The primary receptor expressed in bovine nucleus pulposus cartilage is FGFR1, and this receptor is upregulated in degenerative human IVD tissue compared with normal IVD tissue. Stimulation of bovine nucleus pulposus cells cultured in monolayer with FGF2 augmented the production of MMP-13 at the transcriptional and translational level in a dose-dependent manner. Stimulation of bovine nucleus pulposus cells cultured in alginate beads for 21 days with FGF2 resulted in a dose-dependent decrease in PG accumulation, due at least in part to the inhibition of PG synthesis. Further studies demonstrate that FGF2 (10 ng/ml) antagonizes BMP7-mediated acceleration of PG production in bovine nucleus pulposus cells via the upregulation of noggin, an inhibitor of the transforming growth factor beta/bone morphogenetic protein signaling pathway. Chemical inhibitor studies

  8. Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration

    PubMed Central

    Vasiliadis, Elias S; Pneumaticos, Spyros G; Evangelopoulos, Demitrios S; Papavassiliou, Athanasios G

    2014-01-01

    Disc degeneration is the most common cause of back pain in adults and has enormous socioeconomic implications. Conservative management is ineffective in most cases, and results of surgical treatment have not yet reached desirable standards. Biologic treatment options are an alternative to the above conventional management and have become very attractive in recent years. The present review highlights the currently available biologic treatment options in mild and moderate disc degeneration, where a potential for regeneration still exists. Biologic treatment options include protein-based and cell-based therapies. Protein-based therapies involve administration of biologic factors into the intervertebral disc to enhance matrix synthesis, delay degeneration or impede inflammation. These factors can be delivered by an intradiscal injection, alone or in combination with cells or tissue scaffolds and by gene therapy. Cell-based therapies comprise treatment strategies that aim to either replace necrotic or apoptotic cells, or minimize cell death. Cell-based therapies are more appropriate in moderate stages of degenerated disc disease, when cell population is diminished; therefore, the effect of administration of growth factors would be insufficient. Although clinical application of biologic treatments is far from being an everyday practice, the existing studies demonstrate promising results that will allow the future design of more sophisticated methods of biologic intervention to treat intervertebral disc degeneration. PMID:25171110

  9. Calcification in the ovine intervertebral disc: a model of hydroxyapatite deposition disease

    PubMed Central

    Burkhardt, D.; Taylor, T. K. F.; Dillon, C. T.; Read, R.; Cake, M.; Little, C. B.

    2009-01-01

    The study design included a multidisciplinary examination of the mineral phase of ovine intervertebral disc calcifications. The objective of the study was to investigate the mineral phase and its mechanisms of formation/association with degeneration in a naturally occurring animal model of disc calcification. The aetiology of dystrophic disc calcification in adult humans is unknown, but occurs as a well-described clinical disorder with hydroxyapatite as the single mineral phase. Comparable but age-related pathology in the sheep could serve as a model for the human disorder. Lumbar intervertebral discs (n = 134) of adult sheep of age 6 years (n = 4), 8 years (n = 12) and 11 years (n = 2) were evaluated using radiography, morphology, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray powder diffraction, histology, immunohistology and proteoglycan analysis. Half of the 6-year, 84% of the 8-year and 86% of the 11-year-old discs had calcific deposits. These were not well delineated by plain radiography. They were either: (a) punctate deposits in the outer annulus, (b) diffuse deposits in the transitional zone or inner annulus fibrosus with occasional deposits in the nucleus, or (c) large deposits in the transitional zone extending variably into the nucleus. Their maximal incidence was in the lower lumbar discs (L4/5–L6/7) with no calcification seen in the lumbosacral or lower thoracic discs. All deposits were hydroxyapatite with large crystallite sizes (800–1,300 Å) compared to cortical bone (300–600 Å). No type X-collagen, osteopontin or osteonectin were detected in calcific deposits, although positive staining for bone sialoprotein was evident. Calcified discs had less proteoglycan of smaller hydrodynamic size than non-calcified discs. Disc calcification in ageing sheep is due to hydroxyapatite deposition. The variable, but large, crystal size and lack of protein markers indicate that this does not occur by

  10. High incidence of persistence of sacral and coccygeal intervertebral discs in South Indians - a cadaveric study.

    PubMed

    Satheesha Nayak, B; Ashwini Aithal, P; Kumar, Naveen; George, Bincy M; Deepthinath, R; Shetty, Surekha D

    2016-06-01

    The sacrum, by virtue of its anatomic location plays a key role in providing stability and strength to the pelvis. Presence of intervertebral discs in sacrum and coccyx is rare. Knowledge of its variations is of utmost importance to surgeons and radiologists. The current study focused on the presence of intervertebral discs between the sacral and coccygeal vertebrae in south Indian cadaveric pelvises. We observed 56 adult pelvises of which, 34 (61%) pelvises showed the presence of intervertebral discs between the sacral vertebrae and between the coccygeal vertebrae, while 22 (39%) pelvises did not have the intervertebral discs either in the sacrum or the coccyx. We also found that most of the specimens had discs between S1 and S2 vertebrae (39%), followed by, between S4 and S5 (18%), between S2-S3 (14%) and least being between S3-S4 (13%). In the coccyx it was found that 7% of pelvises had disc between Co1-Co2, 4% of them had between Co2-Co3 and 4% had between Co3-Co4. Knowledge regarding such anatomic variations in the sacro-coccygeal region is important to note because they require alterations in various instrumentation procedures involving the sacrum. PMID:27385838

  11. 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

  12. Relationship between Initial Telomere Length, Initial Telomerase Activity, Age, and Replicative Capacity of Nucleus Pulposus Chondrocytes in Human Intervertebral Discs: What Is a Predictor of Replicative Potential?

    PubMed Central

    Lee, Jun-Seok; Jeong, Seo-Won; Cho, Sung-Wook; Juhn, Joon-Pyo; Kim, Ki-Won

    2015-01-01

    There is evidence that telomere length (TL), telomerase activity (TA), and age are related to the replicative potential of human nucleus pulposus chondrocytes (NPCs). However, it has not yet been established if any of these factors can serve as predictors of the replicative potential of NPCs. To establish predictors of the replicative potential of NPCs, we evaluated potential relationships between replicative capacity of NPCs, initial TL (telomere length at the first passage), initial TA (telomerase activity at the first passage), and age. Nucleus pulposus specimens were obtained from 14 patients of various ages undergoing discectomy. NPCs were serially cultivated until the end of their replicative lifespans. Relationships among cumulative population doubling level (PDL), initial TL, initial TA, and age were analyzed. Initial TA was negatively correlated with age (r = -0.674, P = 0.008). However, no correlation between initial TL and age was observed. Cumulative PDL was also negatively correlated with age (r = -0.585, P = 0.028). Although the cumulative PDL appeared to increase with initial TL or initial TA, this trend was not statistically significant. In conclusion, age is the sole predictor of the replicative potential of human NPCs, and replicative potential decreases with age. Initial TL and initial TA are not predictors of replicative potential, and can serve only as reference values. PMID:26633809

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

    PubMed Central

    2012-01-01

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

  14. Expression of tmp21 in normal adult human tissues

    PubMed Central

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

    2014-01-01

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

  15. 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

  16. Novel surface markers directed against adult human gallbladder

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Bowers, Megan; Jessberger, Sebastian

    2016-07-01

    We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc. PMID:26890418

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

    PubMed

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

    2015-02-01

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

  20. 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

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

    PubMed

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

    2012-01-01

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

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

    ERIC Educational Resources Information Center

    Wright, Joan

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

  3. [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

  4. Decellularized allogeneic intervertebral disc: natural biomaterials for regenerating disc degeneration

    PubMed Central

    Hu, Zhijun; Chen, Kai; Shan, Zhi; Chen, Shuai; Wang, Jiying; Mo, Jian; Ma, Jianjun; Xu, Wenbing; Qin, An; Fan, Shunwu

    2016-01-01

    Intervertebral disc degeneration is associated with back pain and disc herniation. This study established a modified protocol for intervertebral disc (IVD) decellularization and prepared its extracellular matrix (ECM). By culturing mesenchymal stem cells (MSCs)(3, 7, 14 and 21 days) and human degenerative IVD cells (7 days) in the ECM, implanting it subcutaneously in rabbit and injecting ECM microparticles into degenerative disc, the biological safety and efficacy of decellularized IVD was evaluated both in vitro and in vivo. Here, we demonstrated that cellular components can be removed completely after decellularization and maximally retain the structure and biomechanics of native IVD. We revealed that allogeneic ECM did not evoke any apparent inflammatory reaction in vivo and no cytotoxicity was found in vitro. Moreover, IVD ECM can induce differentiation of MSCs into IVD-like cells in vitro. Furthermore, allogeneic ECM microparticles are effective on the treatment of rabbit disc degeneration in vivo. In conclusion, our study developed an optimized method for IVD decellularization and we proved decellularized IVD is safe and effective for the treatment of degenerated disc diseases. PMID:26933821

  5. Telocytes of the human adult trigeminal ganglion.

    PubMed

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

    2016-06-01

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

  6. 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

  7. 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

  8. Comparison of two methods for RNA extraction from the nucleus pulposus of intervertebral discs.

    PubMed

    Gan, M F; Yang, H L; Qian, J L; Wu, C S; Yuan, C X; Li, X F; Zou, J

    2016-01-01

    RNA extraction from the nucleus pulposus of intervertebral discs has been extensively used in orthopedic studies. We compared two methods for extracting RNA from the nucleus pulposus: liquid nitrogen grinding and enzyme digestion. The RNA was detected by agarose gel electrophoresis, and the purity was evaluated by absorbance ratio using a spectrophotometer. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression was assayed by reverse transcription-polymerase chain reaction (RT-PCR). Thirty human lumbar intervertebral discs were used in this study. The liquid nitrogen-grinding method was used for RNA extraction from 15 samples, and the mean RNA concentration was 491.04 ± 44.16 ng/mL. The enzyme digestion method was used on 15 samples, and the mean RNA concentration was 898.42 ± 38.64 ng/mL. The statistical analysis revealed that there was a significant difference in concentration between the different methods. Apparent 28S, 18S, and 5S bands were detectable in RNA extracted using the enzyme digestion method, whereas no 28S or 18S bands were detected in RNA extracted using the liquid nitrogen-grinding method. The GAPDH band was visible, and no non-specific band was detected in the RT-PCR assay by the enzyme digestion method. Therefore, the enzyme digestion method is an efficient and easy method for RNA extraction from the nucleus pulposus of intervertebral discs for further intervertebral disc degeneration-related studies. PMID:27323116

  9. EVALUATION OF MAGNETIC RESONANCE IMAGING GUIDELINES FOR DIFFERENTIATION BETWEEN THORACOLUMBAR INTERVERTEBRAL DISK EXTRUSIONS AND INTERVERTEBRAL DISK PROTRUSIONS IN DOGS.

    PubMed

    De Decker, Steven; Gomes, Sergio A; Packer, Rowena Ma; Kenny, Patrick J; Beltran, Elsa; Parzefall, Birgit; Fenn, Joe; Nair, Devi; Nye, George; Volk, Holger A

    2016-09-01

    Four MRI variables have recently been suggested to be independently associated with a diagnosis of thoracolumbar intervertebral disk extrusion or protrusion. Midline intervertebral disk herniation, and partial intervertebral disk degeneration were associated with intervertebral disk protrusion, while presence of a single intervertebral disk herniation and disk material dispersed beyond the boundaries of the intervertebral disk space were associated with intervertebral disk extrusion. The aim of this retrospective, cross-sectional study was to determine whether using these MRI variables improves differentiation between thoracolumbar intervertebral disk extrusions and protrusions. Eighty large breed dogs with surgically confirmed thoracolumbar intervertebral disk extrusions or protrusions were included. Randomized MRI studies were presented on two occasions to six blinded observers, which were divided into three experience categories. During the first assessment, observers made a presumptive diagnosis of thoracolumbar intervertebral disk extrusion or protrusion without guidelines. During the second assessment they were asked to make a presumptive diagnosis with the aid of guidelines. Agreement was evaluated by Kappa-statistics. Diagnostic accuracy significantly improved from 70.8 to 79.6% and interobserver agreement for making a diagnosis of intervertebral disk extrusion or intervertebral disk protrusion improved from fair (κ = 0.27) to moderate (κ = 0.41) after using the proposed guidelines. Diagnostic accuracy was significantly influenced by degree of observer experience. Intraobserver agreement for the assessed variables ranged from fair to excellent and interobserver agreement ranged from fair to moderate. The results of this study suggest that the proposed imaging guidelines can aid in differentiating thoracolumbar intervertebral disk extrusions from protrusions. PMID:27374979

  10. Adult human sarcomas. II. Medical oncology.

    PubMed

    Sinkovics, Joseph G

    2007-02-01

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

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

    PubMed

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

    2012-12-10

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

  12. Analysis of rabbit intervertebral disc physiology based on water metabolism. II. Changes in normal intervertebral discs under axial vibratory load

    SciTech Connect

    Hirano, N.; Tsuji, H.; Ohshima, H.; Kitano, S.; Itoh, T.; Sano, A.

    1988-11-01

    Metabolic changes induced by axial vibratory load to the spine were investigated based on water metabolism in normal intervertebral discs of rabbits with or without pentobarbital anesthesia. Tritiated water concentration in the intervertebral discs of unanesthetized rabbits was reduced remarkably by axial vibration for 30 minutes using the vibration machine developed for this study. Repeated vibratory load for 18 and 42 hours duration showed the recovery of /sup 3/H/sub 2/O concentration of the intervertebral disc without anesthesia. Computer simulation suggested a reduction of blood flow surrounding the intervertebral disc following the vibration stress. However, no reduction of the /sup 3/H/sub 2/O concentration in the intervertebral disc was noted under anesthesia. Emotional stress cannot be excluded as a factor in water metabolism in the intervertebral disc.

  13. 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

  14. Atomic Absorption Spectrometry Analysis of Trace Elements in Degenerated Intervertebral Disc Tissue

    PubMed Central

    Kubaszewski, Łukasz; Zioła-Frankowska, Anetta; Frankowski, Marcin; Nowakowski, Andrzej; Czabak-Garbacz, Róża; Kaczmarczyk, Jacek; Gasik, Robert

    2014-01-01

    Background Few studies have investigated trace elements (TE) in human intervertebral disc (IVD) tissue. Trace element presence can have diverse meanings: essential TE show the metabolic modalities of the tissue, while environmentally-related TE indicate pollution and tissue-specific absorption and accumulation. IVD is a highly specific compartment with impaired communication with adjacent bone. Analysis of TE in IVD provides new insights regarding tissue metabolism and IVD communication with other tissues. Material/Methods Thirty intervertebral discs were acquired from 22 patients during surgical treatment for degenerative disease. Atomic absorption spectrometry was used to evaluate the concentrations of Al, Cd, Pb, Cu, Ni, Mo, Mg, and Zn. Results Al, Pb, Cu, Mg, and Zn were detected in all samples. Pb was significantly positively correlated with age, and Ni concentration was weakly correlated with population count in the patient’s place of residence. Only Cu was observed in higher concentrations in IVD compared to in other tissues. Significant positive correlations were observed between the following pairs: Mg/Zn, Mg/Al, Mg/Pb, Zn/Al, Zn/Pb, and Al/Pb. Negative correlations were observed between Mg/Cd, Zn/Cd, Mg/Mo, and Mo/Pb. Conclusions This study is one of few to profile the elements in intervertebral discs in patients with degenerative changes. We report significant differences between trace element concentrations in intervertebral discs compared to in other tissues. Knowledge of the TE accumulation pattern is vital for better understanding intervertebral disc nutrition and metabolism. PMID:25366266

  15. Progranulin Knockout Accelerates Intervertebral Disc Degeneration in Aging Mice

    PubMed Central

    Zhao, Yun-peng; Tian, Qing-yun; Liu, Ben; Cuellar, Jason; Richbourgh, Brendon; Jia, Tang-hong; Liu, Chuan-ju

    2015-01-01

    Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-κB signaling and β-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases. PMID:25777988

  16. Molecular mechanisms of cell death in intervertebral disc degeneration (Review)

    PubMed Central

    ZHANG, FAN; ZHAO, XUELING; SHEN, HONGXING; ZHANG, CAIGUO

    2016-01-01

    Intervertebral discs (IVDs) are complex structures that consist of three parts, namely, nucleus pulposus, annulus fibrosus and cartilage endplates. With aging, IVDs gradually degenerate as a consequence of many factors, such as microenvironment changes and cell death. Human clinical trial and animal model studies have documented that cell death, particularly apoptosis and autophagy, significantly contribute to IVD degeneration. The mechanisms underlying this phenomenon include the activation of apoptotic pathways and the regulation of autophagy in response to nutrient deprivation and multiple stresses. In this review, we briefly summarize recent progress in understanding the function and regulation of apoptosis and autophagy signaling pathways. In particular, we focus on studies that reveal the functional mechanisms of these pathways in IVD degeneration. PMID:27121482

  17. Molecular mechanisms of cell death in intervertebral disc degeneration (Review).

    PubMed

    Zhang, Fan; Zhao, Xueling; Shen, Hongxing; Zhang, Caiguo

    2016-06-01

    Intervertebral discs (IVDs) are complex structures that consist of three parts, namely, nucleus pulposus, annulus fibrosus and cartilage endplates. With aging, IVDs gradually degenerate as a consequence of many factors, such as microenvironment changes and cell death. Human clinical trial and animal model studies have documented that cell death, particularly apoptosis and autophagy, significantly contribute to IVD degeneration. The mechanisms underlying this phenomenon include the activation of apoptotic pathways and the regulation of autophagy in response to nutrient deprivation and multiple stresses. In this review, we briefly summarize recent progress in understanding the function and regulation of apoptosis and autophagy signaling pathways. In particular, we focus on studies that reveal the functional mechanisms of these pathways in IVD degeneration. PMID:27121482

  18. Construction of a tissue engineered intervertebral disc with high biological activity using an allogeneic intervertebral disc supplemented with transfected nucleus pulposus cells expressing exogenous dopamine beta-hydroxylase.

    PubMed

    Bai, M; Wang, Y H; Yin, H P; Li, S W

    2015-01-01

    This study addressed the in vitro construction and biological activity of tissue engineered intervertebral discs with exogenous human dopamine beta-hydroxylase (DBH) nucleus pulposus cells. pSNAV2.0-DBH expression plasmids were utilized to enhance the survival rates of intervertebral disc tissue cells. Various concentrations of transfected nucleus pulposus cells were injected into the discs, and DBH mRNA expression was determined using polymerase chain reaction amplification. Polysaccharide content and total collagen protein content in the engineered disc nucleus pulposus tissue were determined. The visible fluorescence intensities of the 1 x 10(5) and 1 x 10(6) groups vs the 1 x 10(4) group were significantly increased (P < 0.05); no significant difference was observed between the 1 x 10(5) and 1 x 10(6) groups (P > 0.05) at 7 days after injection. DBH mRNA expression could be detected in the all but the EGFP control group at 14 days culture. No significant difference was observed in the protein content between the 1 x 10(4) and the control groups at various times, while the protein content was significantly higher in the 1 x 10(5) vs the control and the 1 x 10(4) groups at 7-, 14-, and 21-day cultures. These results demonstrate that a tissue engineered intervertebral disc with high biological activity can be constructed by utilizing allogeneic intervertebral discs stored in liquid nitrogen and a 1 x 10(5) transfected nucleus pulposus cell complex with in vitro culture for 14 days. This model can be used in animal experiments to study the biological activity of the engineered discs. PMID:26400296

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

    PubMed

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

    2010-02-01

    This article reviews key findings about the long-term impact of a nutrition intervention carried out by the Institute of Nutrition of Central America and Panama from 1969 to 1977. Results from follow-up studies in 1988-89 and 2002-04 show substantial impact on adult human capital and economic productivity. The 1988-89 study showed that adult body size and work capacity increased for those provided improved nutrition through age 3 y, whereas the 2002-04 follow-up showed that schooling was increased for women and reading comprehension and intelligence increased in both men and women. Participants were 26-42 y of age at the time of the 2002-04 follow-up, facilitating the assessment of economic productivity. Wages of men increased by 46% in those provided with improved nutrition through age 2 y. Findings for cardiovascular disease risk factors were heterogeneous; however, they suggest that improved nutrition in early life is unlikely to increase cardiovascular disease risk later in life and may indeed lower risk. In conclusion, the substantial improvement in adult human capital and economic productivity resulting from the nutrition intervention provides a powerful argument for promoting improvements in nutrition in pregnant women and young children. PMID:20032473

  20. 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

  1. Construction Strategy and Progress of Whole Intervertebral Disc Tissue Engineering.

    PubMed

    Yang, Qiang; Xu, Hai-Wei; Hurday, Sookesh; Xu, Bao-Shan

    2016-02-01

    Degenerative disc disease (DDD) is the major cause of low back pain, which usually leads to work absenteeism, medical visits and hospitalization. Because the current conservative procedures and surgical approaches to treatment of DDD only aim to relieve the symptoms of disease but not to regenerate the diseased disc, their long-term efficiency is limited. With the rapid developments in medical science, tissue engineering techniques have progressed markedly in recent years, providing a novel regenerative strategy for managing intervertebral disc disease. However, there are as yet no ideal methods for constructing tissue-engineered intervertebral discs. This paper reviews published reports pertaining to intervertebral disc tissue engineering and summarizes data concerning the seed cells and scaffold materials for tissue-engineered intervertebral discs, construction of tissue-engineered whole intervertebral discs, relevant animal experiments and effects of mechanics on the construction of tissue-engineered intervertebral disc and outlines the existing problems and future directions. Although the perfect regenerative strategy for treating DDD has not yet been developed, great progress has been achieved in the construction of tissue-engineered intervertebral discs. It is believed that ongoing research on intervertebral disc tissue engineering will result in revolutionary progress in the treatment of DDD. PMID:27028376

  2. Molecular mechanisms of biological aging in intervertebral discs.

    PubMed

    Vo, Nam V; Hartman, Robert A; Patil, Prashanti R; Risbud, Makarand V; Kletsas, Dimitris; Iatridis, James C; Hoyland, Judith A; Le Maitre, Christine L; Sowa, Gwendolyn A; Kang, James D

    2016-08-01

    Advanced age is the greatest risk factor for the majority of human ailments, including spine-related chronic disability and back pain, which stem from age-associated intervertebral disc degeneration (IDD). Given the rapid global rise in the aging population, understanding the biology of intervertebral disc aging in order to develop effective therapeutic interventions to combat the adverse effects of aging on disc health is now imperative. Fortunately, recent advances in aging research have begun to shed light on the basic biological process of aging. Here we review some of these insights and organize the complex process of disc aging into three different phases to guide research efforts to understand the biology of disc aging. The objective of this review is to provide an overview of the current knowledge and the recent progress made to elucidate specific molecular mechanisms underlying disc aging. In particular, studies over the last few years have uncovered cellular senescence and genomic instability as important drivers of disc aging. Supporting evidence comes from DNA repair-deficient animal models that show increased disc cellular senescence and accelerated disc aging. Additionally, stress-induced senescent cells have now been well documented to secrete catabolic factors, which can negatively impact the physiology of neighboring cells and ECM. These along with other molecular drivers of aging are reviewed in depth to shed crucial insights into the underlying mechanisms of age-related disc degeneration. We also highlight molecular targets for novel therapies and emerging candidate therapeutics that may mitigate age-associated IDD. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1289-1306, 2016. PMID:26890203

  3. Molecular Mechanisms of Biological Aging in Intervertebral Discs

    PubMed Central

    Vo, Nam V.; Hartman, Robert A.; Patil, Prashanti R.; Risbud, Makarand V.; Kletsas, Dimitris; Iatridis, James C.; Hoyland, Judith A.; Le Maitre, Christine L.; Sowa, Gwendolyn A.; Kang, James D.

    2016-01-01

    Advanced age is the greatest risk factor for the majority of human ailments, including spine-related chronic disability and back pain, which stem from age-associated intervertebral disc degeneration (IDD). Given the rapid global rise in the aging population, understanding the biology of intervertebral disc aging in order to develop effective therapeutic interventions to combat the adverse effects of aging on disc health is now imperative. Fortunately, recent advances in aging research have begun to shed light on the basic biological process of aging. Here we review some of these insights and organize the complex process of disc aging into three different phases to guide research efforts to understand the biology of disc aging. The objective of this review is to provide an overview of the current knowledge and the recent progress made to elucidate specific molecular mechanisms underlying disc aging. In particular, studies over the last few years have uncovered cellular senescence and genomic instability as important drivers of disc aging. Supporting evidence comes from DNA repair-deficient animal models that show increased disc cellular senescence and accelerated disc aging. Additionally, stress-induced senescent cells have now been well documented to secrete catabolic factors, which can negatively impact the physiology of neighboring cells and ECM. These along with other molecular drivers of aging are reviewed in depth to shed crucial insights into the underlying mechanisms of age-related disc degeneration. We also highlight molecular targets for novel therapies and emerging candidate therapeutics that may mitigate age-associated IDD. PMID:26890203

  4. High incidence of persistence of sacral and coccygeal intervertebral discs in South Indians – a cadaveric study

    PubMed Central

    Satheesha Nayak, B; Ashwini Aithal, P; Kumar, Naveen; George, Bincy M; Deepthinath, R; Shetty, Surekha D

    2016-01-01

    The sacrum, by virtue of its anatomic location plays a key role in providing stability and strength to the pelvis. Presence of intervertebral discs in sacrum and coccyx is rare. Knowledge of its variations is of utmost importance to surgeons and radiologists. The current study focused on the presence of intervertebral discs between the sacral and coccygeal vertebrae in south Indian cadaveric pelvises. We observed 56 adult pelvises of which, 34 (61%) pelvises showed the presence of intervertebral discs between the sacral vertebrae and between the coccygeal vertebrae, while 22 (39%) pelvises did not have the intervertebral discs either in the sacrum or the coccyx. We also found that most of the specimens had discs between S1 and S2 vertebrae (39%), followed by, between S4 and S5 (18%), between S2–S3 (14%) and least being between S3–S4 (13%). In the coccyx it was found that 7% of pelvises had disc between Co1-Co2, 4% of them had between Co2-Co3 and 4% had between Co3-Co4. Knowledge regarding such anatomic variations in the sacro-coccygeal region is important to note because they require alterations in various instrumentation procedures involving the sacrum. PMID:27385838

  5. 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.

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

    PubMed

    Randler, Christoph

    2016-02-01

    Sleep timing of humans can be classified alongside a continuum from early to late sleepers, with some people (larks) having an early activity, early bed, and rise times and others (owls) with a more nocturnally orientated activity. Only a few studies reported that morningness-eveningness changes significantly during the adult lifespan based on community samples. Here, I applied a different methodological approach to seek for evidence for the age-related changes in morningness-eveningness preferences by using a meta-data from all available studies. The new aspect of this cross-sectional approach is that only a few studies themselves address the age-related changes of the adult lifespan development, but that many studies are available that provide exactly the data needed. The studies came from 27 countries and included 36,939 participants. Age was highly significantly correlated with scores on the Composite Scale of Morningness (r = 0.70). This relationship seems linear, because a linear regression explained nearly the same amount of variance compared to other models such as logarithmic, quadratic, or cubic models. The standard deviation of age correlated with the standard deviation of CSM scores (r = 0.55), suggesting when there is much variance in age in a study; in turn, there is much variance in morningness. This meta-analytical approach shows that morningness-eveningness changes across the adult lifespan and that older age is related to higher morningness. PMID:26715354

  7. Finite element modeling of the cervical spine: role of intervertebral disc under axial and eccentric loads.

    PubMed

    Kumaresan, S; Yoganandan, N; Pintar, F A; Maiman, D J

    1999-12-01

    An anatomically accurate, three-dimensional, nonlinear finite element model of the human cervical spine was developed using computed tomography images and cryomicrotome sections. The detailed model included the cortical bone, cancellous core, endplate, lamina, pedicle, transverse processes and spinous processes of the vertebrae; the annulus fibrosus and nucleus pulposus of the intervertebral discs; the uncovertebral joints; the articular cartilage, the synovial fluid and synovial membrane of the facet joints; and the anterior and posterior longitudinal ligaments, interspinous ligaments, capsular ligaments and ligamentum flavum. The finite element model was validated with experimental results: force-displacement and localized strain responses of the vertebral body and lateral masses under pure compression, and varying eccentric anterior-compression and posterior-compression loading modes. This experimentally validated finite element model was used to study the biomechanics of the cervical spine intervertebral disc by quantifying the internal axial and shear forces resisted by the ventral, middle, and dorsal regions of the disc under the above axial and eccentric loading modes. Results indicated that higher axial forces (compared to shear forces) were transmitted through different regions of the disc under all loading modes. While the ventral region of the disc resisted higher variations in axial force, the dorsal region transmitted higher shear forces under all loading modes. These findings may offer an insight to better understand the biomechanical role of the human cervical spine intervertebral disc. PMID:10717549

  8. Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration

    PubMed Central

    Le Maitre, Christine Lyn; Freemont, Anthony John; Hoyland, Judith Alison

    2007-01-01

    Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated β-galactosidase (SA-β-gal), and replicative potential. Expression of P16INK4A (increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a disintegrin and metalloprotease with thrombospondin motifs 5), and P16INK4A. Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of P16INK4A. Cells from degenerate discs (even from young patients) exhibited increased expression of P16INK4A, increased SA-β-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between P16INK4A and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration. PMID:17498290

  9. Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration.

    PubMed

    Le Maitre, Christine Lyn; Freemont, Anthony John; Hoyland, Judith Alison

    2007-01-01

    Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated beta-galactosidase (SA-beta-gal), and replicative potential. Expression of P16INK4A (increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a disintegrin and metalloprotease with thrombospondin motifs 5), and P16INK4A. Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of P16INK4A. Cells from degenerate discs (even from young patients) exhibited increased expression of P16INK4A, increased SA-beta-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between P16INK4A and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration. PMID:17498290

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

    ERIC Educational Resources Information Center

    Saltiel, Iris M.; Russo, Charline S.

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

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

    ERIC Educational Resources Information Center

    Moran, Joseph J.

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

  12. Unique multipotent cells in adult human mesenchymal cell populations

    PubMed Central

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

    2010-01-01

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

  13. 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

  14. Lumbar intervertebral disc degeneration and related factors in Korean firefighters

    PubMed Central

    Jang, Tae-Won; Ahn, Yeon-Soon; Byun, Junsu; Lee, Jong-In; Kim, Kun-Hyung; Kim, Youngki; Song, Han-Soo; Lee, Chul-Gab; Kwon, Young-Jun; Yoon, Jin-Ha; Jeong, Kyoungsook

    2016-01-01

    Objectives The job of firefighting can cause lumbar burden and low back pain. This study aimed to identify the association between age and lumbar intervertebral disc degeneration and whether the association differs between field and administrative (non-field) firefighters. Methods Subjects were selected using a stratified random sampling method. Firefighters were stratified by geographic area, gender, age and type of job. First, 25 fire stations were randomly sampled considering regional distribution. Then firefighters were stratified by gender, age and their job and randomly selected among the strata. A questionnaire survey and MRI scans were performed, and then four radiologists used Pfirrmann classification methods to determine the grade of lumbar intervertebral disc degeneration. Results Pfirrmann grade increased with lumbar intervertebral disc level. Analysis of covariance showed that age was significantly associated with lumbar intervertebral disc degeneration (p<0.05). The value of β (parameter estimate) was positive at all lumbar intervertebral disc levels and was higher in the field group than in the administrative group at each level. In logistic regression analysis, type of job was statistically significant only with regard to the L4–5 intervertebral disc (OR 3.498, 95% CI 1.241 to 9.860). Conclusions Lumbar intervertebral disc degeneration is associated with age, and field work such as firefighting, emergency and rescue may accelerate degeneration in the L4–5 intervertebral disc. The effects of field work on lumbar intervertebral disc degeneration were not clear in discs other than at the level L4–5. PMID:27354080

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

    PubMed

    Bhattacharjee, Manasi; Bhatia, Renu; Mathur, Rashmi

    2007-01-01

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

  16. Mesenchymal stem cells: potential application in intervertebral disc regeneration

    PubMed Central

    Shen, Bojiang; Williams, Lisa; Diwan, Ashish

    2014-01-01

    Chronic low back pain is one of the leading public health problems in developed countries. Degeneration of the intervertebral disc (IVD) is a major pathological process implicated in low back pain, which is characterized by cellular apoptosis and senescence with reduced synthesis of extracellular matrix (ECM). Currently, there is no clinical therapy targeting the reversal of disc degeneration. Recent advances in cellular and molecular biology have provided an exciting approach to disc regeneration that focuses on the delivery of viable cells to the degenerative disc. Adult mesenchymal stem cells (MSCs) are multipotent stem cells with self-renewal capacities and are able to differentiate into diverse specialized cell types, including chondrocyte lineages. The potential of stem cell therapy in disc degeneration is to repopulate the disc with viable cells capable of producing the ECM and restoring damaged tissue. The present literature review summarizes recent advances in basic research and clinical trials of MSCs to provide an outline of the key roles of MSCs therapies in disc repair. The review also discusses the controversies, challenges and therapeutic concepts for the future. PMID:26835326

  17. Genetic and Functional Studies of the Intervertebral Disc: A Novel Murine Intervertebral Disc Model

    PubMed Central

    Pelle, Dominic W.; Peacock, Jacqueline D.; Schmidt, Courtney L.; Kampfschulte, Kevin; Scholten, Donald J.; Russo, Scott S.; Easton, Kenneth J.; Steensma, Matthew R.

    2014-01-01

    Intervertebral disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of intervertebral disc disease. Specifically, we demonstrate that IVD disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), disc anatomy (H&E), maintenance of extracellular matrix (ECM) (Alcian Blue staining), and native expression profile (qRT-PCR) as well as ex vivo genetic recombination (mT/mG reporter mice; AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1ß and TGF-ß3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1fl/fl explants resulted in constitutively active TGF-ß signaling that matched that of exogenously administered TGF-ß3. Our results illustrate the utility of the murine intervertebral disc explant to investigate mechanisms of intervertebral disc degeneration. PMID:25474689

  18. [Acute rupture of lumbar intervertebral disc caused by violent manipulation].

    PubMed

    Li, J S

    1989-08-01

    Five cases of acute rupture of lumbar intervertebral disc caused by violent manipulation are reported. After protrusion of the lumbar intervertebral disc were treated by violent manipulation, the lumbo-leg pain were severe suddenly. The operations found that the annulus fibrosus had ruptured and the nerve root or cauda equina was constricted by the nucleus pulposus which had entered into the spinal canal. It must be emphasized that their is in danger of more damaging intervertebral disc degenerated by violent manipulation, then the adhesion of the nerve root will occur gradually. We don't suggest to make violent manipulation for the patient with the nerve root injured. We have acquired good results in treating protrusion of lumbar intervertebral disc by combined therapy and they are introduced in this article. PMID:2620603

  19. Linking continuous and discrete intervertebral disc models through homogenisation.

    PubMed

    Karajan, N; Röhrle, O; Ehlers, W; Schmitt, S

    2013-06-01

    At present, there are two main numerical approaches that are frequently used to simulate the mechanical behaviour of the human spine. Researchers with a continuum-mechanical background often utilise the finite-element method (FEM), where the involved biological soft and hard tissues are modelled on a macroscopic (continuum) level. In contrast, groups associated with the science of human movement usually apply discrete multi-body systems (MBS). Herein, the bones are modelled as rigid bodies, which are connected by Hill-type muscles and non-linear rheological spring-dashpot models to represent tendons and cartilaginous connective tissue like intervertebral discs (IVD). A possibility to benefit from both numerical methods is to couple them and use each approach, where it is most appropriate. Herein, the basic idea is to utilise MBS in simulations of the overall body and apply the FEM only to selected regions of interest. In turn, the FEM is used as homogenisation tool, which delivers more accurate non-linear relationships describing the behaviour of the IVD in the multi-body dynamics model. The goal of this contribution is to present an approach to couple both numerical methods without the necessity to apply a gluing algorithm in the context of a co-simulation. Instead, several pre-computations of the intervertebral disc are performed offline to generate an approximation of the homogenised finite-element (FE) result. In particular, the discrete degrees of freedom (DOF) of the MBS, that is, three displacements and three rotations, are applied to the FE model of the IVD, and the resulting homogenised forces and moments are recorded. Moreover, a polynomial function is presented with the discrete DOF of the MBS as variables and the discrete forces an moments as function values. For the sake of a simple verification, the coupling method is applied to a simplified motion segment of the spine. Herein, two stiff cylindrical vertebrae with an interjacent homogeneous

  20. Inflammation in intervertebral disc degeneration and regeneration

    PubMed Central

    Molinos, Maria; Almeida, Catarina R.; Caldeira, Joana; Cunha, Carla; Gonçalves, Raquel M.; Barbosa, Mário A.

    2015-01-01

    Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players. PMID:25673296

  1. Intradural herniation of lumbar intervertebral discs.

    PubMed

    Hodge, C J; Binet, E F; Kieffer, S A

    1978-12-01

    A case of intradural rupture of a lumbar intervertebral disc is reported, and the literature is reviewed. The majority of intradural disc herniations occur at the L4--5 level. These patients usually have neurologic deficits more severe than those found in the much more common extradural disc herniations. The myelographic picture varies from an irregularly marginated intradural lesion overlying the disc space to a complete block. The common factor allowing intradural disc herniation is probably dense adhesions between the dura and the posterior longitudinal ligament, preventing the more common lateral extradural disc herniation. Intradural disc herniation should be included in the differential diagnosis of lumbar intradural lesions causing nerve root or cauda equina compression. PMID:741242

  2. Uncommon Manifestations of Intervertebral Disk Pathologic Conditions.

    PubMed

    Diehn, Felix E; Maus, Timothy P; Morris, Jonathan M; Carr, Carrie M; Kotsenas, Amy L; Luetmer, Patrick H; Lehman, Vance T; Thielen, Kent R; Nassr, Ahmad; Wald, John T

    2016-01-01

    Beyond the familiar disk herniations with typical clinical features, intervertebral disk pathologic conditions can have a wide spectrum of imaging and clinical manifestations. The goal of this review is to illustrate and discuss unusual manifestations of intervertebral disk pathologic conditions that radiologists may encounter, including disk herniations in unusual locations, those with atypical imaging features, and those with uncommon pathophysiologic findings. Examples of atypical disk herniations presented include dorsal epidural, intradural, symptomatic thoracic (including giant calcified), extreme lateral (retroperitoneal), fluorine 18 fluorodeoxyglucose-avid, acute intravertebral (Schmorl node), and massive lumbar disk herniations. Examples of atypical pathophysiologic conditions covered are discal cysts, fibrocartilaginous emboli to the spinal cord, tiny calcified disks or disk-level spiculated osteophytes causing spinal cerebrospinal fluid (CSF) leak and intracranial hypotension, and pediatric acute calcific discitis. This broad gamut of disease includes a variety of sizes of disk pathologic conditions, from the tiny (eg, the minuscule calcified disks causing high-flow CSF leaks) to the extremely large (eg, giant calcified thoracic intradural disk herniations causing myelopathy). A spectrum of clinical acuity is represented, from hyperacute fibrocartilaginous emboli causing spinal cord infarct, to acute Schmorl nodes, to chronic intradural herniations. The entities included are characterized by a range of clinical courses, from the typically devastating cord infarct caused by fibrocartilaginous emboli, to the usually spontaneously resolving pediatric acute calcific discitis. Several conditions have important differential diagnostic considerations, and others have relatively diagnostic imaging findings. The pathophysiologic findings are well understood for some of these entities and poorly defined for others. Radiologists' knowledge of this broad scope of

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

    PubMed Central

    Wyatt, L S; Frenkel, N

    1992-01-01

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

  4. Angiogenesis in the degeneration of the lumbar intervertebral disc

    PubMed Central

    David, Gh; Iencean, SM; Mohan, A

    2010-01-01

    The goal of the study is to show the histological and biochemical changes that indicate the angiogenesis of the intervertebral disc in lumbar intervertebral disc hernia and the existence of epidemiological correlations between these changes and the risk factors of lumbar intervertebral disc hernia, as well as the patient's quality of life (QOL). We have studied 50 patients aged between 18 and 73 years old, who have undergone lumbar intervertebral disc hernia surgery, making fibroblast growth factor and vascular endothelial growth factor level measurements, as elements in the process of appreciating the disc angiogenesis. Also, pre–surgery and post–surgery QOL has been measured, as well as the intensity of the pain syndrome. We have identified factors capable of stimulating vascular endothelial growth (VEGF, FGF–2) for the examined disc material, but histological examination did not show angiogenesis. The process of angiogenesis at the degenerated intervertebral disc level affects the patient's quality of life both pre and postoperatively, and may be a predictive factor for the post–operative results. Patients can prevent the appearance of angiogenesis type degenerative processes of the intervertebral disc by avoiding angiogenesis correlated factors (weight control, physical effort, and smoking). PMID:20968201

  5. Exchange delays and impulsive choice in adult humans.

    PubMed

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

    1994-09-01

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

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

    PubMed

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

    2010-01-01

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

  7. 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.

  8. A biokinetic model for systemic technetium in adult humans

    DOE PAGESBeta

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

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

  9. Ossified Ligamentum Longitudinale Anterius in Adult Human Dry Vertebrae

    PubMed Central

    Venumadhav, Nelluri; KS, Siddaraju

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Peterson, Shari L.; Wiesenberg, Faye

    2004-01-01

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

  11. Lumbar intervertebral disc puncture under C-arm fluoroscopy: a new rat model of lumbar intervertebral disc degeneration.

    PubMed

    Li, Dapeng; Yang, Huilin; Huang, Yonghui; Wu, Yan; Sun, Taicun; Li, Xuefeng

    2014-01-01

    To establish a minimally invasive rat model of lumbar intervertebral disc degeneration (IDD) to better understand the pathophysiology of the human condition. The annulus fibrosus of lumbar level 4-5 (L4-5) and L5-6 discs were punctured by 27-gauge needles using the posterior approach under C-arm fluoroscopic guidance. Magnetic resonance imaging (MRI), histological examination by hematoxylin and eosin (H&E) staining, and reverse transcription polymerase chain reaction (RT-PCR) were performed at baseline and 2, 4, and 8 weeks after disc puncture surgery to determine the degree of degeneration. All sixty discs (thirty rats) were punctured successfully. Only two of thirty rats subjected to the procedure exhibited immediate neurological symptoms. The MRI results indicated a gradual increase in Pfirrmann grade from 4 to 8 weeks post-surgery (P<0.05), and H&E staining demonstrated a parallel increase in histological grade (P<0.05). Expression levels of aggrecan, type II collagen (Col2), and Sox9 mRNAs, which encode disc components, decreased gradually post-surgery. In contrast, mRNA expression of type I collagen (Col1), an indicator of fibrosis, increased (P<0.05). The procedure of annular puncture using a 27-gauge needle under C-arm fluoroscopic guidance had a high success rate. Histological, MRI, and RT-PCR results revealed that the rat model of disc degeneration is a progressive pathological process that is similar to human IDD. PMID:24770648

  12. DISTRIBUTION AND SHORT- AND LONG-TERM EFFECTS OF INJECTED GELIFIED ETHANOL INTO THE LUMBOSACRAL INTERVERTEBRAL DISC IN HEALTHY DOGS.

    PubMed

    Mackenzie, Shawn D; Brisson, Brigitte A; Gaitero, Luis; Caswell, Jeff L; Liao, Penting; Sinclair, Melissa; Chalmers, Heather J

    2016-01-01

    Radiopaque gelified ethanol preparation has been described as a useful agent for treatment of humans with intervertebral disc protrusion. The material is injected into the nucleus pulposus under image guidance with intention to cause the protruded disc material to recede. Because treatment options for dogs with chronic protrusions are limited, new and minimally invasive treatments are desirable. The aim of this experimental, descriptive, prospective study was to assess the feasibility and safety of percutaneous injection of gelified ethanol into the lumbosacral intervertebral disc of dogs. Lumbosacral intervertebral discs of normal dogs (n = 9) were imaged with magnetic resonance imaging and then injected with gelified ethanol using image guidance. The accuracy of gelified ethanol placement in the nucleus pulposus and presence of leakage of the injected material were documented. Postinjection computed tomography (CT) findings (n = 9), short-term (n = 9) and long-term (n = 4) follow-up magnetic resonance imaging and CT findings were compared to document the distribution of the injected preparation and identify effects on adjacent tissues. Percutaneous injection of the intervertebral disc was successful in delivering radiopaque gelified ethanol to the nucleus pulposus in all dogs. Leakage of the injected material into the vertebral canal was present in three dogs immediately following injection and in another additional dog at 1 year following injection. All dogs tolerated the injection well and had no clinical adverse reactions within the study period. Findings indicated that injection of the nucleus pulposus of healthy dogs was well tolerated, even in the presence of mild leakage of material from the intervertebral disc. PMID:26626409

  13. 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…

  14. A Review of Fibrocartilaginous Embolic Myelopathy and Different Types of Peracute Non-Compressive Intervertebral Disk Extrusions in Dogs and Cats

    PubMed Central

    De Risio, Luisa

    2015-01-01

    This review discusses terminology, pathological, clinical, and magnetic resonance imaging (MRI) findings, treatment, outcome, and prognostic factors of fibrocartilaginous embolic myelopathy (FCEM), acute non-compressive nucleus pulposus extrusion (ANNPE), and intradural/intramedullary intervertebral disk extrusion (IIVDE). FCEM, ANNPE, and IIVDE have a similar clinical presentation characterized by peracute onset of neurological dysfunction that is generally non-progressive after the initial 24–48 h. Differentiating between these conditions can be challenging, however, certain clinical and imaging findings can help. FCEM can occur in both adult and immature animals, whereas ANNPE or IIVDE have been reported only in animals older than 1 year. In dogs, ANNPE and IIVDE most commonly occur in the intervertebral disk spaces between T12 and L2, whereas FCEM has not such site predilection. In cats, FCEM occurs more frequently in the cervical spinal cord than in other locations. Data on cats with ANNPE and IIVDE are limited. Optimal MRI definition and experience in neuroimaging can help identify the findings that allow differentiation between FCEM, ANNPE, and IIVDE. In animals with ANNPE and IIVDE, the affected intervertebral disk space is often narrowed and the focal area of intramedullary hyperintensity on T2-weighted images is located above the affected intervertebral disk space. In dogs with ANNPE signal changes associated with the extruded nucleus pulposus and epidural fat disruption can be identified in the epidural space dorsal to the affected intervertebral disk. Identification of a linear tract (predominantly hyperintense on T2-weighted images, iso to hypointense on T1-weighted images and hypointense on T2*-weighted gradient recall echo images) extending from the intervertebral disk into the spinal cord parenchyma is highly suggestive of IIVDE. Treatment of FCEM and ANNPE is conservative. Dogs reported with IIVDE have been managed either conservatively or

  15. MicroRNAs: New players in intervertebral disc degeneration.

    PubMed

    Wang, Cheng; Wang, Wen-Jun; Yan, Yi-Guo; Xiang, Yong-Xiao; Zhang, Jian; Tang, Zhi-Han; Jiang, Zhi-Sheng

    2015-10-23

    Chronic low back pain is generally attributed to intervertebral disc (IVD) degeneration (IDD), which is closely associated with apoptosis, extracellular matrix (ECM) disruption, cell proliferation and inflammatory response. Currently, there is no clinical therapy targeting the pathophysiology of disc degeneration. microRNAs (miRNAs) are a class of small noncoding RNA molecules that negatively regulate gene expression at the post-transcriptional levels. miRNAs not only regulate many normal physiological processes, but also play an important role in the development of most disorders, including degenerative disc disease. A variety of miRNAs are differentially expressed in degenerative human IVD tissues and cells. Among these, some of the miRNAs have been shown to be involved in multiple pathological processes during disc degeneration, including apoptosis, ECM degradation, cell proliferation and inflammatory response. This review will mainly focus on the expression profiles, roles, and therapeutic implications of miRNAs in IDD. With continued efforts, restoration of dysregulated miRNA expression may represent a promising biological treatment approach for mitigating or reversing IVD degeneration. PMID:26368266

  16. 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

  17. 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

  18. Precision of spinal radiographs as a screening test for intervertebral disc calcification in Dachshunds.

    PubMed

    Rosenblatt, Alana J; Hill, Peter B; Davies, Sarah E; Webster, Natalie S; Lappalainen, Anu K; Bottema, Cynthia D K; Caraguel, Charles G B

    2015-11-01

    Among dog breeds, the Dachshund has the highest lifetime incidence of intervertebral disc disease (IVDD). Intervertebral disc (IVD) calcification is an indicator of severe degeneration that predisposes to disc herniation. IVDD is heritable in Dachshunds, and in some countries, breeding candidates are screened to reduce IVDD occurrence by selecting dogs according to their score of radiographically detectable intervertebral disc calcification (RDIDC) and excluding dogs with ≥5 RDIDCs from breeding. This study evaluated the precision of scoring spinal radiographs for IVD calcification and subsequent classification of Dachshund dogs for breeding based on their RDIDC score. Digital radiographs of the spine were obtained in 19 clinically healthy, young adult Dachshunds, and scored for RDIDC independently by five scorers with varying levels of experience, three times each. Within scorer (repeatability) and between scorer (reproducibility) variability was estimated both at the individual IVD level and at the whole dog level for breeding classification purposes. At the IVD level, some degree of scorer effect was supported by the pairwise repeatability (92.3%; 95% CI: 88.8-94.7%) being marginally higher than the reproducibility (89.2%; 95% CI: 85.7-91.8%). Scorer-specific patterns confirmed the presence of scorer subjectivity. Repeatability significantly increased with scorer experience but the reproducibility did not. RDIDC scoring repeatability and reproducibility substantially decreased at the cervicothoracic spine region, likely due to anatomical superimpositions. At the dog level, a breeding classification could be repeated by the same scorer for 83.6% (95% CI: 73.8-90.2%) of the dogs, and was reproduced between two scorers for 80.2% (95% CI: 66.6-89.1%) of the dogs. The repeatability of breeding classification also seemed to increase with scorer experience but not the reproducibility. Overall, RDIDC scoring revealed some degree of inconsistency explained by scorer

  19. Rheological and biological properties of a hydrogel support for cells intended for intervertebral disc repair

    PubMed Central

    2012-01-01

    Background Cell-based approaches towards restoration of prolapsed or degenerated intervertebral discs are hampered by a lack of measures for safe administration and placement of cell suspensions within a treated disc. In order to overcome these risks, a serum albumin-based hydrogel has been developed that polymerizes after injection and anchors the administered cell suspension within the tissue. Methods A hydrogel composed of chemically activated albumin crosslinked by polyethylene glycol spacers was produced. The visco-elastic gel properties were determined by rheological measurement. Human intervertebral disc cells were cultured in vitro and in vivo in the hydrogel and their phenotype was tested by reverse-transcriptase polymerase chain reaction. Matrix production and deposition was monitored by immuno-histology and by biochemical analysis of collagen and glycosaminoglycan deposition. Species specific in situ hybridization was performed to discriminate between cells of human and murine origin in xenotransplants. Results The reproducibility of the gel formation process could be demonstrated. The visco-elastic properties were not influenced by storage of gel components. In vitro and in vivo (subcutaneous implants in mice) evidence is presented for cellular differentiation and matrix deposition within the hydrogel for human intervertebral disc cells even for donor cells that have been expanded in primary monolayer culture, stored in liquid nitrogen and re-activated in secondary monolayer culture. Upon injection into the animals, gels formed spheres that lasted for the duration of the experiments (14 days). The expression of cartilage- and disc-specific mRNAs was maintained in hydrogels in vitro and in vivo, demonstrating the maintenance of a stable specific cellular phenotype, compared to monolayer cells. Significantly higher levels of hyaluronan synthase isozymes-2 and -3 mRNA suggest cell functionalities towards those needed for the support of the regeneration of

  20. A Ganglion Cyst in the Second Lumbar Intervertebral Foramen

    PubMed Central

    Choi, Joon Hyuk; Kim, Min Su; Chang, Chul Hoon

    2011-01-01

    Ganglion cysts usually arise from the tendon sheaths and tissues around the joints. It is usually associated with degenerative arthritic changes in older people. Ganglion cyst in the spine is rare and there is no previous report on case that located in the intervertebral foramen and compressed dorsal root ganglion associated severe radiculopathy. A 29-year-old woman presented with severe left thigh pain and dysesthesia for a month. Magnetic resonance imaging revealed a dumbbell like mass in the intervertebral foramen between second and third lumbar vertebrae on the left side. The lesion was removed after exposure of the L2-L3 intervertebral foramen. The histological examination showed fragmented cystic wall-like structure composed of fibromyxoid tissue but there was no lining epithelium. A ganglion cyst may compromise lumbar dorsal root ganglion when it located in the intervertebral foramen. Although it is very rare location, ganglion cyst should be included in the differential diagnosis for intervertebral foraminal mass lesions. PMID:21607185

  1. In vivo three-dimensional intervertebral kinematics of the subaxial cervical spine during seated axial rotation and lateral bending via a fluoroscopy-to-CT registration approach.

    PubMed

    Lin, Cheng-Chung; Lu, Tung-Wu; Wang, Ting-Ming; Hsu, Chao-Yu; Hsu, Shih-Jung; Shih, Ting-Fang

    2014-10-17

    Accurate measurement of the coupled intervertebral motions is helpful for understanding the etiology and diagnosis of relevant diseases, and for assessing the subsequent treatment. No study has reported the in vivo, dynamic and three-dimensional (3D) intervertebral motion of the cervical spine during active axial rotation (AR) and lateral bending (LB) in the sitting position. The current study fills the gap by measuring the coupled intervertebral motions of the subaxial cervical spine in ten asymptomatic young adults in an upright sitting position during active head LB and AR using a volumetric model-based 2D-to-3D registration method via biplane fluoroscopy. Subject-specific models of the individual vertebrae were derived from each subject's CT data and were registered to the fluoroscopic images for determining the 3D poses of the subaxial vertebrae that were used to obtain the intervertebral kinematics. The averaged ranges of motion to one side (ROM) during AR at C3/C4, C4/C5, C5/C6, and C6/C7 were 4.2°, 4.6°, 3.0° and 1.3°, respectively. The corresponding values were 6.4°, 5.2°, 6.1° and 6.1° during LB. Intervertebral LB (ILB) played an important role in both AR and LB tasks of the cervical spine, experiencing greater ROM than intervertebral AR (IAR) (ratio of coupled motion (IAR/ILB): 0.23-0.75 in LB, 0.34-0.95 in AR). Compared to the AR task, the ranges of ILB during the LB task were significantly greater at C5/6 (p=0.008) and C6/7 (p=0.001) but the range of IAR was significantly smaller at C4/5 (p=0.02), leading to significantly smaller ratios of coupled motions at C4/5 (p=0.0013), C5/6 (p<0.001) and C6/7 (p=0.0037). The observed coupling characteristics of the intervertebral kinematics were different from those in previous studies under discrete static conditions in a supine position without weight-bearing, suggesting that the testing conditions likely affect the kinematics of the subaxial cervical spine. While C1 and C2 were not included owing to

  2. A role for TNFα in intervertebral disc degeneration: A non-recoverable catabolic shift

    SciTech Connect

    Purmessur, D.; Walter, B.A.; Roughley, P.J.; Laudier, D.M.; Hecht, A.C.; Iatridis, James

    2013-03-29

    Highlights: ► TNFα induced catabolic changes similar to human intervertebral disc degeneration. ► The metabolic shift induced by TNFα was sustained following removal. ► TNFα induced changes suggestive of cell senescence without affecting cell viability. ► Interventions are required to stimulate anabolism and increase cell proliferation. -- Abstract: This study examines the effect of TNFα on whole bovine intervertebral discs in organ culture and its association with changes characteristic of intervertebral disc degeneration (IDD) in order to inform future treatments to mitigate the chronic inflammatory state commonly found with painful IDD. Pro-inflammatory cytokines such as TNFα contribute to disc pathology and are implicated in the catabolic phenotype associated with painful IDD. Whole bovine discs were cultured to examine cellular (anabolic/catabolic gene expression, cell viability and senescence using β-galactosidase) and structural (histology and aggrecan degradation) changes in response to TNFα treatment. Control or TNFα cultures were assessed at 7 and 21 days; the 21 day group also included a recovery group with 7 days TNFα followed by 14 days in basal media. TNFα induced catabolic and anti-anabolic shifts in the nucleus pulposus (NP) and annulus fibrosus (AF) at 7 days and this persisted until 21 days however cell viability was not affected. Data indicates that TNFα increased aggrecan degradation products and suggests increased β-galactosidase staining at 21 days without any recovery. TNFα treatment of whole bovine discs for 7 days induced changes similar to the degeneration processes that occur in human IDD: aggrecan degradation, increased catabolism, pro-inflammatory cytokines and nerve growth factor expression. TNFα significantly reduced anabolism in cultured IVDs and a possible mechanism may be associated with cell senescence. Results therefore suggest that successful treatments must promote anabolism and cell proliferation in

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

    PubMed

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

    2016-01-01

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

  4. The fate of transplanted xenogeneic bone marrow-derived stem cells in rat intervertebral discs.

    PubMed

    Wei, Aiqun; Tao, Helen; Chung, Sylvia A; Brisby, Helena; Ma, David D; Diwan, Ashish D

    2009-03-01

    Intervertebral disc degeneration is a major cause and a risk factor for chronic low back pain. The potential of using stem cells to treat disc degeneration has been raised. The aims of our study were to assess whether xenogeneic bone-marrow derived stem cells could survive in a rat disc degeneration model and to determine which cell types, if any, survived and differentiated into disc-like cells. Human bone-marrow derived CD34(+) (hematopoietic progenitor cells) and CD34(-) (nonhematopoietic progenitor cells, including mesenchymal stem cells) cells were isolated, fluorescent-labeled, and injected into rat coccygeal discs. The rats were sacrificed at day 1, 10, 21, and 42. Treated discs were examined by histological and immunostaining techniques and compared to control discs. The survival of transplanted cells was further confirmed with a human nuclear specific marker. Fluorescent labeled CD34(-) cells were detected until day 42 in the nucleus pulposus of the injected discs. After 3 weeks these cells had differentiated into cells expressing chondrocytic phenotype (Collagen II and Sox-9). In contrast, the fluorescent labeled CD34(+) cells could not be detected after day 21. No fluorescence-positive cells were detected in the noninjected control discs. Further, no inflammatory cells infiltrated the nucleus pulposus, even though these animals had not received immunosuppressive treatment. Our data provide evidence that transplanted human BM CD34(-) cells survived and differentiated within the relative immune privileged nucleus pulposus of intervertebral disc degeneration. PMID:18853431

  5. 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

  6. Automatic measurement of intervertebral movements using radiographic images.

    PubMed

    Sun, L W; Yang, Zhengyi; Yw Lee, Raymond; Lu, William; Luk, K D K

    2005-01-01

    Measurement of intervertebral movements is essential in the assessment and diagnosis of patient's instability. However, diagnosis of the underlying causes remains problematic despite of extensive study. Reasons for this arise from the variability of detecting vertebral body landmarks, labor and time-consuming of manual point placement, incompletely description of the vertebral body shape and also from the structural complexity of the spine. In this study, the precision and accuracy of a new automatic method for morphometry of intervertebral movements were estimated. Active Contour is a key feature of segmentation and provides rapid and accurate measurement of vertebral shape. Fourier descriptors are used to represent the vertebral shapes. Genetic Algorithm (GA) is then applied to determine the spinal kinematics. Reproducible and reliable determinations of the intervertebral movements of the lumbosacral spine, when performing Flexion-Extension motions, are addressed. This paper describes the accuracy and feasibility of an active shape model (ASM) and Genetic Algorithm (GA) to measure spine kinematics. PMID:17282925

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

    PubMed

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

    1991-06-01

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

  8. 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.

  9. Potential regenerative treatment strategies for intervertebral disc degeneration in dogs

    PubMed Central

    2014-01-01

    Pain due to spontaneous intervertebral disc (IVD) disease is common in dogs. In chondrodystrophic (CD) dogs, IVD disease typically develops in the cervical or thoracolumbar spine at about 3–7 years of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or lumbosacral spine at about 6–8 years of age. IVD degeneration is characterized by changes in the biochemical composition and mechanical integrity of the IVD. In the degenerated IVD, the content of glycosaminoglycan (GAG, a proteoglycan side chain) decreases and that of denatured collagen increases. Dehydration leads to tearing of the annulus fibrosus (AF) and/or disc herniation, which is clinically characterized by pain and/or neurological signs. Current treatments (physiotherapy, anti-inflammatory/analgesic medication, surgery) for IVD disease may resolve neurological deficits and reduce pain (although in many cases insufficient), but do not lead to repair of the degenerated disc. For this reason, there is interest in new regenerative therapies that can repair the degenerated disc matrix, resulting in restoration of the biomechanical function of the IVD. CD dogs are considered a suitable animal model for human IVD degeneration because of their spontaneous IVD degeneration, and therefore studies investigating cell-, growth factor-, and/or gene therapy-based regenerative therapies with this model provide information relevant to both human and canine patients. The aim of this article is to review potential regenerative treatment strategies for canine IVD degeneration, with specific emphasis on cell-based strategies. PMID:24387033

  10. 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…

  11. 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…

  12. [Principles of intervertebral disc assessment in private accident insurance].

    PubMed

    Steinmetz, M; Dittrich, V; Röser, K

    2015-09-01

    Due to the spread of intervertebral disc degeneration, insurance companies and experts are regularly confronted with related assessments of insured persons under their private accident insurance. These claims pose a particular challenge for experts, since, in addition to the clinical assessment of the facts, extensive knowledge of general accident insurance conditions, case law and current study findings is required. Each case can only be properly assessed through simultaneous consideration of both the medical and legal facts. These guidelines serve as the basis for experts and claims.managers with respect to the appropriate individual factual assessment of intervertebral disc degeneration in private accident insurance. PMID:26548005

  13. Refinement of elastic, poroelastic, and osmotic tissue properties of intervertebral disks to analyze behavior in compression.

    PubMed

    Stokes, Ian A F; Laible, Jeffrey P; Gardner-Morse, Mack G; Costi, John J; Iatridis, James C

    2011-01-01

    Intervertebral disks support compressive forces because of their elastic stiffness as well as the fluid pressures resulting from poroelasticity and the osmotic (swelling) effects. Analytical methods can quantify the relative contributions, but only if correct material properties are used. To identify appropriate tissue properties, an experimental study and finite element analytical simulation of poroelastic and osmotic behavior of intervertebral disks were combined to refine published values of disk and endplate properties to optimize model fit to experimental data. Experimentally, nine human intervertebral disks with adjacent hemi-vertebrae were immersed sequentially in saline baths having concentrations of 0.015, 0.15, and 1.5 M and the loss of compressive force at constant height (force relaxation) was recorded over several hours after equilibration to a 300-N compressive force. Amplitude and time constant terms in exponential force-time curve-fits for experimental and finite element analytical simulations were compared. These experiments and finite element analyses provided data dependent on poroelastic and osmotic properties of the disk tissues. The sensitivities of the model to alterations in tissue material properties were used to obtain refined values of five key material parameters. The relaxation of the force in the three bath concentrations was exponential in form, expressed as mean compressive force loss of 48.7, 55.0, and 140 N, respectively, with time constants of 1.73, 2.78, and 3.40 h. This behavior was analytically well represented by a model having poroelastic and osmotic tissue properties with published tissue properties adjusted by multiplying factors between 0.55 and 2.6. Force relaxation and time constants from the analytical simulations were most sensitive to values of fixed charge density and endplate porosity. PMID:20711754

  14. Adolescent prolapsed lumbar intervertebral disc: Management strategies and outcome

    PubMed Central

    Sarma, Pragyan; Thirupathi, Rajan Thanga; Srinivas, Dwarakanath; Somanna, Sampath

    2016-01-01

    Objective: Lumbar intervertebral disc herniation (LIVDH) is rare in children and adolescents when compared to adults. In literature, children generally constitute around 0.5–3% of surgically treated LIVDH. Though much rarer, they are less likely to respond to conservative treatment than adults. In this study, we analyze our experience in the management of adolescent LIVDH (ALIVDH) (age group 12–18 years) including the demographic, clinico-radiological features; surgical management strategies and outcome. Materials and Methods: This retrospective analysis constituted all patients between 12 and 18 years, who underwent surgery for LIVDH at our institute over a period of 15 years from January 1999 to June 2014. The records of these patients were retrieved, and demographic features, clinical picture, radiological features, operative findings, and postoperative events were evaluated. Follow-up data were obtained either through direct clinical evaluation or mailed self-report questionnaire and telephone conversations. The long-term outcome was analyzed by using standardized and condition specific outcome scales in addition to routine clinical follow-up evaluation. The long-term outcome was analyzed by using the short form-36 (SF-36). Results: There were a total of 32 patients (26 males, eight females) with an average age of 15.64 years. Trauma was a significant etiological factor 57.14% (n = 16/28). Vertebral anomalies were present in 35.7% (n = 10/28) cases. Majority had a neurological deficit at presentation (n = 20/28). The most commonly involved level was the L4–L5 level (n = 18/128) in this series. Multiple level disc degeneration was present in eight patients (28.6%). Immediate postoperative relief was achieved in all but one patient. At long-term follow-up twenty patients were pain-free (71.4%). At follow-up, the physical functioning scale of SF-36 was significantly lower in patients with gross motor deficit prior to surgery. Conclusions: Early diagnosis and

  15. FoxC2 Enhances BMP7-Mediated Anabolism in Nucleus Pulposus Cells of the Intervertebral Disc

    PubMed Central

    Wang, Zheng; Fu, Changfeng; Chen, Yong; Xu, Feng; Wang, Zhenyu; Qu, Zhigang; Liu, Yi

    2016-01-01

    Bone-morphogenetic protein-7 (BMP-7) is a growth factor that plays a major role in mediating anabolism and anti-catabolism of the intervertebral disc matrix and cell homeostasis. In osteoblasts, Forkhead box protein C2 (FoxC2) is a downstream target of BMPs and promotes cell proliferation and differentiation. However, the role FoxC2 may play in degenerative human intervertebral disc tissue and the relationship between FoxC2 and BMP-7 in nucleus pulposus (NP) cells remain to be elucidated. This study aims to investigate the presence and signaling mechanisms of FoxC2 in degenerative human intervertebral disc tissue and NP cells. Western blot and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses were used to measure FoxC2 expression in the NP tissue and cells. Transfections were carried out to measure the effect of FoxC2 on BMP-7-mediated extracellular matrix upregulation. Adenoviral knock-down of Smad1 was performed to investigate the mechanism of BMP-7-induced FoxC2 expression. In degenerative NP tissue, FoxC2 was markedly upregulated and positively correlated with increased disc degeneration. Induction of NP cell proliferation was confirmed by using cell counting kit-8 assay, immunocytochemistry and real-time qRT-PCR for Ki67. FoxC2 led to decreased noggin expression and increased Smad1/5/8 phosphorylation. During combined treatment with BMP-7, FoxC2 greatly potentiated anabolism through synergistic mechanisms on ECM formation. Combination therapy using BMP-7 and FoxC2 may be beneficial to the treatment of intervertebral disc degeneration. PMID:26824865

  16. 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.

  17. A biochemical/biophysical 3D FE intervertebral disc model.

    PubMed

    Schroeder, Y; Huyghe, J M; van Donkelaar, C C; Ito, K

    2010-10-01

    Present research focuses on different strategies to preserve the degenerated disc. To assure long-term success of novel approaches, favorable mechanical conditions in the disc tissue are essential. To evaluate these, a model is required that can determine internal mechanical conditions which cannot be directly measured as a function of assessable biophysical characteristics. Therefore, the objective is to evaluate if constitutive and material laws acquired on isolated samples of nucleus and annulus tissue can be used directly in a whole-organ 3D FE model to describe intervertebral disc behavior. The 3D osmo-poro-visco-hyper-elastic disc (OVED) model describes disc behavior as a function of annulus and nucleus tissue biochemical composition, organization and specific constituent properties. The description of the 3D collagen network was enhanced to account for smaller fibril structures. Tissue mechanical behavior tests on isolated nucleus and annulus samples were simulated with models incorporating tissue composition to calculate the constituent parameter values. The obtained constitutive laws were incorporated into the whole-organ model. The overall behavior and disc properties of the model were corroborated against in vitro creep experiments of human L4/L5 discs. The OVED model simulated isolated tissue experiments on confined compression and uniaxial tensile test and whole-organ disc behavior. This was possible, provided that secondary fiber structures were accounted for. The fair agreement (radial bulge, axial creep deformation and intradiscal pressure) between model and experiment was obtained using constitutive properties that are the same for annulus and nucleus. Both tissue models differed in the 3D OVED model only by composition. The composition-based modeling presents the advantage of reducing the numbers of material parameters to a minimum and to use tissue composition directly as input. Hence, this approach provides the possibility to describe internal

  18. Polarization-sensitive optical coherence tomography applied to intervertebral disk

    NASA Astrophysics Data System (ADS)

    Matcher, Stephen J.; Winlove, Peter; Gangnus, Sergei V.

    2003-07-01

    Polarization-sensitive optical coherence tomography (PSOCT) is a powerful new optical imaging modality that is sensitive to the birefringence properties of tissues. It thus has potential applications in studying the large-scale ordering of collagen fibers within connective tisues and changes related to pathology. As a tissue for study by PSOCT, intervertebral disk respresents an interesting system as the collagen organization is believed to show pronounced variations with depth, on a spatial scale of about 100 μm. We have used a polarization-sensitive optical coherence tomography system to measure the birefringence properties of bovine caudal intervertebral disk and compared this with equine flexor tendon. The result for equine tendon, δ = (3.0 +/- 0.5)x10-3 at 1.3 μm, is in broad agreement with values reported for bovine tendon, while bovine intervertebral disk displays a birefringence of about half this, δ = 1.2 x 10-3 at 1.3 μm. While tendon appears to show a uniform fast-axis over 0.8 mm depth, intervertebral disk shows image contrast at all orientations relative to a linearly polarized input beam, suggesting a variation in fast-axis orientation with depth. These initial results suggest that PSOCT could be a useful tool to study collagen organization within this tissue and its variation with applied load and disease.

  19. Syndecan-4 in intervertebral disc and cartilage: Saint or synner?

    PubMed

    Binch, Abbie L A; Shapiro, Irving M; Risbud, Makarand V

    2016-01-01

    The ECM of the intervertebral disc and articular cartilage contains a highly organised network of collagens and proteoglycans which resist compressive forces applied to these tissues. A pathological hallmark of the intervertebral disc is the imbalance between production of anabolic and catabolic factors by the resident cells. This process is thought to be mediated by pro-inflammatory cytokines, predominantly TNF-α and IL-1β, which upregulate expression of matrix degrading enzymes such as MMPs and ADAMTSs. This imbalance ultimately results in tissue degeneration causing failure of the biomechanical function of the tissues. A similar cascade of events is thought to occur in articular cartilage during development of osteoarthritis. Within these skeletal tissues a small, cell surface heparan sulphate proteoglycan; syndecan-4 (SDC4) has been implicated in maintaining physiological functions. However in the degenerating niche of the intervertebral disc and cartilage, dysregulated activities of this molecule may exacerbate pathological changes. Studies in recent years have elucidated a role for SDC4 in mediating matrix degradation in both intervertebral discs and cartilage by controlling ADAMTS-5 function and MMP3 expression. Discourse presented in this review highlights the potential of SDC4 as a possible therapeutic target in slowing the progression of ECM degradation in both degenerative disc disease and osteoarthritis. PMID:26796346

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

    ERIC Educational Resources Information Center

    Aetna Life and Casualty, Hartford, CT.

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

  1. 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…

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

    ERIC Educational Resources Information Center

    Stanistreet, Paul

    2011-01-01

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

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

    ERIC Educational Resources Information Center

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

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

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

    ERIC Educational Resources Information Center

    Choy, Sarojni; Haukka, Sandra

    2007-01-01

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

  5. Nutrition of the intervertebral disc: effect of fluid flow on solute transport

    SciTech Connect

    Urban, J.P.; Holm, S.; Maroudas, A.; Nachemson, A.

    1982-10-01

    Adult dogs were injected intravenously with /sup 35/S-sulphate, and moderately exercised for one to six hours to measure isotope concentrations and profiles throughout the intervertebral discs. The isotope profiles were also observed in control animals that had been under anesthesia between injections and death. In both sets of animals, the profiles were in agreement with those expected for isotope transport by diffusion. This agreement indicates that fluid pumping during movement has an insignificant effect on transport of nutrients into the disc. Small solutes, e.g., O/sub 2/, glucose, and sulphate, are transported into the disc chiefly by diffusion. However, calculations show that because of their low diffusivities, pumping may increase the rate of transport of large solutes into the disc, as it does in articular cartilage.

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

    PubMed

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

    1998-06-15

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

  7. The imbalance between TIMP3 and matrix-degrading enzymes plays an important role in intervertebral disc degeneration.

    PubMed

    Li, Yan; Li, Kang; Han, Xiuguo; Mao, Chuanyuan; Zhang, Kai; Zhao, Tengfei; Zhao, Jie

    2016-01-15

    It is well-known that one of the most important features of intervertebral disc degeneration (IDD) is the extracellular matrix (ECM) degradation. Collagen and aggrecan are major components of ECM; the degradation of ECM in intervertebral discs (IVDs) is closely related to the activities of collagenase and aggrecanase. TIMP-3 is the most efficient inhibitor of aggrecanase in IVD. However, only few studies focus on the potential relationship between TIMP-3 and IDD. In our study, we found TIMP-3 gene expression was decreased after stimulating with LPS in rat nucleus pulposus (NP) cells. Then we used a lentivirus vector to reconstruct rat NP cells which high expressed TIMP-3 gene (LV-TIMP3). The upregulation of MMPs and ADAMTSs induced by LPS was significantly inhibited in LV-TIMP3 cells. After overexpression of TIMP-3, the aggrecan breakdown caused by LPS was also reduced in both monolayer culture and three-dimension culture model. To further study the relation between TIMP-3 and IDD, we collected human NP tissue samples of different degenerative degrees. Real-time PCR and immunohistochemical staining showed that the expression of TIMP-3 was negatively correlated with the degree of intervertebral disc degeneration, while MMP-1 and ADAMTS-4 were markedly increased in degenerative IVD. Taken together, our results suggest that the imbalance between aggrecanase and TIMP-3 may play an important role in the pathogenesis of IDD and therefore be a potential therapeutic target for treating IDD. PMID:26686417

  8. 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…

  9. Dynamic Compression Effects on Intervertebral Disc Mechanics and Biology

    PubMed Central

    Korecki, Casey L.; MacLean, Jeffrey J.; Iatridis, James C.

    2008-01-01

    Study Design A bovine intervertebral disc organ culture model was used to study the effect of dynamic compression magnitude on mechanical behavior and measurement of biosynthesis rate, cell viability, and mRNA expression. Objective The objective of this study was to examine the effect of loading magnitude on intervertebral disc mechanics and biology in an organ culture model. Summary of Background Data The in vivo and cell culture response of intervertebral disc cells to dynamic mechanical loading provides evidence the disc responds in a magnitude dependant manner. However, the ability to link mechanical behavior of the disc with biologic phenomena has been limited. A large animal organ culture system facilitates measurements of tissue mechanics and biologic response parameters on the same sample allowing a broader understanding of disc mechanobiology. Methods Bovine caudal intervertebral discs were placed in organ culture for 6 days and assigned to a static control or 1 of 2 dynamic compression loading protocols (0.2–1 MPa or 0.2–2.5 MPa) at 1 Hz for 1 hour for 5 days. Disc structure was assessed with measurements of dynamic modulus, creep, height loss, water content, and proteoglycan loss to the culture medium. Cellular responses were assessed through changes in cell viability, metabolism, and qRT-PCR analyses. Results Increasing magnitudes of compression increased disc modulus and creep; however, all mechanical parameters recovered each day. In the anulus, significant increases in gene expression for collagen I and a trend of increasing sulfate incorporation were observed. In the nucleus, increasing gene expression for collagen I and MMP3 was observed between magnitudes and between static controls and the lowest magnitude of loading. Conclusion Results support the hypothesis that biologic remodeling precedes damage to the intervertebral disc structure, that compression is a healthy loading condition for the disc, and further support the link between applied

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

    ERIC Educational Resources Information Center

    Kerka, Sandra

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

  11. The Natural Polyphenol Epigallocatechin Gallate Protects Intervertebral Disc Cells from Oxidative Stress

    PubMed Central

    Krupkova, Olga; Handa, Junichi; Hlavna, Marian; Klasen, Juergen; Ospelt, Caroline; Ferguson, Stephen John; Wuertz-Kozak, Karin

    2016-01-01

    Oxidative stress-related phenotypic changes and a decline in the number of viable cells are crucial contributors to intervertebral disc degeneration. The polyphenol epigallocatechin 3-gallate (EGCG) can interfere with painful disc degeneration by reducing inflammation, catabolism, and pain. In this study, we hypothesized that EGCG furthermore protects against senescence and/or cell death, induced by oxidative stress. Sublethal and lethal oxidative stress were induced in primary human intervertebral disc cells with H2O2 (total n = 36). Under sublethal conditions, the effects of EGCG on p53-p21 activation, proliferative capacity, and accumulation of senescence-associated β-galactosidase were tested. Further, the effects of EGCG on mitochondria depolarization and cell viability were analyzed in lethal oxidative stress. The inhibitor LY249002 was applied to investigate the PI3K/Akt pathway. EGCG inhibited accumulation of senescence-associated β-galactosidase but did not affect the loss of proliferative capacity, suggesting that EGCG did not fully neutralize exogenous radicals. Furthermore, EGCG increased the survival of IVD cells in lethal oxidative stress via activation of prosurvival PI3K/Akt and protection of mitochondria. We demonstrated that EGCG not only inhibits inflammation but also can enhance the survival of disc cells in oxidative stress, which makes it a suitable candidate for the development of novel therapies targeting disc degeneration. PMID:27119009

  12. 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

  13. Investigation of intervertebral disc degeneration using multivariate FTIR spectroscopic imaging.

    PubMed

    Mader, Kerstin T; Peeters, Mirte; Detiger, Suzanne E L; Helder, Marco N; Smit, Theo H; Le Maitre, Christine L; Sammon, Chris

    2016-06-23

    Traditionally tissue samples are analysed using protein or enzyme specific stains on serial sections to build up a picture of the distribution of components contained within them. In this study we investigated the potential of multivariate curve resolution-alternating least squares (MCR-ALS) to deconvolute 2nd derivative spectra of Fourier transform infrared (FTIR) microscopic images measured in transflectance mode of goat and human paraffin embedded intervertebral disc (IVD) tissue sections, to see if this methodology can provide analogous information to that provided by immunohistochemical stains and bioassays but from a single section. MCR-ALS analysis of non-degenerate and enzymatically in vivo degenerated goat IVDs reveals five matrix components displaying distribution maps matching histological stains for collagen, elastin and proteoglycan (PG), as well as immunohistochemical stains for collagen type I and II. Interestingly, two components exhibiting characteristic spectral and distribution profiles of proteoglycans were found, and relative component/tissue maps of these components (labelled PG1 and PG2) showed distinct distributions in non-degenerate versus mildly degenerate goat samples. MCR-ALS analysis of human IVD sections resulted in comparable spectral profiles to those observed in the goat samples, highlighting the inter species transferability of the presented methodology. Multivariate FTIR image analysis of a set of 43 goat IVD sections allowed the extraction of semi-quantitative information from component/tissue gradients taken across the IVD width of collagen type I, collagen type II, PG1 and PG2. Regional component/tissue parameters were calculated and significant correlations were found between histological grades of degeneration and PG parameters (PG1: p = 0.0003, PG2: p < 0.0001); glycosaminoglycan (GAG) content and PGs (PG1: p = 0.0055, PG2: p = 0.0001); and MRI T2* measurements and PGs (PG1: p = 0.0021, PG2: p < 0.0001). Additionally

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

    PubMed

    Danzer, Steve C

    2008-10-01

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

  15. 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…

  16. The Relationship between Disc Degeneration and Morphologic Changes in the Intervertebral Foramen of the Cervical Spine: A Cadaveric MRI and CT Study

    PubMed Central

    Sohn, Hong Moon; Lee, Jun Young

    2004-01-01

    A cadaveric study was performed to investigate the relationship between disc degeneration and morphological changes in the intervertebral foramen of cervical spine, including the effect on the nerve root. Seven fresh frozen human cadavers were dissected from C1 to T1, preserving the ligaments, capsules, intervertebral disc and the neural structures. The specimens were scanned with MRI and then scanned through CT scan in the upright position. Direct mid-sagittal and 45 degree oblique images were obtained to measure the dimension of the intervertebral disc height, foraminal height, width, area and segmental angles. Disc degeneration was inversely correlated with disc height. There was a significant correlation between disc degeneration and foraminal width (p<0.005) and foraminal area (p<0.05), but not with foraminal height. Disc height was correlated with foraminal width but not with height. The segmental angles were decreased more in advanced degenerated discs. There was a correlation between nerve root compression and decreased foraminal width and area (p<0.005). This information and critical dimensions of the intervertebral foramen for nerve root compression should help in the diagnosis of foraminal stenosis of the cervical spine in patients presenting with cervical spondylosis and radiculopathy. PMID:14966350

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

    PubMed

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

    1993-11-01

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

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

    NASA Astrophysics Data System (ADS)

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

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

  19. Epigallocatechin 3-gallate suppresses interleukin-1β-induced inflammatory responses in intervertebral disc cells in vitro and reduces radiculopathic pain in rats.

    PubMed

    Krupkova, O; Sekiguchi, M; Klasen, J; Hausmann, O; Konno, S; Ferguson, S J; Wuertz-Kozak, K

    2014-01-01

    Intervertebral disc (IVD) disease, which is characterised by age-related changes in the adult disc, is the most common cause of disc failure and low back pain. The purpose of this study was to analyse the potential of the biologically active polyphenol epigallocatechin 3-gallate (EGCG) for the treatment of painful IVD disease by identifying and explaining its anti-inflammatory and anti-catabolic activity. Human IVD cells were isolated from patients undergoing surgery due to degenerative disc disease (n = 34) and cultured in 2D or 3D. An inflammatory response was activated by IL-1β, EGCG was added, and the expression/activity of inflammatory mediators and pathways was measured by qRT-PCR, western blotting, ELISA, immunofluorescence and transcription factor assay. The small molecule inhibitor SB203580 was used to investigate the involvement of the p38 pathway in the observed effects. The analgesic properties of EGCG were analysed by the von Frey filament test in Sprague-Dawley rats (n = 60). EGCG significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-κB. PMID:25422948

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

    PubMed Central

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and brain tumors. PMID:27375363

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

    PubMed

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain tumors. PMID:27375363

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

    PubMed

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

    2003-11-01

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

  3. 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

  4. 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

  5. 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

  6. Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration

    PubMed Central

    Vo, Nam V.; Hartman, Robert A.; Yurube, Takashi; Jacobs, Lloydine J.; Sowa, Gwendolyn A.; Kang, James D.

    2013-01-01

    BACKGROUND CONTEXT Destruction of extracellular matrix (ECM) leads to intervertebral disc degeneration (IDD), which underlies many spine-related disorders. Matrix metalloproteinases (MMPs), and disintegrins and metalloproteinases with thrombospondin motifs (ADAMTSs) are believed to be the major proteolytic enzymes responsible for ECM degradation in the intervertebral disc (IVD). PURPOSE To summarize the current literature on gene expression and regulation of MMPs, ADAMTSs, and tissue inhibitors of metalloproteinases (TIMPs) in IVD aging and IDD. METHODS A comprehensive literature review of gene expression of MMP, ADAMTS, and TIMP in human IDD and reported studies on regulatory factors controlling their expressions and activities in both human and animal model systems. RESULTS Upregulation of specific MMPs (MMP-1, -2, -3, -7, -8, -10, and -13) and ADAMTS (ADAMTS-1, -4, and -15) were reported in human degenerated IVDs. However, it is still unclear from conflicting published studies whether the expression of ADAMTS-5, the predominant aggrecanase, is increased with IDD. Tissue inhibitors of metalloproteinase-3 is downregulated, whereas TIMP-1 is upregulated in human degenerated IVDs relative to nondegenerated IVDs. Numerous studies indicate that the expression levels of MMP and ADAMTS are modulated by a combination of many factors, including mechanical, inflammatory, and oxidative stress, some of which are mediated in part through the p38 mitogen-activated protein kinase pathway. Genetic predisposition also plays an important role in determining gene expression of MMP-1, -2, -3, and -9. CONCLUSIONS Upregulation of MMP and ADAMTS expression and enzymatic activity is implicated in disc ECM destruction, leading to the development of IDD. Future IDD therapeutics depends on identifying specific MMPs and ADAMTSs whose dysregulation result in pathological proteolysis of disc ECM. PMID:23369495

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

    PubMed

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

    2015-06-01

    One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p < 0.01) and 1.1-fold (p < 0.01), respectively, and the corresponding increases in the case of 50 µM HSP were 1.9-fold (p < 0.001) and 1.3-fold (p < 0.001). Therefore, HSP could be considered a valuable photoprotective substance if its capacity to increase melanin production in human melanocyte cultures could be reproduced on human skin. PMID:25765751

  8. Intervertebral disc segmentation and volumetric reconstruction from peripheral quantitative computed tomography imaging.

    PubMed

    Wong, Alexander; Mishra, Akshaya; Yates, Justin; Fieguth, Paul; Clausi, David A; Callaghan, Jack P

    2009-11-01

    An automatic system for segmenting and constructing volumetric representations of excised intervertebral discs from peripheral quantitative computed tomography (PQCT) imagery is presented. The system is designed to allow for automatic quantitative analysis of progressive herniation damage to the intervertebral discs under flexion/extension motions combined with a compressive load. Automatic segmentation and volumetric reconstruction of intervertebral disc from PQCT imagery is a very challenging problem due to factors such as streak artifacts and unclear material density separation between contrasted intervertebral disc and surrounding bone in the PQCT imagery, as well as the formation of multiple contrasted regions under axial scans. To address these factors, a novel multiscale level set approach based on the Mumford-Shah energy functional in iterative bilateral scale space is employed to segment the intervertebral disc regions from the PQCT imagery. A Delaunay triangulation is then performed based on the set of points associated with the intervertebral disc regions to construct the volumetric representation of the intervertebral disc. Experimental results show that the proposed system achieves segmentation and volumetric reconstructions of intervertebral discs with mean absolute distance error below 0.8 mm when compared to ground truth measurements. The proposed system is currently in operational use as a visualization tool for studying progressive intervertebral disc damage. PMID:19635691

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

    PubMed

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

    2015-07-01

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

  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. Feasibility of minimally-invasive fiber-based evaluation of chondrodystrophoid canine intervertebral discs by light absorption and scattering spectroscopy

    NASA Astrophysics Data System (ADS)

    Jiang, Yuanyuan; McKeirnan, Kelci; Piao, Daqing; Bartels, Kenneth E.

    2011-03-01

    Extrusion or protrusion of an intervertebral disc is a common, frequently debilitating, painful, and sometimes fatal neurologic disease in the chondrodystrophic dog (dachshund, Pekingese, etc.). A similar condition of intervertebral disc degeneration with extrusion/protrusion is also a relatively common neurologic condition in human patients. Degeneration of the relatively avascular chondrodystrophoid intervertebral disc is associated with loss of water content, increased collagen, and deposits of calcified mineral in the nucleus pulposus. Current diagnostic methods have many limitations for providing accurate information regarding disc composition in situ prior to surgical intervention. Disc composition (i.e., mineralization), can influence the type of treatment regime and potentially prognosis and recurrence rates. The objective of this study is to investigate the feasibility of using a fiber-needle spectroscopy sensor to analyze the changes of tissue compositions involved in the chondrodystrophoid condition of the canine intervertebral disc. The nucleous pulposus, in which the metaplastic process / degeneration develops, is approximately 2mm thick and 5mm in diameter in the dachshund-sized dog. It lies in the center of the disc, surrounded by the annulus fibrosis and is enclosed by cartilaginous vertebral endplates cranially and caudally. This "shallow-and-small-slab" geometry limits the configuration of a fiber probe to sense the disc tissue volume without interference from the vertebrae. A single-fiber sensor is inserted into a 20 gauge myelographic spinal needle for insertion into the disc in situ and connected via a bifurcated fiber to the light source and a spectrometer. A tungsten light source and a 940nm light-emitting-diode are combined for spectral illumination covering VIS/NIR with expected improved sensitivity to water. Analysis of the reflectance spectra is expected to provide information of scattering and absorption compositions of tissue in

  12. Early adolescent lumbar intervertebral disc injury: a case study

    PubMed Central

    2013-01-01

    This article describes and discusses the case of an adolescent male with lumbar intervertebral disc injury characterized by chronic low back pain (LBP) and antalgia. A 13-year-old boy presented for care with a complaint of chronic LBP and subsequent loss of quality of life. The patient was examined and diagnosed by means of history, clinical testing and use of imaging. He had showed failure in natural history and conservative management relief in both symptomatic and functional improvement, due to injury to the intervertebral joints of his lower lumbar spine. Discogenic LBP in the young adolescent population must be considered, particularly in cases involving even trivial minor trauma, and in those in which LBP becomes chronic. More research is needed regarding long-term implications of such disc injuries in young people, and how to best conservatively manage these patients. A discussion of discogenic LBP pertaining to adolescent disc injury is included. PMID:23621900

  13. [Minimally invasive surgery in treatment of lumbar intervertebral disc herniation].

    PubMed

    Rotim, Krešimir; Sajko, Tomislav; Borić, Marta; Subašić, Ante

    2015-01-01

    Surgical treatment of lumbar intervertebral disc herniation is one of the most common neurosurgical procedures. Besides conventional surgical techniques, in the last more than 30 years, different methods with minimal damage to neuromuscular spine structures are being developed and introduced, all having the purpose of reducing postoperative back pain. The advantages of the minimally invasive spine surgery include: possibility of performing procedures under local anaesthesia, reduced hospital stay, limited blood loss with consecutively reduced fibrous tissue development. Patients are capable of return to work and everyday activities early after surgery. From the economical point of view, this kind of treatment is considered to be a cost-effective intervention. Three methods that are being used for treatment of lumbar intervertebral disc herniation are: percutaneous laser disc decompression (PLDD), microdiscectomy using tubular retractor system and selective endoscopic discectomy (SED). Conducted prospective studies have shown that minimally invasive methods are adequate alternative to classic surgical procedures. PMID:26065287

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

    PubMed

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

    2011-11-01

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

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

    PubMed

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

    2015-02-01

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

  16. Polarization-sensitive OCT of bovine intervertebral disk

    NASA Astrophysics Data System (ADS)

    Matcher, Stephen J.; Winlove, C. Peter; Gangnus, Sergei V.

    2003-10-01

    Polarization-sensitive optical coherence tomography (PSOCT) is a powerful new optical imaging modality that is sensitive to the birefringence properties of tissues. It thus has potential applications in studying the large-scale ordering of collagen fibers within connective tissues and changes related to pathology. As a tissue for study by PSOCT, intervertebral disk represents an interesting system as the collagen organisation is believed to show pronounced variations with depth, on a spatial scale of about 100 microns .We have used a polarisation-sensitive optical coherence tomography system to measure the birefringence properties of bovine caudal intervertebral disk and compared this with equine flexor tendon. The result for equine tendon, Δn = (4.4 +/- 0.15) x 10-3 at 1.3μm, is somewhat larger than values reported for bovine tendon. The annulus fibrosus of freshly excised intact bovine intervertebral disk displays an identical value of birefringence, Δn = (4.4 +/- 0.4) x 10-3 at 1.3μm. However the retardance does not increase uniformly with depth into the tissue but displays a pronounced discontinuity at a depth of around 300 microns. This is believed to be related to the lamellar structure of this tissue, in which the collagen fiber orientation alternates between successive lamellae as depth into the tissue increases. The nucleus pulposus displays polarization conversion equivalent to a birefringence an order of magnitude smaller than these values i.e. Delta;n = (0.278 +/- 0.007) x 10-3. Our measurement protocol cannot distinguish this from the effects of depolarization due to multiple scattering. These results imply that PSOCT could be a useful tool to study collagen organisation within intervertebral disk in vivo and its variation with applied load and disease.

  17. Intervertebral disc degeneration in the dog. Part 1: Anatomy and physiology of the intervertebral disc and characteristics of intervertebral disc degeneration.

    PubMed

    Bergknut, Niklas; Smolders, Lucas A; Grinwis, Guy C M; Hagman, Ragnvi; Lagerstedt, Anne-Sofie; Hazewinkel, Herman A W; Tryfonidou, Marianna A; Meij, Björn P

    2013-03-01

    Intervertebral disc (IVD) degeneration is common in dogs and can give rise to a number of diseases, such as IVD herniation, cervical spondylomyelopathy, and degenerative lumbosacral stenosis. Although there have been many reports and reviews on the clinical aspects of canine IVD disease, few reports have discussed and reviewed the process of IVD degeneration. In this first part of a two-part review, the anatomy, physiology, histopathology, and biochemical and biomechanical characteristics of the healthy and degenerated IVD are described. In Part 2, the aspects of IVD degeneration in chondrodystrophic and non-chondrodystrophic dog breeds are discussed in depth. PMID:23177522

  18. Effect of Long-Term Osmotic Loading Culture on Matrix Synthesis from Intervertebral Disc Cells

    PubMed Central

    Newman, Isabella B.; Carapezza, Michael A.

    2014-01-01

    Abstract The intervertebral disc is a highly hydrated tissue that acts to absorb and distribute large complex loads placed on the spine. Diurnal loading and disc degeneration causes significant changes in water volume and proteoglycan content, which alters the internal osmotic environment. Short-term osmotic loading alters disc cell gene expression; however, the long-term effect of osmotic loading on disc cell matrix synthesis is not well understood. The objective of this study was to determine the effect of long-term osmotic loading on matrix turnover and proliferation by juvenile and adult cells from the nucleus pulposus (NP) and the cartilaginous endplate (EP). Matrix synthesis was evaluated using pellets and a 3D agarose system, which has been used for developing engineered tissues. Intervertebral discs were acquired from juvenile and adult cows. Cells were acquired through enzymatic digestion and expanded in culture. Pellets were formed through centrifugation, and constructs were created by encapsulating cells within 2% w/v agarose hydrogel. Pellets and constructs were cultured up to 42 days in chemically defined medium with the osmolality adjusted to 300, 400, or 500 mOsm/kg. EP cells were evaluated as a chondrocyte comparison to chondrocyte-like NP cells. Pellet and agarose cultures of juvenile NP and EP cells demonstrated similarities with respect to cell proliferation and functional mechanical properties. Cell proliferation decreased significantly with increased osmotic loading. The final compressive Young's modulus of juvenile NP cells was 10–40× greater than initial properties (i.e., day 0) and was greater than the final Young's modulus of adult NP and juvenile EP constructs. In juvenile NP constructs, there were no significant differences in GAG content with respect to osmotic loading. However, GAG synthesis and mechanical properties were greatest for the 400 mOsm/kg group in adult NP constructs. Taken together, the results presented here suggest a

  19. Biomechanical study of a hat type cervical intervertebral fusion cage

    PubMed Central

    Jia, Lian-Shun; Chen, Tong-Yi

    2006-01-01

    The purpose of this study was to evaluate the biomechanical effect of a hat type cervical intervertebral fusion cage (HCIFC). In this in vitro biomechanical study, 48 goat cervical spines (C2-5) were tested in flexion, extension, axial rotation, and lateral bending with a nondestructive stiffness method using a nonconstrained testing apparatus, and three-dimensional displacement was measured. Autologous iliac bone and cervical spine intervertebral fusion cage were implanted according to manufacturers’ information after complete discectomy (C3-4). Eight spines in each of the following groups were tested: intact, autologous iliac bone graft, Harms cage, SynCage C, carbon cage, and HCIFC. The mean apparent stiffness values were calculated from the corresponding load-displacement curves. Additionally, cage volume and volume-related stiffness were determined. The stiffness of the SynCage C was statistically greatest in all directions. After implantation of the HCIFC, flexion stiffness increased compared with that of the intact motion segment. There was no significant difference in stiffness between the HCIFC and carbon cage. The stiffness of the HCIFC was statistically higher than that of the Harms cage in axial rotation and significantly lower in flexion, extension, and lateral bending. Volume-related stiffness of all cages was higher than that of iliac bone graft. The Harms cage was highest in volume-related stiffness in all directions. The HCIFC can provide enough primary stability for cervical intervertebral fusion. PMID:16763843

  20. The Effects of Simulated Microgravity on Intervertebral Disc Degeneration

    PubMed Central

    Jin, Li; Feng, Gang; Reames, Davis L; Shimer, Adam L; Shen, Francis H; Li, Xudong

    2012-01-01

    BACKGROUND CONTEXT Astronauts experience back pain, particularly low back pain, during and after spaceflight. Recent studies have described histological and biochemical changes in rat intervertebral discs after space travel, but there is still no in vitro model to investigate the effects of microgravity on disc metabolism. PURPOSE To study the effects of microgravity on disc degeneration and to establish an in vitro simulated microgravity study model STUDY DESIGN Discs were cultured in static and rotating conditions in bioreactor, and the characteristics of disc degeneration were evaluated METHODS The mice discs were cultured in a rotating wall vessel bioreactor where the microgravity condition was simulated. Intervertebral discs were cultured in static and microgravity condition. Histology, biochemistry, and immunohistochemical assays were performed to evaluate the characteristics of the discs in microgravity condition. RESULTS Intervertebral discs cultured in rotating bioreactors were found to develop changes of disc degeneration manifested by reduced red Safranin-o staining within the annulus fibrosus, downregulated GAG content and GAG/Hypro ratio, increased MMP-3 expression, and upregulated apoptosis. CONCLUSIONS We conclude that simulated microgravity induces the molecular changes of disc degeneration. The rotating bioreactor model will provide a foundation to investigate the effects of microgravity on disc metabolism. PMID:23537452

  1. Notochord Cells in Intervertebral Disc Development and Degeneration

    PubMed Central

    McCann, Matthew R.; Séguin, Cheryle A.

    2016-01-01

    The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID:27252900

  2. Inflammatory Mediators in Intervertebral Disk Degeneration and Discogenic Pain

    PubMed Central

    Wuertz, Karin; Haglund, Lisbet

    2013-01-01

    Although degeneration of the intervertebral disk has historically been described as a misbalance between anabolic and catabolic factors, the role of inflammatory mediators has long been neglected. However, past research clearly indicates that inflammatory mediators such as interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α are expressed at higher levels in “diseased” intervertebral disks. Both disk cells as well as invading macrophages can be the source of the detected cytokines. Importantly, occurrence of inflammatory mediators in the disk can worsen the progress of degeneration by inducing the expression of matrix degrading enzymes as well as by inhibiting extracellular matrix synthesis. In addition, inflammatory mediators play a crucial role in pain development during intervertebral disk herniation (i.e., sciatica) and disk degeneration (i.e., discogenic pain). This review provides information on the most relevant inflammatory mediators during different types of disk diseases and explains how these factors can induce disk degeneration and the development of discogenic and sciatic/radiculopathic pain. PMID:24436868

  3. 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

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

    PubMed

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

    2016-05-01

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

  5. Bacteriology of severe periodontitis in young adult humans.

    PubMed Central

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

    1982-01-01

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

  6. Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs

    PubMed Central

    Nakamichi, Ryo; Ito, Yoshiaki; Inui, Masafumi; Onizuka, Naoko; Kayama, Tomohiro; Kataoka, Kensuke; Suzuki, Hidetsugu; Mori, Masaki; Inagawa, Masayo; Ichinose, Shizuko; Lotz, Martin K.; Sakai, Daisuke; Masuda, Koichi; Ozaki, Toshifumi; Asahara, Hiroshi

    2016-01-01

    The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx−/− mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration. PMID:27527664

  7. Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs.

    PubMed

    Nakamichi, Ryo; Ito, Yoshiaki; Inui, Masafumi; Onizuka, Naoko; Kayama, Tomohiro; Kataoka, Kensuke; Suzuki, Hidetsugu; Mori, Masaki; Inagawa, Masayo; Ichinose, Shizuko; Lotz, Martin K; Sakai, Daisuke; Masuda, Koichi; Ozaki, Toshifumi; Asahara, Hiroshi

    2016-01-01

    The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx(-/-) mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration. PMID:27527664

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

    ERIC Educational Resources Information Center

    Peterson, Shari L.; Provo, Joanne

    1998-01-01

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

  9. 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…

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  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. 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

  13. 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

  14. 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

  15. 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).…

  16. 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…

  17. 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…

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

    EPA Science Inventory

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

  19. 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…

  20. 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…

  1. 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…

  2. 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).…

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Scott, Jake; Goetz, Matthew Bidwell

    2016-08-01

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

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

    PubMed

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

    2011-04-01

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

  6. Canonical Genetic Signatures of the Adult Human Brain

    PubMed Central

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

    2015-01-01

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

  7. Canonical genetic signatures of the adult human brain.

    PubMed

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

    2015-12-01

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

  8. Double and zero quantum filtered 2H NMR analysis of D2O in intervertebral disc tissue

    NASA Astrophysics Data System (ADS)

    Ooms, Kristopher J.; Vega, Alexander J.; Polenova, Tatyana; Cannella, Marco; Marcolongo, Michele

    2015-09-01

    The analysis of double and zero quantum filtered 2H NMR spectra obtained from D2O perfused in the nucleus pulposus of human intervertebral disc tissue samples is reported. Fitting the spectra with a three-site model allows for residual quadrupolar couplings and T2 relaxation times to be measured. The analysis reveals changes in both the couplings and relaxation times as the tissue begins to show signs of degradation. The full analysis demonstrates that information about tissue hydration, water collagen interactions, and sample heterogeneity can be obtained and used to better understand the biochemical differences between healthy and degraded tissue.

  9. 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…

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

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

    PubMed

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

    2016-07-13

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

  19. 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

  20. 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}.

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

    PubMed

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

    2015-11-01

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

  2. 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

  3. 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.

  4. 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

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

    PubMed

    Overton, J H; Graham, R C

    1989-01-01

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

  6. 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

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

    PubMed

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

    2015-06-01

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

  8. 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

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

    ERIC Educational Resources Information Center

    Lawler, Patricia A.; King, Kathleen P.

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

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

    PubMed

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

    2013-05-01

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

  11. 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

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

    PubMed

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

    2015-01-01

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1(HIGH) cell subpopulation described in rodents. Our results support the existence of ependymal CB1(HIGH) cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions. PMID:26634814

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

    PubMed

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

    2013-01-01

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

  14. Dynamics of an intervertebral disc prosthesis in human cadaveric spines.

    PubMed

    Meyers, Kathleen N; Campbell, Deirdre A; Lipman, Joseph D; Zhang, Kai; Myers, Elizabeth R; Girardi, Federico P; Cammisa, Frank P; Wright, Timothy M

    2007-09-01

    Low-back pain is a common, disabling medical condition, and one of the major causes is disc degeneration. Total disc replacements are intended to treat back pain by restoring disc height and re-establishing functional motion and stability at the index level. The objective of this study was to determine the effect on range of motion (ROM) and stiffness after implantation of the ProDisc-L device in comparison to the intact state. Twelve L5-S1 lumbar spine segments were tested in flexion/extension, lateral bending, and axial rotation with axial compressive loads of 600 N and 1,200 N. Specimens were tested in the intact state and after implantation with the ProDisc-L device. ROM was not significantly different in the implanted spines when compared to their intact state in flexion/extension and axial rotation but increased in lateral bending. Increased compressive load did not affect ROM in flexion/extension or axial rotation but did result in decreased ROM in lateral bending and increased stiffness in both intact and implanted spine segments. The ProDisc-L successfully restored or maintained normal spine segment motion. PMID:18751788

  15. Incidental extraspinal findings on magnetic resonance imaging of intervertebral discs

    PubMed Central

    Ayaz, Umit Yasar; Turanlı, Sevim; Saltas, Hakan; Karabacak, Osman Raif; Damar, Cagrı; Hekimoglu, Baki

    2014-01-01

    Introduction We aimed to evaluate pathological extraspinal findings and congenital anomalies/anatomical variations that were incidentally detected on the magnetic resonance imaging (MRI) scans of intervertebral discs, to find the frequencies of these incidental findings, and to emphasise the clinical importance of them. Material and methods A retrospective study including 1031 consecutive patients (730 females and 301 males, with a median age of 46 years) was conducted by evaluating a total of 1106 MRI examinations of intervertebral discs. Examinations were performed with a 1.5 T MRI unit. Incidental findings were classified as pathological findings and congenital anomalies/anatomical variations. Results The percentages of incidental extraspinal pathological findings and congenital anomalies/anatomical variations were 16.6% (95% confidence interval (CI): 14.4–18.8) and 3.7% (95% CI: 2.6–4.3), respectively. The percentage of incidental extraspinal pathological findings on cervical spinal MRI was 25.7% (95% CI: 20.1–31.7), thyroid nodules being the most common incidental findings. On thoracic spinal MRI (n = 19), inferior pole thyroid nodules were demonstrated as incidental extraspinal pathological findings, with a percentage of 10.5% (95% CI: 9.6–11.5). On lumbar spinal MRI, incidental pathological findings were detected with a percentage of 14.2% (95% CI: 11.9–16.6), while the percentage of congenital anomalies/anatomical variations was 4.8% (95% CI: 3.4–6.3). Eventually, 6.5% (95% CI: 2.6–9.4) of all cases with incidental extraspinal pathological findings underwent surgery. Conclusions On MRI examination of intervertebral discs, paying attention to incidentally detected pathological extraspinal findings and congenital anomalies/anatomical variations is very important due to the fact that they can alter the treatment of the patient or affect the patient's life. PMID:25276162

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

    PubMed

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

    2011-03-15

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

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

    PubMed

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

    2014-01-01

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

  18. Emerging technologies for molecular therapy for intervertebral disc degeneration

    PubMed Central

    Bae, Won C.; Masuda, Koichi

    2014-01-01

    Intervertebral discs are biologically regulated by the maintenance of a balance between the anabolic and catabolic activities of disc cells. Therapeutic agents, initially evaluated using in vitro studies on disc cells and explants, have been used as intradiscal injections in preclinical settings to test in vivo efficacy. These include anabolic growth factors and other biostimulatory agents as well as antagonistic agents against matrix-degrading enzymes and cytokines. Additional work is needed to identify suitable patient populations, using methods such as MRI, and to better understand the mechanism of healing. Clinical trials are currently underway for a few of these agents, while many other promising candidates are on the horizon. PMID:21944594

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Melching, L I; Roughley, P J

    1989-01-01

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

  1. No Acceleration of Intervertebral Disc Degeneration after a Single Injection of Bupivacaine in Young Age Group with Follow-Up of 5 Years

    PubMed Central

    Inoue, Gen; Orita, Sumihisa; Eguchi, Yawara; Ochiai, Nobuyasu; Kishida, Shunji; Kuniyoshi, Kazuki; Nakamura, Junichi; Aoki, Yasuchika; Ishikawa, Tetsuhiro; Miyagi, Masayuki; Kamoda, Hiroto; Suzuki, Miyako; Takaso, Masashi; Toyone, Tomoaki; Kubota, Gou; Sakuma, Yoshihiro; Oikawa, Yasuhiro; Inage, Kazuhide; Sainoh, Takeshi; Takahashi, Kazuhisa

    2013-01-01

    Study Design Prospective study of changes in intervertebral disc degeneration after injection of bupivacaine. Purpose To examine whether injection of bupivacaine into human intervertebral discs accelerates their degeneration. Overview of Literature Bupivacaine is commonly used for therapy and diagnosis of discogenic low back pain. However, several in vitro studies have reported toxic effects of bupivacaine to disc cells. We sought to evaluate whether this finding is clinically relevant. Methods We selected 46 patients with low back pain who showed disc degeneration at only one level (L4-L5 or L5-S1) on magnetic resonance imaging (MRI) (discography group, n=18), discoblock group (injection of bupivacaine, n=18), and a control group, n=10). There were no significant differences in baseline characteristics across the 3 groups. The two experimental groups underwent either discography or anesthetic discoblock, respectively. All three groups were followed up 5 years after the examination. Results At 5 years follow-up, there was no significant difference in the rate of disc degeneration among the 3 groups (p>0.1). Moreover, X-ray images showed that there was no significant difference in disc height, range of motion, or translation between flex and extension position (p>0.1). Conclusions In conclusion, radiologic and MRI findings did not show acceleration of intervertebral disc degeneration at 5 years after a single injection of bupivacaine into human discs. PMID:24066217

  2. 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

  3. 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

  4. 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

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

    PubMed Central

    2013-01-01

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

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

    PubMed

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

    2000-08-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Guo, Zhiru; Draheim, Kyle; Lyle, Stephen

    2011-01-01

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

  9. 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

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

    PubMed

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

    2013-10-01

    Parabens are widely used as preservatives in foods, cosmetics, and pharmaceuticals. However, recent studies have indicated that high and systemic exposure to parabens can be harmful to human health. Although a few studies have reported urinary paraben levels in western countries, studies on paraben exposure in the Chinese population are limited. China is currently a major producer of parabens in the world. In this study, 109 urine samples collected from Chinese young adults (approximately 20 years old) were analyzed for five parabens (methyl-, ethyl-, propyl-, butyl-, and benzyl-parabens) by high-performance liquid chromatography-tandem mass spectrometry. Methyl-, propyl-, and ethyl-parabens were the three major paraben analogues found in all (100%) samples. The concentration of the sum of the five parabens ranged from 0.82 to 728 ng/mL with a geometric mean value of 17.4 ng/mL. Urinary concentration of parabens was 2-fold greater in females than in males. Based on the measured urinary concentrations, daily intake of parabens by the Chinese young adults was estimated and compared with those reported for United States adults. The estimated daily intakes (EDIurine) of parabens were 18.4 and 40.8 μg/kg bw/day for Chinese males and females, respectively, values that were lower than those reported for United States adults (74.7 μg/kg bw/day). Based on the reported concentrations of parabens in foods from China and the United States, the contribution of dietary intake to EDIurine was estimated to be 5.5, 2.6, and 0.42% for Chinese males, Chinese females, and United States adults, respectively, which indicates the significance of nondietary sources of parabens to human exposures. PMID:23744051

  11. Mechanisms for mechanical damage in the intervertebral disc annulus fibrosus.

    PubMed

    Iatridis, J C James C; ap Gwynn, Iolo

    2004-08-01

    Intervertebral disc degeneration results in disorganization of the laminate structure of the annulus that may arise from mechanical microfailure. Failure mechanisms in the annulus were investigated using composite lamination theory and other analyses to calculate stresses in annulus layers, interlaminar shear stress, and the region of stress concentration around a fiber break. Scanning electron microscopy (SEM) was used to evaluate failure patterns in the annulus and evaluate novel structural features of the disc tissue. Stress concentrations in the annulus due to an isolated fiber break were localized to approximately 5 microm away from the break, and only considered a likely cause of annulus fibrosus failure (i.e., radial tears in the annulus) under extreme loading conditions or when collagen damage occurs over a relatively large region. Interlaminar shear stresses were calculated to be relatively large, to increase with layer thickness (as reported with degeneration), and were considered to be associated with propagation of circumferential tears in the annulus. SEM analysis of intervertebral disc annulus fibrosus tissue demonstrated a clear laminate structure, delamination, matrix cracking, and fiber failure. Novel structural features noted with SEM also included the presence of small tubules that appear to run along the length of collagen fibers in the annulus and a distinct collagenous structure representative of a pericellular matrix in the nucleus region. PMID:15212921

  12. Effect of Hydration on Healthy Intervertebral Disk Mechanical Stiffness.

    PubMed

    Bezci, Semih E; Nandy, Aditya; O'Connell, Grace D

    2015-10-01

    The intervertebral disk has an excellent swelling capacity to absorb water, which is thought to be largely due to the high proteoglycan composition. Injury, aging, degeneration, and diurnal loading are all noted by a significant decrease in water content and tissue hydration. The objective of this study was to evaluate the effect of hydration, through osmotic loading, on tissue swelling and compressive stiffness of healthy intervertebral disks. The wet weight of nucleus pulposus (NP) and annulus fibrosus (AF) explants following swelling was 50% or greater, demonstrating significant ability to absorb water under all osmotic loading conditions (0.015 M-3.0 M phosphate buffered saline (PBS)). Estimated NP residual strains, calculated from the swelling ratio, were approximately 1.5 × greater than AF residual strains. Compressive stiffness increased with hyperosmotic loading, which is thought to be due to material compaction from osmotic-loading and the nonlinear mechanical behavior. Importantly, this study demonstrated that residual strains and material properties are greatly dependent on osmotic loading. The findings of this study support the notion that swelling properties from osmotic loading will be important for accurately describing the effect of degeneration and injury on disk mechanics. Furthermore, the tissue swelling will be an important consideration for developing biological repair strategies aimed at restoring mechanical behavior toward a healthy disk. PMID:26300418

  13. 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

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

    PubMed Central

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

    Batchelder, John Stuart; Byxbe, Ferris

    2002-01-01

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

  16. 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...

  17. 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...

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

    PubMed

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

    2011-01-01

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

  19. 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

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

    PubMed

    Webb, Angela; Li, Amy; Kaur, Pritinder

    2004-10-01

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

  1. Intervertebral disk width in dogs with and without clinical signs of disk associated cervical spondylomyelopathy

    PubMed Central

    2012-01-01

    Background Disk-associated cervical spondylomyelopathy (DA-CSM) is a multifactorial neurological disorder in which progressive caudal cervical spinal cord compression is mainly caused by one or more intervertebral disk protrusions. The Doberman pinscher breed seems predisposed for this condition. The underlying cause and pathophysiology of DA-CSM are currently unknown. Recently, wider intervertebral disks have been put forward as a risk factor for development of clinically relevant DA-CSM. However, little is known about other factors affecting intervertebral disk width. Therefore the aim of this study was to assess the association between intervertebral disk width, measured on magnetic resonance imaging (MRI), and clinical status, age, gender and intervertebral disk location in dogs with and without clinical signs of DA-CSM. Methods Doberman pinschers with clinical signs of DA-CSM (N=17),clinically normal Doberman pinschers (N=20), and clinically normal English Foxhounds (N=17), underwent MRI of the cervical vertebral column. On sagittal T2-weighted images, intervertebral disk width was measured from C2-C3 to C6-C7. Intra –and interobserver agreement were assessed on a subset of 20 of the 54 imaging studies. Results Intervertebral disk width was not significantly different between Doberman pinschers with clinical signs of DA-CSM, clinically normal Doberman pinschers or clinically normal English Foxhounds (p=0.43). Intervertebral disk width was positively associated with increasing age (p=0.029). Each monthly increase in age resulted in an increase of disk width by 0.0057mm. Intervertebral disk width was not significantly affected by gender (p=0.056), but was significantly influenced by intervertebral disk location (p <0.0001). The assessed measurements were associated with a good intra –and interobserver agreement. Conclusions The present study does not provide evidence that wider intervertebral disks are associated with clinical status in dogs with and without

  2. Antioxidative nanofullerol prevents intervertebral disk degeneration

    PubMed Central

    Yang, Xinlin; Jin, Li; Yao, Lu; Shen, Francis H; Shimer, Adam L; Li, Xudong

    2014-01-01

    Compelling evidence suggests that reactive oxygen species (ROS) play a pivotal role in disk degeneration. Fullerol nanoparticles prepared in aqueous solution have been demonstrated to have outstanding ability to scavenge ROS. In this report, in vitro and in vivo models were used to study the efficacy of fullerol in preventing disk degeneration. For in vitro experiments, a pro-oxidant H2O2 or an inflammatory cytokine interleukin (IL)-1β was employed to induce degenerated phenotypes in human nucleus pulposus cells encapsulated in alginate beads, and fullerol was added in the culture medium. For the animal study, an annulus-puncture model with rabbit was created, and fullerol was injected into disks. It was shown that cytotoxicity and cellular ROS level induced by H2O2 were significantly diminished by fullerol. IL-1β-induced nitric oxide generation in culture medium was suppressed by fullerol as well. Gene-profile and biochemical assays showed that fullerol effectively reversed the matrix degradation caused by either H2O2 or IL-1β. The animal study delineated that intradiskal injection of fullerol prevented disk degeneration, increasing water and proteoglycan content and inhibiting ectopic bone formation. These results suggest that antioxidative fullerol may have a potential therapeutic application for disk degeneration. PMID:24876775

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

    PubMed Central

    Llamazares, Marco; Smith?, Robert J

    2008-01-01

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

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

    PubMed Central

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

    2016-01-01

    Breast milk is replete with nutritional content as well as nucleic acids including microRNAs (miRNAs). In a recent report, adult humans who drank bovine milk appeared to have increased circulating levels of miRNAs miR-29b-3p and miR-200c-3p. Since these miRNAs are homologous between human and cow, these results could be explained by xeno-miRNA influx, endogenous miRNA regulation, or both. More data were needed to validate the results and explore for additional milk-related alterations in circulating miRNAs. Samples from the published study were obtained, and 223 small RNA features were profiled with a custom OpenArray, followed by individual quantitative PCR assays for selected miRNAs. Additionally, small RNA sequencing (RNA-seq) data obtained from plasma samples of the same project were analyzed to find human and uniquely bovine miRNAs. OpenArray revealed no significantly altered miRNA signals after milk ingestion, and this was confirmed by qPCR. Plasma sequencing data contained no miR-29b or miR-200c reads and no intake-consistent mapping of uniquely bovine miRNAs. In conclusion, the results do not support transfer of dietary xenomiRs into the circulation of adult humans. PMID:27158459

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

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2013-04-01

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

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

    NASA Astrophysics Data System (ADS)

    Gadotti, Moacir

    2011-08-01

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

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

    SciTech Connect

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

    1985-10-01

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

  9. Effects of follower load and rib cage on intervertebral disc pressure and sagittal plane curvature in static tests of cadaveric thoracic spines.

    PubMed

    Anderson, Dennis E; Mannen, Erin M; Sis, Hadley L; Wong, Benjamin M; Cadel, Eileen S; Friis, Elizabeth A; Bouxsein, Mary L

    2016-05-01

    The clinical relevance of mechanical testing studies of cadaveric human thoracic spines could be enhanced by using follower preload techniques, by including the intact rib cage, and by measuring thoracic intervertebral disc pressures, but studies to date have not incorporated all of these components simultaneously. Thus, this study aimed to implement a follower preload in the thoracic spine with intact rib cage, and examine the effects of follower load, rib cage stiffening and rib cage removal on intervertebral disc pressures and sagittal plane curvatures in unconstrained static conditions. Intervertebral disc pressures increased linearly with follower load magnitude. The effect of the rib cage on disc pressures in static conditions remains unclear because testing order likely confounded the results. Disc pressures compared well with previous reports in vitro, and comparison with in vivo values suggests the use of a follower load of about 400N to approximate loading in upright standing. Follower load had no effect on sagittal plane spine curvature overall, suggesting successful application of the technique, although increased flexion in the upper spine and reduced flexion in the lower spine suggest that the follower load path was not optimized. Rib cage stiffening and removal both increased overall spine flexion slightly, although with differing effects at specific spinal locations. Overall, the approaches demonstrated here will support the use of follower preloads, intact rib cage, and disc pressure measurements to enhance the clinical relevance of future studies of the thoracic spine. PMID:26944690

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2001-12-01

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

  12. Acid-sensing ion channel 2 (asic 2) and trkb interrelationships within the intervertebral disc

    PubMed Central

    Cuesta, Antonio; Viña, Eliseo; Cabo, Roberto; Vázquez, Gorka; Cobo, Ramón; García-Suárez, Olivia; García-Cosamalón, José; Vega, José A

    2015-01-01

    The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. They express acid-sensing ion channels (ASICs), gated by extracellular protons and mechanical forces, as well as neurotrophins and their signalling receptors. In the nervous tissues some neurotrophins regulate the expression of ASICs. The expression of ASIC2 and TrkB in human normal and degenerated IVD was assessed using quantitative-PCR, Western blot, and immunohistochemistry. Moreover, we investigated immunohistochemically the expression of ASIC2 in the IVD of TrkB-deficient mice. ASIC2 and TrkB mRNAs were found in normal human IVD and both increased significantly in degenerated IVD. ASIC2 and TrkB proteins were also found co-localized in a variable percentage of cells, being significantly higher in degenerated IVD than in controls. The murine IVD displayed ASIC2 immunoreactivity which was absent in the IVD of TrkB-deficient mice. Present results demonstrate the occurrence of ASIC2 and TrkB in the human IVD, and the increased expression of both in pathological IVD suggest their involvement in IVD degeneration. These data also suggest that TrkB-ligands might be involved in the regulation of ASIC2 expression, and therefore in mechanisms by which the IVD cells accommodate to low pH and hypertonicity. PMID:26617738

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

    PubMed Central

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

    2016-01-01

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

  14. Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs.

    PubMed

    Nasto, Luigi A; Wang, Dong; Robinson, Andria R; Clauson, Cheryl L; Ngo, Kevin; Dong, Qing; Roughley, Peter; Epperly, Michael; Huq, Saiful M; Pola, Enrico; Sowa, Gwendolyn; Robbins, Paul D; Kang, James; Niedernhofer, Laura J; Vo, Nam V

    2013-01-01

    Intervertebral disc degeneration (IDD) is the leading cause of debilitating spinal disorders such as chronic lower back pain. Aging is the greatest risk factor for IDD. Previously, we demonstrated IDD in a murine model of a progeroid syndrome caused by reduced expression of a key DNA repair enzyme. This led us to hypothesize that DNA damage promotes IDD. To test our hypothesis, we chronically exposed adult wild-type (Wt) and DNA repair-deficient Ercc1(-/Δ) mice to the cancer therapeutic agent mechlorethamine (MEC) or ionization radiation (IR) to induce DNA damage and measured the impact on disc structure. Proteoglycan, a major structural matrix constituent of the disc, was reduced 3-5× in the discs of MEC- and IR-exposed animals compared to untreated controls. Expression of the protease ADAMTS4 and aggrecan proteolytic fragments was significantly increased. Additionally, new PG synthesis was reduced 2-3× in MEC- and IR-treated discs compared to untreated controls. Both cellular senescence and apoptosis were increased in discs of treated animals. The effects were more severe in the DNA repair-deficient Ercc1(-/Δ) mice than in Wt littermates. Local irradiation of the vertebra in Wt mice elicited a similar reduction in PG. These data demonstrate that genotoxic stress drives degenerative changes associated with IDD. PMID:23262094

  15. Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs

    PubMed Central

    Nasto, Luigi A.; Wang, Dong; Robinson, Andria R.; Clauson, Cheryl L.; Ngo, Kevin; Dong, Qing; Roughley, Peter; Epperly, Michael; Huq, Saiful M.; Pola, Enrico; Sowa, Gwendolyn; Robbins, Paul D.; Kang, James; Niedernhofer, Laura J.; Vo, Nam V.

    2013-01-01

    Intervertebral disc degeneration (IDD) is the leading cause of debilitating spinal disorders such as chronic lower back pain. Aging is the greatest risk factor for IDD. Previously, we demonstrated IDD in a murine model of a progeroid syndrome caused by reduced expression of a key DNA repair enzyme. This led us to hypothesize that DNA damage promotes IDD. To test our hypothesis, we chronically exposed adult wild-type (Wt) and DNA repair-deficient Ercc1−/Δ mice to the cancer therapeutic agent mechlorethamine (MEC) or ionization radiation (IR) to induce DNA damage and measured the impact on disc structure. Proteoglycan, a major structural matrix constituent of the disc, was reduced 3-5x in the discs of MEC- and IR-exposed animals compared to untreated controls. Expression of the protease ADAMTS4 and aggrecan proteolytic fragments were significantly increased. Additionally, new PG synthesis was reduced 2-3x in MEC- and IR-treated discs compared to untreated controls. Both cellular senescence and apoptosis were increased in discs of treated animals. The effects were more severe in the DNA repair-deficient Ercc1−/Δ mice than in Wt littermates. Local irradiation of the vertebra in Wt mice elicited a similar reduction in PG. These data demonstrate that genotoxic stress drives degenerative changes associated with IDD. PMID:23262094

  16. A comparison between porcine, ovine, and bovine intervertebral disc anatomy and single lamella annulus fibrosus tensile properties.

    PubMed

    Monaco, Lauren A; DeWitte-Orr, Stephanie J; Gregory, Diane E

    2016-02-01

    This project aimed to compare gross anatomical measures and biomechanical properties of single lamellae from the annulus fibrosus of ovine and porcine lumbar vertebrae, and bovine tail vertebrae. The morphology of the vertebrae of these species differ significantly both from each other and from human, yet how these differences alter biomechanical properties is unknown. Geometric parameters measured in this study included: 1) absolute and relative intervertebral (IVD) and vertebral body height and 2) absolute and relative intervertebral disc (IVD) anterior-posterior (AP) and medial-lateral (ML) widths. Single lamella tensile properties included toe-region stress and stretch ratio, stiffness, and tensile strength. As expected, the bovine tail IVD revealed a more circular shape compared with both the ovine and porcine lumbar IVD. The bovine tail also had the largest IVD to vertebral body height ratio (due to having the highest absolute IVD height). Bovine tail lamellae were also found to be strongest and stiffest (in tension) while ovine lumbar lamellae were weakest and most compliant. Histological analysis revealed the greatest proportion of collagen in the bovine corroborating findings of increased strength and stiffness. The observed differences in anatomical shape, connective tissue composition, and tensile properties need to be considered when choosing an appropriate model for IVD research. PMID:26558749

  17. A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype.

    PubMed

    Hirata, Hiroaki; Yurube, Takashi; Kakutani, Kenichiro; Maeno, Koichiro; Takada, Toru; Yamamoto, Junya; Kurakawa, Takuto; Akisue, Toshihiro; Kuroda, Ryosuke; Kurosaka, Masahiro; Nishida, Kotaro

    2014-03-01

    The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types-notochordal cells (NCs) and non-notochordal chondrocyte-like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI-positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, identified as NCs. The proportion of TUNEL-positive cells, which predominantly comprised non-NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2α-1 mRNA levels were down-regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration. PMID:24285589

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

    NASA Astrophysics Data System (ADS)

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

    2012-11-01

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

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

    PubMed

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

    2016-04-22

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

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

    PubMed Central

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

    2011-01-01

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

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

    ERIC Educational Resources Information Center

    Page, Garnet T.; Caldwell, George

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

  4. [The height of intervertebral foramen in operative treatment of isthmic spondylolisthesis].

    PubMed

    Smoczyński, Andrzej; Pankowski, Rafał; Smoczyński, Maciej; Łuczkiewicz, Piotr; Debski, Janusz

    2008-01-01

    49 patients with spondylolisthesis isthmica were treated in the years 1991-2006. The age of patients varied between 21 and 65 years, 43.7 year on average. Two stages operative protocol consisted of reduction of the slip by pedicular implant and anterior interbody fusion with the cages was used. The evaluation was based on x-rays height of the lumbar intervertebral foramen and posterior disc height in the 2 distal lumbar vertebrae pre and post operatively. This results showed clearly a decrease of both these values on the level of the slip, demonstrating the lumbar intervertebral stenosis. Te operative procedure decomprssed the lumbar intervertebral foramen and increased both values evaluated Postoperatively in the neighbor vertebrae a height lumbar intervertebral foramen was increased but posterior disc height a unchanged. PMID:18847000

  5. Distraction-stabilisation of two adjacent intervertebral spaces in a Dalmatian dog with caudal cervical spondylomyelopathy.

    PubMed

    Beranek, J; Tomek, A; Lorinson, D

    2013-05-01

    A 4-year-old, 40-kg, male, entire Dalmatian was presented for evaluation of chronic neck pain and pelvic limb ataxia. Myelography revealed ventrodorsal (hourglass) extradural compression over the intervertebral space between the 5th and 6th cervical vertebra and ventral extradural compression between the 6th and 7th cervical vertebra. Cranial compression disappeared and caudal compression markedly diminished after performing cervical traction. MRI scan confirmed protrusion of intervertebral discs and spinal cord compression in previously mentioned intervertebral spaces. Surgical distraction-stabilization of both intervertebral spaces was performed using threaded pins and polymethylmethacrylate. The convalescence from surgery was uneventful and the dog was walking without any signs of paresis until 5 months after surgery when radiography revealed implants loosening. The dog recovered fully of the implant removal and remained asymptomatic for more than 30 months. PMID:23644293

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  8. 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

  9. 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

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

    PubMed

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

    2014-01-01

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

  11. 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…

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

    PubMed Central

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

    2012-01-01

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

  13. Delivery systems for the treatment of degenerated intervertebral discs.

    PubMed

    Blanquer, S B G; Grijpma, D W; Poot, A A

    2015-04-01

    The intervertebral disc (IVD) is the most avascular and acellular tissue in the body and therefore prone to degeneration. During IVD degeneration, the balance between anabolic and catabolic processes in the disc is deregulated, amongst others leading to alteration of extracellular matrix production, abnormal enzyme activities and production of pro-inflammatory substances like cytokines. The established treatment strategy for IVD degeneration consists of physiotherapy, pain medication by drug therapy and if necessary surgery. This approach, however, has shown limited success. Alternative strategies to increase and prolong the effects of bioactive agents and to reverse the process of IVD degeneration include the use of delivery systems for drugs, proteins, cells and genes. In view of the specific anatomy and physiology of the IVD and depending on the strategy of the therapy, different delivery systems have been developed which are reviewed in this article. PMID:25451138

  14. Autophagy: A double-edged sword in intervertebral disk degeneration.

    PubMed

    Zhang, Shu-Jun; Yang, Wei; Wang, Cheng; He, Wen-Si; Deng, Hai-Yang; Yan, Yi-Guo; Zhang, Jian; Xiang, Yong-Xiao; Wang, Wen-Jun

    2016-06-01

    Autophagy is a homeostatic mechanism through which intracellular damaged organelles and proteins are degraded and recycled in response to increased metabolic demands or stresses. Although primarily cytoprotective, dysfunction of autophagy is often associated with many degenerative diseases, including intervertebral disc (IVD) degeneration (IDD). As a main contributing factor to low back pain, IDD is the pathological basis for various debilitating spinal diseases. Either higher or lower levels of autophagy are observed in degenerative IVD cells. Despite the precise role of autophagy in disc degeneration that is still controversial, with difference from protection to aggravation, targeting autophagy has shown promise for mitigating disc degeneration. In the current review, we summarize the changes of autophagy in degenerative IVD cells and mainly discuss the relationship between autophagy and IDD. With continued efforts, modulation of the autophagic process could be a potential and attractive therapeutic strategy for degenerative disc disease. PMID:27018178

  15. Indigo Carmine for the Selective Endoscopic Intervertebral Nuclectomy

    PubMed Central

    Kim, Inn-Se; Shin, Sang-Wook; Kim, Tae-Kyun; Kim, Jeung-Il

    2005-01-01

    This study was undertaken to prove that the selectively infiltrated parts of nucleus pulposus with indigo carmine was degenerated parts of nucleus pulposus. This study was done, between August and October 2002, in 5 patients, who received endoscopic discectomy, due to intervertebral disc herniation. Discogram was done with mixture of indigo carmine and radioactive dye. Blue discolored part was removed through endoscope, and small undiscolored part was removed together for the control. The two parts were stained with hematoxylin and eosin and compared under the microscope. Undiscolored part was normal nucleus pulposus, composed of chondrocytes with a matrix of type II collagen and proteoglycan, mainly aggrecan. However, in discolored part, slits with destruction of collagen fiber array and ingrowth of vessel and nerve were observed. Using indigo carmine in endoscopic discectomy gives us selective removal of degenerated disc. PMID:16100472

  16. 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.

  17. Painful, degenerating intervertebral discs up-regulate neurite sprouting and CGRP through nociceptive factors.

    PubMed

    Krock, Emerson; Rosenzweig, Derek H; Chabot-Doré, Anne-Julie; Jarzem, Peter; Weber, Michael H; Ouellet, Jean A; Stone, Laura S; Haglund, Lisbet

    2014-06-01

    Intervertebral disc degeneration (IVD) can result in chronic low back pain, a common cause of morbidity and disability. Inflammation has been associated with IVD degeneration, however the relationship between inflammatory factors and chronic low back pain remains unclear. Furthermore, increased levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are both associated with inflammation and chronic low back pain, but whether degenerating discs release sufficient concentrations of factors that induce nociceptor plasticity remains unclear. Degenerating IVDs from low back pain patients and healthy, painless IVDs from human organ donors were cultured ex vivo. Inflammatory and nociceptive factors released by IVDs into culture media were quantified by enzyme-linked immunosorbent assays and protein arrays. The ability of factors released to induce neurite growth and nociceptive neuropeptide production was investigated. Degenerating discs release increased levels of tumour necrosis factor-α, interleukin-1β, NGF and BDNF. Factors released by degenerating IVDs increased neurite growth and calcitonin gene-related peptide expression, both of which were blocked by anti-NGF treatment. Furthermore, protein arrays found increased levels of 20 inflammatory factors, many of which have nociceptive effects. Our results demonstrate that degenerating and painful human IVDs release increased levels of NGF, inflammatory and nociceptive factors ex vivo that induce neuronal plasticity and may actively diffuse to induce neo-innervation and pain in vivo. PMID:24650225

  18. Painful, degenerating intervertebral discs up-regulate neurite sprouting and CGRP through nociceptive factors

    PubMed Central

    Krock, Emerson; Rosenzweig, Derek H; Chabot-Doré, Anne-Julie; Jarzem, Peter; Weber, Michael H; Ouellet, Jean A; Stone, Laura S; Haglund, Lisbet

    2014-01-01

    Intervertebral disc degeneration (IVD) can result in chronic low back pain, a common cause of morbidity and disability. Inflammation has been associated with IVD degeneration, however the relationship between inflammatory factors and chronic low back pain remains unclear. Furthermore, increased levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are both associated with inflammation and chronic low back pain, but whether degenerating discs release sufficient concentrations of factors that induce nociceptor plasticity remains unclear. Degenerating IVDs from low back pain patients and healthy, painless IVDs from human organ donors were cultured ex vivo. Inflammatory and nociceptive factors released by IVDs into culture media were quantified by enzyme-linked immunosorbent assays and protein arrays. The ability of factors released to induce neurite growth and nociceptive neuropeptide production was investigated. Degenerating discs release increased levels of tumour necrosis factor-α, interleukin-1β, NGF and BDNF. Factors released by degenerating IVDs increased neurite growth and calcitonin gene-related peptide expression, both of which were blocked by anti-NGF treatment. Furthermore, protein arrays found increased levels of 20 inflammatory factors, many of which have nociceptive effects. Our results demonstrate that degenerating and painful human IVDs release increased levels of NGF, inflammatory and nociceptive factors ex vivo that induce neuronal plasticity and may actively diffuse to induce neo-innervation and pain in vivo. PMID:24650225

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2014-08-27

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

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

    PubMed

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

    2009-05-01

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

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

    PubMed Central

    Wyatt, L S; Rodriguez, W J; Balachandran, N; Frenkel, N

    1991-01-01

    The recent isolation of human herpesvirus 7 (HHV-7) from activated CD4+ T lymphocytes of a healthy individual raises questions regarding the prevalence of this virus in humans and its immunological relationship to previously characterized human herpesviruses. We report that HHV-7 is a ubiquitous virus which is immunologically distinct from the highly prevalent T-lymphotropic HHV-6. Thus, (i) only two of six monoclonal antibodies to HHV-6 cross-reacted with HHV-7-infected cells, (ii) Western immunoblot analyses of viral proteins revealed different patterns for HHV-6- and HHV-7-infected cells, (iii) tests of sequential serum samples from children revealed seroconversion to HHV-6 without concomitant seroconversion to HHV-7, and (iv) in some instances HHV-7 infection occurred in the presence of high titers of HHV-6 antibodies, suggesting the lack of apparent protection of children seropositive for HHV-6 against subsequent infection with HHV-7. On the basis of the analyses of sera from children and adults it can be concluded that HHV-7 is a prevalent human herpesvirus which, like other human herpesviruses, infects during childhood. The age of infection appears to be somewhat later than the very early age documented for HHV-6. Images PMID:1656093

  3. Proteome Mapping of Adult Zebrafish Marrow Neutrophils Reveals Partial Cross Species Conservation to Human Peripheral Neutrophils

    PubMed Central

    Singh, Sachin Kumar; Sethi, Sachin; Aravamudhan, Sriram; Krüger, Marcus; Grabher, Clemens

    2013-01-01

    Neutrophil granulocytes are pivotal cells within the first line of host defense of the innate immune system. In this study, we have used a gel-based LC-MS/MS approach to explore the proteome of primary marrow neutrophils from adult zebrafish. The identified proteins originated from all major cellular compartments. Gene ontology analysis revealed significant association of proteins with different immune-related network and pathway maps. 75% of proteins identified in neutrophils were identified in neutrophils only when compared to neutrophil-free brain tissue. Moreover, cross-species comparison with human peripheral blood neutrophils showed partial conservation of immune-related proteins between human and zebrafish. This study provides the first zebrafish neutrophil proteome and may serve as a valuable resource for an understanding of neutrophil biology and innate immunity. PMID:24019943

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

    PubMed

    Schlenker, R A

    1988-04-01

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

  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 arterial smooth muscle cells in primary culture. Modulation from contractile to synthetic phenotype.

    PubMed

    Thyberg, J; Nilsson, J; Palmberg, L; Sjölund, M

    1985-01-01

    Smooth muscle cells were isolated enzymatically from adult human arteries, grown in primary culture in medium containing 10% whole blood serum, and studied by transmission electron microscopy and [3H]thymidine autoradiography. In the intact arterial wall and directly after isolation, each smooth muscle cell had a nucleus with a wide peripheral zone of condensed chromatin and a cytoplasm dominated by myofilament bundles with associated dense bodies. After 1-2 days of culture, the cells had attached to the substrate and started to spread out. At the same time, a characteristic fine-structural modification took place. It included nuclear enlargement, dispersion of the chromatin and formation of large nucleoli. Moreover, myofilament bundles disappeared and an extensive rough endoplasmic reticulum and a large Golgi complex were organized in the cytoplasm. This morphological transformation of the cells was completed in 3-4 days. It was accompanied by initiation of DNA replication and mitosis. The observations demonstrate that adult human arterial smooth muscle cells, when cultivated in vitro, pass through a phenotypic modulation of the same type as arterial smooth muscle cells from experimental animals. This modulation gives the cells morphological and functional properties resembling those of the modified smooth muscle cells found in fibroproliferative lesions of atherosclerosis. Further studies of the regulation of smooth muscle phenotype and growth may provide important clues for a better understanding of the pathogenesis of atherosclerosis. PMID:3967287

  7. The Human Adult Skeletal Muscle Transcriptional Profile Reconstructed by a Novel Computational Approach

    PubMed Central

    Bortoluzzi, Stefania; d'Alessi, Fabio; Romualdi, Chiara; Danieli, Gian Antonio

    2000-01-01

    By applying a novel software tool, information on 4080 UniGene clusters was retrieved from three adult human skeletal muscle cDNA libraries, which were selected for being neither normalized nor subtracted. Reconstruction of a transcriptional profile of the corresponding tissue was attempted by a computational approach, classifying each transcript according to its level of expression. About 25% of the transcripts accounted for about 80% of the detected transcriptional activity, whereas most genes showed a low level of expression. This in silico transcriptional profile was then compared with data obtained by a SAGE study. A fairly good agreement between the two methods was observed. About 400 genes, highly expressed in skeletal muscle or putatively skeletal muscle-specific, may represent the minimal set of genes needed to determine the tissue specificity. These genes could be used as a convenient reference to monitor major changes in the transcriptional profile of adult human skeletal muscle in response to different physiological or pathological conditions, thus providing a framework for designing DNA microarrays and initiating biological studies. PMID:10720575

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

    PubMed

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

    2014-03-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic. PMID:24172073

  9. 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

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

    PubMed

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

    2015-09-01

    In this study, we examined the validity and reliability of the Revised Humane Caring Scale as used by adult patients in a tertiary hospital in Singapore. A three-phase descriptive quantitative study was conducted. In phase I, an expert panel of nurses and inpatients examined the content validity of the scale; phase II comprised a pilot study on 20 patients; and in phase III, a large-scale study on 235 patients was implemented to test the internal consistency of the scale. The results revealed that the content validity index of the scale ranged from 0.856 to 1, and the scale had a high inter-rater agreement kappa value of 0.940. Cronbach's alpha ranged from 0.798 to 0.877 in phase II, and from 0.579 to 0.760 in phase III, respectively. The Revised Humane Caring Scale revealed good content validity and an acceptable level of internal consistency. The scale is an acceptable measurement tool for evaluating adult patients' satisfaction during hospitalization. PMID:25783792

  11. 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

  12. BCRP protein levels do not differ regionally in adult human livers, but decline in the elderly.

    PubMed

    Riches, Zoe; Abanda, Ngu; Collier, Abby C

    2015-12-01

    The aim of this study was to characterize the ontogeny and variability of the BCRP (ABCG2) transporter in healthy human liver. Levels of BCRP mRNA and protein were determined with q-RT-PCR and western blot in a cohort of 87 human livers aged from 7 days to 87 years. A study of the regional expression of BCRP within adult livers was also performed in a nested cohort of 14 individuals with multiple samples per person collected from pre-selected sites. Levels of BCRP mRNA were not significantly different at any age, but protein levels for BCRP were lower in the elderly compared with adults (p < 0.001) and children (p < 0.05). The intra-liver levels of BCRP protein ranged approximately 6.5-fold and inter-liver BCRP protein varied 8.5-fold in the cohort. No differences in BCRP mRNA or protein were observed with sex or ethnicity, although higher levels of BCRP mRNA were observed in livers from overweight individuals (Body Mass Index ≥ 25-29.9) as compared to underweight or ideal weight individuals. There were no differences in the levels of BCRP mRNA or protein in different regions of the large lobe (n = 3 regions), small lobe (n = 3 regions), directly adjacent to the portal vein or directly adjacent to the common bile duct. This indicates that BCRP researchers can source tissue from all parts of the adult liver without artificial bias in their results. Lower BCRP protein expression in the elderly may be associated with compromised xeno- and endobiotic transport. PMID:26462791

  13. Body size and human energy requirements: Reduced mass-specific total energy expenditure in tall adults.

    PubMed

    Heymsfield, Steven B; Pietrobelli, Angelo

    2010-01-01

    Mammalian resting energy expenditure (REE) increases as approximately weight(0.75) while mass-specific REE scales as approximately weight(-0.25). Energy needs for replacing resting losses are thus less relative to weight (W) in large compared with small mammals, a classic observation with biological implications. Human weight scales as approximately height(2) and tall adults thus have a greater weight than their short counterparts. However, it remains unknown if mass-specific energy requirements are less in tall adults; allometric models linking total energy expenditure (TEE) and weight with height (H) are lacking. We tested the hypothesis that mass-specific energy requirements scale inversely to height in adults by evaluating TEE (doubly labeled water) data collected by the National Academy of Sciences. Activity energy expenditure (AEE) was calculated from TEE, REE (indirect calorimetry), and estimated diet-induced energy expenditure. Main analyses focused on nonmorbidly obese subjects < or =50 yrs of age with non-negative AEE values (n = 404), although results were directionally similar for all samples. Allometric models, including age as a covariate, revealed significantly (P < 0.05) greater REE, AEE, and TEE as a function of height (range H(1.5-1.7)) in both men and women. TEE/W scaled negatively to height ( approximately H(-0.7), P < 0.01) with predicted mass-specific TEE (kcal/kg/d) at +/-2 SD for US height lower in tall compared with short men (40.3 vs. 46.5) and women (37.7 vs. 42.7). REE/W also scaled negatively to height in men (P < 0.001) and women (P < 0.01). Results were generally robust across several different analytic strategies. These observations reveal previously unforeseen associations between human stature and energy requirements that have implications for modeling efforts and provide new links to mammalian biology as a whole. PMID:19856424

  14. Artificial Cervical Vertebra and Intervertebral Complex Replacement through the Anterior Approach in Animal Model: A Biomechanical and In Vivo Evaluation of a Successful Goat Model

    PubMed Central

    Qin, Jie; He, Xijing; Wang, Dong; Qi, Peng; Guo, Lei; Huang, Sihua; Cai, Xuan; Li, Haopeng; Wang, Rui

    2012-01-01

    This was an in vitro and in vivo study to develop a novel artificial cervical vertebra and intervertebral complex (ACVC) joint in a goat model to provide a new method for treating degenerative disc disease in the cervical spine. The objectives of this study were to test the safety, validity, and effectiveness of ACVC by goat model and to provide preclinical data for a clinical trial in humans in future. We designed the ACVC based on the radiological and anatomical data on goat and human cervical spines, established an animal model by implanting the ACVC into goat cervical spines in vitro prior to in vivo implantation through the anterior approach, and evaluated clinical, radiological, biomechanical parameters after implantation. The X-ray radiological data revealed similarities between goat and human intervertebral angles at the levels of C2-3, C3-4, and C4-5, and between goat and human lordosis angles at the levels of C3-4 and C4-5. In the in vivo implantation, the goats successfully endured the entire experimental procedure and recovered well after the surgery. The radiological results showed that there was no dislocation of the ACVC and that the ACVC successfully restored the intervertebral disc height after the surgery. The biomechanical data showed that there was no significant difference in range of motion (ROM) or neural zone (NZ) between the control group and the ACVC group in flexion-extension and lateral bending before or after the fatigue test. The ROM and NZ of the ACVC group were greater than those of the control group for rotation. In conclusion, the goat provides an excellent animal model for the biomechanical study of the cervical spine. The ACVC is able to provide instant stability after surgery and to preserve normal motion in the cervical spine. PMID:23300816

  15. 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.

  16. 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

  17. Application of the polynomial chaos expansion to approximate the homogenised response of the intervertebral disc.

    PubMed

    Karajan, N; Otto, D; Oladyshkin, S; Ehlers, W

    2014-10-01

    A possibility to simulate the mechanical behaviour of the human spine is given by modelling the stiffer structures, i.e. the vertebrae, as a discrete multi-body system (MBS), whereas the softer connecting tissue, i.e. the softer intervertebral discs (IVD), is represented in a continuum-mechanical sense using the finite-element method (FEM). From a modelling point of view, the mechanical behaviour of the IVD can be included into the MBS in two different ways. They can either be computed online in a so-called co-simulation of a MBS and a FEM or offline in a pre-computation step, where a representation of the discrete mechanical response of the IVD needs to be defined in terms of the applied degrees of freedom (DOF) of the MBS. For both methods, an appropriate homogenisation step needs to be applied to obtain the discrete mechanical response of the IVD, i.e. the resulting forces and moments. The goal of this paper was to present an efficient method to approximate the mechanical response of an IVD in an offline computation. In a previous paper (Karajan et al. in Biomech Model Mechanobiol 12(3):453-466, 2012), it was proven that a cubic polynomial for the homogenised forces and moments of the FE model is a suitable choice to approximate the purely elastic response as a coupled function of the DOF of the MBS. In this contribution, the polynomial chaos expansion (PCE) is applied to generate these high-dimensional polynomials. Following this, the main challenge is to determine suitable deformation states of the IVD for pre-computation, such that the polynomials can be constructed with high accuracy and low numerical cost. For the sake of a simple verification, the coupling method and the PCE are applied to the same simplified motion segment of the spine as was used in the previous paper, i.e. two cylindrical vertebrae and a cylindrical IVD in between. In a next step, the loading rates are included as variables in the polynomial response functions to account for a more

  18. Examining the relationship between childhood animal cruelty motives and recurrent adult violent crimes toward humans.

    PubMed

    Overton, Joshua C; Hensley, Christopher; Tallichet, Suzanne E

    2012-03-01

    Few researchers have studied the predictive ability of childhood animal cruelty motives as they are associated with later recurrent violence toward humans. Based on a sample of 180 inmates at one medium- and one maximum-security prison in a Southern state, the present study examines the relationship among several retrospectively identified motives (fun, out of anger, hate for the animal, and imitation) for childhood animal cruelty and the later commission of violent crimes (murder, rape, assault, and robbery) against humans. Almost two thirds of the inmates reported engaging in childhood animal cruelty for fun, whereas almost one fourth reported being motivated either out of anger or imitation. Only one fifth of the respondents reported they had committed acts of animal cruelty because they hated the animal. Regression analyses revealed that recurrent animal cruelty was the only statistically significant variable in the model. Respondents who had committed recurrent childhood animal cruelty were more likely to have had committed recurrent adult violence toward humans. None of the motives for committing childhood animal cruelty had any effect on later violence against humans. PMID:22007109

  19. 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

  20. Inhibition of ZEB1 expression induces redifferentiation of adult human β cells expanded in vitro

    PubMed Central

    Sintov, Elad; Nathan, Gili; Knoller, Sarah; Pasmanik-Chor, Metsada; Russ, Holger A.; Efrat, Shimon

    2015-01-01

    In-vitro expansion of functional adult human β-cells is an attractive approach for generating insulin-producing cells for transplantation. However, human islet cell expansion in culture results in loss of β-cell phenotype and epithelial-mesenchymal transition (EMT). This process activates expression of ZEB1 and ZEB2, two members of the zinc-finger homeobox family of E-cadherin repressors, which play key roles in EMT. Downregulation of ZEB1 using shRNA in expanded β-cell-derived (BCD) cells induced mesenchymal-epithelial transition (MET), β-cell gene expression, and proliferation attenuation. In addition, inhibition of ZEB1 expression potentiated redifferentiation induced by a combination of soluble factors, as judged by an improved response to glucose stimulation and a 3-fold increase in the fraction of C-peptide-positive cells to 60% of BCD cells. Furthermore, ZEB1 shRNA led to increased insulin secretion in cells transplanted in vivo. Our findings suggest that the effects of ZEB1 inhibition are mediated by attenuation of the miR-200c target genes SOX6 and SOX2. These findings, which were reproducible in cells derived from multiple human donors, emphasize the key role of ZEB1 in EMT in cultured BCD cells and support the value of ZEB1 inhibition for BCD cell redifferentiation and generation of functional human β-like cells for cell therapy of diabetes. PMID:26264186

  1. The Model Human Processor and the Older Adult: Parameter Estimation and Validation Within a Mobile Phone Task

    PubMed Central

    Jastrzembski, Tiffany S.; Charness, Neil

    2009-01-01

    The authors estimate weighted mean values for nine information processing parameters for older adults using the Card, Moran, and Newell (1983) Model Human Processor model. The authors validate a subset of these parameters by modeling two mobile phone tasks using two different phones and comparing model predictions to a sample of younger (N = 20; Mage = 20) and older (N = 20; Mage = 69) adults. Older adult models fit keystroke-level performance at the aggregate grain of analysis extremely well (R = 0.99) and produced equivalent fits to previously validated younger adult models. Critical path analyses highlighted points of poor design as a function of cognitive workload, hardware/software design, and user characteristics. The findings demonstrate that estimated older adult information processing parameters are valid for modeling purposes, can help designers understand age-related performance using existing interfaces, and may support the development of age-sensitive technologies. PMID:18194048

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

    PubMed

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

    2016-06-01

    The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts. Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone through electron microscopy and analysis of molecular markers. Periosteoclastic reversal cells show direct contacts with the osteoclasts and with the demineralized resorption debris. These early reversal cells show (1) ¾-collagen fragments typically generated by extracellular collagenases of the MMP family, (2) MMP-13 (collagenase-3) and (3) the endocytic collagen receptor uPARAP/Endo180. The prevalence of these markers was lower in the later reversal cells, which are located near the osteoid surfaces and morphologically resemble mature bone-forming osteoblasts. In conclusion, this study demonstrates that reversal cells colonizing bone surfaces right after resorption are osteoblast-lineage cells, and extends to adult human bone remodeling their role in rendering eroded surfaces osteogenic. PMID:26860863

  3. The Involvement of Protease Nexin-1 (PN1) in the Pathogenesis of Intervertebral Disc (IVD) Degeneration

    PubMed Central

    Wu, Xinghuo; Liu, Wei; Duan, Zhenfeng; Gao, Yong; Li, Shuai; Wang, Kun; Song, Yu; Shao, Zengwu; Yang, Shuhua; Yang, Cao

    2016-01-01

    Protease nexin-1 (PN-1) is a serine protease inhibitor belonging to the serpin superfamily. This study was undertaken to investigate the regulatory role of PN-1 in the pathogenesis of intervertebral disk (IVD) degeneration. Expression of PN-1 was detected in human IVD tissue of varying grades. Expression of both PN-1 mRNA and protein was significantly decreased in degenerated IVD, and the expression levels of PN-1 were correlated with the grade of disc degeneration. Moreover, a decrease in PN-1 expression in primary NP cells was confirmed. On induction by IL-1β, the expression of PN-1 in NP cells was decreased at day 7, 14, and 21, as shown by western blot analysis and immunofluorescence staining. PN-1 administration decreased IL-1β-induced MMPs and ADAMTS production and the loss of Agg and Col II in NP cell cultures through the ERK1/2/NF-kB signaling pathway. The changes in PN-1 expression are involved in the pathogenesis of IVD degeneration. Our findings indicate that PN-1 administration could antagonize IL-1β-induced MMPs and ADAMTS, potentially preventing degeneration of IVD tissue. This study also revealed new insights into the regulation of PN-1 expression via the ERK1/2/NF-kB signaling pathway and the role of PN-1 in the pathogenesis of IVD degeneration. PMID:27460424

  4. Intervertebral disc creep behavior assessment through an open source finite element solver.

    PubMed

    Castro, A P G; Wilson, W; Huyghe, J M; Ito, K; Alves, J L

    2014-01-01

    Degenerative Disc Disease (DDD) is one of the largest health problems faced worldwide, based on lost working time and associated costs. By means of this motivation, this work aims to evaluate a biomimetic Finite Element (FE) model of the Intervertebral Disc (IVD). Recent studies have emphasized the importance of an accurate biomechanical modeling of the IVD, as it is a highly complex multiphasic medium. Poroelastic models of the disc are mostly implemented in commercial finite element packages with limited access to the algorithms. Therefore, a novel poroelastic formulation implemented on a home-developed open source FE solver is briefly addressed throughout this paper. The combination of this formulation with biphasic osmotic swelling behavior is also taken into account. Numerical simulations were devoted to the analysis of the non-degenerated human lumbar IVD time-dependent behavior. The results of the tests performed for creep assessment were inside the scope of the experimental data, with a remarkable improvement of the numerical accuracy when compared with previously published results obtained with ABAQUS(®). In brief, this in-development open-source FE solver was validated with literature experimental data and aims to be a valuable tool to study the IVD biomechanics and DDD mechanisms. PMID:24210477

  5. Finite element simulation of an artificial intervertebral disk using fiber reinforced laminated composite model.

    PubMed

    Shahmohammadi, Mehrdad; Asgharzadeh Shirazi, Hadi; Karimi, Alireza; Navidbakhsh, Mahdi

    2014-10-01

    Degeneration of intervertebral disk (IVD) has been increased in recent years. The lumbar herniation can be cured using conservative and surgical procedures. Surgery is considered after failure of conservative treatment. Partial discectomy, fusion, and total disk replacement (TDR) are also common surgical treatments for degenerative disk disease. However, due to limitations and disadvantages of the current treatments, many studies have been carried out to approach the best design of mimicking natural disk. Recently, a new method of TDRs has been introduced using nature deformation of IVD by reinforced fibers of annulus fibrosis. Nonetheless, owing to limitations of experimental works on the human body, numerical studies of IVD may help to understand load transfer and biomechanical properties within the disks with reinforced fibers. In this study, a three-dimensional (3D) finite element model of the L2-L3 disk vertebrae unit with 12 vertical fibers embedded into annulus fibrosis was constructed. The IVD was subjected to compressive force, bending moment, and axial torsion. The most important parameters of disk failures were compared to that of experimental data. The results showed that the addition of reinforced fibers into the disk invokes a significant decrease of stress in the nucleus and annulus. The findings of this study may have implications not only for developing IVDs with reinforced fibers but also for the application of fiber reinforced IVD in orthopedics surgeries as a suitable implant. PMID:24981720

  6. Experimental studies on the effect of chymopapain on nerve root compression caused by intervertebral disk material.

    PubMed

    Krempen, J F; Minnig, D I; Smith, B S

    1975-01-01

    Chymopapain degrades the nucleus pulposus portion of the intervertebral disk of rabbits. The degradation is not grossly visible until 15 days post-injection. Depolymerization of the chondromucoprotein and decreases in the ability of a disk to imbibe fluid, is, in effect, a "chemical decompression" of the nucleur pulposus. The enzyme must come into direct contact with the chondromucoprotein complex of the disk material, and to a significant extent also must reach the area of disk material adjacent to the herniated annulus. Rapid depolymerization of the chondromucoprotein complex on a biomechanical level, and "decompression" of disk material on a biomechanical level can be correlated with relief of pain in all types of disk herniation in human beings. A primary biochemical change in the disk material would lead to a secondary decrease in inflammation if the change led to a "decompression" of the chondromucoprotein. Since the primary effect of chymopapain is on the chondromucoprotein of the disk, beneficial results would not be expected if nerve root compression is due to bony impingement or scar tissue following previous surgery. Chymopapain did not seem to possess any anti-inflammatory properties when bone was used as an irritant under a nerve root. However, this was technically difficult to evaluate and the possibility that chymopapain may also interfere with a chemical mediator of pain or interfere directly with an inflammatory reaction secondary to root compression can not be excluded. PMID:1126086

  7. 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

  8. A novel technique for the contrast-enhanced microCT imaging of murine intervertebral discs.

    PubMed

    Lin, Kevin H; Wu, Qi; Leib, Daniel J; Tang, Simon Y

    2016-10-01

    Disc degeneration is one of the leading factors that contribute to low back pain. Thus, the further understanding of the mechanisms contributing to degeneration of the intervertebral disc degeneration is critical for the development of therapies and strategies for treating low back pain. Rodent models are attractive for conducting mechanistic studies particularly because of the availability of genetically modified animals. However, current imaging technologies such as magnetic resonance imaging, do not have the ability to resolve spatial features at the tens- to single- micrometer scale. We propose here a contrast-enhanced microCT technique to conduct high-resolution imaging of the rodent intervertebral discs at 10µm spatial resolution. Based on the iodinated-hydrophilic contrast agent Ioversol, we are able to conduct high resolution imaging on rat and mouse intervertebral discs. Leveraging the hydrophilic characteristic of the contrast agent, we are able to discriminate the annulus fibrosus from the water-rich nucleus pulposus. Moreover, this technique allows for the quantitative measurement of disc morphologies and volumes, and we demonstrate the versatility of this technique on cultured live intervertebral discs. Coupled with our semi-automated segmentation technique, we are able to quantify the intervertebral disc volumes with a high degree of reproducibility. The contrast-enhanced microCT images were qualitatively and quantitatively indistinguishable from the traditional histological assessment of the same sample. Furthermore, stereological measures compared well between histology and microCT images. Taken together, the results reveal that rat and mouse intervertebral discs can be imaged longitudinally in vitro at high resolutions, with no adverse effects on viability and features of the intervertebral disc. PMID:27341292

  9. Investigation of the intervertebral disc and fused joint dynamics through experimental modal analysis and the receptance coupling method.

    PubMed

    Malekian, M; Trieu, D; Owoc, J S; Park, S S; Hunter, C J

    2010-04-01

    Identification of intervertebral disc (IVD) dynamics is important in understanding the spine mechanism and behavior. This paper experimentally identifies the dynamics of the bovine caudal IVD using experimental modal analysis and the inverse receptance coupling method. Experimental modal analysis was performed on free-free mounted bovine caudal vertebrae joined by an IVD and a fused IVD joint. Shear, rotational, and axial dynamics of the joints are identified by curve fitting of the frequency response functions, and identifying the damping ratio, stiffness, and modal frequency in each axis. The identified dynamics are compared with the IVD joints with and without fusion. Results provide important insight into IVD dynamics and fused IVD dynamics. This method can be extended to identify human IVD joint dynamics. PMID:20387967

  10. 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

  11. CLINICAL AND MAGNETIC RESONANCE IMAGING CHARACTERISTICS OF THORACOLUMBAR INTERVERTEBRAL DISK EXTRUSIONS AND PROTRUSIONS IN LARGE BREED DOGS.

    PubMed

    Gomes, Sergio A; Volk, Holger A; Packer, Rowena Ma; Kenny, Patrick J; Beltran, Elsa; De Decker, Steven

    2016-07-01

    Treatment recommendations differ for dogs with intervertebral disk extrusion vs. intervertebral disk protrusion. The aim of this retrospective, cross-sectional study was to determine whether clinical and magnetic resonance imaging (MRI) variables could be used to predict a diagnosis of thoracolumbar intervertebral disk extrusion or protrusion in dogs. Dogs were included if they were large breed dogs, had an MRI study of the thoracolumbar or lumbar vertebral column, had undergone spinal surgery, and had the type of intervertebral disk herniation (intervertebral disk extrusion or protrusion) clearly stated in surgical reports. A veterinary neurologist unaware of surgical findings reviewed MRI studies and recorded number, location, degree of degeneration and morphology of intervertebral disks, presence of nuclear clefts, disk space narrowing, extent, localization and lateralization of herniated disk material, degree of spinal cord compression, intraparenchymal intensity changes, spondylosis deformans, spinal cord swelling, spinal cord atrophy, vertebral endplate changes, and presence of extradural hemorrhage. Ninety-five dogs were included in the sample. Multivariable statistical models indicated that longer duration of clinical signs (P = 0.01), midline instead of lateralized disk herniation (P = 0.007), and partial instead of complete disk degeneration (P = 0.01) were associated with a diagnosis of intervertebral disk protrusion. The presence of a single intervertebral herniation (P = 0.023) and dispersed intervertebral disk material not confined to the disk space (P = 0.06) made a diagnosis of intervertebral disk extrusion more likely. Findings from this study identified one clinical and four MRI variables that could potentially facilitate differentiating intervertebral disk extrusions from protrusions in dogs. PMID:27038182

  12. Extensive Neuronal Differentiation of Human Neural Stem Cell Grafts in Adult Rat Spinal Cord

    PubMed Central

    Yan, Jun; Xu, Leyan; Welsh, Annie M; Hatfield, Glen; Hazel, Thomas; Johe, Karl; Koliatsos, Vassilis E

    2007-01-01

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

  13. 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

  14. High mechanical strain of primary intervertebral disc cells promotes secretion of inflammatory factors associated with disc degeneration and pain

    PubMed Central

    2014-01-01

    Introduction Excessive mechanical loading of intervertebral discs (IVDs) is thought to alter matrix properties and influence disc cell metabolism, contributing to degenerative disc disease and development of discogenic pain. However, little is known about how mechanical strain induces these changes. This study investigated the cellular and molecular changes as well as which inflammatory receptors and cytokines were upregulated in human intervertebral disc cells exposed to high mechanical strain (HMS) at low frequency. The impact of these metabolic changes on neuronal differentiation was also explored to determine a role in the development of disc degeneration and discogenic pain. Methods Isolated human annulus fibrosus (AF) and nucleus pulposus (NP) cells were exposed to HMS (20% cyclical stretch at 0.001 Hz) on high-extension silicone rubber dishes coupled to a mechanical stretching apparatus and compared to static control cultures. Gene expression of Toll-like receptors (TLRs), neuronal growth factor (NGF) and tumour necrosis factor α (TNFα) was assessed. Collected conditioned media were analysed for cytokine content and applied to rat pheocromocytoma PC12 cells for neuronal differentiation assessment. Results HMS caused upregulation of TLR2, TLR4, NGF and TNFα gene expression in IVD cells. Medium from HMS cultures contained elevated levels of growth-related oncogene, interleukin 6 (IL-6), IL-8, IL-15, monocyte chemoattractant protein 1 (MCP-1), MCP-3, monokine induced by γ interferon, transforming growth factor β1, TNFα and NGF. Exposure of PC12 cells to HMS-conditioned media resulted in both increased neurite sprouting and cell death. Conclusions HMS culture of IVD cells in vitro drives cytokine and inflammatory responses associated with degenerative disc disease and low-back pain. This study provides evidence for a direct link between cellular strain, secretory factors, neoinnervation and potential degeneration and discogenic pain in vivo. PMID:24457003

  15. Isolation of high-purity myenteric plexus from adult human and mouse gastrointestinal tract

    PubMed Central

    Grundmann, David; Klotz, Markus; Rabe, Holger; Glanemann, Matthias; Schäfer, Karl-Herbert

    2015-01-01

    The enteric nervous system (ENS) orchestrates a broad range of important gastrointestinal functions such as intestinal motility and gastric secretion. The ENS can be affected by environmental factors, diet and disease. Changes due to these alterations are often hard to evaluate in detail when whole gut samples are used. Analyses based on pure ENS tissue can more effectively reflect the ongoing changes during pathological processes. Here, we present an optimized approach for the isolation of pure myenteric plexus (MP) from adult mouse and human. To do so, muscle tissue was individually digested with a purified collagenase. After incubation and a gentle mechanical disruption step, MP networks could be collected with anatomical integrity. These tissues could be stored and used either for immediate genomic, proteomic or in vitro approaches, and enteric neurospheres could be generated and differentiated. In a pilot experiment, the influence of bacterial lipopolysaccharide on human MP was analyzed using 2-dimensional gel electrophoresis. The method also allows investigation of factors that are secreted by myenteric tissue in vitro. The isolation of pure MP in large amounts allows new analytical approaches that can provide a new perspective in evaluating changes of the ENS in experimental models, human disease and aging. PMID:25791532

  16. 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

  17. Adipogenic potential in human mesenchymal stem cells strictly depends on adult or foetal tissue harvest.

    PubMed

    Ragni, Enrico; Viganò, Mariele; Parazzi, Valentina; Montemurro, Tiziana; Montelatici, Elisa; Lavazza, Cristiana; Budelli, Silvia; Vecchini, Alba; Rebulla, Paolo; Giordano, Rosaria; Lazzari, Lorenza

    2013-11-01

    Cell-based therapies promise important developments for regenerative medicine purposes. Adipose tissue and the adipogenic process has become central to an increasing number of translational efforts in addition to plastic and reconstructive surgical applications. In recent experimental clinical trials, human mesenchymal stem cells (MSC) have been proven to be well tolerated because of their low immunoreactivity. MSC are multipotent cells found among mature cells in different tissues and organs with the potentiality to differentiate in many cell types, including osteocytes, chondrocytes and adipocytes, thus being a suitable cell source for tissue engineering strategies. We compared the adipogenic potential of MSC originated from two adult sources as fat pads and bone marrow, and from four foetal sources as umbilical cord blood, Wharton's jelly, amniotic fluid and preterm umbilical cord perivascular cells. Surprisingly, adult MSC displayed higher differentiation capacities confirmed by gene expression analysis on a selected panel of adipogenesis-related genes. Further, an in-depth molecular analysis highlighted the early and vigorous activation of the PPARγ transcription factor-cascade in adipose-derived MSC that resulted to be both delayed and reduced in foetal MSC accounting for their lack of adipogenic potential. Thus, MSC show a different degree of phenotypic plasticity depending on the source tissue, that should be taken into consideration for the selection of the most appropriate MSC type for specific tissue regeneration purposes. PMID:23942228

  18. 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

  19. Human-figure drawing and memory functioning across the adult life span.

    PubMed

    Ericsson, K; Winblad, B; Nilsson, L -G.

    2001-03-01

    The main objective was to evaluate changes in the ability to draw the human figure (HFD) across adult life span and to relate these changes to those known to exist in memory function. Healthy adults (1000) from each of 10 five-year cohorts between 35 and 80 years were recruited randomly from a population in northern Sweden. Each participant was administered a health examination including cognitive testing and a drawing test, and an extensive examination of memory functions. For the drawing variables HFDarch and HFDtot, there is a steady decrease in episodic memory with poor drawers performing at a lower level. For semantic memory up to 65 years of age, there is no difference in performance, but thereafter a decrease. Good drawers show a better memory performance than poor drawers. For priming data for both HFDarch and HFDtot, there seems to be an interaction between age and drawing, such that poor drawers perform at a lower level for the two oldest groups but not for the youngest group. The HFDess is a valuable instrument and can support clinical evaluation as a screening for cognitive decline. The reduction of essential body details was strongly related to dementia progression, and thus as good a predictor of cognitive decline as episodic memory performance. The reduced capacity to perform a complex HFD declines with age and is most pronounced in the oldest age groups. PMID:11313105

  20. 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

  1. 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

  2. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain

    PubMed Central

    Richards, Alexander L; Jones, Lesley; Moskvina, Valentina; Kirov, George; Gejman, Pablo V; Levinson, Douglas F; Sanders, Alan R; Purcell, Shaun; Visscher, Peter M; Craddock, Nick; Owen, Michael J; Holmans, Peter; O’Donovan, Michael C

    2016-01-01

    It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. Since only a small proportion of the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and that schizophrenia risk alleles are enriched among SNPs selected for marginal evidence for association (p<0.5) from genome wide association studies (GWAS). It follows that if schizophrenia susceptibility alleles are enriched for those that affect gene expression, those marginally associated SNPs which are also eQTLs should carry more true association signals compared with SNPs which are not. To test this, we identified marginally associated (p<0.5) SNPs from two of the largest available schizophrenia GWAS datasets. We assigned eQTL status to those SNPs based upon an eQTL dataset derived from adult human brain. Using the polygenic score method of analysis reported by the ISC, we observed and replicated the observation that higher probability cis-eQTLs predicted schizophrenia better than those with a lower probability for being a cis-eQTL. Our data support the hypothesis that alleles conferring risk of schizophrenia are enriched among those that affect gene expression. Moreover, our data show that notwithstanding the likely developmental origin of schizophrenia, studies of adult brain tissue can in principle allow relevant susceptibility eQTLs to be identified. PMID:21339752

  3. Experimental Infection of Adults With Recombinant Wild-Type Human Metapneumovirus

    PubMed Central

    Talaat, Kawsar R.; Karron, Ruth A.; Thumar, Bhagvanji; McMahon, Bridget A.; Schmidt, Alexander C.; Collins, Peter L.; Buchholz, Ursula J.

    2013-01-01

    Background. Human metapneumovirus (HMPV) causes lower respiratory tract infections in young children. rHMPV-SHs is a recombinant HMPV (rHMPV) based on a biologically derived wild-type HMPV strain. We characterized its infectivity and immunogenicity in healthy adults to determine whether it would be suitable for use as the parent virus for the development of live attenuated rHMPV vaccines. Methods. Twenty-one healthy adults were inoculated intranasally with 106 plaque-forming units of rHMPV-SHs. Respiratory symptoms and shedding of challenge virus were assessed. Neutralizing antibody responses, serum immunoglobulin G and A, and nasal wash specimen immunoglobulin A antibody responses to the HMPV F protein were also measured. Induction of nasal cytokines was assessed with electrochemiluminescence assays. Results. Nine subjects (43%) were infected with challenge virus as determined by virus detection and/or ≥4-fold rise in serum antibody titers. Peak viral shedding occurred on days 7–9 after infection. Four weeks after inoculation, 35% of subjects had any antibody response. Six of 9 infected subjects had respiratory symptoms, and 3 had headache after inoculation. Cytokine patterns differed considerably between subjects with similar illness severity and viral shedding. Conclusions. The rHMPV-SHs virus is infectious and is a suitable parent virus for development of live-attenuated HMPV vaccine candidates. Clinical Trials Registration. NCT01109329. PMID:23908489

  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. Localization of cyclooxygenase-1 and -2 in adult and fetal human kidney: implication for renal function.

    PubMed

    Kömhoff, M; Grone, H J; Klein, T; Seyberth, H W; Nüsing, R M

    1997-04-01

    To gain insight into the roles of cyclooxygenase (COX)-1 and -2 in human kidney, we analyzed their expressions and localization in adult and fetal normal kidney. Immunohistology showed expression of COX-1 in collecting duct cells, interstitial cells, endothelial cells, and smooth muscle cells of pre- and postglomerular vessels. Expression of COX-2 immunoreactive protein could be localized to endothelial and smooth muscle cells of arteries and veins and intraglomerularly in podocytes. In contrast to the rat, COX isoforms were not detected in the macula densa. These data were confirmed by in situ mRNA analysis using digoxigenin-labeled riboprobes. In fetal kidney, COX-1 was primarily expressed in podocytes and collecting duct cells. Expression levels of COX-1 in both cell types increased markedly from subcapsular to juxtamedullary cortex. Glomerular staining of COX-2 was detectable in podocytes only at the endstage of renal development. In summary, the localization of COX-2 suggests that this enzyme may be primarily involved in the regulation of renal perfusion and glomerular hemodynamics. The expression of COX-1 in podocytes of the fetal kidney and its absence in adult glomeruli suggests that this isoform might be involved in glomerulogenesis. PMID:9140046

  6. Pharmacological Induction of Human Fetal Globin Gene in Hydroxyurea-Resistant Primary Adult Erythroid Cells.

    PubMed

    Chou, Yu-Chi; Chen, Ruei-Lin; Lai, Zheng-Sheng; Song, Jen-Shin; Chao, Yu-Sheng; Shen, Che-Kun James

    2015-07-01

    Pharmacological induction of the fetal γ globin gene and the consequent formation of HbF (α2/γ2) in adult erythroid cells are one feasible therapeutic strategy for sickle cell disease (SCD) and severe β-thalassemias. Hydroxyurea (HU) is the current drug of choice for SCD, but serious side effects limit its clinical use. Moreover, 30 to 50% of patients are irresponsive to HU treatment. We have used high-throughput screening to identify benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one and its derivatives (compounds I to VI) as potent γ globin inducers. Of the compounds, I to V exert superior γ globin induction and have better therapeutic potential than HU, likely because of their activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway and modulation of expression levels and/or chromosome binding of γ globin gene regulators, including BCL11A, and chromatin structure over the γ globin promoter. Unlike sodium butyrate (NaB), the global levels of acetylated histones H3 and H4 are not changed by compound II treatment. Remarkably, compound II induces the γ globin gene in HU-resistant primary human adult erythroid cells, the p38 signaling pathway of which appears to be irresponsive to HU and NaB as well as compound II. This study provides a new framework for the development of new and superior compounds for treating SCD and severe β-thalassemias. PMID:25986606

  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. Large-scale remapping of visual cortex is absent in adult humans with macular degeneration.

    PubMed

    Baseler, Heidi A; Gouws, André; Haak, Koen V; Racey, Christopher; Crossland, Michael D; Tufail, Adnan; Rubin, Gary S; Cornelissen, Frans W; Morland, Antony B

    2011-05-01

    The occipital lobe contains retinotopic representations of the visual field. The representation of the central retina in early visual areas (V1-3) is found at the occipital pole. When the central retina is lesioned in both eyes by macular degeneration, this region of visual cortex at the occipital pole is accordingly deprived of input. However, even when such lesions occur in adulthood, some visually driven activity in and around the occipital pole can be observed. It has been suggested that this activity is a result of remapping of this area so that it now responds to inputs from intact, peripheral retina. We evaluated whether or not remapping of visual cortex underlies this activity. Our functional magnetic resonance imaging results provide no evidence of remapping, questioning the contemporary view that early visual areas of the adult human brain have the capacity to reorganize extensively. PMID:21441924

  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. PMID:25070322

  10. STUDIES OF MOLECULAR CHANGES IN INTERVERTEBRAL DISC DEGENERATION IN ANIMAL MODEL

    PubMed Central

    de Campos, Marcelo Ferraz; de Oliveira, Cintia Pereira; Neff, Charles Benjamin; Correa, Olga Maria de Toledo; Pinhal, Maria Aparecida Silva; Rodrigues, Luciano Miller Reis

    2016-01-01

    ABSTRACT Objective: To evaluate the structural and molecular changes in the extracellular matrix (ECM) during the process of intervertebral disc degeneration, using animal model. Methods: Wistar rats underwent intervertebral disc degeneration through 20-gauge needle puncture, and 360° rotation applied for 30 sec, representing the degenerated group, while control group was not submitted to this procedure. Histological parameters and expression of extracellular matrix molecules were evaluated in the 15th and 28th days after degenerative induction. Results: Fifteen days after the induction of intervertebral disc degeneration, significant changes were observed, such as reduction in the expression metalloprotease-9 (MMP9) and interleukins (IL-6 and IL-10). There was a significant increase in the expression of vascular endothelial growth factor (VEGF) and caspase-3. However, different alterations in the ECM were observed at 28 days, the level of collagen I, metalloprotease-2 (MMP2) and caspase-3 were enhanced. Furthermore, expression of heparanase isoforms (HPSE1 and HPSE2) mRNA were increased in the degenerative intervertebral disc. Conclusion: The different profiles of ECM molecules observed during the intervertebral disc degeneration suggest that molecular processes such as ECM remodeling, neovascularization, apoptosis and inflammation occur. Experimental Study. PMID:26997908

  11. Neuroanatomic and pathophysiologic aspects of intervertebral disc disease in the dog.

    PubMed

    Thacher, C

    1989-01-01

    A sound understanding of anatomy and the pathophysiology of disease is important in all branches of medicine, but nowhere is it more critical to success than in the medical and surgical management of intervertebral disc disease. Due to the remote location and unforgiving nature of the spinal cord, the veterinary surgeon must possess an intimate working knowledge of the surgical anatomy of the vertebrae, ligaments and joints of the spine, intervertebral discs, spinal cord, and spinal nerves. In addition, proper localization of spinal cord lesions during the neurological evaluation requires awareness of the functional neuroanatomy of the upper and lower motor motor neurons, the sensory systems and tracts, and the reflex arcs. Knowledge of the pathophysiology the intervertebral disc degeneration and the response of the spinal cord to disc extrusions are also important in the overall understanding of the disease and enhances proper decision making for its management. This chapter reviews the portions of the gross and functional neuroanatomy and the pathophysiology of the intervertebral disc and the spinal cord that are pertinent to the dog with intervertebral disc disease. Emphasis is placed on concepts that are critical for the veterinary surgeon who is involved in the surgical management of the disc patient. PMID:2520119

  12. Intervertebral and intravertebral ratios in Doberman pinscher dogs with cervical spondylomyelopathy.

    PubMed

    da Costa, Ronaldo C; Johnson, Jacqueline A

    2012-01-01

    No screening method is currently available to differentiate dogs with and without cervical spondylomyelopathy. Intravertebral and intervertebral ratios are used in horses and can predict cervical vertebral malformation. Intervertebral ratios could be a useful screening method for canine cervical spondylomyelopathy. Our purpose was to compare cervical intervertebral and intravertebral ratios in normal vs. affected Doberman pinschers. Forty dogs were studied, 27 affected and 13 normal. Cervical radiographs were obtained in all dogs. The minimum intra- and intervertebral sagittal diameter ratios were established for each cervical vertebrae and disc space from C(2) to C(7) . Comparisons were made between groups and specific vertebral body and disc levels. The effect of gender, age, and method of measurement (analog or digital radiographs) was also studied. There was no difference in either the intervertebral or intravertebral ratio between normal vs. affected dogs. The ratios decreased progressively along the cervical spine, being smallest at C(6) -C(7) and C(7) , respectively. Age, gender, and method of measurement had a significant influence on both inter- and intravertebral ratios, with smaller ratios seen as dogs aged and in male dogs. Based on our results, inter- or intravertebral ratios have no value to distinguish between clinically normal Doberman pinschers and Doberman pinschers with cervical spondylomyelopathy. PMID:22702434

  13. Clarifying the nomenclature of intervertebral disc degeneration and displacement: from bench to bedside

    PubMed Central

    Wang, Hai-Qiang; Samartzis, Dino

    2014-01-01

    As a significant determinant of low back pain, intervertebral disc degeneration (IDD) has attracted more and more attention of both investigators and physicians. Disc herniation, termed as intervertebral disc displacement, is amongst the most prevalent spinal diseases closely linked with IDD. Due to the same origins and similar pathophysiology, the ambiguity regarding the similarity and difference of IDD and intervertebral disc displacement thus remains. The aim of this study was to clarify the nomenclature of IDD and disc herniation in terms of molecular etiology, pathophysiology, nature history and clinical outcomes. Collectively, IDD is a type of multifaceted, progressive spinal disease with or without clinical symptoms as back pain, characterized by extracellular matrix and the integrity of NP and AF lost, fissures formation. Disc herniation (termed as intervertebral disc displacement) is a type of spinal disease based on IDD or not, with local pain and/or sciatica due to mechanical compression and autoimmune cascades upon the corresponding nerve roots. Clarifying the nomenclature of intervertebral disc degeneration and displacement has important implications both for investigators and for physicians. PMID:24817926

  14. 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

  15. 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

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

    PubMed

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

    2015-11-01

    In this review, a companion piece to our recent examination of choroid plexus (CP), the organ that secretes the cerebrospinal fluid (CSF), we focus on recent information in the context of reliable older data concerning the composition and functions of adult human CSF. To accomplish this, we define CSF, examine the methodology employed in studying the CSF focusing on ideal or near ideal experiments and discuss the pros and cons of several widely used analogical descriptions of the CSF including: the CSF as the "third circulation," the CSF as a "nourishing liquor," the similarities of the CSF/choroid plexus to the glomerular filtrate/kidney and finally the CSF circulation as part of the "glymphatic system." We also consider the close interrelationship between the CSF and extracellular space of brain through gap junctions and the paucity of data suggesting that the cerebral capillaries secrete a CSF-like fluid. Recently human CSF has been shown to be in dynamic flux with heart-beat, posture and especially respiration. Functionally, the CSF provides buoyancy, nourishment (e.g., vitamins) and endogenous waste product removal for the brain by bulk flow into the venous (arachnoid villi and nerve roots) and lymphatic (nasal) systems, and by carrier-mediated reabsorptive transport systems in CP. The CSF also presents many exogenous compounds to CP for metabolism or removal, indirectly cleansing the extracellular space of brain (e.g., of xenobiotics like penicillin). The CSF also carries hormones (e.g., leptin) from blood via CP or synthesized in CP (e.g., IGF-2) to the brain. In summary the CP/CSF, the third circulation, performs many functions comparable to the kidney including nourishing the brain and contributing to a stable internal milieu for the brain. These tasks are essential to normal adult brain functioning. PMID:26247808

  17. Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain.

    PubMed

    Forsyth, Jennifer K; Bachman, Peter; Mathalon, Daniel H; Roach, Brian J; Asarnow, Robert F

    2015-12-15

    Experience-dependent plasticity is a fundamental property of the brain. It is critical for everyday function, is impaired in a range of neurological and psychiatric disorders, and frequently depends on long-term potentiation (LTP). Preclinical studies suggest that augmenting N-methyl-d-aspartate receptor (NMDAR) signaling may promote experience-dependent plasticity; however, a lack of noninvasive methods has limited our ability to test this idea in humans until recently. We examined the effects of enhancing NMDAR signaling using d-cycloserine (DCS) on a recently developed LTP EEG paradigm that uses high-frequency visual stimulation (HFvS) to induce neural potentiation in visual cortex neurons, as well as on three cognitive tasks: a weather prediction task (WPT), an information integration task (IIT), and a n-back task. The WPT and IIT are learning tasks that require practice with feedback to reach optimal performance. The n-back assesses working memory. Healthy adults were randomized to receive DCS (100 mg; n = 32) or placebo (n = 33); groups were similar in IQ and demographic characteristics. Participants who received DCS showed enhanced potentiation of neural responses following repetitive HFvS, as well as enhanced performance on the WPT and IIT. Groups did not differ on the n-back. Augmenting NMDAR signaling using DCS therefore enhanced activity-dependent plasticity in human adults, as demonstrated by lasting enhancement of neural potentiation following repetitive HFvS and accelerated acquisition of two learning tasks. Results highlight the utility of considering cellular mechanisms underlying distinct cognitive functions when investigating potential cognitive enhancers. PMID:26621715

  18. Alpha actin isoforms expression in human and rat adult cardiac conduction system.

    PubMed

    Orlandi, Augusto; Hao, Hiroyuki; Ferlosio, Amedeo; Clément, Sophie; Hirota, Seiichi; Spagnoli, Luigi Giusto; Gabbiani, Giulio; Chaponnier, Christine

    2009-04-01

    In the adult heart, cardiac muscle comprises the working myocardium and the conduction system (CS). The latter includes the sinoatrial node (SAN), the internodal tract or bundle (IB), the atrioventricular node (AVN), the atrioventricular bundle (AVB), the bundle branches (BB) and the peripheral Purkinje fibers (PF). Most of the information concerning the phenotypic features of CS tissue derives from the characterization of avian and rodent developing hearts; data concerning the expression of actin isoforms in adult CS cardiomyocytes are scarce. Using specific antibodies, we investigated the distribution of alpha-skeletal (alpha-SKA), alpha-cardiac (alpha-CA), alpha-smooth muscle (alpha-SMA) actin isoforms and other muscle-typical proteins in the CS of human and rat hearts at different ages. SAN and IB cardiomyocytes were characterized by the presence of alpha-SMA, alpha-CA, calponin and caldesmon, whereas alpha-SKA and vimentin were absent. Double immunofluorescence demonstrated the co-localisation of alpha-SMA and alpha-CA in I-bands of SAN cardiomyocytes. AVN, AVB, BB and PF cardiomyocytes were alpha-SMA, calponin, caldesmon and vimentin negative, and alpha-CA and alpha-SKA positive. No substantial differences in actin isoform distribution were observed in human and rat hearts, except for the presence of isolated subendocardial alpha-SMA positive cardiomyocytes co-expressing alpha-CA in the ventricular septum of the rat. Aging did not influence CS cardiomyocyte actin isoform expression profile. These findings support the concept that cardiomyocytes of SAN retain the phenotype of a developing myogenic cell throughout the entire life span. PMID:19281784

  19. Technological Overview of iPS Induction from Human Adult Somatic Cells

    PubMed Central

    Bayart, Emilie; Cohen-Haguenauer, Odile

    2013-01-01

    The unlimited proliferation capacity of embryonic stem cells (ESCs) combined with their pluripotent differentiation potential in various lineages raised great interest in both the scientific community and the public at large with hope for future prospects of regenerative medicine. However, since ESCs are derived from human embryos, their use is associated with significant ethical issues preventing broad studies and therapeutic applications. To get around this bottleneck, Takahashi and Yamanaka have recently achieved the conversion of adult somatic cells into ES-like cells via the forced expression of four transcription factors: Oct3/4, Sox2, Klf4 and c-Myc. This first demonstration attracted public attention and opened a new field of stem cells research with both cognitive – such as disease modeling - and therapeutic prospects. This pioneer work just received the 2012 Nobel Prize in Physiology or Medicine. Many methods have been reported since 2006, for the generation of induced pluripotent stem (iPS) cells. Most strategies currently under use are based on gene delivery via gamma-retroviral or lentiviral vectors; some experiments have also been successful using plasmids or transposons-based systems and few with adenovirus. However, most experiments involve integration in the host cell genome with an identified risk for insertional mutagenesis and oncogenic transformation. To circumvent such risks which are deemed incompatible with therapeutic prospects, significant progress has been made with transgene-free reprogramming methods based on e.g.: sendaï virus or direct mRNA or protein delivery to achieve conversion of adult cells into iPS. In this review we aim to cover current knowledge relating to both delivery systems and combinations of inducing factors including chemicals which are used to generate human iPS cells. Finally, genetic instability resulting from the reprogramming process is also being considered as a safety bottleneck for future clinical

  20. Technological overview of iPS induction from human adult somatic cells.

    PubMed

    Bayart, Emilie; Cohen-Haguenauer, Odile

    2013-04-01

    The unlimited proliferation capacity of embryonic stem cells (ESCs) combined with their pluripotent differentiation potential in various lineages raised great interest in both the scientific community and the public at large with hope for future prospects of regenerative medicine. However, since ESCs are derived from human embryos, their use is associated with significant ethical issues preventing broad studies and therapeutic applications. To get around this bottleneck, Takahashi and Yamanaka have recently achieved the conversion of adult somatic cells into ES-like cells via the forced expression of four transcription factors: Oct3/4, Sox2, Klf4 and c-Myc. This first demonstration attracted public attention and opened a new field of stem cells research with both cognitive - such as disease modeling - and therapeutic prospects. This pioneer work just received the 2012 Nobel Prize in Physiology or Medicine. Many methods have been reported since 2006, for the generation of induced pluripotent stem (iPS) cells. Most strategies currently under use are based on gene delivery via gamma-retroviral or lentiviral vectors; some experiments have also been successful using plasmids or transposons- based systems and few with adenovirus. However, most experiments involve integration in the host cell genome with an identified risk for insertional mutagenesis and oncogenic transformation. To circumvent such risks which are deemed incompatible with therapeutic prospects, significant progress has been made with transgene-free reprogramming methods based on e.g.: sendai virus or direct mRNA or protein delivery to achieve conversion of adult cells into iPS. In this review we aim to cover current knowledge relating to both delivery systems and combinations of inducing factors including chemicals which are used to generate human iPS cells. Finally, genetic instability resulting from the reprogramming process is also being considered as a safety bottleneck for future clinical translation

  1. Alloproliferation of purified CD4+ T cells to adult human heart endothelial cells, and study of second-signal requirements.

    PubMed Central

    McDouall, R M; Page, C S; Hafizi, S; Yacoub, M H; Rose, M L

    1996-01-01

    Human endothelial cells have been shown to be capable of causing direct allostimulation of T cells. However, the majority of immunological studies of human endothelial cells have been performed on cells of fetal origin. Here we use endothelial cells isolated from the adult human heart, both large vessel (coronary artery, pulmonary artery and aorta) and also microvascular. We have examined the ability of all these endothelial cells to cause direct allostimulation of T cells, and show that purified CD4+ T cells can proliferate in response to adult human heart endothelial cells, the response being dependent on pretreatment of the endothelial cells with interferon-gamma (IFN-gamma) and inhibited by anti-HLA-DR monoclonal antibody. The proliferative responses of CD8+ T cells to adult but not fetal endothelial cells was inconsistent and weak. Proliferative responses were not blocked by CTLA4-Ig, which inhibits T-cell responses to "classical' antigen-presenting cells (APC), but > 50% inhibition was achieved with monoclonal antibody to lymphocyte function-associated antigen-3 (LFA-3). These results show that adult human cardiovascular endothelial cells are capable of causing allostimulation of resting CD4+ T cells, using a different second signal to classical APC. In view of these findings endothelial cells should be considered as APC following solid organ transplantation. PMID:8943718

  2. Substructuring and poroelastic modelling of the intervertebral disc.

    PubMed

    Swider, P; Pédrono, A; Ambard, D; Accadbled, F; Sales de Gauzy, J

    2010-05-01

    We proposed a substructure technique to predict the time-dependant response of biological tissue within the framework of a finite element resolution. Theoretical considerations in poroelasticity preceded the calculation of the sub-structured poroelastic matrix. The transient response was obtained using an exponential fitting method. We computed the creep response of an MRI 3D reconstructed L(5)-S(1) intervertebral disc of a scoliotic spine. The FE model was reduced from 10,000 degrees of freedom for the full 3D disc to only 40 degrees of freedom for the sub-structured model defined by 10 nodes attached to junction nodes located on both lower and upper surfaces of the disc. Comparisons of displacement fields were made between the full poroelastic FE model and the sub-structured model in three different loading conditions: compression, offset compression and torsion. Discrepancies in displacement were lower than 10% for the first time steps when time-dependant events were significant. The substructuring technique provided an exact solution in quasi-static behavior after pressure relaxation. Couplings between vertical and transversal displacements predicted by the reference FE model were well stored by the sub-structured model despite the drastic reduction of degrees of freedom. Finally, we demonstrated that substructuring was very efficient to reduce the size of numerical models while respecting the time-dependant behavior of the structure. This result highlighted the potential interest of substructure techniques in large-scale models of musculoskeletal structures. PMID:20170917

  3. Minimally invasive photopolymerization in intervertebral disc tissue cavities

    NASA Astrophysics Data System (ADS)

    Schmocker, Andreas M.; Khoushabi, Azadeh; Gantenbein-Ritter, Benjamin; Chan, Samantha; Bonél, Harald Marcel; Bourban, Pierre-Etienne; Mânson, Jan Anders; Schizas, Constantin; Pioletti, Dominique; Moser, Christophe

    2014-03-01

    Photopolymerized hydrogels are commonly used for a broad range of biomedical applications. As long as the polymer volume is accessible, gels can easily be hardened using light illumination. However, in clinics, especially for minimally invasive surgery, it becomes highly challenging to control photopolymerization. The ratios between polymerizationvolume and radiating-surface-area are several orders of magnitude higher than for ex-vivo settings. Also tissue scattering occurs and influences the reaction. We developed a Monte Carlo model for photopolymerization, which takes into account the solid/liquid phase changes, moving solid/liquid-boundaries and refraction on these boundaries as well as tissue scattering in arbitrarily designable tissue cavities. The model provides a tool to tailor both the light probe and the scattering/absorption properties of the photopolymer for applications such as medical implants or tissue replacements. Based on the simulations, we have previously shown that by adding scattering additives to the liquid monomer, the photopolymerized volume was considerably increased. In this study, we have used bovine intervertebral disc cavities, as a model for spinal degeneration, to study photopolymerization in-vitro. The cavity is created by enzyme digestion. Using a custom designed probe, hydrogels were injected and photopolymerized. Magnetic resonance imaging (MRI) and visual inspection tools were employed to investigate the successful photopolymerization outcomes. The results provide insights for the development of novel endoscopic light-scattering polymerization probes paving the way for a new generation of implantable hydrogels.

  4. Mesenchymal stem cell tracking in the intervertebral disc

    PubMed Central

    Handley, Charles; Goldschlager, Tony; Oehme, David; Ghosh, Peter; Jenkin, Graham

    2015-01-01

    Low back pain is a common clinical problem, which leads to significant social, economic and public health costs. Intervertebral disc (IVD) degeneration is accepted as a common cause of low back pain. Initially, this is characterized by a loss of proteoglycans from the nucleus pulposus resulting in loss of tissue hydration and hydrostatic pressure. Conservative management, including analgesia and physiotherapy often fails and surgical treatment, such as spinal fusion, is required. Stem cells offer an exciting possible regenerative approach to IVD disease. Preclinical research has demonstrated promising biochemical, histological and radiological results in restoring degenerate IVDs. Cell tracking provides an opportunity to develop an in-depth understanding of stem cell survival, differentiation and migration, enabling optimization of stem cell treatment. Magnetic Resonance Imaging (MRI) is a non-invasive, non-ionizing imaging modality with high spatial resolution, ideally suited for stem cell tracking. Furthermore, novel MRI sequences have the potential to quantitatively assess IVD disease, providing an improved method to review response to biological treatment. Superparamagnetic iron oxide nanoparticles have been extensively researched for the purpose of cell tracking. These particles are biocompatible, non-toxic and act as excellent MRI contrast agents. This review will explore recent advances and issues in stem cell tracking and molecular imaging in relation to the IVD. PMID:25621106

  5. Cellular Mechanobiology of the Intervertebral Disc: New Directions and Approaches

    PubMed Central

    Hsieh, Adam H.; Twomey, Julianne D.

    2009-01-01

    The more we learn about the intervertebral disc (IVD), the more we come to appreciate the intricacies involved in transmission of forces through the ECM to the cell, and in the biological determinants of its response to mechanical stress. This review highlights recent developments in our knowledge of IVD physiology and examines their impact on cellular mechanobiology. Discussion centers around the continually evolving cellular and microstructural anatomy of the nucleus pulposus (NP) and the annulus fibrosus (AF) in response to complex stresses generated in support of axial load and spinal motion. Particular attention has been given to cells from the immature NP and the interlamellar AF, and assessment of their potential mechanobiologic contributions to the health and function of the IVD. In addition, several innovative approaches that have been brought to bear on studying the interplay between disc cells and their micromechanical environment are discussed. Techniques for “engineering” cellular function and technologies for fabricating more structurally defined biomaterial scaffolds have recently been employed in disc research. Such tools can be used to elucidate the biological and physical mechanisms by which different IVD cell populations are regulated by mechanical stress, and contribute to advancement of preventative and therapeutic measures. PMID:19828150

  6. Obesity and recurrent intervertebral disc prolapse after lumbar microdiscectomy

    PubMed Central

    Syme, G; Swamy, GN; Nanjayan, S; Fowler, A; Calthorpe, D

    2014-01-01

    Introduction The primary aim of this study was to investigate the relationship between obesity and recurrent intervertebral disc prolapse (IDP) following lumbar microdiscectomy. Methods A retrospective review of case notes from 2008 to 2012 was conducted for all patients who underwent single level lumbar microdiscectomy performed by a single surgeon. All patients were followed up at two weeks and six weeks following surgery, and given an open appointment for a further six months. Results A total of 283 patients were available for analysis: 190 (67%) were in the non-obese group and 93 (32.9%) in the obese group. There was no statistical difference in postoperative infection, dural tear or length of stay between the non-obese and obese groups. Recurrent symptomatic IDP was seen in 27 patients (9.5%) confirmed by magnetic resonance imaging. Nineteen (10.0%) were in the non-obese group and eight (8.6%) in the obese group (p>0.8). Conclusions In our study, obesity was not a predictor of recurrent IDP following lumbar microdiscectomy. Our literature review confirmed that this study reports the largest series to date analysing the relationship between obesity and recurrent IDP following lumbar microdiscectomy in the British population. PMID:24780673

  7. 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

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

    PubMed

    Boecker, Werner; Buerger, Horst

    2003-10-01

    Although experimental data clearly confirm the existence of self-renewing mammary stem cells, the characteristics of such progenitor cells have never been satisfactorily defined. Using a double immunofluorescence technique for simultaneous detection of the basal cytokeratin 5, the glandular cytokeratins 8/18 and the myoepithelial differentiation marker smooth muscle actin (SMA), we were able to demonstrate the presence of CK5+ cells in human adult breast epithelium. These cells have the potential to differentiate to either glandular (CK8/18+) or myoepithelial cells (SMA+) through intermediary cells (CK5+ and CK8/18+ or SMA+). We therefore proceeded on the assumption that the CK5+ cells are phenotypically and behaviourally progenitor (committed adult stem) cells of human breast epithelium. Furthermore, we furnish evidence that most of these progenitor cells are located in the luminal epithelium of the ductal lobular tree. Based on data obtained in extensive analyses of proliferative breast disease lesions, we have come to regard usual ductal hyperplasia as a progenitor cell-derived lesion, whereas most breast cancers seem to evolve from differentiated glandular cells. Double immunofluorescence experiments provide a new tool to characterize phenotypically progenitor (adult stem) cells and their progenies. This model has been shown to be of great value for a better understanding not only of normal tissue regeneration but also of proliferative breast disease. Furthermore, this model provides a new tool for unravelling further the regulatory mechanisms that govern normal and pathological cell growth. PMID:14521517

  9. Variant Human T-cell Lymphotropic Virus Type 1c and Adult T-cell Leukemia, Australia

    PubMed Central

    Cassar, Olivier; Bardy, Peter; Kearney, Daniel; Gessain, Antoine

    2013-01-01

    Human T-cell lymphotropic virus type 1 is endemic to central Australia among Indigenous Australians. However, virologic and clinical aspects of infection remain poorly understood. No attempt has been made to control transmission to indigenous children. We report 3 fatal cases of adult T-cell leukemia/lymphoma caused by human T-cell lymphotropic virus type 1 Australo-Melanesian subtype c. PMID:24047544

  10. 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

  11. Intervertebral Fusion with Mobile Microendoscopic Discectomy for Lumbar Degenerative Disc Disease.

    PubMed

    Xu, Bao-Shan; Liu, Yue; Xu, Hai-Wei; Yang, Qiang; Ma, Xin-Long; Hu, Yong-Cheng

    2016-05-01

    The aim of this article is to introduce a technique for lumbar intervertebral fusion that incorporates mobile microendoscopic discectomy (MMED) for lumbar degenerative disc disease. Minimally invasive transforaminal lumbar interbody fusion is frequently performed to treat degenerative diseases of the lumbar spine; however, the scope of such surgery and vision is limited by what the naked eye can see through the expanding channel system. To expand the visual scope and reduce trauma, we perform lumbar intervertebral fusion with the aid of a MMED system that provides a wide field through freely tilting the surgical instrument and canals. We believe that this technique is a good option for treating lumbar degenerative disc disease that requires lumbar intervertebral fusion. PMID:27384734

  12. Design Concepts of Polycarbonate-Based Intervertebral Lumbar Cages: Finite Element Analysis and Compression Testing

    PubMed Central

    Figueroa-Cavazos, J. Obedt; Flores-Villalba, Eduardo; Diaz-Elizondo, José A.

    2016-01-01

    This work explores the viability of 3D printed intervertebral lumbar cages based on biocompatible polycarbonate (PC-ISO® material). Several design concepts are proposed for the generation of patient-specific intervertebral lumbar cages. The 3D printed material achieved compressive yield strength of 55 MPa under a specific combination of manufacturing parameters. The literature recommends a reference load of 4,000 N for design of intervertebral lumbar cages. Under compression testing conditions, the proposed design concepts withstand between 7,500 and 10,000 N of load before showing yielding. Although some stress concentration regions were found during analysis, the overall viability of the proposed design concepts was validated. PMID:27578960

  13. Intramedullary spinal cord damage associated with intervertebral disk material in a dog.

    PubMed

    Sanders, Sean G; Bagley, Rodney S; Gavin, Patrick R

    2002-12-01

    Intervertebral disk extrusions into the spinal cord are rarely reported in veterinary medicine, and only necropsy findings are described in previous reports. It is hypothesized that a disk lesion results in forceful injection of disk material into the spinal cord. In the 3-year-old Miniature Doberman Pinscher of our report, acute clinical signs and results of magnetic resonance imaging were consistent with this disease and helped determine the extent and character of the lesions. Alteration in the appearance of the nucleus pulposus was important in determining that intervertebral disk disease may have been present in this dog. However, a definitive diagnosis of intramedullary disk extrusion can be made only via histologic examination of a biopsy specimen or at necropsy. The dog improved substantially after surgical decompression of the spinal cord, and histologic findings in a biopsy specimen of material found within the spinal cord were consistent with mature degenerate intervertebral disk material. PMID:12479331

  14. Design Concepts of Polycarbonate-Based Intervertebral Lumbar Cages: Finite Element Analysis and Compression Testing.

    PubMed

    Figueroa-Cavazos, J Obedt; Flores-Villalba, Eduardo; Diaz-Elizondo, José A; Martínez-Romero, Oscar; Rodríguez, Ciro A; Siller, Héctor R

    2016-01-01

    This work explores the viability of 3D printed intervertebral lumbar cages based on biocompatible polycarbonate (PC-ISO® material). Several design concepts are proposed for the generation of patient-specific intervertebral lumbar cages. The 3D printed material achieved compressive yield strength of 55 MPa under a specific combination of manufacturing parameters. The literature recommends a reference load of 4,000 N for design of intervertebral lumbar cages. Under compression testing conditions, the proposed design concepts withstand between 7,500 and 10,000 N of load before showing yielding. Although some stress concentration regions were found during analysis, the overall viability of the proposed design concepts was validated. PMID:27578960

  15. [INFLUENCE OF AUTOLOGOUS CHONDROCYTES TRANSPLANTATION ON THE INTERVERTEBRAL DISC STATE IN EXPERIMENTAL MODEL OF OSTEOCHONDROSIS].

    PubMed

    Khyzhnyak, M V

    2015-07-01

    The degenerative changes in the nucleus pulposus and fibrous ring of the intervertebral discs are the basis of spinal osteochondrosis. A large number of models, including biological, where some mechanisms of their development were worked out and studied, was used to study the morphogenesis and pathogenesis of degenerative spinal changes. The deserved place in the comparative experiments and especially the different methods of therapeutic effects on the tissues of the intervertebral discs in degenerative spinal changes is taken by the experimental methods. The biochemical changes of the intervertebral disc structures were analyzed under the administration of cultured autologous cell of nucleus pulposus suspension against a background of experimental model of rat osteochondrosis. PMID:26591226

  16. ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs.

    PubMed

    Lee, Michelle H; Goralczyk, Anna G; Kriszt, Rókus; Ang, Xiu Min; Badowski, Cedric; Li, Ying; Summers, Scott A; Toh, Sue-Anne; Yassin, M Shabeer; Shabbir, Asim; Sheppard, Allan; Raghunath, Michael

    2016-01-01

    Key to realizing the diagnostic and therapeutic potential of human brown/brite adipocytes is the identification of a renewable, easily accessible and safe tissue source of progenitor cells, and an efficacious in vitro differentiation protocol. We show that macromolecular crowding (MMC) facilitates brown adipocyte differentiation in adult human bone marrow mesenchymal stem cells (bmMSCs), as evidenced by substantially upregulating uncoupling protein 1 (UCP1) and uncoupled respiration. Moreover, MMC also induced 'browning' in bmMSC-derived white adipocytes. Mechanistically, MMC creates a 3D extracellular matrix architecture enshrouding maturing adipocytes in a collagen IV cocoon that is engaged by paxillin-positive focal adhesions also at the apical side of cells, without contact to the stiff support structure. This leads to an enhanced matrix-cell signaling, reflected by increased phosphorylation of ATF2, a key transcription factor in UCP1 regulation. Thus, tuning the dimensionality of the microenvironment in vitro can unlock a strong brown potential dormant in bone marrow. PMID:26883894

  17. 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

  18. Electrophysiological Profiles of Induced Neurons Converted Directly from Adult Human Fibroblasts Indicate Incomplete Neuronal Conversion

    PubMed Central

    Koppensteiner, Peter; Boehm, Stefan

    2014-01-01

    Abstract The direct conversion of human fibroblasts to neuronal cells, termed human induced neuronal (hiN) cells, has great potential for future clinical advances. However, previous studies have not provided an in-depth analysis of electrophysiological properties of adult fibroblast-derived hiN cultures. We have examined the electrophysiological profile of hiN cells by measuring passive and active membrane properties, as well as spontaneous and evoked neurotransmission. We found that hiN cells exhibited passive membrane properties equivalent to perinatal rodent neurons. In addition, 30% of hiN cells were incapable of action potential (AP) generation and did not exhibit rectifying membrane currents, and none of the cells displayed firing patterns of typical glutamatergic pyramidal neurons. Finally, hiN cells exhibited neither spontaneous nor evoked neurotransmission. Our results suggest that current methods used to produce hiN cells provide preparations in which cells do not achieve the cellular properties of fully mature neurons, rendering these cells inadequate to investigate pathophysiological mechanisms. PMID:25437871

  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

    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. 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

  1. Expression of gangliosides on glial and neuronal cells in normal and pathological adult human brain.

    PubMed

    Marconi, Silvia; De Toni, Luca; Lovato, Laura; Tedeschi, Elisa; Gaetti, Luigi; Acler, Michele; Bonetti, Bruno

    2005-12-30

    Few studies have assessed the glycolipid phenotype of glial cells in the human central nervous system (CNS) in situ. We investigated by immunohistochemistry the expression and cellular distribution of a panel of gangliosides (GM1, GM2, acetyl-GM3, GD1a, GD1b, GD2, GD3, GT1b, GQ1b and the A2B5 antibody) in adult, human normal and pathological brain, namely multiple sclerosis (MS) and other neurological diseases (OND). In normal conditions, we found diffuse expression in the white matter of most gangliosides tested, with the exception of acetyl-GM3, GT1b and GQ1b. By double immunofluorescence with phenotypic markers, GM1 and GD1b were preferentially expressed on GFAP+ astrocytes, GD1a on NG2+ oligodendrocyte precursors, A2B5 immunostained both populations, while GD2 was selectively present on mature oligodendrocytes. In the gray matter, only GM1, GD2 and A2B5 were present on neuronal cells. Interestingly, those gangliosides present on astrocytes in normal conditions were preferentially expressed on NG2+ cells in chronic MS lesions and in OND. Selective expression of GT1b upon astrocytes and NG2+ cells was instead observed in MS lesions, but not in OND. The definition of the glycolipid phenotype of CNS glial cells may be useful to identify distinct biological glial subsets and provide insights on the potential autoantigenic role of gangliosides in CNS autoimmune diseases. PMID:16313974

  2. Defining the role of common variation in the genomic and biological architecture of adult human height

    PubMed Central

    Chu, Audrey Y; Estrada, Karol; Luan, Jian’an; Kutalik, Zoltán; Amin, Najaf; Buchkovich, Martin L; Croteau-Chonka, Damien C; Day, Felix R; Duan, Yanan; Fall, Tove; Fehrmann, Rudolf; Ferreira, Teresa; Jackson, Anne U; Karjalainen, Juha; Lo, Ken Sin; Locke, Adam E; Mägi, Reedik; Mihailov, Evelin; Porcu, Eleonora; Randall, Joshua C; Scherag, André; Vinkhuyzen, Anna AE; Westra, Harm-Jan; Winkler, Thomas W; Workalemahu, Tsegaselassie; Zhao, Jing Hua; Absher, Devin; Albrecht, Eva; Anderson, Denise; Baron, Jeffrey; Beekman, Marian; Demirkan, Ayse; Ehret, Georg B; Feenstra, Bjarke; Feitosa, Mary F; Fischer, Krista; Fraser, Ross M; Goel, Anuj; Gong, Jian; Justice, Anne E; Kanoni, Stavroula; Kleber, Marcus E; Kristiansson, Kati; Lim, Unhee; Lotay, Vaneet; Lui, Julian C; Mangino, Massimo; Leach, Irene Mateo; Medina-Gomez, Carolina; Nalls, Michael A; Nyholt, Dale R; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Prokopenko, Inga; Ried, Janina S; Ripke, Stephan; Shungin, Dmitry; Stancáková, Alena; Strawbridge, Rona J; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; van der Laan, Sander W; van Setten, Jessica; Van Vliet-Ostaptchouk, Jana V; Wang, Zhaoming; Yengo, Loïc; Zhang, Weihua; Afzal, Uzma; Ärnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Bolton, Jennifer L; Böttcher, Yvonne; Boyd, Heather A; Bruinenberg, Marcel; Buckley, Brendan M; Buyske, Steven; Caspersen, Ida H; Chines, Peter S; Clarke, Robert; Claudi-Boehm, Simone; Cooper, Matthew; Daw, E Warwick; De Jong, Pim A; Deelen, Joris; Delgado, Graciela; Denny, Josh C; Dhonukshe-Rutten, Rosalie; Dimitriou, Maria; Doney, Alex SF; Dörr, Marcus; Eklund, Niina; Eury, Elodie; Folkersen, Lasse; Garcia, Melissa E; Geller, Frank; Giedraitis, Vilmantas; Go, Alan S; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grönberg, Henrik; de Groot, Lisette C.P.G.M.; Groves, Christopher J; Haessler, Jeffrey; Hall, Per; Haller, Toomas; Hallmans, Goran; Hannemann, Anke; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heard-Costa, Nancy L; Helmer, Quinta; Hemani, Gibran; Henders, Anjali K; Hillege, Hans L; Hlatky, Mark A; Hoffmann, Wolfgang; Hoffmann, Per; Holmen, Oddgeir; Houwing-Duistermaat, Jeanine J; Illig, Thomas; Isaacs, Aaron; James, Alan L; Jeff, Janina; Johansen, Berit; Johansson, Åsa; Jolley, Jennifer; Juliusdottir, Thorhildur; Junttila, Juhani; Kho, Abel N; Kinnunen, Leena; Klopp, Norman; Kocher, Thomas; Kratzer, Wolfgang; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Lu, Yingchang; Lyssenko, Valeriya; Magnusson, Patrik KE; Mahajan, Anubha; Maillard, Marc; McArdle, Wendy L; McKenzie, Colin A; McLachlan, Stela; McLaren, Paul J; Menni, Cristina; Merger, Sigrun; Milani, Lili; Moayyeri, Alireza; Monda, Keri L; Morken, Mario A; Müller, Gabriele; Müller-Nurasyid, Martina; Musk, Arthur W; Narisu, Narisu; Nauck, Matthias; Nolte, Ilja M; Nöthen, Markus M; Oozageer, Laticia; Pilz, Stefan; Rayner, Nigel W; Renstrom, Frida; Robertson, Neil R; Rose, Lynda M; Roussel, Ronan; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Schumacher, Fredrick R; Schunkert, Heribert; Scott, Robert A; Sehmi, Joban; Seufferlein, Thomas; Shi, Jianxin; Silventoinen, Karri; Smit, Johannes H; Smith, Albert Vernon; Smolonska, Joanna; Stanton, Alice V; Stirrups, Kathleen; Stott, David J; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorleifsson, Gudmar; Tyrer, Jonathan P; van Dijk, Suzanne; van Schoor, Natasja M; van der Velde, Nathalie; van Heemst, Diana; van Oort, Floor VA; Vermeulen, Sita H; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Waldenberger, Melanie; Wennauer, Roman; Wilkens, Lynne R; Willenborg, Christina; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Wright, Alan F; Zhang, Qunyuan; Arveiler, Dominique; Bakker, Stephan JL; Beilby, John; Bergman, Richard N; Bergmann, Sven; Biffar, Reiner; Blangero, John; Boomsma, Dorret I; Bornstein, Stefan R; Bovet, Pascal; Brambilla, Paolo; Brown, Morris J; Campbell, Harry; Caulfield, Mark J; Chakravarti, Aravinda; Collins, Rory; Collins, Francis S; Crawford, Dana C; Cupples, L Adrienne; Danesh, John; de Faire, Ulf; den Ruijter, Hester M; Erbel, Raimund; Erdmann, Jeanette; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Ford, Ian; Forouhi, Nita G; Forrester, Terrence; Gansevoort, Ron T

    2014-01-01

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

  3. 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

  4. 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

  5. Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke.

    PubMed

    Duricki, Denise A; Hutson, Thomas H; Kathe, Claudia; Soleman, Sara; Gonzalez-Carter, Daniel; Petruska, Jeffrey C; Shine, H David; Chen, Qin; Wood, Tobias C; Bernanos, Michel; Cash, Diana; Williams, Steven C R; Gage, Fred H; Moon, Lawrence D F

    2016-01-01

    There is an urgent need for a therapy that reverses disability after stroke when initiated in a time frame suitable for the majority of new victims. We show here that intramuscular delivery of neurotrophin-3 (NT3, encoded by NTF3) can induce sensorimotor recovery when treatment is initiated 24 h after stroke. Specifically, in two randomized, blinded preclinical trials, we show improved sensory and locomotor function in adult (6 months) and elderly (18 months) rats treated 24 h following cortical ischaemic stroke with human NT3 delivered using a clinically approved serotype of adeno-associated viral vector (AAV1). Importantly, AAV1-hNT3 was given in a clinically-feasible timeframe using a straightforward, targeted route (injections into disabled forelimb muscles). Magnetic resonance imaging and histology showed that recovery was not due to neuroprotection, as expected given the delayed treatment. Rather, treatment caused corticospinal axons from the less affected hemisphere to sprout in the spinal cord. This treatment is the first gene therapy that reverses disability after stroke when administered intramuscularly in an elderly body. Importantly, phase I and II clinical trials by others show that repeated, peripherally administered high doses of recombinant NT3 are safe and well tolerated in humans with other conditions. This paves the way for NT3 as a therapy for stroke. PMID:26614754

  6. 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

  7. 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.

  8. Carbon turnover in the water-soluble protein of the adult human lens

    PubMed Central

    Stewart, Daniel N.; Lango, Jozsef; Nambiar, Krishnan P.; Falso, Miranda J. S.; FitzGerald, Paul G.; Rocke, David M.; Hammock, Bruce D.

    2013-01-01

    Purpose Human eye lenses contain cells that persist from embryonic development. These unique, highly specialized fiber cells located at the core (nucleus) of the lens undergo pseudo-apoptosis to become devoid of cell nuclei and most organelles. Ostensibly lacking in protein transcriptional capabilities, it is currently believed that these nuclear fiber cells owe their extreme longevity to the perseverance of highly stable and densely packed crystallin proteins. Maintaining the structural and functional integrity of lenticular proteins is necessary to sustain cellular transparency and proper vision, yet the means by which the lens actually copes with a lifetime of oxidative stress, seemingly without any capacity for protein turnover and repair, is not completely understood. Although many years of research have been predicated upon the assumption that there is no protein turnover or renewal in nuclear fiber cells, we investigated whether or not different protein fractions possess protein of different ages by using the 14C bomb pulse. Methods Adult human lenses were concentrically dissected by gently removing the cell layers in water or shaving to the nucleus with a curved micrometer-controlled blade. The cells were lysed, and the proteins were separated into water-soluble and water-insoluble fractions. The small molecules were removed using 3 kDa spin filters. The 14C/C was measured in paired protein fractions by accelerator mass spectrometry, and an average age for the material within the sample was assigned using the 14C bomb pulse. Results The water-insoluble fractions possessed 14C/C ratios consistent with the age of the cells. In all cases, the water-soluble fractions contained carbon that was younger than the paired water-insoluble fraction. Conclusions As the first direct evidence of carbon turnover in protein from adult human nuclear fiber cells, this discovery supports the emerging view of the lens nucleus as a dynamic system capable of maintaining

  9. 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

  10. 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…

  11. Expression levels of IL-17 and TNF-α in degenerated lumbar intervertebral discs and their correlation

    PubMed Central

    LIU, XIAO-GANG; HOU, HONG-WEI; LIU, YI-LIN

    2016-01-01

    The present study aimed to investigate the expression and roles of interleukin (IL)-17 and tumor necrosis factor (TNF)-α in intervertebral disc degeneration (IDD) and to identify the association between the effects of IL-17 and TNF-α in IDD. This may increase understanding of the pathogenic mechanism underlying IDD, and aid the development of alternative therapies. The experimental group consisted of 40 samples of nucleus pulposus tissue obtained from the intervertebral discs (IVDs) of patients with IDD by surgical intervention, and was further divided into an annulus fibrosus disrupted group, comprising 18 patients in which the external annulus was ruptured, and an annulus fibrosus intact group comprising 22 patients. The control group consisted of 20 samples of nucleus pulposus tissue from the IVDs of patients with traumatic lumbar disc fractures. The mRNA and protein expression levels of IL-17 and TNF-α in the 50 tissue samples were detected by semi-quantitative reverse transcription polymerase chain reaction and immunohistochemical staining, respectively, and the results were statistically analyzed. The IL-17 and TNF-α protein and mRNA expression levels in the annulus fibrosus disrupted and annulus fibrosus intact groups were both higher compared with those in the control group. In addition, the expression levels of IL-17 and TNF-α in the annulus fibrosus disrupted group were significantly higher compared with those in the annulus fibrosus intact group (P<0.01). A positive correlation was identified between the mRNA and protein expression levels of IL-17 and TNF-α in the experimental group (r=0.957, P<0.01). IL-17 and TNF-α may therefore be involved in the progression of human IDD, and may have synergistic effects in the development of IDD. PMID:27284317

  12. Enhancement of Runx2 expression is potentially linked to β-catenin accumulation in canine intervertebral disc degeneration.

    PubMed

    Iwata, Munetaka; Aikawa, Takeshi; Hakozaki, Takaharu; Arai, Kiyotaka; Ochi, Hiroki; Haro, Hirotaka; Tagawa, Masahiro; Asou, Yoshinori; Hara, Yasushi

    2015-01-01

    Intervertebral disc degeneration (IVDD) greatly affects the quality of life. The nucleus pulposus (NP) of chondrodystrophic dog breeds (CDBs) is similar to the human NP because the cells disappear with age and are replaced by fibrochondrocyte-like cells. Because IVDD develops as early as within the first year of life, we used canines as a model to investigate the in vitro mechanisms underlying IVDD. The mechanism underlying age-related IVDD, however, is poorly understood. Several research groups have suggested that Wnt/β-catenin signaling plays an important role in IVDD. However, the role of Wnt/β-catenin signals in IVD cells is not yet well understood. Here, we demonstrate that Wnt/β-catenin signaling could enhance Runx2 expression in IVDD and lead to IVD calcification. Nucleus pulposus (NP) tissue was obtained from Beagle dogs after evaluation of the degeneration based on magnetic resonance imaging (MRI). Histological analysis showed that lack of Safranin-O staining, calcified area, and matrix metalloproteinase (MMP) 13-positive cells increased with progression of the degeneration. Furthermore, the levels of β-catenin- and Runx2-positive cells also increased. Real-time reverse-transcription polymerase chain reaction analysis showed that the MRI signal intensity and mRNA expression levels of β-catenin and Runx2 are correlated in NP tissues. Moreover, supplementation of LiCl induced β-catenin accumulation and Runx2 expression. In contrast, FH535 inhibited LiCl-induced upregulation. These results suggest that Runx2 transcript and protein expression, potentially in combination with β-catenin accumulation, are enhanced in degenerated and calcified intervertebral discs of CDBs. PMID:24916026

  13. 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;…

  14. 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...

  15. Determination of the intervertebral disc space from CT images of the lumbar spine

    NASA Astrophysics Data System (ADS)

    Korez, Robert; Å tern, Darko; Likar, Boštjan; Pernuš, Franjo; Vrtovec, Tomaž

    2014-03-01

    Degenerative changes of the intervertebral disc are among the most common causes of low back pain, where for individuals with significant symptoms surgery may be needed. One of the interventions is the total disc replacement surgery, where the degenerated disc is replaced by an artificial implant. For designing implants with good bone contact and continuous force distribution, the morphology of the intervertebral disc space and vertebral body endplates is of considerable importance. In this study we propose a method for the determination of the intervertebral disc space from three-dimensional (3D) computed tomography (CT) images of the lumbar spine. The first step of the proposed method is the construction of a model of vertebral bodies in the lumbar spine. For this purpose, a chain of five elliptical cylinders is initialized in the 3D image and then deformed to resemble vertebral bodies by introducing 25 shape parameters. The parameters are obtained by aligning the chain to the vertebral bodies in the CT image according to image intensity and appearance information. The determination of the intervertebral disc space is finally achieved by finding the planes that fit the endplates of the obtained parametric 3D models, and placing points in the space between the planes of adjacent vertebrae that enable surface reconstruction of the intervertebral disc space. The morphometric analysis of images from 20 subjects yielded 11:3 +/- 2:6, 12:1 +/- 2:4, 12:8 +/- 2:0 and 12:9 +/- 2:7 cm3 in terms of L1-L2, L2-L3, L3-L4 and L4-L5 intervertebral disc space volume, respectively.

  16. 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

  17. 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

  18. Effect of repetitive laser pulses on the electrical conductivity of intervertebral disc tissue

    SciTech Connect

    Omel'chenko, A I; Sobol', E N

    2009-03-31

    The thermomechanical effect of 1.56-{mu}m fibre laser pulses on intervertebral disc cartilage has been studied using ac conductivity measurements with coaxial electrodes integrated with an optical fibre for laser radiation delivery to the tissue. The observed time dependences of tissue conductivity can be interpreted in terms of hydraulic effects and thermomechanical changes in tissue structure. The laserinduced changes in the electrical parameters of the tissue are shown to correlate with the structural changes, which were visualised using shadowgraph imaging. Local ac conductivity measurements in the bulk of tissue can be used to develop a diagnostic/monitoring system for laser regeneration of intervertebral discs. (laser biology and medicine)

  19. Standards of Practice: Quality Assurance Guidelines for Percutaneous Treatments of Intervertebral Discs

    SciTech Connect

    Kelekis, Alexis D. Filippiadis, Dimitris K.; Martin, Jean-Baptiste; Brountzos, Elias

    2010-10-15

    Percutaneous treatments are used in the therapy of small- to medium-sized hernias of intervertebral discs to reduce the intradiscal pressure in the nucleus and theoretically create space for the herniated fragment to implode inward, thus reducing pain and improving mobility and quality of life. These techniques involve the percutaneous removal of the nucleus pulposus by using a variety of chemical, thermal, or mechanical techniques and consist of removal of all or part of nucleus pulposus to induce more rapid healing of the abnormal lumbar disc. These guidelines are written to be used in quality improvement programs for assessing fluoroscopy- and/or computed tomography-guided percutaneous intervertebral disc ablative techniques.

  20. The effectiveness of percutaneous laser disc decompression for the prolapsed lumbar intervertebral disc

    NASA Astrophysics Data System (ADS)

    Mu, Ming Wei; Liu, Wei; Feng, Wei; Ma, Nan

    2009-07-01

    Objective: to investigate the role of associated factors in the effectiveness of laser treatment for prolapsed lumber intervertebral disc. Method: 302 prolapsed lumber intervertebral discs in 212 patients were treated with percutaneous laser disc decompression (PLDD). Patients were followed up by 12month, the associated factors which affecting the effectiveness of treatment, ie age, duration of illness were analyzed. Results: Punctual Success rate was 100%. After 12 month's follow up, 86% successful outcomes were obtained, in which 93% successful outcomes were obtained in patients less than 50 years old, 92% successful outcomes was obtained in the patients whose duration of illness less than 1 year.

  1. Intervertebral disk degeneration in dogs: consequences, diagnosis, treatment, and future directions.

    PubMed

    Jeffery, N D; Levine, J M; Olby, N J; Stein, V M

    2013-01-01

    Evidence of intervertebral disk degeneration (IVDD) is extremely common in dogs, and its prevalence increases with age. It has many important consequences because degeneration of the intervertebral disks often is a prelude to disk herniation, which can injure the spinal cord, spinal nerves, or both. This review summarizes the advances in diagnosis and treatment of IVDD that have been made since the 1950s when the first detailed description of the degenerative changes was published. It also discusses new approaches to treatment of the associated spinal cord injury and new methods by which to classify injury severity that are currently under development. PMID:24010573

  2. Growth Factors and Anticatabolic Substances for Prevention and Management of Intervertebral Disc Degeneration

    PubMed Central

    Longo, Umile Giuseppe; Petrillo, Stefano; Franceschetti, Edoardo; Maffulli, Nicola; Denaro, Vincenzo

    2012-01-01

    Intervertebral disc (IVD) degeneration is frequent, appearing from the second decade of life and progressing with age. Conservative management often fails, and patients with IVD degeneration may need surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. Biological strategies aim to prevent and manage IVD degeneration, improving the function and anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells and inhibiting matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of growth factors and anticatabolic substances for prevention and management of intervertebral disc degeneration. PMID:25098367

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

    PubMed

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

    2016-05-01

    Major long-range white matter pathways (cingulum, fornix, uncinate fasciculus [UF], inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus [ILF], thalamocortical [TC], and corpus callosal [CC] pathways) were identified in eighty-three healthy humans ranging from newborn to adult ages. We tracked developmental changes using high-angular resolution diffusion MR tractography. Fractional anisotropy (FA), apparent diffusion coefficient, number, length, and volume were measured in pathways in each subject. Newborns had fewer, and more sparse, pathways than those of the older subjects. FA, number, length, and volume of pathways gradually increased with age and reached a plateau between 3 and 5 years of age. Data were further analyzed by normalizing with mean adult values as well as with each subject's whole brain values. Comparing subjects of 3 years old and under to those over 3 years old, the studied pathways showed differential growth patterns. The CC, bilateral cingulum, bilateral TC, and the left IFOF pathways showed significant growth both in volume and length, while the bilateral fornix, bilateral ILF and bilateral UF showed significant growth only in volume. The TC and CC took similar growth patterns with the whole brain. FA values of the cingulum and IFOF, and the length of ILF showed leftward asymmetry. The fornix, ILF and UF occupied decreased space compared to the whole brain during development with higher FA values, likely corresponding to extensive maturation of the pathways compared to the mean whole brain maturation. We believe that the outcome of this study will provide an important database for future reference. PMID:26948153

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

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. PMID:26890892

  5. Human fetal and adult chondrocytes. Effect of insulinlike growth factors I and II, insulin, and growth hormone on clonal growth.

    PubMed Central

    Vetter, U; Zapf, J; Heit, W; Helbing, G; Heinze, E; Froesch, E R; Teller, W M

    1986-01-01

    Clonal proliferation of freshly isolated human fetal chondrocytes and adult chondrocytes in response to human insulinlike growth factors I and II (IGF I, IGF II), human biosynthetic insulin, and human growth hormone (GH) was assessed. IGF I (25 ng/ml) stimulated clonal growth of fetal chondrocytes (54 +/- 12 colonies/1,000 inserted cells, mean +/- 1 SD), but IGF II (25 ng/ml) was significantly more effective (106 +/- 12 colonies/1,000 inserted cells, P less than 0.05, unstimulated control: 14 +/- 4 colonies/1,000 inserted cells). In contrast, IGF I (25 ng/ml) was more effective in adult chondrocytes (42 +/- 6 colonies/1,000 inserted cells) than IGF II (25 ng/ml) (21 +/- 6 colonies/1,000 inserted cells; P less than 0.05, unstimulated control: 6 +/- 3 colonies/1,000 inserted cells). GH and human biosynthetic insulin did not affect clonal growth of fetal or adult chondrocytes. The clonal growth pattern of IGF-stimulated fetal and adult chondrocytes was not significantly changed when chondrocytes were first grown in monolayer culture, harvested, and then inserted in the clonal culture system. However, the adult chondrocytes showed a time-dependent decrease of stimulation of clonal growth by IGF I and II. This was not true for fetal chondrocytes. The results are compatible with the concept that IGF II is a more potent stimulant of clonal growth of chondrocytes during fetal life, whereas IGF I is more effective in stimulating clonal growth of chondrocytes during postnatal life. Images PMID:3519682

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

    PubMed Central

    Tong, Fei; Yao, Dongqi; Walline, Joseph; Xu, Jun; Yu, Xuezhong

    2016-01-01

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

  7. A Critical Evaluation of Adult Learning Theories and Implication for Human Resource Development

    ERIC Educational Resources Information Center

    Yang, Baiyin

    2004-01-01

    Based on a newly developed holistic theory of knowledge and learning, this paper critically evaluates several contemporary theories of adult learning. Most of existing adult learning theories tend to narrowly define knowledge and learning and fail to offer adequate explanation for adult learning. Implications for HRD theory, research, and practice…

  8. Intervertebral Disk Tissue Engineering Using Biphasic Silk Composite Scaffolds

    PubMed Central

    Park, Sang-Hyug; Gil, Eun Seok; Cho, Hongsik; Mandal, Biman B.; Tien, Lee W.; Min, Byoung-Hyun

    2012-01-01

    Scaffolds composed of synthetic, natural, and hybrid materials have been investigated as options to restore intervertebral disk (IVD) tissue function. These systems fall short of the lamellar features of the native annulus fibrosus (AF) tissue or focus only on the nucleus pulposus (NP) tissue. However, successful regeneration of the entire IVD requires a combination approach to restore functions of both the AF and NP. To address this need, a biphasic biomaterial structure was generated by using silk protein for the AF and fibrin/hyaluronic acid (HA) gels for the NP. Two cell types, porcine AF cells and chondrocytes, were utilized. For the AF tissue, two types of scaffold morphologies, lamellar and porous, were studied with the porous system serving as a control. Toroidal scaffolds formed out of the lamellar, and porous silk materials were used to generate structures with an outer diameter of 8 mm, inner diameter of 3.5 mm, and a height of 3 mm (the interlamellar distance in the lamellar scaffold was 150–250 μm, and the average pore sizes in the porous scaffolds were 100–250 μm). The scaffolds were seeded with porcine AF cells to form AF tissue, whereas porcine chondrocytes were encapsulated in fibrin/HA hydrogels for the NP tissue and embedded in the center of the toroidal disk. Histology, biochemical assays, and gene expression indicated that the lamellar scaffolds supported AF-like tissue over 2 weeks. Porcine chondrocytes formed the NP phenotype within the hydrogel after 4 weeks of culture with the AF tissue that had been previously cultured for 2 weeks, for a total of 6 weeks of cultivation. This biphasic scaffold simulating in combination of both AF and NP tissues was effective in the formation of the total IVD in vitro. PMID:21919790

  9. Simulation of biological therapies for degenerated intervertebral discs.

    PubMed

    Zhu, Qiaoqiao; Gao, Xin; Temple, H Thomas; Brown, Mark D; Gu, Weiyong

    2016-04-01

    The efficacy of biological therapies on intervertebral disc repair was quantitatively studied using a three-dimensional finite element model based on a cell-activity coupled multiphasic mixture theory. In this model, cell metabolism and matrix synthesis and degradation were considered. Three types of biological therapies-increasing the cell density (Case I), increasing the glycosaminoglycan (GAG) synthesis rate (Case II), and decreasing the GAG degradation rate (Case III)-to the nucleus pulposus (NP) of each of two degenerated discs [one mildly degenerated (e.g., 80% viable cells in the NP) and one severely degenerated (e.g., 30% viable cells in the NP)] were simulated. Degenerated discs without treatment were also simulated as a control. The cell number needed, nutrition level demanded, time required for the repair, and the long-term outcomes of these therapies were analyzed. For Case I, the repair process was predicted to be dependent on the cell density implanted and the nutrition level at disc boundaries. With sufficient nutrition supply, this method was predicted to be effective for treating both mildly and severely degenerated discs. For Case II, the therapy was predicted to be effective for repairing the mildly degenerated disc, but not for the severely degenerated disc. Similar results were predicted for Case III. No change in cell density for Cases II and III were predicted under normal nutrition level. This study provides a quantitative guide for choosing proper strategies of biological therapies for different degenerated discs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:699-708, 2016. PMID:26425965

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

    PubMed Central

    Mustafa, Mohamed S.; Mahmoud, Omayma M.; El Raouf, Hoda H. A.; Atef, Hosam M.

    2012-01-01

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

  11. Ex vivo Expansion of Human Adult Pancreatic Cells with Properties of Distributed Stem Cells by Suppression of Asymmetric Cell Kinetics

    PubMed Central

    Paré, JF; Sherley, JL

    2013-01-01

    Transplantation therapy for type I diabetes (T1D) might be improved if pancreatic stem cells were readily available for investigation. Unlike macroscopic islets, pancreatic tissue stem cells could more easily access the retroperitoneal pancreatic environment and thereby might achieve more effective pancreatic regeneration. Unfortunately, whether the adult pancreas actually contains renewing stem cells continues as a controversial issue in diabetes research. We evaluated a new method developed in our lab for expanding renewing distributed stem cells (DSCs) from adult tissues as a means to provide more evidence for adult pancreatic stem cells, and potentially advance their availability for future clinical investigation. The new method was designed to switch DSCs from asymmetric self-renewal to symmetric self-renewal, which promotes their exponential expansion in culture with reduced production of differentiated cells. Called suppression of asymmetric cell kinetics (SACK), the method uses natural purine metabolites to accomplish the self-renewal pattern shift. The SACK purine metabolites xanthine, xanthosine, and hypoxanthine were evaluated for promoting expansion of DSCs from the pancreas of adult human postmortem donors. Xanthine and xanthosine were effective for deriving both pooled and clonal populations of cells with properties indicative of human pancreatic DSCs. The expanded human cell strains had signature SACK agent-suppressible asymmetric cell kinetics, produced Ngn3+ bipotent precursors for α-cells and β-cells, and were non-tumorigenic in immunodeficient mice. Our findings support the existence of pancreatic DSCs in the adult human pancreas and indicate a potential path to increasing their availability for future clinical evaluation. PMID:25197614

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

    PubMed Central

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

    2012-01-01

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

  13. 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

  14. 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

  15. 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

  16. 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

  17. GENIPIN-CROSSLINKED FIBRIN HYDROGELS AS A POTENTIAL ADHESIVE TO AUGMENT INTERVERTEBRAL DISC ANNULUS REPAIR

    PubMed Central

    Schek, R.M.; Michalek, A.J.; Iatridis, J.C.

    2011-01-01

    Treatment of damaged intervertebral discs is a significant clinical problem and, despite advances in the repair and replacement of the nucleus pulposus, there are few effective strategies to restore defects in the annulus fibrosus. An annular repair material should meet three specifications: have a modulus similar to the native annulus tissue, support the growth of disc cells, and maintain adhesion to tissue under physiological strain levels. We hypothesized that a genipin crosslinked fibrin gel could meet these requirements. Our mechanical results showed that genipin crosslinked fibrin gels could be created with a modulus in the range of native annular tissue. We also demonstrated that this material is compatible with the in vitro growth of human disc cells, when genipin:fibrin ratios were 0.25:1 or less, although cell proliferation was slower and cell morphology more rounded than for fibrin alone. Finally, lap tests were performed to evaluate adhesion between fibrin gels and pieces of annular tissue. Specimens created without genipin had poor handling properties and readily delaminated, while genipin crosslinked fibrin gels remained adhered to the tissue pieces at strains exceeding physiological levels and failed at 15–30%. This study demonstrated that genipin crosslinked fibrin gels show promise as a gap-filling adhesive biomaterial with tunable material properties, yet the slow cell proliferation suggests this biomaterial may be best suited as a sealant for small annulus fibrosus defects or as an adhesive to augment large annulus repairs. Future studies will evaluate degradation rate, fatigue behaviors, and long-term biocompatibility. PMID:21503869

  18. Aquaporin 3 protects against lumbar intervertebral disc degeneration via the Wnt/β-catenin pathway.

    PubMed

    Xie, Huanxin; Jing, Yongbin; Xia, Jingjun; Wang, Xintao; You, Changcheng; Yan, Jinglong

    2016-03-01

    Previous studies have demonstrated that the expression of aquaporin 3 (AQP3), a water channel which promotes glycerol permeability and water transport across cell membranes, is reduced in degenerative lumbar intervertebral disc (IVD) tissues. However, the role of AQP3 in the pathogenesis of IVD degeneration has not recieved much scholarly attention. The objective of the present study was to investigate the effect of AQP3 on cell proliferation and extracellular matrix (ECM) degradation in human nucleus pulposus cells (hNPCs) using gain-of-function and loss-of-function experiments, and to determine whether Wnt/β-catenin signaling is involved in the effect of AQP3 on IVD degeneration. hNPCs were transfected with the AQP3-pcDNA3.1 plasmid or AQP3 siRNA to overexpress or suppress AQP3. An MTT assay was performed to determine cell proliferation, and we found that AQP3 promoted hNPC proliferation. The expression of aggrecan, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5 was detected using western blot analysis, to examine the effect of AQP3 on ECM degradation in hNPCs. The results revealed that AQP3 inhibited ECM degradation in hNPCs. In addition, we found that Wnt/β-catenin signaling was suppressed by AQP3. However, the effect of AQP3 on hNPC proliferation and ECM degradation was reversed by treatment with lithium chloride, a known activator of Wnt/β‑catenin signaling. In conclusion, using in vitro and in vivo tests, we have reported for the first time, to the best of our knowledge, that AQP3 exerts protective effects against IVD degeneration, and these are effected, at least partially, through the inhibition of Wnt/β-catenin signaling. PMID:26820815

  19. MR Monitoring of Minimally Invasive Delivery of Mesenchymal Stem Cells into the Porcine Intervertebral Dis