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Sample records for adult cell types

  1. 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.

  2. Pulmonary Alveolar Type II Epithelial Cells and Adult Respiratory Distress Syndrome

    PubMed Central

    Mason, Robert J.

    1985-01-01

    During the past ten years, functions of alveolar type II cells have been well characterized with isolated cells in vitro. Some of the functions were well known from studies in vivo, but others such as transepithelial sodium transport were unsuspected. A better understanding of this important pulmonary cell type improves our knowledge of the pathophysiology of adult respiratory distress syndrome and may in time lead to new therapeutic strategies. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:3909639

  3. Retinyl ester synthesis by isolated adult rabbit lung type II cells.

    PubMed

    Zachman, R D; Tsao, F H

    1988-01-01

    Type II alveolar cells were isolated from adult rabbit lungs and then cultured on monolayers for 16 hours. These cells were then covered with buffered medium containing [3H]-retinol. After 30-120 minutes incubation, the cells were extracted with Hexane: Ethanol and the hexane extract analyzed by HPLC. A linear synthesis of [3H]-retinyl palmitate with time of incubation was demonstrated. PMID:3170088

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

    PubMed

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

    2014-06-26

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

  5. Inhibition of Adult Rat Retinal Ganglion Cells by D1-type Dopamine Receptor Activation

    PubMed Central

    Hayashida, Yuki; Rodríguez, Carolina Varela; Ogata, Genki; Partida, Gloria J.; Oi, Hanako; Stradleigh, Tyler W.; Lee, Sherwin C.; Colado, Anselmo Felipe; Ishida, Andrew T.

    2011-01-01

    The spike output of neural pathways can be regulated by modulating output neuron excitability and/or their synaptic inputs. Dopaminergic interneurons synapse onto cells that route signals to mammalian retinal ganglion cells, but it is unknown whether dopamine can activate receptors in these ganglion cells and, if it does, how this affects their excitability. Here, we show D1a-receptor-like immunoreactivity in ganglion cells identified in adult rats by retrogradely transported dextran, and that dopamine, D1-type receptor agonists, and cAMP analogs inhibit spiking in ganglion cells dissociated from adult rats. These ligands curtailed repetitive spiking during constant current injections, and reduced the number and rate of rise of spikes elicited by fluctuating current injections without significantly altering the timing of the remaining spikes. Consistent with mediation by D1-type receptors, SCH-23390 reversed the effects of dopamine on spikes. Contrary to a recent report, spike inhibition by dopamine was not precluded by blocking Ih. Consistent with the reduced rate of spike rise, dopamine reduced voltage-gated Na+ current (INa) amplitude and tetrodotoxin, at doses that reduced INa as moderately as dopamine, also inhibited spiking. These results provide the first direct evidence that D1-type dopamine receptor activation can alter mammalian retinal ganglion cell excitability, and demonstrate that dopamine can modulate spikes in these cells by a mechanism different from the pre- and postsynaptic means proposed by previous studies. To our knowledge, our results also provide the first evidence that dopamine receptor activation can reduce excitability without altering the temporal precision of spike firing. PMID:19940196

  6. A Distinct Perisynaptic Glial Cell Type Forms Tripartite Neuromuscular Synapses in the Drosophila Adult

    PubMed Central

    Strauss, Alexandra L.; Kawasaki, Fumiko; Ordway, Richard W.

    2015-01-01

    Previous studies of Drosophila flight muscle neuromuscular synapses have revealed their tripartite architecture and established an attractive experimental model for genetic analysis of glial function in synaptic transmission. Here we extend these findings by defining a new Drosophila glial cell type, designated peripheral perisynaptic glia (PPG), which resides in the periphery and interacts specifically with fine motor axon branches forming neuromuscular synapses. Identification and specific labeling of PPG was achieved through cell type-specific RNAi-mediated knockdown (KD) of a glial marker, Glutamine Synthetase 2 (GS2). In addition, comparison among different Drosophila neuromuscular synapse models from adult and larval developmental stages indicated the presence of tripartite synapses on several different muscle types in the adult. In contrast, PPG appear to be absent from larval body wall neuromuscular synapses, which do not exhibit a tripartite architecture but rather are imbedded in the muscle plasma membrane. Evolutionary conservation of tripartite synapse architecture and peripheral perisynaptic glia in vertebrates and Drosophila suggests ancient and conserved roles for glia-synapse interactions in synaptic transmission. PMID:26053860

  7. Beta Cell Formation in vivo Through Cellular Networking, Integration and Processing (CNIP) in Wild Type Adult Mice.

    PubMed

    Doiron, Bruno; Hu, Wenchao; DeFronzo, Ralph A

    2016-01-01

    Insulin replacement therapy is essential in type 1 diabetic individuals and is required in ~40- 50% of type 2 diabetics during their lifetime. Prior attempts at beta cell regeneration have relied upon pancreatic injury to induce beta cell proliferation, dedifferentiation and activation of the embryonic pathway, or stem cell replacement. We report an alternative method to transform adult non-stem (somatic) cells into pancreatic beta cells. The Cellular Networking, Integration and Processing (CNIP) approach targets cellular mechanisms involved in pancreatic function in the organ's adult state and utilizes a synergistic mechanism that integrates three important levels of cellular regulation to induce beta cell formation: (i) glucose metabolism, (ii) membrane receptor function, and (iii) gene transcription. The aim of the present study was to induce pancreatic beta cell formation in vivo in adult animals without stem cells and without dedifferentiating cells to recapitulate the embryonic pathway as previously published (1-3). Our results employing CNIP demonstrate that: (i) insulin secreting cells can be generated in adult pancreatic tissue in vivo and circumvent the problem of generating endocrine (glucagon and somatostatin) cells that exert deleterious effects on glucose homeostasis, and (ii) longterm normalization of glucose tolerance and insulin secretion can be achieved in a wild type diabetic mouse model. The CNIP cocktail has the potential to be used as a preventative or therapeutic treatment or cure for both type 1 and type 2 diabetes. PMID:26696016

  8. A new type of Schwann cell graft transplantation to promote optic nerve regeneration in adult rats.

    PubMed

    Fang, Yuan; Mo, Xiaofen; Guo, Wenyi; Zhang, Meng; Zhang, Peihua; Wang, Yan; Rong, Xianfang; Tian, Jie; Sun, Xinghuai

    2010-12-01

    Like other parts of the central nervous system, the adult mammalian optic nerve is difficult to regenerate after injury. Transplantation of the peripheral nerve or a Schwann cell (SC) graft can promote injured axonal regrowth. We tried to develop a new type of tissue-engineered SC graft that consisted of SCs seeded onto a poly(lactic-co-glycolic acid)/chitosan conduit. Meanwhile, SCs were transfected along the ciliary neurotrophic factor (CNTF) gene in vitro by electroporation to increase their neurotrophic effect. Four weeks after transplantation, GAP-43 labelled regenerating axons were found in the SC grafts, and axons in the CNTF-SC graft were longer than those in the SC graft. Tissue-engineered SC grafts can provide a feasible environment for optic nerve regeneration and may become an alternative for bridging damaged nerves and repairing nerve defects in the future.

  9. Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells.

    PubMed

    Kozako, Tomohiro; Soeda, Shuhei; Yoshimitsu, Makoto; Arima, Naomichi; Kuroki, Ayako; Hirata, Shinya; Tanaka, Hiroaki; Imakyure, Osamu; Tone, Nanako; Honda, Shin-Ichiro; Soeda, Shinji

    2016-05-01

    Adult T-cell leukemia/lymphoma (ATL), an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukemia virus (HTLV-1), requires new treatments. Drug repositioning, reuse of a drug previously approved for the treatment of another condition to treat ATL, offers the possibility of reduced time and risk. Among clinically available angiotensin II receptor blockers, telmisartan is well known for its unique ability to activate peroxisome proliferator-activated receptor-γ, which plays various roles in lipid metabolism, cellular differentiation, and apoptosis. Here, telmisartan reduced cell viability and enhanced apoptotic cells via caspase activation in ex vivo peripheral blood monocytes from asymptomatic HTLV-1 carriers (ACs) or via caspase-independent cell death in acute-type ATL, which has a poor prognosis. Telmisartan also induced significant growth inhibition and apoptosis in leukemia cell lines via caspase activation, whereas other angiotensin II receptor blockers did not induce cell death. Interestingly, telmisartan increased the LC3-II-enriched protein fraction, indicating autophagosome accumulation and autophagy. Thus, telmisartan simultaneously caused caspase activation and autophagy. A hypertension medication with antiproliferation effects on primary and leukemia cells is intriguing. Patients with an early diagnosis of ATL are generally monitored until the disease progresses; thus, suppression of progression from AC and indolent ATL to acute ATL is important. Our results suggest that telmisartan is highly effective against primary cells and leukemia cell lines in caspase-dependent and -independent manners, and its clinical use may suppress acute transformation and improve prognosis of patients with this mortal disease. This is the first report demonstrating a cell growth-inhibitory effect of telmisartan in fresh peripheral blood mononuclear cells from leukemia patients. PMID:27419050

  10. Cloning of calves from various somatic cell types of male and female adult, newborn and fetal cows.

    PubMed

    Kato, Y; Tani, T; Tsunoda, Y

    2000-11-01

    Twenty-four calves were cloned from six somatic cell types of female and male adult, newborn and fetal cows. The clones were derived from female cumulus (n = 3), oviduct (n = 2) and uterine (n = 2) cells, female and male skin cells (n = 10), and male ear (n = 5) and liver (n = 2) cells. On the basis of the number of cloned embryos transferred (n = 172) to surrogate cows, the overall rate of success was 14%, but based on the number of surrogate mothers that became pregnant (n = 50), the success rate was 48%. Cell nuclei from uterus, ear and liver cells, which have not been tested previously, developed into newborn calves after nuclear transfer into enucleated oocytes. To date, seven female and six male calves have survived: six of the females were from adult cells (cumulus (n = 3), oviduct (n = 2) and skin (n = 1) cells) and one was from newborn skin cells, whereas the male calves were derived from adult ear cells (n = 3), newborn liver and skin cells (n = 2), and fetal cells (n = 1). Clones derived from adult cells frequently aborted in the later stages of pregnancy and calves developing to term showed a higher number of abnormalities than did those derived from newborn or fetal cells. The telomeric DNA lengths in the ear cells of three male calves cloned from the ear cells of a bull aged 10 years were similar to those of the original bull. However, the telomeric DNA lengths from the white blood cells of the clones, although similar to those in an age-matched control, were shorter than those of the original bull, which indicates that telomeric shortening varies among tissues.

  11. [Molecular pathogenesis of peripheral T cell lymphoma (2): extranodal NK/T cell lymphoma, nasal type, adult T cell leukemia/lymphoma and enteropathy associated T cell lymphoma].

    PubMed

    Couronné, Lucile; Bastard, Christian; Gaulard, Philippe; Hermine, Olivier; Bernard, Olivier

    2015-11-01

    Peripheral T-cell lymphomas (PTCL) belong to the group of non-Hodgkin lymphoma and particularly that of mature T /NK cells lymphoproliferative neoplasms. The 2008 WHO classification describes different PTCL entities with varying prevalence. With the exception of histologic subtype "ALK positive anaplastic large cell lymphoma", PTCL are characterized by a poor prognosis. The mechanisms underlying the pathogenesis of these lymphomas are not yet fully understood, but development of genomic high-throughput analysis techniques now allows to extensively identify the molecular abnormalities present in tumor cells. This review aims to summarize the current knowledge and recent advances about the molecular events occurring at the origin or during the natural history of main entities of PTCL. The first part published in the October issue was focused on the three more frequent entities, i.e. angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, and anaplastic large cell lymphoma. The second part presented herein will describe other subtypes less frequent and of poor prognosis : extranodal NK/T-cell lymphoma, nasal type, adult T-cell leukemia/lymphoma, and enteropathy-associated T-cell lymphoma. PMID:26576610

  12. Principles of connectivity among morphologically defined cell types in adult neocortex.

    PubMed

    Jiang, Xiaolong; Shen, Shan; Cadwell, Cathryn R; Berens, Philipp; Sinz, Fabian; Ecker, Alexander S; Patel, Saumil; Tolias, Andreas S

    2015-11-27

    Since the work of Ramón y Cajal in the late 19th and early 20th centuries, neuroscientists have speculated that a complete understanding of neuronal cell types and their connections is key to explaining complex brain functions. However, a complete census of the constituent cell types and their wiring diagram in mature neocortex remains elusive. By combining octuple whole-cell recordings with an optimized avidin-biotin-peroxidase staining technique, we carried out a morphological and electrophysiological census of neuronal types in layers 1, 2/3, and 5 of mature neocortex and mapped the connectivity between more than 11,000 pairs of identified neurons. We categorized 15 types of interneurons, and each exhibited a characteristic pattern of connectivity with other interneuron types and pyramidal cells. The essential connectivity structure of the neocortical microcircuit could be captured by only a few connectivity motifs.

  13. Transforming growth factor type beta specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells.

    PubMed Central

    Chen, J K; Hoshi, H; McKeehan, W L

    1987-01-01

    Myo-intimal proteoglycan metabolism is thought to be important in blood vessel homeostasis, blood clotting, atherogenesis, and atherosclerosis. Human platelet-derived transforming growth factor type beta (TGF-beta) specifically stimulated synthesis of at least two types of chondroitin sulfate proteoglycans in nonproliferating human adult arterial smooth muscle cells in culture. Stimulation of smooth muscle cell proteoglycan synthesis by smooth muscle cell growth promoters (epidermal growth factor, platelet-derived growth factor, and heparin-binding growth factors) was less than 20% of that elicited by TGF-beta. TGF-beta neither significantly stimulated proliferation of quiescent smooth muscle cells nor inhibited proliferating cells. The extent of TGF-beta stimulation of smooth muscle cell proteoglycan synthesis was similar in both nonproliferating and growth-stimulated cells. TGF-beta, which is a reversible inhibitor of endothelial cell proliferation, had no comparable effect on endothelial cell proteoglycan synthesis. These results are consistent with the hypothesis that TGF-beta is a cell-type-specific regulator of proteoglycan synthesis in human blood vessels and may contribute to the myo-intimal accumulation of proteoglycan in atherosclerotic lesions. Images PMID:3474655

  14. Response to Comment on "Principles of connectivity among morphologically defined cell types in adult neocortex".

    PubMed

    Jiang, Xiaolong; Shen, Shan; Sinz, Fabian; Reimer, Jacob; Cadwell, Cathryn R; Berens, Philipp; Ecker, Alexander S; Patel, Saumil; Denfield, George H; Froudarakis, Emmanouil; Li, Shuang; Walker, Edgar; Tolias, Andreas S

    2016-09-01

    The critique of Barth et al centers on three points: (i) the completeness of our study is overstated; (ii) the connectivity matrix we describe is biased by technical limitations of our brain-slicing and multipatching methods; and (iii) our cell classification scheme is arbitrary and we have simply renamed previously identified interneuron types. We address these criticisms in our Response. PMID:27609883

  15. Response to Comment on "Principles of connectivity among morphologically defined cell types in adult neocortex".

    PubMed

    Jiang, Xiaolong; Shen, Shan; Sinz, Fabian; Reimer, Jacob; Cadwell, Cathryn R; Berens, Philipp; Ecker, Alexander S; Patel, Saumil; Denfield, George H; Froudarakis, Emmanouil; Li, Shuang; Walker, Edgar; Tolias, Andreas S

    2016-09-01

    The critique of Barth et al centers on three points: (i) the completeness of our study is overstated; (ii) the connectivity matrix we describe is biased by technical limitations of our brain-slicing and multipatching methods; and (iii) our cell classification scheme is arbitrary and we have simply renamed previously identified interneuron types. We address these criticisms in our Response.

  16. Mediation of Autophagic Cell Death by Type 3 Ryanodine Receptor (RyR3) in Adult Hippocampal Neural Stem Cells

    PubMed Central

    Chung, Kyung Min; Jeong, Eun-Ji; Park, Hyunhee; An, Hyun-Kyu; Yu, Seong-Woon

    2016-01-01

    Cytoplasmic Ca2+ actively engages in diverse intracellular processes from protein synthesis, folding and trafficking to cell survival and death. Dysregulation of intracellular Ca2+ levels is observed in various neuropathological states including Alzheimer’s and Parkinson’s diseases. Ryanodine receptors (RyRs) and inositol 1,4,5-triphosphate receptors (IP3Rs), the main Ca2+ release channels located in endoplasmic reticulum (ER) membranes, are known to direct various cellular events such as autophagy and apoptosis. Here we investigated the intracellular Ca2+-mediated regulation of survival and death of adult hippocampal neural stem (HCN) cells utilizing an insulin withdrawal model of autophagic cell death (ACD). Despite comparable expression levels of RyR and IP3R transcripts in HCN cells at normal state, the expression levels of RyRs—especially RyR3—were markedly upregulated upon insulin withdrawal. While treatment with the RyR agonist caffeine significantly promoted the autophagic death of insulin-deficient HCN cells, treatment with its inhibitor dantrolene prevented the induction of autophagy following insulin withdrawal. Furthermore, CRISPR/Cas9-mediated knockout of the RyR3 gene abolished ACD of HCN cells. This study delineates a distinct, RyR3-mediated ER Ca2+ regulation of autophagy and programmed cell death in neural stem cells. Our findings provide novel insights into the critical, yet understudied mechanisms underlying the regulatory function of ER Ca2+ in neural stem cell biology. PMID:27199668

  17. Potential in two types of collagen scaffolds for urological tissue engineering applications - Are there differences in growth behaviour of juvenile and adult vesical cells?

    PubMed

    Leonhäuser, D; Vogt, M; Tolba, R H; Grosse, J O

    2016-02-01

    The aging society has a deep impact on patient care in urology. The number of patients in need of partial or whole bladder wall replacement is increasing simultaneously with the number of cancer incidents. Therefore, urological research requires a model of bladder wall replacement in adult and elderly people. Two types of porcine collagen I/III scaffolds were used in vitro for comparison of cell growth of two different pig breeds at different growth stages. Scaffolds were characterised with scanning electron and laser scanning microscopy. Urothelial and detrusor smooth muscle cells were isolated from 15 adult Göttingen minipigs and 15 juvenile German Landrace pigs. Growth behaviour was examined in cell culture and seeded onto the collagen scaffolds via immunohistochemistry, two-photon laser scanning microscopy and a viability assay. The collagen scaffolds showed different structured surfaces which are appropriate for seeding of the two different cell types. Moisturisation of the scaffolds resulted in a change of the structure. Cell growth of German Landrace urothelial cells and smooth muscle cells was significantly higher than cell growth of the Göttingen minipig cells. Seeding of scaffolds with both cell types from both pig races was possible which could be shown by immunohistochemistry and two-photon laser scanning microscopy. Growth behaviour on the scaffolds was significantly increased for the German Landrace compared to Göttingen minipig. Nevertheless, seeding with the adult Göttingen minipig cells resulted in a closed layer on the surface and urothelial cells and smooth muscle cells showed increasing growth until day 14. The results show that these collagen scaffolds are adequate for the seeding with vesical cells. Moreover, they seem appropriate for the use as an in vitro model for the adult or elderly as the cells of the adult Göttingen minipig too, show good growth behaviour.

  18. Identification and Validation of Differential Phosphorylation Sites of the Nuclear FOXL2 Protein as Potential Novel Biomarkers for Adult-Type Granulosa Cell Tumors.

    PubMed

    Suh, Dae-Shik; Oh, Hoon Kyu; Kim, Jae-Hong; Park, Seeun; Shin, Eunkyoung; Lee, Kangseok; Kim, Yong-Hak; Bae, Jeehyeon

    2015-06-01

    Granulosa cell tumor (GCT) is a rare form of ovarian cancer classified as a sex cord-stromal tumor. The c.402C→G missense mutation in the FOXL2 gene that changes cysteine 134 to tryptophan (C134W) is found in more than 97% of adult-type GCTs, and the C134W FOXL2 mutant is hyperphosphorylated. We identified three differential phosphorylation sites, at serine 33 (S33), tyrosine 186 (Y186), and serine 238 (S238), of the C134W mutant by tandem mass spectrometry. Among these sites, antibodies were raised against the pS33 and pY186 epitopes using specific peptides, and they were tested by immunostaining tissue microarrays of archival adult-type GCT specimens, other tumors, and normal tissues. The pS33 antibody showed greater sensitivity and specificity for the detection of adult-type GCTs than that of the other phospho and nonphospho antibodies. The specificity of the pS33 antibody to the pS33 epitope was further confirmed by enriching the pS33 peptide by affinity chromatography using the immobilized antibody, followed by mass spectrometric and western blot analyses from whole cell lysates of the adult-type GCT cell line, KGN. pS33 FOXL2 immunostaining levels were significantly higher in adult-type GCTs than those in other tumors and tissues. The receiver operating characteristic curve analysis of pS33 FOXL2 showed high sensitivity (1.0) and specificity (0.76) to adult-type GCTs with a cutoff score of >30% positive cells, and the area under the curve was 0.96. This suggests the potential of pS33 FOXL2 to serve as a new biomarker for the diagnosis of adult-type GCT.

  19. The Bone Morphogenetic Protein Type Ib Receptor Is a Major Mediator of Glial Differentiation and Cell Survival in Adult Hippocampal Progenitor Cell Culture

    PubMed Central

    Brederlau, A.; Faigle, R.; Elmi, M.; Zarebski, A.; Sjöberg, S.; Fujii, M.; Miyazono, K.; Funa, K.

    2004-01-01

    Bone morphogenetic proteins (BMPs) act as growth regulators and inducers of differentiation. They transduce their signal via three different type I receptors, termed activin receptor-like kinase 2 (Alk2), Alk3, or bone morphogenetic protein receptor Ia (BMPRIa) and Alk6 or BMPRIb. Little is known about functional differences between the three type I receptors. Here, we have investigated consequences of constitutively active (ca) and dominant negative (dn) type I receptor overexpression in adult-derived hippocampal progenitor cells (AHPs). The dn receptors have a nonfunctional intracellular but functional extracellular domain. They thus trap BMPs that are endogenously produced by AHPs. We found that effects obtained by overexpression of dnAlk2 and dnAlk6 were similar, suggesting similar ligand binding patterns for these receptors. Thus, cell survival was decreased, glial fibrillary acidic protein (GFAP) expression was reduced, whereas the number of oligodendrocytes increased. No effect on neuronal differentiation was seen. Whereas the expression of Alk2 and Alk3 mRNA remained unchanged, the Alk6 mRNA was induced after impaired BMP signaling. After dnAlk3 overexpression, cell survival and astroglial differentiation increased in parallel to augmented Alk6 receptor signaling. We conclude that endogenous BMPs mediate cell survival, astroglial differentiation and the suppression of oligodendrocytic cell fate mainly via the Alk6 receptor in AHP culture. PMID:15194807

  20. Adult T-cell leukemia-lymphoma in a pregnant woman diagnosed as a human T-cell lymphotropic virus type 1 carrier.

    PubMed

    Fuchi, Naoki; Miura, Kiyonori; Imaizumi, Yoshitaka; Hasegawa, Hiroo; Yanagihara, Katsunori; Miyazaki, Yasushi; Masuzaki, Hideaki

    2016-03-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia-lymphoma (ATL), which is difficult to cure. In Japan, a nationwide HTLV-1 screening test in pregnant women has been recommended since 2011. A 30-year-old woman was diagnosed as being an HTLV-1 carrier in her previous pregnancy. During the current pregnancy, she had persistent fever and cough. Although she had treatment with antibiotics, peripheral white blood cell count remained high, with an abnormal lymphocyte count. Given that she was an HTLV-1 carrier, she was diagnosed with unfavorable chronic ATL (aggressive ATL) at 12 weeks gestation. After pregnancy termination, her ATL status became favorable chronic ATL (indolent ATL). Therefore, watchful waiting was performed until disease progression. This is the first case report of chronic ATL in early pregnancy, in a woman already diagnosed as an HTLV-1 carrier on screening test. PMID:26663442

  1. Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.

    PubMed

    Lu, Chenggang; Fuller, Margaret T

    2015-12-01

    Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s). In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC), a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs), spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages. PMID:26624996

  2. Induction of Adult T-Cell Leukemia-Like Lymphoproliferative Disease and Its Inhibition by Adoptive Immunotherapy in T-Cell-Deficient Nude Rats Inoculated with Syngeneic Human T-Cell Leukemia Virus Type 1-Immortalized Cells

    PubMed Central

    Ohashi, Takashi; Hanabuchi, Shino; Kato, Hirotomo; Koya, Yoshihiro; Takemura, Fumiyo; Hirokawa, Katsuiku; Yoshiki, Takashi; Tanaka, Yuetsu; Fujii, Masahiro; Kannagi, Mari

    1999-01-01

    Human T-cell leukemia virus type 1 (HTLV-1) has been shown to be the etiologic agent of adult T-cell leukemia (ATL), but the in vivo mechanism by which the virus causes the malignant transformation is largely unknown. In order to investigate the mechanisms of HTLV-1 leukemogenesis, we developed a rat model system in which ATL-like disease was reproducibly observed, following inoculation of various rat HTLV-1-immortalized cell lines. When previously established cell lines, F344-S1 and TARS-1, but not TART-1 or W7TM-1, were inoculated, systemic multiple tumor development was observed in adult nude (nu/nu) rats. FPM1 cells, newly established from a heterozygous (nu/+) rat syngeneic to nu/nu rats, caused transient tumors only at the injection site in adult nu/nu rats, but could progressively grow in newborn nu/nu rats and metastasize in lymph nodes. The derivative cell line (FPM1-V1AX) serially passed through newborn nu/nu rats acquired the potency to grow in adult nu/nu rats. These results indicated that only some with additional changes but not all of the in vitro HTLV-1-immortalized cell lines possessed in vivo tumorigenicity. Using the syngeneic system, we further showed the inhibition of tumor development by transferring splenic T cells from immunized rats, suggesting the involvement of T cells in the regression of tumors. This novel and reproducible nude rat model of human ATL would be useful for investigation of leukemogenesis and antitumor immune responses in HTLV-1 infection. PMID:10364355

  3. Human T-cell lymphotropic virus type I-associated adult T-cell leukemia-lymphoma: new directions in clinical research.

    PubMed

    Tsukasaki, Kunihiro; Tobinai, Kensei

    2014-10-15

    Adult T-cell leukemia-lymphoma (ATL) is a distinct malignancy of regulatory T cell (Treg)/TH2 cells caused by human T-cell lymphotropic virus type I (HTLV-1), with a high frequency of expression of CD3/CD4/CD25/CCR4 and FoxP3 in about half of the cells. However, in primary ATL cells, although expression of the virus, including the Tax oncoprotein, appears just after an in vitro culture, integration sites of the provirus into the host genome are random, and chromosomal/genetic abnormalities are complex. ATL is thus a single disease entity that is caused by HTLV-1 and possesses diverse molecular features. The clinical features and prognosis of ATL vary, and this has led to subtypes classified into four categories: acute, lymphomatous, chronic, and smoldering types, based on lactate dehydrogenase and calcium values and organ involvement. Approximately 15 to 20 million individuals are infected with HTLV-1 worldwide, 1.1 million of whom reside in Japan, and the annual incidence of ATL has been estimated to be approximately 1,000. HTLV-1 infection early in life, mainly from breast feeding, is crucial for the development of ATL. The age-specific occurrence of ATL and complex genome abnormalities that accumulate with disease progression suggest a multistep carcinogenesis model following HTLV-1 infection. Various treatment options are available for ATL and consist of watchful waiting for indolent ATL, intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation for aggressive ATL, and a combination of IFNα and zidovudine for ATL with leukemic manifestation. Several promising new agents, including an anti-CCR4 antibody, are currently undergoing clinical trials associated with translational research. See all articles in this CCR Focus section, "Paradigm Shifts in Lymphoma." PMID:25320371

  4. Generalized Potential of Adult Neural Stem Cells

    NASA Astrophysics Data System (ADS)

    Clarke, Diana L.; Johansson, Clas B.; Wilbertz, Johannes; Veress, Biborka; Nilsson, Erik; Karlström, Helena; Lendahl, Urban; Frisén, Jonas

    2000-06-01

    The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

  5. Immunocytochemical and ultrastructural identification of pituitary cell types in the protogynous Thalassoma duperrey during adult sexual ontogeny

    USGS Publications Warehouse

    Parhar, I.S.; Nagahama, Y.; Grau, E.G.; Ross, R.M.

    1998-01-01

    Protogynous wrasses (Thalassoma duperrey): females (F), primary males (PM) along with a few terminal-phase males (TM) and sex-changed males (SM), were used to characterize the topographical organization of the pituitary. In general, immunocytochemical and ultrastructural features of the adenohypophyseal cell types of the saddleback wrasse pituitary resemble those of other teleosts. In the rostral pars distalis (RPD), corticotropic cells were found bordering the neurohypophysis (NH) and surrounding the centroventrally located prolactin cells. Thyrotropic cells formed a small group in the anteriodorsal part of the rostral and proximal pars distalis (PPD). The somatotropic cells were distributed in large clusters, mostly organized in cell cords around the interdigitations of the NH of the dorsal PPD. Cells containing gonadotropin I?? subunit were localized in the dorsal parts of the PPD, in close association with somatotropic cells and gonadotropin II?? subunit containing cells were seen in the centroventral parts of the PPD and along the periphery of the pars intermedia (PI). The pars intermedia was composed of melanotropic cells and somatolactin cells that lined the neurohypohysis. Distinct ultrastructural differences in corticotropic and somatotropic cells were not observed between the four groups. In all groups, prolactin cells in the ventral-most RPD could be immature cells or actively secreting prolactin. Gonadotropic II cells of PM and F had relatively higher incidence of "nuclear budding" and cell organelles compared to TM and SM. Besides gonadotropic, the active melanotropic and somatolactin cells might be associated with some aspect(s) of reproduction.

  6. Progenitor cells in the adult pancreas.

    PubMed

    Holland, Andrew M; Góñez, L Jorge; Harrison, Leonard C

    2004-01-01

    The beta-cell mass in the adult pancreas possesses the ability to undergo limited regeneration following injury. Identifying the progenitor cells involved in this process and understanding the mechanisms leading to their maturation will open new avenues for the treatment of type 1 diabetes. However, despite steady advances in determining the molecular basis of early pancreatic development, the identification of pancreatic stem cells or beta-cell progenitors and the molecular mechanisms underlying beta-cell regeneration remain unclear. Recent advances in the directed differentiation of embryonic and adult stem cells has heightened interest in the possible application of stem cell therapy in the treatment of type 1 diabetes. Drawing on the expanding knowledge of pancreas development, beta-cell regeneration and stem cell research, this review focuses on progenitor cells in the adult pancreas as a potential source of beta-cells. PMID:14737742

  7. Adult Stem and Progenitor Cells

    NASA Astrophysics Data System (ADS)

    Geraerts, Martine; Verfaillie, Catherine M.

    The discovery of adult stem cells in most adult tissues is the basis of a number of clinical studies that are carried out, with therapeutic use of hematopoietic stem cells as a prime example. Intense scientific debate is still ongoing as to whether adult stem cells may have a greater plasticity than previously thought. Although cells with some features of embryonic stem cells that, among others, express Oct4, Nanog and SSEA1 are isolated from fresh tissue, it is not clear if the greater differentiation potential is acquired during cell culture. Moreover, adult more pluripotent cells do not have all pluripotent characteristics typical for embryonic stem cells. Recently, some elegant studies were published in which adult cells could be completely reprogrammed to embryonic stem cell-like cells by overexpression of some key transcription factors for pluripotency (Oct4, Sox2, Klf4 and c-Myc). It will be interesting for the future to investigate the exact mechanisms underlying this reprogramming and whether similar transcription factor pathways are present and/or can be activated in adult more pluripotent stem cells.

  8. Adult Mouse Cortical Cell Taxonomy by Single Cell Transcriptomics

    PubMed Central

    Tasic, Bosiljka; Menon, Vilas; Nguyen, Thuc Nghi; Kim, Tae Kyung; Jarsky, Tim; Yao, Zizhen; Levi, Boaz; Gray, Lucas T.; Sorensen, Staci A.; Dolbeare, Tim; Bertagnolli, Darren; Goldy, Jeff; Shapovalova, Nadiya; Parry, Sheana; Lee, Changkyu; Smith, Kimberly; Bernard, Amy; Madisen, Linda; Sunkin, Susan M.; Hawrylycz, Michael; Koch, Christof; Zeng, Hongkui

    2016-01-01

    Nervous systems are composed of various cell types, but the extent of cell type diversity is poorly understood. Here, we construct a cellular taxonomy of one cortical region, primary visual cortex, in adult mice based on single cell RNA-sequencing. We identify 49 transcriptomic cell types including 23 GABAergic, 19 glutamatergic and seven non-neuronal types. We also analyze cell-type specific mRNA processing and characterize genetic access to these transcriptomic types by many transgenic Cre lines. Finally, we show that some of our transcriptomic cell types display specific and differential electrophysiological and axon projection properties, thereby confirming that the single cell transcriptomic signatures can be associated with specific cellular properties. PMID:26727548

  9. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics.

    PubMed

    Tasic, Bosiljka; Menon, Vilas; Nguyen, Thuc Nghi; Kim, Tae Kyung; Jarsky, Tim; Yao, Zizhen; Levi, Boaz; Gray, Lucas T; Sorensen, Staci A; Dolbeare, Tim; Bertagnolli, Darren; Goldy, Jeff; Shapovalova, Nadiya; Parry, Sheana; Lee, Changkyu; Smith, Kimberly; Bernard, Amy; Madisen, Linda; Sunkin, Susan M; Hawrylycz, Michael; Koch, Christof; Zeng, Hongkui

    2016-02-01

    Nervous systems are composed of various cell types, but the extent of cell type diversity is poorly understood. We constructed a cellular taxonomy of one cortical region, primary visual cortex, in adult mice on the basis of single-cell RNA sequencing. We identified 49 transcriptomic cell types, including 23 GABAergic, 19 glutamatergic and 7 non-neuronal types. We also analyzed cell type-specific mRNA processing and characterized genetic access to these transcriptomic types by many transgenic Cre lines. Finally, we found that some of our transcriptomic cell types displayed specific and differential electrophysiological and axon projection properties, thereby confirming that the single-cell transcriptomic signatures can be associated with specific cellular properties.

  10. Neural Crest As the Source of Adult Stem Cells

    PubMed Central

    Pierret, Chris; Spears, Kathleen; Maruniak, Joel A.; Kirk, Mark D.

    2012-01-01

    Recent studies suggest that adult stem cells can cross germ layer boundaries. For example, bone marrow-derived stem cells appear to differentiate into neurons and glial cells, as well as other types of cells. How can stem cells from bone marrow, pancreas, skin, or fat become neurons and glia; in other words, what molecular and cellular events direct mesodermal cells to a neural fate? Transdifferentiation, dediffereniation, and fusion of donor adult stem cells with fully differentiated host cells have been proposed to explain the plasticity of adult stem cells. Here we review the origin of select adult stem cell populations and propose a unifying hypothesis to explain adult stem cell plasticity. In addition, we outline specific experiments to test our hypothesis. We propose that peripheral, tissue-derived, or adult stem cells are all progeny of the neural crest. PMID:16646675

  11. Activation of hypoxia-inducible factor 1 in human T-cell leukaemia virus type 1-infected cell lines and primary adult T-cell leukaemia cells

    PubMed Central

    Tomita, Mariko; Semenza, Gregg L.; Michiels, Canine; Matsuda, Takehiro; Uchihara, Jun-Nosuke; Okudaira, Taeko; Tanaka, Yuetsu; Taira, Naoya; Ohshiro, Kazuiku; Mori, Naoki

    2007-01-01

    HTLV-1 (human T-cell leukaemia virus type 1) is the causative agent for ATL (adult T-cell leukaemia). HTLV-1 Tax can activate the PI3K (phosphoinositide 3-kinase)/Akt signalling pathway, which is responsible for survival of HTLV-1-infected T-cells. HIFs (hypoxia-inducible factors) are transcriptional regulators that play a central role in the response to hypoxia. Overexpression of HIF-1α in many cancers is associated with a poor response to treatment and increased patient mortality. Our objectives in the present study were to investigate whether HIF-1 was activated in HTLV-1-infected T-cells and to elucidate the molecular mechanisms of HIF-1 activation by focusing on the PI3K/Akt signalling pathway. We detected a potent pathway that activated HIF-1 in the HTLV-1-infected T-cells under a normal oxygen concentration. Enhanced HIF-1α protein expression and HIF-1 DNA-binding activity were exhibited in HTLV-1-infected T-cell lines. Knockdown of HIF-1α by siRNA (small interfering RNA) suppressed the growth and VEGF (vascular endothelial growth factor) expression of the HTLV-1-infected T-cell line. HIF-1 protein accumulation and transcriptional activity were enhanced by Tax, which was inhibited by dominant-negative Akt. Importantly, mutant forms of Tax that are defective in activation of the PI3K/Akt pathway failed to induce HIF-1 transcriptional activity. The PI3K inhibitor LY294002 suppressed HIF-1α protein expression, HIF-1 DNA-binding and HIF-1 transcriptional activity in HTLV-1-infected T-cell lines. In primary ATL cells, HIF-1α protein levels were strongly correlated with levels of phosphorylated Akt. The results of the present study suggest that PI3K/Akt activation induced by Tax leads to activation of HIF-1. As HIF-1 plays a major role in tumour progression, it may represent a molecular target for the development of novel ATL therapeutics. PMID:17576198

  12. Adult Stem Cell Responses to Nanostimuli

    PubMed Central

    Tsimbouri, Penelope M.

    2015-01-01

    Adult or mesenchymal stem cells (MSCs) have been found in different tissues in the body, residing in stem cell microenvironments called “stem cell niches”. They play different roles but their main activity is to maintain tissue homeostasis and repair throughout the lifetime of an organism. Their ability to differentiate into different cell types makes them an ideal tool to study tissue development and to use them in cell-based therapies. This differentiation process is subject to both internal and external forces at the nanoscale level and this response of stem cells to nanostimuli is the focus of this review. PMID:26193326

  13. Antibody to the central region of human T-lymphotropic virus type 1 gp46 is associated with the progression of adult T-cell leukemia.

    PubMed

    Sagara, Yasuko; Inoue, Yukiko; Ohshima, Koichi; Kojima, Eijiro; Utsunomiya, Atae; Tsujimura, Mitsushi; Shiraki, Hiroshi; Kashiwagi, Seizaburo

    2007-02-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia/lymphoma (ATL). HTLV-1 is spread by cell-to-cell transmission via the gp46-197 region, Asp197 to Leu216, on the envelope protein gp46. In the present study, we revealed a positive correlation between the appearance of an antibody recognizing the gp46-197 region (anti-gp46-197 antibody) and the severity of ATL. The prevalence and titer of the anti-gp46-197 antibody were found to be elevated along with the progression of ATL. In serial samples obtained from a single patient, the anti-gp46-197 antibody was detected before treatment in acute phase, then diminished after allogeneic bone marrow transplantation, to which the patient had a complete response. However, the antibody appeared again before a relapse, along with an increase of the serum-soluble interleukin-2 receptor level and proviral load. The results from the other six patients also indicate that seroconversion of this antibody was synchronized with the deterioration of ATL. Taken together, the findings indicate that the anti-gp46-197 antibody may be a novel beacon for gauging the efficacy of therapeutic approaches to ATL, and a survey of this antibody would be useful for identifying asymptomatic carriers infected with HTLV-1 who are at high risk of developing ATL.

  14. Adult stem-like cells in kidney

    PubMed Central

    Hishikawa, Keiichi; Takase, Osamu; Yoshikawa, Masahiro; Tsujimura, Taro; Nangaku, Masaomi; Takato, Tsuyoshi

    2015-01-01

    Human pluripotent cells are promising for treatment for kidney diseases, but the protocols for derivation of kidney cell types are still controversial. Kidney tissue regeneration is well confirmed in several lower vertebrates such as fish, and the repair of nephrons after tubular damages is commonly observed after renal injury. Even in adult mammal kidney, renal progenitor cell or system is reportedly presents suggesting that adult stem-like cells in kidney can be practical clinical targets for kidney diseases. However, it is still unclear if kidney stem cells or stem-like cells exist or not. In general, stemness is defined by several factors such as self-renewal capacity, multi-lineage potency and characteristic gene expression profiles. The definite use of stemness may be obstacle to understand kidney regeneration, and here we describe the recent broad findings of kidney regeneration and the cells that contribute regeneration. PMID:25815133

  15. Adult stem-like cells in kidney.

    PubMed

    Hishikawa, Keiichi; Takase, Osamu; Yoshikawa, Masahiro; Tsujimura, Taro; Nangaku, Masaomi; Takato, Tsuyoshi

    2015-03-26

    Human pluripotent cells are promising for treatment for kidney diseases, but the protocols for derivation of kidney cell types are still controversial. Kidney tissue regeneration is well confirmed in several lower vertebrates such as fish, and the repair of nephrons after tubular damages is commonly observed after renal injury. Even in adult mammal kidney, renal progenitor cell or system is reportedly presents suggesting that adult stem-like cells in kidney can be practical clinical targets for kidney diseases. However, it is still unclear if kidney stem cells or stem-like cells exist or not. In general, stemness is defined by several factors such as self-renewal capacity, multi-lineage potency and characteristic gene expression profiles. The definite use of stemness may be obstacle to understand kidney regeneration, and here we describe the recent broad findings of kidney regeneration and the cells that contribute regeneration. PMID:25815133

  16. Treating young adults with type 2 diabetes or monogenic diabetes.

    PubMed

    Owen, Katharine R

    2016-06-01

    It is increasingly recognised that diabetes in young adults has a wide differential diagnosis. There are many monogenic causes, including monogenic beta-cell dysfunction, mitochondrial diabetes and severe insulin resistance. Type 2 diabetes in the young is becoming more prevalent, particularly after adolescence. It's important to understand the clinical features and diagnostic tools available to classify the different forms of young adult diabetes. Classic type 1 diabetes is characterised by positive β-cell antibodies and absence of endogenous insulin secretion. Young type 2 diabetes is accompanied by metabolic syndrome with obesity, hypertension and dyslipidaemia. Monogenic β-cell dysfunction is characterised by non-autoimmune, C-peptide positive diabetes with a strong family history, while mitochondrial diabetes features deafness and other neurological involvement. Severe insulin resistance involves a young-onset metabolic syndrome often with a disproportionately low BMI. A suspected diagnosis of monogenic diabetes is confirmed with genetic testing, which is widely available in specialist centres across the world. Treatment of young adult diabetes is similarly diverse. Mutations in the transcription factors HNF1A and HNF4A and in the β-cell potassium ATP channel components cause diabetes which responds to low dose and high dose sulfonylurea agents, respectively, while glucokinase mutations require no treatment. Monogenic insulin resistance and young-onset type 2 diabetes are both challenging to treat, but first line management involves insulin sensitisers and aggressive management of cardiovascular risk. Outcomes are poor in young-onset type 2 diabetes compared to both older onset type 2 and type 1 diabetes diagnosed at a similar age. The evidence base for treatments in monogenic and young-onset type 2 diabetes relies on studies of moderate quality at best and largely on extrapolation from work conducted in older type 2 diabetes subjects. Better quality

  17. Adult neural stem cells stake their ground

    PubMed Central

    Lim, Daniel A.; Alvarez-Buylla, Arturo

    2014-01-01

    The birth of new neurons in the walls of the adult brain lateral ventricles has captured the attention of many neuroscientists for over two decades, yielding key insights into the identity and regulation of neural stem cells (NSCs). In the adult ventricular-subventricular zone (V-SVZ), NSCs are a specialized form of astrocyte that generates several types of neurons for the olfactory bulb. Here we discuss recent findings regarding the unique organization of the V-SVZ NSCs niche, the multiple regulatory controls of neuronal production, the distinct regional identities of adult NSCs, and the epigenetic mechanisms that maintain adult neurogenesis. Understanding how V-SVZ NSCs establish and maintain lifelong neurogenesis continues to provide surprising insights into the cellular and molecular regulation of neural development. PMID:25223700

  18. [Langerhans cell histiocytosis in adults].

    PubMed

    Néel, A; Artifoni, M; Donadieu, J; Lorillon, G; Hamidou, M; Tazi, A

    2015-10-01

    Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells, most often organized in granulomas. The disease has been initially described in children. The clinical picture of LCH is highly variable. Bone, skin, pituitary gland, lung, central nervous system, lymphoid organs are the main organs involved whereas liver and intestinal tract localizations are less frequently encountered. LCH course ranges from a fulminant multisystem disease to spontaneous resolution. Several randomized controlled trials have enable pediatricians to refine the management of children with LCH. Adult LCH has some specific features and poses distinct therapeutic challenges, knowing that data on these patients are limited. Herein, we will provide an overview of current knowledge regarding adult LCH and its management. We will also discuss recent advances in the understanding of the disease, (i.e. the role of BRAF oncogene) that opens the way toward targeted therapies.

  19. [Langerhans cell histiocytosis in adults].

    PubMed

    Néel, A; Artifoni, M; Donadieu, J; Lorillon, G; Hamidou, M; Tazi, A

    2015-10-01

    Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells, most often organized in granulomas. The disease has been initially described in children. The clinical picture of LCH is highly variable. Bone, skin, pituitary gland, lung, central nervous system, lymphoid organs are the main organs involved whereas liver and intestinal tract localizations are less frequently encountered. LCH course ranges from a fulminant multisystem disease to spontaneous resolution. Several randomized controlled trials have enable pediatricians to refine the management of children with LCH. Adult LCH has some specific features and poses distinct therapeutic challenges, knowing that data on these patients are limited. Herein, we will provide an overview of current knowledge regarding adult LCH and its management. We will also discuss recent advances in the understanding of the disease, (i.e. the role of BRAF oncogene) that opens the way toward targeted therapies. PMID:26150351

  20. [Progress in treating diabetes mellitus with adult stem cells].

    PubMed

    Zhang, Lixin; Teng, Chunbo; An, Tiezhu

    2008-02-01

    Diabetes mellitus is a metabolic diseases, mainly including type 1 and type 2 diabetes. Treatment for type 1 and part of type 2 often involves regular insulin injection. However, this treatment neither precisely controls the blood sugar levels, nor prevents the diabetes complications. Transplantation of islets of Langerhans offers an attractive strategy for diabetes therapies, but its wide application has been limited by donor shortage and immunological rejection after transplantation. Stem cells with strong proliferation capacity and multipotential may be potential cell sources in diabetes therapies. For this, adult stem cells are interesting because of absence of teratoma formation and ethnical problems. Adult pancreatic stem cells (PSCs) really exist and could produce insulin-secreting cells both under the condition of pancreatic injury and in vitro culture, but lack of effective markers to enrich PSCs hampers the studies of exploring the expanding and differentiating conditions in vitro. Some other adult stem cells, such as hepatic stem cells, marrow stem cells or intestine stem cells, were also suggested to transdifferentiate into insulin-producing cells under special culture conditions in vitro or by genetic modifications. Moreover, transplanting these adult stem cells-derived insulin-secreting cells into the diabetic mouse could cure diabetes. Thus, adult stem cells would supply the abundant beta-cell sources for cell replacement therapy of diabetes. PMID:18464596

  1. [Progress in treating diabetes mellitus with adult stem cells].

    PubMed

    Zhang, Lixin; Teng, Chunbo; An, Tiezhu

    2008-02-01

    Diabetes mellitus is a metabolic diseases, mainly including type 1 and type 2 diabetes. Treatment for type 1 and part of type 2 often involves regular insulin injection. However, this treatment neither precisely controls the blood sugar levels, nor prevents the diabetes complications. Transplantation of islets of Langerhans offers an attractive strategy for diabetes therapies, but its wide application has been limited by donor shortage and immunological rejection after transplantation. Stem cells with strong proliferation capacity and multipotential may be potential cell sources in diabetes therapies. For this, adult stem cells are interesting because of absence of teratoma formation and ethnical problems. Adult pancreatic stem cells (PSCs) really exist and could produce insulin-secreting cells both under the condition of pancreatic injury and in vitro culture, but lack of effective markers to enrich PSCs hampers the studies of exploring the expanding and differentiating conditions in vitro. Some other adult stem cells, such as hepatic stem cells, marrow stem cells or intestine stem cells, were also suggested to transdifferentiate into insulin-producing cells under special culture conditions in vitro or by genetic modifications. Moreover, transplanting these adult stem cells-derived insulin-secreting cells into the diabetic mouse could cure diabetes. Thus, adult stem cells would supply the abundant beta-cell sources for cell replacement therapy of diabetes.

  2. Molecular genetics of adult-type hypolactasia.

    PubMed

    Järvelä, Irma E

    2005-01-01

    Adult-type hypolactasia (lactase non-persistence; primary lactose malabsorption) is characterized by the down-regulation of the lactase enzyme activity in the intestinal wall after weaning. The down-regulation is genetically determined and a mutation has occurred that has made part of mankind tolerate milk (lactase persistence). A DNA-variant, single nucleotide polymorphism C/T-13910 located 13 910 base pairs (bp) upstream of the lactase gene (LCT) at chromosome 2q21-22 has been shown to associate with the lactase persistence/non-persistence trait both in family and case-control studies. The C/T-13910 variant is located in a non-coding region in the genome in intron 13 of the minichromosome maintenance type 6 gene (MCM6). Significant correlation between the C/T-13910-variant and lactase activity in the intestinal biopsy specimens has been demonstrated. Molecular epidemiological studies on the prevalence of the C/C-13910 genotype associated with low lactase activity are in agreement with the prevalence figures for adult type hypolactasia in>70 diverse ethnic groups studied. Recent functional studies have suggested that this variant has an enhancer effect over the lactase gene. Based on the biochemical, functional, genetic and molecular epidemiological studies of the C/T-13910 variant, genetic testing for adult type hypolactasia has been introduced into clinical practice in Finland. Identification of the genetic change has highlighted the role of non-coding variants in the regulation of common genes and created new tools to study the mechanism of lactase enzyme activation.

  3. Types of Stem Cells

    MedlinePlus

    ... PDF) Download an introduction to stem cells and stem cell research. Stem Cell Glossary Stem cell terms to know. ... stem cells blog from the International Society for Stem Cell Research. Learn About Stem Cells From Lab to You ...

  4. Fatherhood reduces the survival of adult-generated cells and affects various types of behavior in the prairie vole (Microtus ochrogaster ).

    PubMed

    Lieberwirth, Claudia; Wang, Yue; Jia, Xixi; Liu, Yan; Wang, Zuoxin

    2013-11-01

    Motherhood has profound effects on physiology, neuronal plasticity, and behavior. We conducted a series of experiments to test the hypothesis that fatherhood, similarly to motherhood, affects brain plasticity (such as cell proliferation and survival) and various behaviors in the highly social prairie vole (Microtus ochrogaster). In Experiment 1, adult males were housed with their same-sex cage mate (control), single-housed (isolation), or housed with a receptive female to mate and produce offspring (father) for 6 weeks. Fatherhood significantly reduced cell survival (assessed by bromodeoxyuridine labeling), but not cell proliferation (assessed by Ki67-labeling), in the amygdala, dentate gyrus of the hippocampus, and ventromedial hypothalamus, suggesting that fatherhood affects brain plasticity. In Experiment 2, neither acute (20 min) nor chronic (20 min daily for 10 consecutive days) pup exposure altered cell proliferation or survival in the brain, but chronic pup exposure increased circulating corticosterone levels. These data suggest that reduced cell survival in the brain of prairie vole fathers was unlikely to be due to the level of pup exposure and display of paternal behavior, and may not be mediated by circulating corticosterone. The effects of fatherhood on various behaviors (including anxiety-like, depression-like, and social behaviors) were examined in Experiment 3. The data indicated that fatherhood increased anxiety- and depression-like behaviors as well as altered aggression and social recognition memory in male prairie voles. These results warrant further investigation of a possible link between brain plasticity and behavioral changes observed due to fatherhood.

  5. Dopamine and Full-Field Illumination Activate D1 and D2–D5-Type Receptors in Adult Rat Retinal Ganglion Cells

    PubMed Central

    Ogata, Genki; Stradleigh, Tyler W.; Partida, Gloria J.; Ishida, Andrew T.

    2012-01-01

    Dopamine can regulate signal generation and transmission by activating multiple receptors and signaling cascades, especially in striatum, hippocampus, and cerebral cortex. Dopamine modulates an even larger variety of cellular properties in retina, yet has been reported to do so by only D1 receptor-driven cyclic adenosine monophosphate (cAMP) increases or D2 receptor-driven cAMP decreases. Here, we test the possibility that dopamine operates differently on retinal ganglion cells, because the ganglion cell layer binds D1 and D2 receptor ligands, and displays changes in signaling components other than cAMP under illumination that should release dopamine. In adult rat retinal ganglion cells, based on patch-clamp recordings, Ca2+ imaging, and immunohistochemistry, we find that 1) spike firing is inhibited by dopamine and SKF 83959 (an agonist that does not activate homomeric D1 receptors or alter cAMP levels in other systems); 2) D1 and D2 receptor antagonists (SCH 23390, eticlopride, raclopride) counteract these effects; 3) these antagonists also block light-induced rises in cAMP, light-induced activation of Ca2+/calmodulin-dependent protein kinase II, and dopamine-induced Ca2+ influx; and 4) the Ca2+ rise is markedly reduced by removing extracellular Ca2+ and by an IP3 receptor antagonist (2-APB). These results provide the first evidence that dopamine activates a receptor in adult mammalian retinal neurons that is distinct from classical D1 and D2 receptors, and that dopamine can activate mechanisms in addition to cAMP and cAMP-dependent protein kinase to modulate retinal ganglion cell excitability. PMID:22678972

  6. Adult stem cells and tissue repair.

    PubMed

    Körbling, M; Estrov, Z; Champlin, R

    2003-08-01

    Recently, adult stem cells originating from bone marrow or peripheral blood have been suggested to contribute to repair and genesis of cells specific for liver, cardiac and skeletal muscle, gut, and brain tissue. The mechanism involved has been termed transdifferentiation, although other explanations including cell fusion have been postulated. Using adult stem cells to generate or repair solid organ tissue obviates the immunologic, ethical, and teratogenic issues that accompany embryonic stem cells.

  7. Tax fingerprint in adult T-cell leukemia.

    PubMed

    Bazarbachi, Ali

    2016-04-01

    In this issue of Blood, Fujikawa et al demonstrate that the human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax induces an epigenetic-dependent global modification of host gene expression in adult T-cell leukemia-lymphoma (ATL). Hence, the fingerprint of Tax is all over ATL and this may be used for finally capturing ATL. PMID:27056993

  8. Reprogramming adult cells during organ regeneration in forest species

    PubMed Central

    Abarca, Dolores

    2009-01-01

    The possibility of regenerating whole plants from somatic differentiated cells emphasizes the plasticity of plant development. Cell-type respecification during regeneration can be induced in adult tissues as a consequence of injuries, changes in external or internal stimuli or changes in positional information. However, in many plant species, switching the developmental program of adult cells prior to organ regeneration is difficult, especially in forest species. Besides its impact on forest productivity, basic information on the flexibility of cell differentiation is necessary for a comprehensive understanding of the epigenetic control of cell differentiation and plant development. Studies of reprogramming adult cells in terms of regulative expression changes of selected genes will be of great interest to unveil basic mechanisms regulating cellular plasticity. PMID:19820297

  9. Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers

    PubMed Central

    YU, YA-FENG; WU, WEN-YING; XIAO, GEN-SHENG; LING, HONG-YANG; PAN, CHEN

    2016-01-01

    The aim of the present study was to investigate the protective effect of T-type calcium channel blockers against presbycusis, using a C57BL/6J mice model. The expression of three T-type calcium channel receptor subunits in the cochlea of 6–8-week-old C57BL/6J mice was evaluated using reverse transcription-quantitative polymerase chain reaction. The results confirmed that the three subunits were expressed in the cochlea. In addition, the capacity of T-type calcium channel blockers to protect the cochlear hair cells of 24–26-week-old C57BL/6J mice was investigated in mice treated with mibefradil, benidipine or saline for 4 weeks. Differences in hearing threshold were detected using auditory brainstem recording (ABR), while differences in amplitudes were measured using a distortion product otoacoustic emission (DPOAE) test. The ABR test results showed that the hearing threshold significantly decreased at 24 kHz in the mibefradil-treated and benidipine-treated groups compared with the saline-treated group. The DPOAE amplitudes in the mibefradil-treated group were increased compared with those in the saline-treated group at the F2 frequencies of 11.3 and 13.4 kHz. Furthermore, the DPOAE amplitudes in the benidipine-treated group were increased compared with those in the saline-treated group at an F2 frequency of 13.4 kHz. The loss of outer hair cells (OHCs) was not evident in the mibefradil-treated group; however, the stereocilia of the inner hair cells (IHCs) were disorganised and sparse. In summary, these results indicate that the administration of a T-type calcium channel blocker for four consecutive weeks may improve the hearing at 24 kHz of 24–26-week-old C57BL/6J mice. The function and morphology of the OHCs of the C57BL/6J mice were significantly altered by the administration of a T-type calcium channel blocker; however, the IHCs were unaffected. PMID:26998034

  10. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    PubMed Central

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-01-01

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications. PMID:27338364

  11. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration.

    PubMed

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-06-21

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  12. 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

  13. Emerging restorative treatments for Parkinson's disease: manipulation and inducement of dopaminergic neurons from adult stem cells.

    PubMed

    Zhao, Junpeng; Xu, Qunyuan

    2011-06-01

    Parkinson's disease (PD) is a common neurodegenerative disease, characterized by a selective loss of midbrain Dopaminergic (DA) neurons. To address this problem, various types of stem cells that have potential to differentiate into DA neurons are being investigated as cellular therapies for PD, including cells derived from embryonic or adult donor tissue, and embryonic stem cells. These cell sources, however, have raised certain questions with regard to ethical and rejection issues. Recent progress in adult stems has further proved that the cells derived from adult tissue could be expanded and differentiated into DA precursor cells in vitro, and cell therapy with adult stem cells could produce a clear improvement for PD models. Using adult stem cells for clinic application may not only overcome the ethical problem inherent in using human fetal tissue or embryonic stem cells, but also open the possibility for autologous transplantation. The patient-specific adult stem cell is therefore a potential and prospective candidate for PD treatment.

  14. Therapeutics from Adult Stem Cells and the Hype Curve.

    PubMed

    Maguire, Greg

    2016-05-12

    The Gartner curve for regenerative and stem cell therapeutics is currently climbing out of the "trough of disillusionment" and into the "slope of enlightenment". Understanding that the early years of stem cell therapy relied on the model of embryonic stem cells (ESCs), and then moved into a period of the overhype of induced pluripotent stem cells (iPSCs), instead of using the model of 40 years of success, i.e. adult stem cells used in bone marrow transplants, the field of stem cell therapy has languished for years, trying to move beyond the early and poorly understood success of bone marrow transplants. Recent studies in the lab and clinic show that adult stem cells of various types, and the molecules that they release, avoid the issues associated with ESCs and iPSCs and lead to better therapeutic outcomes and into the slope of enlightenment. PMID:27190588

  15. Therapeutics from Adult Stem Cells and the Hype Curve.

    PubMed

    Maguire, Greg

    2016-05-12

    The Gartner curve for regenerative and stem cell therapeutics is currently climbing out of the "trough of disillusionment" and into the "slope of enlightenment". Understanding that the early years of stem cell therapy relied on the model of embryonic stem cells (ESCs), and then moved into a period of the overhype of induced pluripotent stem cells (iPSCs), instead of using the model of 40 years of success, i.e. adult stem cells used in bone marrow transplants, the field of stem cell therapy has languished for years, trying to move beyond the early and poorly understood success of bone marrow transplants. Recent studies in the lab and clinic show that adult stem cells of various types, and the molecules that they release, avoid the issues associated with ESCs and iPSCs and lead to better therapeutic outcomes and into the slope of enlightenment.

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

    PubMed

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

    2009-05-01

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

  17. Wharton's jelly mesenchymal stem cells as candidates for beta cells regeneration: extending the differentiative and immunomodulatory benefits of adult mesenchymal stem cells for the treatment of type 1 diabetes.

    PubMed

    Anzalone, Rita; Lo Iacono, Melania; Loria, Tiziana; Di Stefano, Antonino; Giannuzzi, Pantaleo; Farina, Felicia; La Rocca, Giampiero

    2011-06-01

    Mesenchymal stem cells (MSC) are uniquely capable of crossing germinative layers borders (i.e. are able to differentiate towards ectoderm-, mesoderm- and endoderm-derived cytotypes) and are viewed as promising cells for regenerative medicine approaches in several diseases. Type I diabetes therapy should potentially benefit from such differentiated cells: the search for alternatives to organ/islet transplantation strategies via stem cells differentiation is an ongoing task, significant goals having been achieved in most experimental settings (e.g. insulin production and euglycaemia restoration), though caution is still needed to ensure safe and durable effects in vivo. MSC are obtainable in high numbers via ex vivo culture and can be differentiated towards insulin-producing cells (IPC). Moreover, recent reports evidenced that MSC possess immunomodulatory activities (acting on both innate and acquired immunity effectors) which should result in a reduction of the immunogenicity of transplanted cells, thus limiting rejection. Moreover it has been proposed that MSC administration should be used to attenuate the autoimmune processes which lead to the destruction of beta cells. This review illustrates the recent advances made in differentiating human MSC to IPC. In particular, we compare the effectiveness of the differentiation protocols applied, the markers and functional assays used to characterize differentiated progeny, and the in vivo controls. We further speculate on how MSC derived from Wharton's jelly of human umbilical cord may represent a more promising regenerative medicine tool, as recently demonstrated for endoderm-derived organs (as liver) in human subjects, also considering their peculiar immunomodulatory features compared to other MSC populations. PMID:20972649

  18. Immunological control of adult neural stem cells

    PubMed Central

    Gonzalez-Perez, Oscar; Quiñones-Hinojosa, Alfredo; Garcia-Verdugo, Jose Manuel

    2010-01-01

    Adult neurogenesis occurs only in discrete regions of adult central nervous system: the subventricular zone and the subgranular zone. These areas are populated by adult neural stem cells (aNSC) that are regulated by a number of molecules and signaling pathways, which control their cell fate choices, survival and proliferation rates. For a long time, it was believed that the immune system did not exert any control on neural proliferative niches. However, it has been observed that many pathological and inflammatory conditions significantly affect NSC niches. Even more, increasing evidence indicates that chemokines and cytokines play an important role in regulating proliferation, cell fate choices, migration and survival of NSCs under physiological conditions. Hence, the immune system is emerging is an important regulator of neurogenic niches in the adult brain, which may have clinical relevance in several brain diseases. PMID:20861925

  19. Adult Stem Cells and Diabetes Therapy

    PubMed Central

    Ilgun, Handenur; Kim, Joseph William; Luo, LuGuang

    2016-01-01

    The World Health Organization estimates that diabetes will be the fourth most prevalent disease by 2050. Developing a new therapy for diabetes is a challenge for researchers and clinicians in field. Many medications are being used for treatment of diabetes however with no conclusive and effective results therefore alternative therapies are required. Stem cell therapy is a promising tool for diabetes therapy, and it has involved embryonic stem cells, adult stem cells, and pluripotent stem cells. In this review, we focus on adult stem cells, especial human bone marrow stem cells (BM) for diabetes therapy, its history, and current development. We discuss prospects for future diabetes therapy such as induced pluripotent stem cells which have popularity in stem cell research area. PMID:27123495

  20. A case of extranodal NK/T-cell lymphoma, nasal type mimicking typical manifestations of adult-onset Still's disease (AOSD) with hemophagocytic syndrome: diagnostic consideration between malignant lymphoma without lymphadenopathy and AOSD.

    PubMed

    Kato, Takashi; Tanabe, Juichi; Kanemoto, Motoko; Kobayashi, Chiharu; Morita, Sho; Karahashi, Taro

    2009-01-01

    A 25-year-old Japanese man was suffering from high fever, sore throat, arthralgia, and macular salmon-pink eruption. The superficial lymph node was not palpable, and computed tomographic scans from the neck to pelvis demonstrated hepatosplenomegaly without apparent lymphadenopathy. Therefore, the possibility of malignant lymphoma was considered to be extremely low. Serology for Epstein Barr virus (EBV) and cytomegalovirus showed a postinfectious state, and blood culture was negative. Serum rheumatoid factor and antinuclear antibody were negative. Leukocytopenia (2.4 x 10(3)/mul) was observed, and thus a diagnosis of adult-onset Still's disease (AOSD) with hemophagocytic syndrome (HPS) was made. Fifty-five milligrams of prednisolone daily improved his symptoms and leukocytopenia promptly, but high fever with severe and progressive thrombocytopenia occurred 12 days later. Bone marrow aspiration revealed the presence of lymphoma cells and hemophagocytosis, and the CD45 gating analysis showed expanding population of CD2(+), CD3(-), and CD56(+) cells. Further, mucosal ulceration in the nasal cavity was detected. Therefore, a diagnosis of extranodal natural killer (NK)/T-cell lymphoma, nasal type, concomitant with HPS was made, and treatment with dexamethasone, etoposide, ifosfamide, carboplatin (DeVIC) regimen ameliorated his symptoms and platelet transfusion dependency. Later, a high titer of serum EBV-DNA was detected, which supported the diagnosis. Diagnosing AOSD, extranodal presentation of malignant lymphoma such as extranodal NK/T-cell lymphoma, nasal type, should be carefully considered. PMID:19609486

  1. Immature rat Leydig cells are intrinsically less sensitive than adult Leydig cells to ethane dimethanesulfonate.

    PubMed

    Kelce, W R; Zirkin, B R; Ewing, L L

    1991-11-01

    Leydig cells from immature rat testes appear to be insensitive to doses of ethane-1,2-dimethanesulfonate (EDS) which eliminate Leydig cells from adult rat testes. We sought to determine whether this differential response to EDS is intrinsic to the Leydig cell or mediated by other intra- or extratesticular differences between adult and immature rats. To differentiate among these possibilities, Leydig cells were exposed to EDS (1) in vivo, (2) through in vitro testicular perfusion, or (3) in highly purified Leydig cell primary cultures. Four days after ip injections of 85 mg EDS/kg body wt Leydig cells were eliminated from testes of adult, but not immature rats. Total androgen production by testes perfused in vitro with 94 micrograms EDS/ml was dramatically reduced in adult, but not immature rats. Highly purified adult, but not immature, rat Leydig cells were far more sensitive to the effects of EDS on luteinizing hormone-stimulated androgen production (functional effects; apparent EC50 = 94 for adult and 407 micrograms/ml for immature rat Leydig cells) and on [35S]methionine incorporation (cytotoxic effects; apparent EC50 = 140 for adult and 1000 micrograms/ml for immature rat Leydig cells). Finally, the in vitro effects of EDS were both cell type and chemical specific. Since the differential response of adult and immature rat Leydig cells to EDS was manifest in vivo, during in vitro testicular perfusion, and in highly purified Leydig cell primary cultures, we conclude that immature rat Leydig cells are intrinsically less sensitive to the specific cytotoxic effects of EDS than adult rat Leydig cells.

  2. Conserved POU-binding site linked to SP1-binding site within FZD5 promoter: Transcriptional mechanisms of FZD5 in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse-type gastric cancer.

    PubMed

    Katoh, Yuriko; Katoh, Masaru

    2007-03-01

    Canonical WNT signals are transduced through Frizzled (FZD) family receptor and LRP5/LRP6 co-receptor to upregulate FGF20, JAG1, DKK1, WISP1, CCND1 and MYC genes for cell-fate determination, while non-canonical WNT signals are transduced through FZD family receptor and ROR2/PTK7/RYK co-receptor to activate RHOA/RHOU/RAC/CDC42, JNK, PKC, NLK and NFAT signaling cascades for the regulation of tissue polarity, cell movement, and adhesion. We previously reported molecular cloning and characterization of human FZD5, which showed six amino-acid substitutions with human Hfz5. FZD5, functioning as WNT5A receptor, is the key molecule in the fields of oncology, regenerative medicine, cardiology, rheumatology, diabetology, and gastroenterology. Here, comparative integromics analyses on FZD5 orthologs were performed by using bioinformatics (Techint) and human intelligence (Humint). Chimpanzee FZD5 and cow Fzd5 genes were identified within NW_104292.1 and AC166656.2 genome sequences, respectively. FZD5 orthologs were seven-transmembrane proteins with extracellular Frizzled domain, leucine zipper motif around the 5th transmembrane domain, and cytoplasmic DVL- and PDZ-binding motifs. Ser523 and Ser529 around the DVL-binding motif of FZD5 orthologs were putative aPKC phosphorylation sites. POU5F1 (OCT4)-binding site linked to SP1-binding site within the 5'-promoter region of human FZD5 gene was evolutionarily conserved among mammalian FZD5 orthologs. POU5F1 was more related to POU2F and POU3F subfamily members. POU5F1 was preferentially expressed in undifferentiated human embryonic stem (ES) cells, pancreatic islet, and diffuse-type gastric cancer. POU2F1 (OCT1) was expressed in ES cells, fetal liver/spleen, adult colon, POU2F2 in ES cells, fetal liver/spleen, and POU2F3 in diffuse-type gastric cancer. Multiple SP1/KLF family members, other than KLF2 or KLF4, were expressed in undifferentiated human ES cells. Together, these facts indicate that POU5F1 and POU2F subfamily members

  3. Cholesterol and Alzheimer Type Dementia among Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Buckley, Frank

    2008-01-01

    This article reports a summary of research by Warren Zigman and colleagues investigating the link between cholesterol levels and Alzheimer type dementia among adults with Down syndrome. Warren Zigman and colleagues followed 123 adults with Down syndrome between May 1998 and April 2006. The participants were aged between 41 and 78 years at the…

  4. Adult-type hypolactasia and regulation of lactase expression.

    PubMed

    Troelsen, Jesper T

    2005-05-25

    A common genetically determined polymorphism in the human population leads to two distinct phenotypes in adults, lactase persistence and adult-type hypolactasia (lactase non-persistence). All healthy newborn children express high levels of lactase and are able to digest large quantities of lactose, the main carbohydrate in milk. Individuals with adult-type hypolactasia lose their lactase expression before adulthood and consequently often become lactose intolerant with associated digestive problems (e.g. diarrhoea). In contrast, lactase persistent individuals have a lifelong lactase expression and are able to digest lactose as adults. Lactase persistence can be regarded as the mutant phenotype since other mammals down-regulate their lactase expression after weaning (the postweaning decline). This phenomenon does not occur in lactase persistent individuals. The regulation of lactase expression is mainly transcriptional and it is well established that adult-type hypolactasia is inherited in an autosomal recessive manner, whereas persistence is dominant. The recent findings of single nucleotide polymorphisms associated with lactase persistence have made it possible to study the potential mechanisms underlying adult-type hypolactasia. This work has led to the identification of gene-regulatory sequences located far from the lactase gene (LCT). The present review describes the recent advances in the understanding of the regulation of lactase expression and the possible mechanisms behind adult-type hypolactasia.

  5. Adult T-cell leukemia-lymphoma.

    PubMed

    Tsukasaki, Kunihiro

    2012-04-01

    Adult T-cell leukemia-lymphoma (ATL) was first described in 1977 as a distinct clinico-pathological entity with a suspected viral etiology. Subsequently, a novel RNA retrovirus, human T-cell leukemia/lymphotropic virus type 1 (HTLV-1) was isolated from a cell line established from the leukemic cells of an ATL patient, and the finding of a clear association with ATL led to its inclusion among human carcinogenic pathogens. The three major routes of HTLV-1 transmission are mother-to-child infections via breast milk, sexual intercourse, and blood transfusions. HTLV-1 infection early in life, presumably from breast feeding, is crucial in the development of ATL. The diversity in clinical features and prognosis of patients with this disease has led to its subtype-classification into four categories, acute, lymphoma, chronic, and smoldering types defined by organ involvement, and LDH and calcium values. In cases of acute, lymphoma, or unfavorable chronic subtypes (aggressive ATL), intensive chemotherapy such as VCAP-AMP-VECP is usually recommended. In cases of favorable chronic or smoldering ATL (indolent ATL), watchful waiting until disease progression has been recommended although the long term prognosis was inferior to those of, for instance, chronic lymphoid leukemia. Retrospective analysis suggested that the combination of interferon alpha and zidovudine was apparently promising for the treatment of ATL, especially for types with leukemic manifestation. Allogeneic hematopoietic stem cell transplantation is also promising for the treatment of aggressive ATL possibly reflecting graft vs. ATL effect. Several new agent-trials for ATL are ongoing and in preparation, including a defucosylated humanized anti-CC chemokine receptor 4 monoclonal antibody. Two steps should be considered for the prevention of HTLV-1-associated ATL. The first is the prevention of HTLV-1 infections and the second is the prevention of ATL among HTLV-1 carriers. So far, no agent has been found to be

  6. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

  7. Type 2 Diabetes Widespread in Adults

    MedlinePlus

    ... be able to prevent or delay type 2 diabetes by cutting calories and increasing your physical activity to lose a modest amount of weight. A major study of people with pre-diabetes showed that lifestyle changes leading to a 5- ...

  8. Purinergic signaling promotes proliferation of adult mouse subventricular zone cells.

    PubMed

    Suyama, Satoshi; Sunabori, Takehiko; Kanki, Hiroaki; Sawamoto, Kazunobu; Gachet, Christian; Koizumi, Schuichi; Okano, Hideyuki

    2012-07-01

    In adult mammalian brains, neural stem cells (NSCs) exist in the subventricular zone (SVZ), where persistent neurogenesis continues throughout life. Those NSCs produce neuroblasts that migrate into the olfactory bulb via formation of transit-amplifying cells, which are committed precursor cells of the neuronal lineage. In this SVZ niche, cell-cell communications conducted by diffusible factors as well as physical cell-cell contacts are important for the regulation of the proliferation and fate determination of NSCs. Previous studies have suggested that extracellular purinergic signaling, which is mediated by purine compounds such as ATP, plays important roles in cell-cell communication in the CNS. Purinergic signaling also promotes the proliferation of adult NSCs in vitro. However, the in vivo roles of purinergic signaling in the neurogenic niche still remain unknown. In this study, ATP infusion into the lateral ventricle of the mouse brain resulted in an increase in the numbers of rapidly dividing cells and Mash1-positive transit-amplifying cells (Type C cells) in the SVZ. Mash1-positive cells express the P2Y1 purinergic signaling receptor and infusion of the P2Y1 receptor-specific antagonist MRS2179 decreased the number of rapidly dividing bromodeoxyuridine (BrdU)-positive cells and Type C cells. Moreover, a 17% reduction of rapidly dividing BrdU-positive cells and a 19% reduction of Mash1-positive cells were observed in P2Y1 knock-out mice. Together, these results suggest that purinergic signaling promotes the proliferation of rapidly dividing cells and transit-amplifying cells, in the SVZ niche through the P2Y1 receptor. PMID:22764232

  9. Identification of a variant associated with adult-type hypolactasia.

    PubMed

    Enattah, Nabil Sabri; Sahi, Timo; Savilahti, Erkki; Terwilliger, Joseph D; Peltonen, Leena; Järvelä, Irma

    2002-02-01

    Adult-type hypolactasia, also known as lactase non-persistence (lactose intolerance), is a common autosomal recessive condition resulting from the physiological decline in activity of the lactase-phlorizin hydrolase (LPH) in intestinal cells after weaning. LPH hydrolyzes lactose into glucose and galactose. Sequence analyses of the coding and promoter regions of LCT, the gene encoding LPH, has revealed no DNA variations correlating with lactase non-persistence. An associated haplotype spanning LCT, as well as a distinct difference in the transcript levels of 'non-persistence' and 'persistence' alleles in heterozygotes, suggest that a cis-acting element contributes to the lactase non-persistence phenotype. Using linkage disequilibrium (LD) and haplotype analysis of nine extended Finnish families, we restricted the locus to a 47-kb interval on 2q21. Sequence analysis of the complete region and subsequent association analyses revealed that a DNA variant, C/T-13910, roughly 14 kb upstream from the LCT locus, completely associates with biochemically verified lactase non-persistence in Finnish families and a sample set of 236 individuals from four different populations. A second variant, G/A-22018, 8 kb telomeric to C/T-13910, is also associated with the trait in 229 of 236 cases. Prevalence of the C/T-13910 variant in 1,047 DNA samples is consistent with the reported prevalence of adult-type hypolactasia in four different populations. That the variant (C/T-13910) occurs in distantly related populations indicates that it is very old. PMID:11788828

  10. Primary Afferent Synapses on Developing and Adult Renshaw Cells

    PubMed Central

    Mentis, George Z.; Siembab, Valerie C.; Zerda, Ricardo; O’Donovan, Michael J.; Alvarez, Francisco J.

    2010-01-01

    The mechanisms that diversify adult interneurons from a few pools of embryonic neurons are unknown. Renshaw cells, Ia inhibitory interneurons (IaINs), and possibly other types of mammalian spinal interneurons have common embryonic origins within the V1 group. However, in contrast to IaINs and other V1-derived interneurons, adult Renshaw cells receive motor axon synapses and lack proprioceptive inputs. Here, we investigated how this specific pattern of connectivity emerges during the development of Renshaw cells. Tract tracing and immunocytochemical markers [parvalbumin and vesicular glutamate transporter 1 (VGLUT1)] showed that most embryonic (embryonic day 18) Renshaw cells lack dorsal root inputs, but more than half received dorsal root synapses by postnatal day 0 (P0) and this input spread to all Renshaw cells by P10–P15. Electrophysiological recordings in neonates indicated that this input is functional and evokes Renshaw cell firing. VGLUT1-IR bouton density on Renshaw cells increased until P15 but thereafter decreased because of limited synapse proliferation coupled with the enlargement of Renshaw cell dendrites. In parallel, Renshaw cell postsynaptic densities apposed to VGLUT1-IR synapses became smaller in adult compared with P15. In contrast, vesicular acetylcholine transporter-IR motor axon synapses contact embryonic Renshaw cells and proliferate postnatally matching Renshaw cell growth. Like other V1 neurons, Renshaw cells are thus competent to receive sensory synapses. However, after P15, these sensory inputs appear deselected through arrested proliferation and synapse weakening. Thus, Renshaw cells shift from integrating sensory and motor inputs in neonates to predominantly motor inputs in adult. Similar synaptic weight shifts on interneurons may be involved in the maturation of motor reflexes and locomotor circuitry. PMID:17182780

  11. Single nucleotide polymorphisms in type 2 diabetes among Hispanic adults.

    PubMed

    Watson, Amanda L; Hu, Jie; Chiu, Norman H L

    2015-05-01

    In this pilot study, we explore the genetic variation that may relate to type 2 diabetes (T2D) among Hispanic adults. The genotypes of 36 Hispanic adults were analyzed by using the Cardio-Metabochip. The goal is to identify single nucleotide polymorphisms (SNPs) associated to T2D among Hispanic adults. A total of 26 SNPs were identified to be associated with T2D among Hispanic adults. None of these SNPs have been reported for T2D. By using the principle components analysis to analyze the genotype of 26 SNPs in 36 samples, the samples obtained from diabetic patients could be distinguished from the control samples. The findings support genetic involvement in T2D among Hispanic adults.

  12. Distinguishing cell type using epigenotype

    NASA Astrophysics Data System (ADS)

    Wytock, Thomas; Motter, Adilson E.

    Recently, researchers have proposed that unique cell types are attractors of their epigenetic dynamics including gene expression and chromatin conformation patterns. Traditionally, cell types have been classified by their function, morphology, cytochemistry, and other macroscopically observable properties. Because these properties are the result of many proteins working together, it should be possible to predict cell types from gene expression or chromatin conformation profiles. In this talk, I present a maximum entropy approach to identify and distinguish cell type attractors on the basis of correlations within these profiles. I will demonstrate the flexibility of this method through its separate application to gene expression and chromatin conformation datasets. I show that our method out-performs other machine-learning techniques and uncorrelated benchmarks. We adapt our method to predict growth rate from gene expression in E. coli and S. cerevisiae and compare our predictions with those from metabolic models. In addition, our method identifies a nearly convex region of state-space associated with each cell type attractor basin. Estimates of the growth rate and attractor basin make it possible to rationally control gene regulatory networks independent of a model. This research was supported by NSF-GRFP, NSF-GK12, GAANN, and Northwestern's NIH-NIGMS Molecular Biophysics Training Grant.

  13. Differentiation of embryonic and adult stem cells into insulin producing cells.

    PubMed

    Zulewski, H

    2008-03-01

    Replacement of insulin producing cells represents an almost ideal treatment for patients with diabetes mellitus type 1. Transplantation of pancreatic islets of Langerhans is successful in experienced centers. The wider application of this therapy, however, is limited by the lack of donor organs. Insulin producing cells generated from stem cells represent an attractive alternative. Stem cells with the potential to differentiate into insulin producing cells include embryonic stem cells (ESC) as well as adult stem cells from various tissues including the pancreas, liver, bone marrow and adipose tissue. The use of human ESC is hampered by ethical concerns but research with human ESC may help us to decipher important steps in the differentiation process in vitro since almost all information available on pancreas development are based on animal studies. The present review summarizes the current knowledge on the development of insulin producing cells from embryonic and adult stem cells with special emphasis on pancreatic, hepatic and human mesenchymal stem cells. PMID:18427390

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

    NASA Astrophysics Data System (ADS)

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

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

  15. Translational research of adult stem cell therapy.

    PubMed

    Suzuki, Gen

    2015-11-26

    Congestive heart failure (CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.

  16. Spatial control of adult stem cell fate using nanotopographic cues

    PubMed Central

    An, Steven S.; Afzal, Junaid; Lee, Suengwon; Kwak, Moonkyu; Suh, Kahp-Yang; Levchenko, Andre

    2015-01-01

    Adult stem cells hold great promise as a source of diverse terminally differentiated cell types for tissue engineering applications. However, due to the complexity of chemical and mechanical cues specifying differentiation outcomes, development of arbitrarily complex geometric and structural arrangements of cells, adopting multiple fates from the same initial stem cell population, has been difficult. Here, we show that the topography of the cell adhesion substratum can be an instructive cue to adult stem cells and topographical variations can strongly bias the differentiation outcome of the cells towards adipocyte or osteocyte fates. Switches in cell fate decision from adipogenic to osteogenic lineages were accompanied by changes in cytoskeletal stiffness, spanning a considerable range in the cell softness/rigidity spectrum. Our findings suggest that human mesenchymal stem cells (hMSC) can respond to the varying density of nanotopographical cues by regulating their internal cytoskeletal network and use these mechanical changes to guide them toward making cell fate decisions. We used this finding to design a complex two-dimensional pattern of co-localized cells preferentially adopting two alternative fates, thus paving the road for designing and building more complex tissue constructs with diverse biomedical applications. PMID:24388388

  17. Adult stem cells and their ability to differentiate.

    PubMed

    Tarnowski, Maciej; Sieron, Aleksander L

    2006-08-01

    This is a review of the current status of knowledge on adult stem cells as well as the criteria and evidence for their potential to transform into different cell types and cell lineages. Reports on stem cell sources, focusing on tissues from adult subjects, were also investigated. Numerous reports have been published on the search for early markers of both stem cells and the precursors of various cell lineages. The question is still open about the characteristics of the primary stem cell. The existing proofs and hypotheses have not yielded final solutions to this problem. From a practical point of view it is also crucial to find a minimal set of markers determining the phenotypes of the precursor cells of a particular cell lineage. Several lines of evidence seem to bring closer the day when we will be able to detect the right stem cell niche and successfully isolate precursor cells that are needed for the treatment of a particular disorder. Recent reports on cases of cancer in patients subjected to stem cell therapy are yet another controversial issue looked into in this review, although the pros and cons emerging from the results of published studies still do not provide satisfying evidence to fully understand this issue.

  18. Nephrocalcinosis as adult presentation of Bartter syndrome type II.

    PubMed

    Huang, L; Luiken, G P M; van Riemsdijk, I C; Petrij, F; Zandbergen, A A M; Dees, A

    2014-02-01

    Bartter syndrome consists a group of rare autosomal-recessive renal tubulopathies characterised by renal salt wasting, hypokalaemic metabolic alkalosis, hypercalciuria and hyperreninaemic hyperaldosteronism. It is classified into five types. Mutations in the KCNJ1 gene (classified as type II) usually cause the neonatal form of Bartter syndrome. We describe an adult patient with a homozygous KCNJ1 mutation resulting in a remarkably mild phenotype of neonatal type Bartter syndrome. PMID:24659592

  19. Type I interferon pathway in adult and juvenile dermatomyositis

    PubMed Central

    2011-01-01

    Gene expression profiling and protein studies of the type I interferon pathway have revealed important insights into the disease process in adult and juvenile dermatomyositis. The most prominent and consistent feature has been a characteristic whole blood gene signature indicating upregulation of the type I interferon pathway. Upregulation of the type I interferon protein signature has added additional markers of disease activity and insight into the pathogenesis of the disease. PMID:22192711

  20. Hematopoietic stem cells, progenitor cells and leukemic stem cells in adult myeloproliferative neoplasms.

    PubMed

    Ng, Ashley P

    2013-05-01

    The understanding of myeloproliferative neoplasms has changed dramatically since Dameshek proposed his classification over 50 years ago. Our knowledge of the types of cells which constitute the hematopoietic system and of how they are regulated has also appreciated significantly over this time. This review relates what is currently known about the acquired genetic mutations associated with adult myeloproliferative neoplasms to how they lead to the hematopoietic perturbations of myeloproliferative disease. There is a particular focus on how stem and progenitor cell compartments are affected by BCR-ABL1 and JAK2V617F mutations, and the particular issue of resistance of leukemic stem cells to conventional and targeted therapies. PMID:23013358

  1. Galvanic cell type oxygen sensor

    SciTech Connect

    Fujita, Y.; Kudo, H.; Tanigawa, I.

    1985-01-22

    A galvanic cell type oxygen sensor comprising a galvanic cell comprised of a cathode made up of metal effective for the electrolytic reduction of oxygen, an anode made up of lead material and an electrolyte made up of an aqueous mixed solution of organic acid and organic acid salt, which has a long life and a high output voltage, is not at all affected by carbon dioxide and which can prevent the generation of hydrogen from the cathode, is disclosed.

  2. Expression of DNA methyltransferases in adult dorsal root ganglia is cell-type specific and up regulated in a rodent model of neuropathic pain

    PubMed Central

    Pollema-Mays, Sarah L.; Centeno, Maria V.; Apkarian, A. V.; Martina, Marco

    2014-01-01

    Neuropathic pain is associated with hyperexcitability and intrinsic firing of dorsal root ganglia (DRG) neurons. These phenotypical changes can be long lasting, potentially spanning the entire life of animal models, and depend on altered expression of numerous proteins, including many ion channels. Yet, how DRGs maintain long-term changes in protein expression in neuropathic conditions remains unclear. DNA methylation is a well-known mechanism of epigenetic control of gene expression and is achieved by the action of three enzymes: DNA methyltransferase (DNMT) 1, 3a, and 3b, which have been studied primarily during development. We first performed immunohistochemical analysis to assess whether these enzymes are expressed in adult rat DRGs (L4–5) and found that DNMT1 is expressed in both glia and neurons, DNMT3a is preferentially expressed in glia and DNMT3b is preferentially expressed in neurons. A rat model of neuropathic pain was then used to determine whether nerve injury may induce epigenetic changes in DRGs at multiple time points after pain onset. Real-time RT PCR analysis revealed robust and time-dependent changes in DNMT transcript expression in ipsilateral DRGs from spared nerve injury (SNI) but not sham rats. Interestingly, DNMT3b transcript showed a robust upregulation that appeared already 1 week after surgery and persisted at 4 weeks (our endpoint); in contrast, DNMT1 and DNMT3a transcripts showed only moderate upregulation that was transient and did not appear until the second week. We suggest that DNMT regulation in adult DRGs may be a contributor to the pain phenotype and merits further study. PMID:25152711

  3. Germ Cell Tumors in Adolescents and Young Adults.

    PubMed

    Calaminus, Gabriele; Joffe, Jonathan

    2016-01-01

    Germ cell tumors (GCTs) represent a group of biologically complex malignancies that affect patients at different sites within the body and at different ages. The varying nature of these tumors reflects their cell of origin which is the primordial germ cell, which normally gives rise to ovarian and testicular egg and sperm producing cells. These cells retain an ability to give rise to all types of human tissues, and this is illustrated by the different kinds of GCTs that occur. In adolescent and young adult (AYA) patients, GCTs predominantly present as testicular, ovarian or mediastinal primary GCTs, and represent some of the most complex therapeutic challenges within any AYA practice. The varying types of GCTs, defined by primary site and/or age at presentation, can look very similar microscopically. However, there is growing evidence that they may have different molecular characteristics, different biology and different requirements for curative treatments. Whilst in adult testicular GCTs there is evidence for an environmental cause during fetal development and a genetic component, these causative factors are much less well understood in other GCTs. GCTs are some of the most curable cancers in adults, but some patients exhibit resistance to standard treatments. Because of this, today's clinical research is directed at understanding how to best utilize toxic therapies and promote healthy survivorship. This chapter explores the biology, behavior and treatment of GCTs and discusses how the AYA group of GCTs may hold some of the keys to understanding fundamental unanswered questions of biological variance and curability in GCTs. PMID:27595361

  4. Syncytial-Type Cell Plates

    PubMed Central

    Otegui, Marisa; Staehelin, L. Andrew

    2000-01-01

    Cell wall formation in the syncytial endosperm of Arabidopsis was studied by using high-pressure-frozen/freeze-substituted developing seeds and immunocytochemical techniques. The endosperm cellularization process begins at the late globular embryo stage with the synchronous organization of small clusters of oppositely oriented microtubules (∼10 microtubules in each set) into phragmoplast-like structures termed mini-phragmoplasts between both sister and nonsister nuclei. These mini-phragmoplasts produce a novel kind of cell plate, the syncytial-type cell plate, from Golgi-derived vesicles ∼63 nm in diameter, which fuse by way of hourglass-shaped intermediates into wide (∼45 nm in diameter) tubules. These wide tubules quickly become coated and surrounded by a ribosome-excluding matrix; as they grow, they branch and fuse with each other to form wide tubular networks. The mini-phragmoplasts formed between a given pair of nuclei produce aligned tubular networks that grow centrifugally until they merge into a coherent wide tubular network with the mini-phragmoplasts positioned along the network margins. The individual wide tubular networks expand laterally until they meet and eventually fuse with each other at the sites of the future cell corners. Transformation of the wide tubular networks into noncoated, thin (∼27 nm in diameter) tubular networks begins at multiple sites and coincides with the appearance of clathrin-coated budding structures. After fusion with the syncytial cell wall, the thin tubular networks are converted into fenestrated sheets and cell walls. Immunolabeling experiments show that the cell plates and cell walls of the endosperm differ from those of the embryo and maternal tissue in two features: their xyloglucans lack terminal fucose residues on the side chain, and callose persists in the cell walls after the cell plates fuse with the parental plasma membrane. The lack of terminal fucose residues on xyloglucans suggests that these cell wall

  5. Articulation in Schoolchildren and Adults with Neurofibromatosis Type 1

    ERIC Educational Resources Information Center

    Cosyns, Marjan; Mortier, Geert; Janssens, Sandra; Bogaert, Famke; D'Hondt, Stephanie; Van Borsel, John

    2012-01-01

    Several authors mentioned the occurrence of articulation problems in the neurofibromatosis type 1 (NF1) population. However, few studies have undertaken a detailed analysis of the articulation skills of NF1 patients, especially in schoolchildren and adults. Therefore, the aim of the present study was to examine in depth the articulation skills of…

  6. A web-server of cell type discrimination system.

    PubMed

    Wang, Anyou; Zhong, Yan; Wang, Yanhua; He, Qianchuan

    2014-01-01

    Discriminating cell types is a daily request for stem cell biologists. However, there is not a user-friendly system available to date for public users to discriminate the common cell types, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and somatic cells (SCs). Here, we develop WCTDS, a web-server of cell type discrimination system, to discriminate the three cell types and their subtypes like fetal versus adult SCs. WCTDS is developed as a top layer application of our recent publication regarding cell type discriminations, which employs DNA-methylation as biomarkers and machine learning models to discriminate cell types. Implemented by Django, Python, R, and Linux shell programming, run under Linux-Apache web server, and communicated through MySQL, WCTDS provides a friendly framework to efficiently receive the user input and to run mathematical models for analyzing data and then to present results to users. This framework is flexible and easy to be expended for other applications. Therefore, WCTDS works as a user-friendly framework to discriminate cell types and subtypes and it can also be expended to detect other cell types like cancer cells. PMID:24578634

  7. A web-server of cell type discrimination system.

    PubMed

    Wang, Anyou; Zhong, Yan; Wang, Yanhua; He, Qianchuan

    2014-01-01

    Discriminating cell types is a daily request for stem cell biologists. However, there is not a user-friendly system available to date for public users to discriminate the common cell types, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and somatic cells (SCs). Here, we develop WCTDS, a web-server of cell type discrimination system, to discriminate the three cell types and their subtypes like fetal versus adult SCs. WCTDS is developed as a top layer application of our recent publication regarding cell type discriminations, which employs DNA-methylation as biomarkers and machine learning models to discriminate cell types. Implemented by Django, Python, R, and Linux shell programming, run under Linux-Apache web server, and communicated through MySQL, WCTDS provides a friendly framework to efficiently receive the user input and to run mathematical models for analyzing data and then to present results to users. This framework is flexible and easy to be expended for other applications. Therefore, WCTDS works as a user-friendly framework to discriminate cell types and subtypes and it can also be expended to detect other cell types like cancer cells.

  8. Live Imaging of Adult Neural Stem Cells in Rodents

    PubMed Central

    Ortega, Felipe; Costa, Marcos R.

    2016-01-01

    The generation of cells of the neural lineage within the brain is not restricted to early development. New neurons, oligodendrocytes, and astrocytes are produced in the adult brain throughout the entire murine life. However, despite the extensive research performed in the field of adult neurogenesis during the past years, fundamental questions regarding the cell biology of adult neural stem cells (aNSCs) remain to be uncovered. For instance, it is crucial to elucidate whether a single aNSC is capable of differentiating into all three different macroglial cell types in vivo or these distinct progenies constitute entirely separate lineages. Similarly, the cell cycle length, the time and mode of division (symmetric vs. asymmetric) that these cells undergo within their lineage progression are interesting questions under current investigation. In this sense, live imaging constitutes a valuable ally in the search of reliable answers to the previous questions. In spite of the current limitations of technology new approaches are being developed and outstanding amount of knowledge is being piled up providing interesting insights in the behavior of aNSCs. Here, we will review the state of the art of live imaging as well as the alternative models that currently offer new answers to critical questions. PMID:27013941

  9. Survival of glucose phosphate isomerase null somatic cells and germ cells in adult mouse chimaeras.

    PubMed

    Keighren, Margaret A; Flockhart, Jean H; West, John D

    2016-05-15

    The mouse Gpi1 gene encodes the glycolytic enzyme glucose phosphate isomerase. Homozygous Gpi1(-/-) null mouse embryos die but a previous study showed that some homozygous Gpi1(-/-) null cells survived when combined with wild-type cells in fetal chimaeras. One adult female Gpi1(-/-)↔Gpi1(c/c) chimaera with functional Gpi1(-/-) null oocytes was also identified in a preliminary study. The aims were to characterise the survival of Gpi1(-/-) null cells in adult Gpi1(-/-)↔Gpi1(c/c) chimaeras and determine if Gpi1(-/-) null germ cells are functional. Analysis of adult Gpi1(-/-)↔Gpi1(c/c) chimaeras with pigment and a reiterated transgenic lineage marker showed that low numbers of homozygous Gpi1(-/-) null cells could survive in many tissues of adult chimaeras, including oocytes. Breeding experiments confirmed that Gpi1(-/-) null oocytes in one female Gpi1(-/-)↔Gpi1(c/c) chimaera were functional and provided preliminary evidence that one male putative Gpi1(-/-)↔Gpi1(c/c) chimaera produced functional spermatozoa from homozygous Gpi1(-/-) null germ cells. Although the male chimaera was almost certainly Gpi1(-/-)↔Gpi1(c/c), this part of the study is considered preliminary because only blood was typed for GPI. Gpi1(-/-) null germ cells should survive in a chimaeric testis if they are supported by wild-type Sertoli cells. It is also feasible that spermatozoa could bypass a block at GPI, but not blocks at some later steps in glycolysis, by using fructose, rather than glucose, as the substrate for glycolysis. Although chimaera analysis proved inefficient for studying the fate of Gpi1(-/-) null germ cells, it successfully identified functional Gpi1(-/-) null oocytes and revealed that some Gpi1(-/-) null cells could survive in many adult tissues.

  10. Dental Stem Cell in Tooth Development and Advances of Adult Dental Stem Cell in Regenerative Therapies.

    PubMed

    Tan, Jiali; Xu, Xin; Lin, Jiong; Fan, Li; Zheng, Yuting; Kuang, Wei

    2015-01-01

    Stem cell-based therapies are considered as a promising treatment for many clinical usage such as tooth regeneration, bone repairation, spinal cord injury, and so on. However, the ideal stem cell for stem cell-based therapy still remains to be elucidated. In the past decades, several types of stem cells have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs) and stem cells from apical papilla (SCAP), which may be a good source for stem cell-based therapy in certain disease, especially when they origin from neural crest is considered. In this review, the specific characteristics and advantages of the adult dental stem cell population will be summarized and the molecular mechanisms of the differentiation of dental stem cell during tooth development will be also discussed.

  11. In vivo cell tracking and quantification method in adult zebrafish

    NASA Astrophysics Data System (ADS)

    Zhang, Li; Alt, Clemens; Li, Pulin; White, Richard M.; Zon, Leonard I.; Wei, Xunbin; Lin, Charles P.

    2012-03-01

    Zebrafish have become a powerful vertebrate model organism for drug discovery, cancer and stem cell research. A recently developed transparent adult zebrafish using double pigmentation mutant, called casper, provide unparalleled imaging power in in vivo longitudinal analysis of biological processes at an anatomic resolution not readily achievable in murine or other systems. In this paper we introduce an optical method for simultaneous visualization and cell quantification, which combines the laser scanning confocal microscopy (LSCM) and the in vivo flow cytometry (IVFC). The system is designed specifically for non-invasive tracking of both stationary and circulating cells in adult zebrafish casper, under physiological conditions in the same fish over time. The confocal imaging part in this system serves the dual purposes of imaging fish tissue microstructure and a 3D navigation tool to locate a suitable vessel for circulating cell counting. The multi-color, multi-channel instrument allows the detection of multiple cell populations or different tissues or organs simultaneously. We demonstrate initial testing of this novel instrument by imaging vasculature and tracking circulating cells in CD41: GFP/Gata1: DsRed transgenic casper fish whose thrombocytes/erythrocytes express the green and red fluorescent proteins. Circulating fluorescent cell incidents were recorded and counted repeatedly over time and in different types of vessels. Great application opportunities in cancer and stem cell researches are discussed.

  12. A novel type of self-beating cardiomyocytes in adult mouse ventricles

    SciTech Connect

    Omatsu-Kanbe, Mariko; Matsuura, Hiroshi

    2009-04-10

    This study was designed to investigate the presence of resident heart cells that are distinct from terminally-differentiated cardiomyocytes. Adult mouse heart was coronary perfused with collagenase, and ventricles were excised and further digested. After spinning cardiomyocyte-containing fractions down, the supernatant fraction was collected and cultured without adding any chemicals. Two to five days after plating, some of rounded cells adhered to the culture dish, gradually changed their shape and then started self-beating. These self-beating cells did not appreciably proliferate but underwent a further morphological maturation process to form highly branched shapes with many projections. These cells were mostly multinucleated, well sarcomeric-organized and expressed cardiac marker proteins, defined as atypically-shaped cardiomyocytes (ACMs). Patch-clamp experiments revealed that ACMs exhibited spontaneous action potentials arising from the preceding slow diastolic depolarization. We thus found a novel type of resident heart cells in adult cardiac ventricles that spontaneously develop into self-beating cardiomyocytes.

  13. Ascl3 marks adult progenitor cells of the mouse salivary gland.

    PubMed

    Rugel-Stahl, Anastasia; Elliott, Marilyn E; Ovitt, Catherine E

    2012-05-01

    The Ascl3 transcription factor marks a subset of salivary gland duct cells present in the three major salivary glands of the mouse. In vivo, these cells generate both duct and secretory acinar cell descendants. Here, we have analyzed whether Ascl3-expressing cells retain this multipotent lineage potential in adult glands. Cells isolated from mouse salivary glands were cultured in vitro as non-adherent spheres. Lineage tracing of the Ascl3-expressing cells within the spheres demonstrates that Ascl3+ cells isolated from adult glands remain multipotent, generating both duct and acinar cell types in vitro. Furthermore, we demonstrate that the progenitor cells characterized by Keratin 5 expression are an independent population from Ascl3+ progenitor cells. We conclude that the Ascl3+ cells are intermediate lineage-restricted progenitor cells of the adult salivary glands.

  14. Surgical Outcome of Adult Idiopathic Chiari Malformation Type 1

    PubMed Central

    Yuh, Woon Tak; Kim, Chi Heon; Kim, Hyun-Jib; Jahng, Tae-Ahn; Park, Sung Bae

    2016-01-01

    Objective The pathophysiology of idiopathic Chiari malformation (CM) type 1 is disturbance of free cerebrospinal fluid (CSF) flow and restoration of normal CSF flow is the mainstay of treatment. Additional migration of the medulla oblongata in pediatric patients is referred to as CM type 1.5, but its significance in adult patients is unknown. This study is to compare surgical outcomes of adult idiopathic CM type 1.5 with that of type 1. Methods Thirty-eight consecutive adult patients (M : F=11 : 27; median, 33.5; range, 18–63) with syringomyelia due to idiopathic CM type 1 were reviewed. Migration of the medulla oblongata was noted in 13 patients. The modified McCormick scale (MMS) was used to evaluate functional status before and one year after surgery. All patients underwent foramen magnum decompression and duroplasty. Factors related to radiological success (≥50% decrease in the diameter of the syrinx) were investigated. The follow-up period was 72.7±55.6 months. Results Preoperative functional status were MMS I in 11 patients and MMS II in 14 of CM type 1 and MMS I in 8 and II in 5 of CM type 1.5. Of patients with MMS II, 5/14 patients in group A and 3/5 patients in group B showed improvement and there was no case of deterioration. Radiological success was achieved in 32 (84%) patients and restoration of the cisterna magna (p=0.01; OR, 46.5) was the only significant factor. Conclusion Migration of the medulla oblongata did not make a difference in the surgical outcome when the cisterna magna was restored. PMID:27651871

  15. Surgical Outcome of Adult Idiopathic Chiari Malformation Type 1

    PubMed Central

    Yuh, Woon Tak; Kim, Chi Heon; Kim, Hyun-Jib; Jahng, Tae-Ahn; Park, Sung Bae

    2016-01-01

    Objective The pathophysiology of idiopathic Chiari malformation (CM) type 1 is disturbance of free cerebrospinal fluid (CSF) flow and restoration of normal CSF flow is the mainstay of treatment. Additional migration of the medulla oblongata in pediatric patients is referred to as CM type 1.5, but its significance in adult patients is unknown. This study is to compare surgical outcomes of adult idiopathic CM type 1.5 with that of type 1. Methods Thirty-eight consecutive adult patients (M : F=11 : 27; median, 33.5; range, 18–63) with syringomyelia due to idiopathic CM type 1 were reviewed. Migration of the medulla oblongata was noted in 13 patients. The modified McCormick scale (MMS) was used to evaluate functional status before and one year after surgery. All patients underwent foramen magnum decompression and duroplasty. Factors related to radiological success (≥50% decrease in the diameter of the syrinx) were investigated. The follow-up period was 72.7±55.6 months. Results Preoperative functional status were MMS I in 11 patients and MMS II in 14 of CM type 1 and MMS I in 8 and II in 5 of CM type 1.5. Of patients with MMS II, 5/14 patients in group A and 3/5 patients in group B showed improvement and there was no case of deterioration. Radiological success was achieved in 32 (84%) patients and restoration of the cisterna magna (p=0.01; OR, 46.5) was the only significant factor. Conclusion Migration of the medulla oblongata did not make a difference in the surgical outcome when the cisterna magna was restored.

  16. Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors

    SciTech Connect

    Greene, Carol Ann Chang, Chuan-Yuan; Fraser, Cameron J.; Nelidova, Dasha E.; Chen, Jing A.; Lim, Angela; Brebner, Alex; McGhee, Jennifer; Sherwin, Trevor; Green, Colin R.

    2014-03-10

    Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. The switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors.

  17. Potassium currents in rat type II alveolar epithelial cells.

    PubMed Central

    DeCoursey, T E; Jacobs, E R; Silver, M R

    1988-01-01

    1. Type II alveolar epithelial cells isolated from adult rats and grown in primary culture were studied using the whole-cell configuration of the gigohm-seal voltage clamp technique. 2. The average specific capacitance of type II cells was 2.5 microF/cm2, suggesting that type II cell membranes in vitro are irregular, with an actual area more than twice the apparent area. 3. Most type II cells have time- and voltage-dependent outward currents carried by potassium ions. Potassium currents activate with a sigmoid time course upon membrane depolarization, and inactivate during maintained depolarization. The average maximum whole-cell K+ conductance was 1.6 nS. 4. Two distinct types of K+-selective channels underlie outward currents in type II cells. Most cells have currents resembling delayed rectifier K+ currents in skeletal muscle, nerve and immune cells. A few cells had a different type of K+ conductance which is more sensitive to block by tetraethylammonium ions, has faster 'tail currents', and activates at more positive potentials. 5. In some experiments, individual type II cells were identified by staining with phosphine, a fluorescent dye which is concentrated in lamellar bodies. Both types of K+ channels were seen in type II cells identified with this dye. 6. Phosphine added to the bathing solution reversibly reduced K+ currents and shifted K+ channel activation to more positive potentials. Excitation of phosphine to fluoresce reduced irreversibly K+ currents in type II cells. The usefulness of phosphine as a means of identifying cells for study is discussed. PMID:2457683

  18. Ovarian adult stem cells: hope or pitfall?

    PubMed Central

    2014-01-01

    For many years, ovarian biology has been based on the dogma that oocytes reserve in female mammals included a finite number, established before or at birth and it is determined by the number and quality of primordial follicles developed during the neonatal period. The restricted supply of oocytes in adult female mammals has been disputed in recent years by supporters of postnatal neo-oogenesis. Recent experimental data showed that ovarian surface epithelium and cortical tissue from both mouse and human were proved to contain very low proportion of cells able to propagate themselves, but also to generate immature oocytes in vitro or in vivo, when transplanted into immunodeficient mice ovaries. By mentioning several landmarks of ovarian stem cell reserve and addressing the exciting perspective of translation into clinical practice as treatment for infertility pathologies, the purpose of this article is to review the knowledge about adult mammalian ovarian stem cells, a topic that, since the first approach quickly attracted the attention of both the scientific media and patients. PMID:25018783

  19. Switching roles: the functional plasticity of adult tissue stem cells

    PubMed Central

    Wabik, Agnieszka; Jones, Philip H

    2015-01-01

    Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept of the niche, the micro-environment that sustains and regulates stem cells, is broadening, with a new appreciation of the role of physical factors and hormonal signals. Here, we review different functions of SCs, the cellular mechanisms that underlie them and the signals that bias the fate of SCs as they switch between roles. PMID:25812989

  20. Embryonic and adult stem cell therapy.

    PubMed

    Brignier, Anne C; Gewirtz, Alan M

    2010-02-01

    There are many types of stem cells. All share the characteristics of being able to self-renew and to give rise to differentiated progeny. Over the last decades, great excitement has been generated by the prospect of being able to exploit these properties for the repair, improvement, and/or replacement of damaged organs. However, many hurdles, both scientific and ethical, remain in the path of using human embryonic stem cells for tissue-engineering purposes. In this report we review current strategies for isolating, enriching, and, most recently, inducing the development of human pluripotent stem cells. In so doing, we discuss the scientific and ethical issues associated with this endeavor. Finally, progress in the use of stem cells as therapies for type 1 diabetes mellitus, congestive heart failure, and various neurologic and immunohematologic disorders, and as vehicles for the delivery of gene therapy, is briefly discussed. PMID:20061008

  1. A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

    PubMed

    Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom

    2015-11-01

    Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs.

  2. Adult Stem Cell Therapy for Stroke: Challenges and Progress

    PubMed Central

    Bang, Oh Young; Kim, Eun Hee; Cha, Jae Min; Moon, Gyeong Joon

    2016-01-01

    Stroke is one of the leading causes of death and physical disability among adults. It has been 15 years since clinical trials of stem cell therapy in patients with stroke have been conducted using adult stem cells like mesenchymal stem cells and bone marrow mononuclear cells. Results of randomized controlled trials showed that adult stem cell therapy was safe but its efficacy was modest, underscoring the need for new stem cell therapy strategies. The primary limitations of current stem cell therapies include (a) the limited source of engraftable stem cells, (b) the presence of optimal time window for stem cell therapies, (c) inherited limitation of stem cells in terms of growth, trophic support, and differentiation potential, and (d) possible transplanted cell-mediated adverse effects, such as tumor formation. Here, we discuss recent advances that overcome these hurdles in adult stem cell therapy for stroke. PMID:27733032

  3. Transcription factors that convert adult cell identity are differentially polycomb repressed.

    PubMed

    Davis, Fred P; Eddy, Sean R

    2013-01-01

    Transcription factors that can convert adult cells of one type to another are usually discovered empirically by testing factors with a known developmental role in the target cell. Here we show that standard genomic methods (RNA-seq and ChIP-seq) can help identify these factors, as most are more strongly Polycomb repressed in the source cell and more highly expressed in the target cell. This criterion is an effective genome-wide screen that significantly enriches for factors that can transdifferentiate several mammalian cell types including neural stem cells, neurons, pancreatic islets, and hepatocytes. These results suggest that barriers between adult cell types, as depicted in Waddington's "epigenetic landscape", consist in part of differentially Polycomb-repressed transcription factors. This genomic model of cell identity helps rationalize a growing number of transdifferentiation protocols and may help facilitate the engineering of cell identity for regenerative medicine.

  4. The effect of replacement of methionine by homocystine on survival of malignant and normal adult mammalian cells in culture.

    PubMed

    Halpern, B C; Clark, B R; Hardy, D N; Halpern, R M; Smith, R A

    1974-04-01

    In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.

  5. Adult stem cells for cardiac repair: a choice between skeletal myoblasts and bone marrow stem cells.

    PubMed

    Ye, Lei; Haider, Husnain Kh; Sim, Eugene K W

    2006-01-01

    The real promise of a stem cell-based approach for cardiac regeneration and repair lies in the promotion of myogenesis and angiogenesis at the site of the cell graft to achieve both structural and functional benefits. Despite all of the progress and promise in this field, many unanswered questions remain; the answers to these questions will provide the much-needed breakthrough to harness the real benefits of cell therapy for the heart in the clinical perspective. One of the major issues is the choice of donor cell type for transplantation. Multiple cell types with varying potentials have been assessed for their ability to repopulate the infarcted myocardium; however, only the adult stem cells, that is, skeletal myoblasts (SkM) and bone marrow-derived stem cells (BMC), have been translated from the laboratory bench to clinical use. Which of these two cell types will provide the best option for clinical application in heart cell therapy remains arguable. With results pouring in from the long-term follow-ups of previously conducted phase I clinical studies, and with the onset of phase II clinical trials involving larger population of patients, transplantation of stem cells as a sole therapy without an adjunct conventional revascularization procedure will provide a deeper insight into the effectiveness of this approach. The present article discusses the pros and cons of using SkM and BMC individually or in combination for cardiac repair, and critically analyzes the progress made with each cell type.

  6. Pancreas β cell regeneration and type 1 diabetes (Review)

    PubMed Central

    WU, JINXIAO; YANG, XIYAN; CHEN, BIN; XU, XIUPING

    2015-01-01

    Diabetes mellitus, which may cause hyperglycemia and a number of complications, mostly results from a deficiency of β cell mass (type 1 diabetes) or a limitation of β cell function (type 2 diabetes). Currently, enhancing β cell regeneration and increasing cell proliferation have not only been described in experimental diabetes models, but have also been proven to improve outcomes for patients with diabetes. Therefore, understanding the mechanisms controlling the development and regeneration of β cells in the human pancreas may be helpful for the treatment of β cell-deficient disease. In this review, we first introduce the various cell types in the adult pancreas and thereby clarify their functions and origins. Then, the known mechanisms of β cell development and expansion in the normal human pancreas are described. The potential mechanisms of β cell regeneration, including β cell self-replication, neogenesis from non-β cell precursors and transdifferentiation from α cells, are discussed in the next part. Finally, the ability of the pancreas to regenerate mature β cells is explored in pathological conditions, including type 1 diabetes, chronic pancreatitis and persistent hyperinsulinemic hypoglycemia of infancy. PMID:25667609

  7. Combinations of Types of Mental Health Services Received in the Past Year Among Young Adults

    MedlinePlus

    ... 08, 2015* Combinations of types of mental health services received in the past year among young adults Combinations of types of mental health services received in the past year among young adults ...

  8. Falls risk in older adults with type 2 diabetes.

    PubMed

    Vinik, Aaron I; Vinik, Etta J; Colberg, Sheri R; Morrison, Steven

    2015-02-01

    Falls are a major health issue for older adults, especially for those who develop type 2 diabetes who must contend with age-related declines in balance, muscle strength, and walking ability. They must also contend with health-related issues specific to the disease process. Given the general association between these variables and falls, being able to identify which measures negatively impact on balance in older diabetic persons is a critical step. Moreover, designing specific interventions to target these physiologic functions underlying balance and gait control will produce the greatest benefit for reducing falls in older persons with diabetes.

  9. Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons?

    PubMed

    Liao, Song-Yan; Tse, Hung-Fat

    2013-12-24

    Heart failure after myocardial infarction is the leading cause of mortality and morbidity worldwide. Existing medical and interventional therapies can only reduce the loss of cardiomyocytes during myocardial infarction but are unable to replenish the permanent loss of cardiomyocytes after the insult, which contributes to progressive pathological left ventricular remodeling and progressive heart failure. As a result, cell-based therapies using multipotent (adult) stem cells and pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) have been explored as potential therapeutic approaches to restore cardiac function in heart failure. Nevertheless, the optimal cell type with the best therapeutic efficacy and safety for heart regeneration is still unknown. In this review, the potential pros and cons of different types of multipotent (adult) stem cells and pluripotent stem cells that have been investigated in preclinical and clinical studies are reviewed, and the future perspective of stem cell-based therapy for heart regeneration is discussed.

  10. Survival of glucose phosphate isomerase null somatic cells and germ cells in adult mouse chimaeras

    PubMed Central

    Keighren, Margaret A.; Flockhart, Jean H.

    2016-01-01

    ABSTRACT The mouse Gpi1 gene encodes the glycolytic enzyme glucose phosphate isomerase. Homozygous Gpi1−/− null mouse embryos die but a previous study showed that some homozygous Gpi1−/− null cells survived when combined with wild-type cells in fetal chimaeras. One adult female Gpi1−/−↔Gpi1c/c chimaera with functional Gpi1−/− null oocytes was also identified in a preliminary study. The aims were to characterise the survival of Gpi1−/− null cells in adult Gpi1−/−↔Gpi1c/c chimaeras and determine if Gpi1−/− null germ cells are functional. Analysis of adult Gpi1−/−↔Gpi1c/c chimaeras with pigment and a reiterated transgenic lineage marker showed that low numbers of homozygous Gpi1−/− null cells could survive in many tissues of adult chimaeras, including oocytes. Breeding experiments confirmed that Gpi1−/− null oocytes in one female Gpi1−/−↔Gpi1c/c chimaera were functional and provided preliminary evidence that one male putative Gpi1−/−↔Gpi1c/c chimaera produced functional spermatozoa from homozygous Gpi1−/− null germ cells. Although the male chimaera was almost certainly Gpi1−/−↔Gpi1c/c, this part of the study is considered preliminary because only blood was typed for GPI. Gpi1−/− null germ cells should survive in a chimaeric testis if they are supported by wild-type Sertoli cells. It is also feasible that spermatozoa could bypass a block at GPI, but not blocks at some later steps in glycolysis, by using fructose, rather than glucose, as the substrate for glycolysis. Although chimaera analysis proved inefficient for studying the fate of Gpi1−/− null germ cells, it successfully identified functional Gpi1−/− null oocytes and revealed that some Gpi1−/− null cells could survive in many adult tissues. PMID:27103217

  11. Integrated molecular analysis of adult T cell leukemia/lymphoma.

    PubMed

    Kataoka, Keisuke; Nagata, Yasunobu; Kitanaka, Akira; Shiraishi, Yuichi; Shimamura, Teppei; Yasunaga, Jun-Ichirou; Totoki, Yasushi; Chiba, Kenichi; Sato-Otsubo, Aiko; Nagae, Genta; Ishii, Ryohei; Muto, Satsuki; Kotani, Shinichi; Watatani, Yosaku; Takeda, June; Sanada, Masashi; Tanaka, Hiroko; Suzuki, Hiromichi; Sato, Yusuke; Shiozawa, Yusuke; Yoshizato, Tetsuichi; Yoshida, Kenichi; Makishima, Hideki; Iwanaga, Masako; Ma, Guangyong; Nosaka, Kisato; Hishizawa, Masakatsu; Itonaga, Hidehiro; Imaizumi, Yoshitaka; Munakata, Wataru; Ogasawara, Hideaki; Sato, Toshitaka; Sasai, Ken; Muramoto, Kenzo; Penova, Marina; Kawaguchi, Takahisa; Nakamura, Hiromi; Hama, Natsuko; Shide, Kotaro; Kubuki, Yoko; Hidaka, Tomonori; Kameda, Takuro; Nakamaki, Tsuyoshi; Ishiyama, Ken; Miyawaki, Shuichi; Yoon, Sung-Soo; Tobinai, Kensei; Miyazaki, Yasushi; Takaori-Kondo, Akifumi; Matsuda, Fumihiko; Takeuchi, Kengo; Nureki, Osamu; Aburatani, Hiroyuki; Watanabe, Toshiki; Shibata, Tatsuhiro; Matsuoka, Masao; Miyano, Satoru; Shimoda, Kazuya; Ogawa, Seishi

    2015-11-01

    Adult T cell leukemia/lymphoma (ATL) is a peripheral T cell neoplasm of largely unknown genetic basis, associated with human T cell leukemia virus type-1 (HTLV-1) infection. Here we describe an integrated molecular study in which we performed whole-genome, exome, transcriptome and targeted resequencing, as well as array-based copy number and methylation analyses, in a total of 426 ATL cases. The identified alterations overlap significantly with the HTLV-1 Tax interactome and are highly enriched for T cell receptor-NF-κB signaling, T cell trafficking and other T cell-related pathways as well as immunosurveillance. Other notable features include a predominance of activating mutations (in PLCG1, PRKCB, CARD11, VAV1, IRF4, FYN, CCR4 and CCR7) and gene fusions (CTLA4-CD28 and ICOS-CD28). We also discovered frequent intragenic deletions involving IKZF2, CARD11 and TP73 and mutations in GATA3, HNRNPA2B1, GPR183, CSNK2A1, CSNK2B and CSNK1A1. Our findings not only provide unique insights into key molecules in T cell signaling but will also guide the development of new diagnostics and therapeutics in this intractable tumor. PMID:26437031

  12. Chinmo is sufficient to induce male fate in somatic cells of the adult Drosophila ovary.

    PubMed

    Ma, Qing; de Cuevas, Margaret; Matunis, Erika L

    2016-03-01

    Sexual identity is continuously maintained in specific differentiated cell types long after sex determination occurs during development. In the adult Drosophila testis, the putative transcription factor Chronologically inappropriate morphogenesis (Chinmo) acts with the canonical male sex determinant DoublesexM (Dsx(M)) to maintain the male identity of somatic cyst stem cells and their progeny. Here we find that ectopic expression of chinmo is sufficient to induce a male identity in adult ovarian somatic cells, but it acts through a Dsx(M)-independent mechanism. Conversely, the feminization of the testis somatic stem cell lineage caused by loss of chinmo is enhanced by expression of the canonical female sex determinant Dsx(F), indicating that chinmo acts in parallel with the canonical sex determination pathway to maintain the male identity of testis somatic cells. Consistent with this finding, ectopic expression of female sex determinants in the adult testis disrupts tissue morphology. The miRNA let-7 downregulates chinmo in many contexts, and ectopic expression of let-7 in the adult testis is sufficient to recapitulate the chinmo loss-of-function phenotype, but we find no apparent phenotypes upon removal of let-7 in the adult ovary or testis. Our finding that chinmo is necessary and sufficient to promote a male identity in adult gonadal somatic cells suggests that the sexual identity of somatic cells can be reprogrammed in the adult Drosophila ovary as well as in the testis. PMID:26811385

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. GD3+ cells in the adult rat optic nerve are ramified microglia rather than O-2Aadult progenitor cells.

    PubMed

    Wolswijk, G

    1994-04-01

    The adult central nervous system (CNS) contains a population of adult oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells (O-2Aadult progenitor cells). These cells may provide a source of the new oligodendrocytes that are needed to repair demyelinated lesions. In order to examine the role of O-2Aadult progenitor cells in the regeneration of the oligodendrocyte population following demyelinating damage, it is essential to be able to identify such cells unambiguously in sections of adult CNS tissue. The present study examined whether antibodies to the ganglioside GD3 specifically label O-2Aadult progenitor cells in cultures and sections of adult optic nerve, since previous studies on the developing CNS had suggested that O-2Aperinatal progenitor cells were GD3+ in vitro and in vivo. Evidence is presented indicating that, although O-2Aadult progenitor cells in vitro were labelled with the R24 mAb (an anti-GD3 mAb), all GD3+ cells in sections of adult optic nerve bound the OX-42 mAb and the B4 isolectin derived from Griffonia Simplicifolia, and thus were not O-2Aadult progenitor cells, but ramified microglia. The data suggest that O-2Aadult progenitor cells become GD3+ when placed in culture and that ramified microglia lose GD3-expression in vitro.

  16. Young adults' experience of living with neurofibromatosis type 1.

    PubMed

    Hummelvoll, Grete; Antonsen, Kjell Magnus

    2013-04-01

    Neurofibromatosis Type 1 (NF1) may have many psychosocial consequences for affected adults. More knowledge is needed about the experience of psychosocial aspects in different stages of adulthood. This qualitative study aims to describe the experiences and concerns of persons living with NF1 in the early stages of adulthood. In semi-structured interviews, Norwegian adults with NF1 (n = 15) between 18 and 37 years of age described their experiences and concerns. Interview transcripts were analysed in a both concept and data driven way. Severity of NF1 was assessed from interview data. Our data indicate that many informants have more friends than in childhood, including friends with NF1. An important topic is whether or not to inform others about the NF1 diagnosis . Low self-confidence is common, often related to early school failure and bullying or to visible neurofibromas. The unpredictable development of NF1 causes much concern. The experience of NF1's impact seems less associated with the assessed severity than with social network, relation to the labour market, and psychological factors. PMID:22815101

  17. Regulatory System for Stem/Progenitor Cell Niches in the Adult Rodent Pituitary

    PubMed Central

    Yoshida, Saishu; Kato, Takako; Kato, Yukio

    2016-01-01

    The anterior lobe of the pituitary gland is a master endocrine tissue composed of five types of endocrine cells. Although the turnover rate of pituitary endocrine cells is as low as about 1.6% per day, recent studies have demonstrated that Sex-determining region Y-box 2 (SOX2)+-cells exist as pituitary stem/progenitor cells in the adult anterior lobe and contribute to cell regeneration. Notably, SOX2+-pituitary stem/progenitor cells form two types of niches in this tissue: the marginal cell layer (MCL-niche) and the dense cell clusters scattering in the parenchyma (parenchymal-niche). However, little is known about the mechanisms and factors for regulating the pituitary stem/progenitor cell niches, as well as the functional differences between the two types of niches. Elucidation of the regulatory mechanisms in the niches might enable us to understand the cell regeneration system that acts in accordance with physiological demands in the adult pituitary. In this review, so as to reveal the regulatory mechanisms of the two types of niche, we summarize the regulatory factors and their roles in the adult rodent pituitary niches by focusing on three components: soluble factors, cell surface proteins and extracellular matrixes. PMID:26761002

  18. Analysis of gene expression in fetal and adult cells infected with rubella virus

    SciTech Connect

    Adamo, Maria Pilar; Zapata, Marta; Frey, Teryl K.

    2008-01-05

    Congenital infection with rubella virus (RUB) leads to persistent infection and congenital defects and we showed previously that primary human fetal fibroblasts did not undergo apoptosis when infected with RUB, which could promote fetal virus persistence [Adamo, P., Asis, L., Silveyra, P., Cuffini, C., Pedranti, M., Zapata, M., 2004. Rubella virus does not induce apoptosis in primary human embryo fibroblasts cultures: a possible way of viral persistence in congenital infection. Viral Immunol. 17, 87-100]. To extend this observation, gene chip analysis was performed on a line of primary human fetal fibroblasts (10 weeks gestation) and a line of human adult lung fibroblasts (which underwent apoptosis in response to RUB infection) to compare gene expression in infected and uninfected cells. A total of 632 and 516 genes were upregulated or downregulated in the infected fetal and adult cells respectively in comparison to uninfected cells, however only 52 genes were regulated in both cell types. Although the regulated genes were different, across functional gene categories the patterns of gene regulation were similar. In general, regulation of pro- and anti-apoptotic genes following infection appeared to favor apoptosis in the adult cells and lack of apoptosis in the fetal cells, however there was a greater relative expression of anti-apoptotic genes and reduced expression of pro-apoptotic genes in uninfected fetal cells versus uninfected adult cells and thus the lack of apoptosis in fetal cells following RUB infection was also due to the prevailing background of gene expression that is antagonistic to apoptosis. In support of this hypothesis, it was found that of a battery of five chemicals known to induce apoptosis, two induced apoptosis in the adult cells, but not in fetal cells, and two induced apoptosis more rapidly in the adult cells than in fetal cells (the fifth did not induce apoptosis in either). A robust interferon-stimulated gene response was induced

  19. Adult stem cells in neural repair: Current options, limitations and perspectives.

    PubMed

    Mariano, Eric Domingos; Teixeira, Manoel Jacobsen; Marie, Suely Kazue Nagahashi; Lepski, Guilherme

    2015-03-26

    Stem cells represent a promising step for the future of regenerative medicine. As they are able to differentiate into any cell type, tissue or organ, these cells are great candidates for treatments against the worst diseases that defy doctors and researchers around the world. Stem cells can be divided into three main groups: (1) embryonic stem cells; (2) fetal stem cells; and (3) adult stem cells. In terms of their capacity for proliferation, stem cells are also classified as totipotent, pluripotent or multipotent. Adult stem cells, also known as somatic cells, are found in various regions of the adult organism, such as bone marrow, skin, eyes, viscera and brain. They can differentiate into unipotent cells of the residing tissue, generally for the purpose of repair. These cells represent an excellent choice in regenerative medicine, every patient can be a donor of adult stem cells to provide a more customized and efficient therapy against various diseases, in other words, they allow the opportunity of autologous transplantation. But in order to start clinical trials and achieve great results, we need to understand how these cells interact with the host tissue, how they can manipulate or be manipulated by the microenvironment where they will be transplanted and for how long they can maintain their multipotent state to provide a full regeneration.

  20. Insights from a Chimpanzee Adipose Stromal Cell Population: Opportunities for Adult Stem Cells to Expand Primate Functional Genomics

    PubMed Central

    Pfefferle, Lisa W.; Wray, Gregory A.

    2013-01-01

    Comparisons between humans and chimpanzees are essential for understanding traits unique to each species. However, linking important phenotypic differences to underlying molecular changes is often challenging. The ability to generate, differentiate, and profile adult stem cells provides a powerful but underutilized opportunity to investigate the molecular basis for trait differences between species within specific cell types and in a controlled environment. Here, we characterize adipose stromal cells (ASCs) from Clint, the chimpanzee whose genome was first sequenced. Using imaging and RNA-Seq, we compare the chimpanzee ASCs with three comparable human cell lines. Consistent with previous studies on ASCs in humans, the chimpanzee cells have fibroblast-like morphology and express genes encoding components of the extracellular matrix at high levels. Differentially expressed genes are enriched for distinct functional classes between species: immunity and protein processing are higher in chimpanzees, whereas cell cycle and DNA processing are higher in humans. Although hesitant to draw definitive conclusions from these data given the limited sample size, we wish to stress the opportunities that adult stem cells offer for studying primate evolution. In particular, adult stem cells provide a powerful means to investigate the profound disease susceptibilities unique to humans and a promising tool for conservation efforts with nonhuman primates. By allowing for experimental perturbations in relevant cell types, adult stem cells promise to complement classic comparative primate genomics based on in vivo sampling. PMID:24092797

  1. Cell Phone Use by Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Bryen, Diane Nelson; Carey, Allison; Friedman, Mark

    2007-01-01

    Although cell phone use has grown dramatically, there is a gap in cell phone access between people with disabilities and the general public. The importance of cell phone use among people with intellectual disabilities and studies about use of cell phones by adults with intellectual disabilities was described. Our goal was to determine the extent…

  2. Insulin withdrawal-induced cell death in adult hippocampal neural stem cells as a model of autophagic cell death.

    PubMed

    Baek, Seung-Hoon; Kim, Eun-Kyoung; Goudreau, John L; Lookingland, Keith J; Kim, Seong Who; Yu, Seong-Woon

    2009-02-01

    The term "autophagic cell death" was coined to describe a form of cell death associated with the massive formation of autophagic vacuoles without signs of apoptosis. However, questions about the actual role of autophagy and its molecular basis in cell death remain to be elucidated. We recently reported that adult hippocampal neural stem (HCN) cells undergo autophagic cell death following insulin withdrawal. Insulin-deprived HCN cells exhibit morphological and biochemical markers of autophagy, including accumulation of Beclin 1 and the type II form of microtubule-associated protein 1 light chain 3 (LC3) without evidence of apoptosis. Suppression of autophagy by knockdown of Atg7 reduces cell death, whereas promotion of autophagy with rapamycin augments cell death in insulin-deficient HCN cells. These data reveal a causative role of autophagy in insulin withdrawal-induced HCN cell death. HCN cells have intact apoptotic capability despite the lack of apoptosis following insulin withdrawal. Our study demonstrates that autophagy is the default cell death mechanism in insulin-deficient HCN cells, and provides a genuine model of autophagic cell death in apoptosis-intact cells. Novel insight into molecular mechanisms of this underappreciated form of programmed cell death should facilitate the development of therapeutic methods to cope with human diseases caused by dysregulated cell death.

  3. Markers of epidermal stem cell subpopulations in adult mammalian skin.

    PubMed

    Kretzschmar, Kai; Watt, Fiona M

    2014-10-01

    The epidermis is the outermost layer of mammalian skin and comprises a multilayered epithelium, the interfollicular epidermis, with associated hair follicles, sebaceous glands, and eccrine sweat glands. As in other epithelia, adult stem cells within the epidermis maintain tissue homeostasis and contribute to repair of tissue damage. The bulge of hair follicles, where DNA-label-retaining cells reside, was traditionally regarded as the sole epidermal stem cell compartment. However, in recent years multiple stem cell populations have been identified. In this review, we discuss the different stem cell compartments of adult murine and human epidermis, the markers that they express, and the assays that are used to characterize epidermal stem cell properties.

  4. Cell-Type-Specific Optogenetics in Monkeys.

    PubMed

    Namboodiri, Vijay Mohan K; Stuber, Garret D

    2016-09-01

    The recent advent of technologies enabling cell-type-specific recording and manipulation of neuronal activity spurred tremendous progress in neuroscience. However, they have been largely limited to mice, which lack the richness in behavior of primates. Stauffer et al. now present a generalizable method for achieving cell-type specificity in monkeys. PMID:27610562

  5. Potential of embryonic and adult stem cells in vitro.

    PubMed

    Czyz, Jaroslaw; Wiese, Cornelia; Rolletschek, Alexandra; Blyszczuk, Przemyslaw; Cross, Michael; Wobus, Anna M

    2003-01-01

    Recent developments in the field of stem cell research indicate their enormous potential as a source of tissue for regenerative therapies. The success of such applications will depend on the precise properties and potentials of stem cells isolated either from embryonic, fetal or adult tissues. Embryonic stem cells established from the inner cell mass of early mouse embryos are characterized by nearly unlimited proliferation, and the capacity to differentiate into derivatives of essentially all lineages. The recent isolation and culture of human embryonic stem cell lines presents new opportunities for reconstructive medicine. However, important problems remain; first, the derivation of human embryonic stem cells from in vitro fertilized blastocysts creates ethical problems, and second, the current techniques for the directed differentiation into somatic cell populations yield impure products with tumorigenic potential. Recent studies have also suggested an unexpectedly wide developmental potential of adult tissue-specific stem cells. Here too, many questions remain concerning the nature and status of adult stem cells both in vivo and in vitro and their proliferation and differentiation/transdifferentiation capacity. This review focuses on those issues of embryonic and adult stem cell biology most relevant to their in vitro propagation and differentiation. Questions and problems related to the use of human embryonic and adult stem cells in tissue regeneration and transplantation are discussed.

  6. 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

  7. Regenerative capacity of adult cortical thymic epithelial cells.

    PubMed

    Rode, Immanuel; Boehm, Thomas

    2012-02-28

    Involution of the thymus is accompanied by a decline in the number of thymic epithelial cells (TECs) and a severely restricted peripheral repertoire of T-cell specificities. TECs are essential for T-cell differentiation; they originate from a bipotent progenitor that gives rise to cells of cortical (cTEC) and medullary (mTEC) phenotypes, via compartment-specific progenitors. Upon acute selective near-total ablation during embryogenesis, regeneration of TECs fails, suggesting that losses from the pool of TEC progenitors are not compensated. However, it is unclear whether this is also true for the compartment-specific progenitors. The decline of cTECs is a prominent feature of thymic involution. Because cTECs support early stages of T-cell development and hence determine the overall lymphopoietic capacity of the thymus, it is possible that the lack of sustained regenerative capacity of cTEC progenitor cells underlies the process of thymic involution. Here, we examine this hypothesis by cell-type-specific conditional ablation of cTECs. Expression of the human diphtheria toxin receptor (hDTR) gene under the regulatory influence of the chemokine receptor Ccx-ckr1 gene renders cTECs sensitive to the cytotoxic effects of diphtheria toxin (DT). As expected, DT treatment of preadolescent and adult mice led to a dramatic loss of cTECs, accompanied by a rapid demise of immature thymocytes. Unexpectedly, however, the cTEC compartment regenerated after cessation of treatment, accompanied by the restoration of T-cell development. These findings provide the basis for the development of targeted interventions unlocking the latent regenerative potential of cTECs to counter thymic involution.

  8. A Cell-type-resolved Liver Proteome*

    PubMed Central

    Ding, Chen; Li, Yanyan; Guo, Feifei; Jiang, Ying; Ying, Wantao; Li, Dong; Yang, Dong; Xia, Xia; Liu, Wanlin; Zhao, Yan; He, Yangzhige; Li, Xianyu; Sun, Wei; Liu, Qiongming; Song, Lei; Zhen, Bei; Zhang, Pumin; Qian, Xiaohong; Qin, Jun; He, Fuchu

    2016-01-01

    Parenchymatous organs consist of multiple cell types, primarily defined as parenchymal cells (PCs) and nonparenchymal cells (NPCs). The cellular characteristics of these organs are not well understood. Proteomic studies facilitate the resolution of the molecular details of different cell types in organs. These studies have significantly extended our knowledge about organogenesis and organ cellular composition. Here, we present an atlas of the cell-type-resolved liver proteome. In-depth proteomics identified 6000 to 8000 gene products (GPs) for each cell type and a total of 10,075 GPs for four cell types. This data set revealed features of the cellular composition of the liver: (1) hepatocytes (PCs) express the least GPs, have a unique but highly homogenous proteome pattern, and execute fundamental liver functions; (2) the division of labor among PCs and NPCs follows a model in which PCs make the main components of pathways, but NPCs trigger the pathways; and (3) crosstalk among NPCs and PCs maintains the PC phenotype. This study presents the liver proteome at cell resolution, serving as a research model for dissecting the cell type constitution and organ features at the molecular level. PMID:27562671

  9. Molecular Pathology of Adult T-Cell Leukemia/Lymphoma.

    PubMed

    Ohshima, Koichi

    2015-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm of highly pleomorphic lymphoid cells. ATLL is usually widely disseminated, and it is caused by human T-cell leukemia virus type 1 (HTLV-1). It is a disease with a long latency, and affected individuals are usually exposed to the virus very early in life. The cumulative incidence of ATLL is estimated to be 2.5% among HTLV-1 carriers. ATLL cells express CD2, CD3, CD5, CD4, and CD25, as well as CCR4 and FoxP3 of the regulatory T-cell marker. HTLV-1 is causally linked to ATLL, but infection alone is not sufficient to result in neoplastic transformation. A significant finding in this connection is that the Tax viral protein leads to transcriptional activation of many genes, while the HTLV-1 basic leucine zipper factor is thought to be important for T-cell proliferation and oncogenesis. Half of ATLL cases retain the ability to express HTLV-1 Tax, which is a target of HTLV-1-specific cytotoxic T lymphocytes (CTL). An increase in HTLV-1-specific CTL responses is observed in some asymptomatic HTLV-1 carriers. Although HTLV-1-specific CTL are also present in the peripheral blood of ATLL patients, they do not expand sufficiently. We investigated the clinicopathological features and analyzed the staining of Tax-specific CTL and FoxP3. Tax-specific CTL correlated inversely with FoxP3, an increase in the ratio of CD163+ tumor-associated macrophages was associated with worse clinical prognosis, and ATLL cell lines proliferated significantly following direct co-culture with M2 macrophages. Several clinical variants of ATLL have been identified: acute, lymphomatous, chronic, and smoldering. Oligo-array comparative genomic hybridization revealed that genomic loss of 9p21.3 was a significant characteristic of acute-type, but not of chronic-type ATLL. Furthermore, we found that genomic alteration of CD58, which is implicated in immune escape, is more frequently observed in acute than in chronic ATLL. Interestingly

  10. Molecular Biomarkers for Embryonic and Adult Neural Stem Cell and Neurogenesis

    PubMed Central

    Zhang, Juan; Jiao, Jianwei

    2015-01-01

    The procedure of neurogenesis has made numerous achievements in the past decades, during which various molecular biomarkers have been emerging and have been broadly utilized for the investigation of embryonic and adult neural stem cell (NSC). Nevertheless, there is not a consistent and systematic illustration to depict the functional characteristics of the specific markers expressed in distinct cell types during the different stages of neurogenesis. Here we gathered and generalized a series of NSC biomarkers emerging during the procedures of embryonic and adult neural stem cell, which may be used to identify the subpopulation cells with distinguishing characters in different timeframes of neurogenesis. The identifications of cell patterns will provide applications to the detailed investigations of diverse developmental cell stages and the extents of cell differentiation, which will facilitate the tracing of cell time-course and fate determination of specific cell types and promote the further and literal discoveries of embryonic and adult neurogenesis. Meanwhile, via the utilization of comprehensive applications under the aiding of the systematic knowledge framework, researchers may broaden their insights into the derivation and establishment of novel technologies to analyze the more detailed process of embryogenesis and adult neurogenesis. PMID:26421301

  11. Stem cell approaches for the treatment of type 1 diabetes mellitus.

    PubMed

    Wagner, Ryan T; Lewis, Jennifer; Cooney, Austin; Chan, Lawrence

    2010-09-01

    Type 1 diabetes is characterized by near total absence of pancreatic b cells. Current treatments consisting of insulin injections and islet transplantation are clinically unsatisfactory. In order to develop a cure for type 1 diabetes, we must find a way to reverse autoimmunity, which underlies b cell destruction, as well as an effective strategy to generate new b cells. This article reviews the different approaches that are being taken to produce new b cells. Much emphasis has been placed on selecting the right non-b cell population, either in vivo or in vitro, as the starting material. Different cell types, including adult stem cells, other types of progenitor cells in situ, and even differentiated cell populations, as well as embryonic stem cells and induced pluripotent stem cells, will require different methods for islet and b cell induction. We discussed the pros and cons of the different strategies that are being used to re-invent the pancreatic b cell.

  12. Molecular differentiation of congenital lactase deficiency from adult-type hypolactasia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A limited fraction of the human adult population retains intestinal lactase-phlorizin hydrolase (LPH) activity during adulthood, and this is called the lactase persistence phenotype. However, 95% of all adults have adult-type hypolactasia (ATH) and have difficulty digesting milk sugar. Rarely, some ...

  13. Role for protein geranylgeranylation in adult T-cell leukemia cell survival

    SciTech Connect

    Nonaka, Mizuho; Uota, Shin; Saitoh, Yasunori; Takahashi, Mayumi; Sugimoto, Haruyo; Amet, Tohti; Arai, Ayako; Miura, Osamu; Yamamoto, Naoki; Yamaoka, Shoji

    2009-01-15

    Adult T-cell leukemia (ATL) is a fatal lymphoproliferative disease that develops in human T-cell leukemia virus type I (HTLV-I)-infected individuals. Despite the accumulating knowledge of the molecular biology of HTLV-I-infected cells, effective therapeutic strategies remain to be established. Recent reports showed that the hydroxyl-3-methylglutaryl (HMG)-CoA reductase inhibitor statins have anti-proliferative and apoptotic effects on certain tumor cells through inhibition of protein prenylation. Here, we report that statins hinder the survival of ATL cells and induce apoptotic cell death. Inhibition of protein geranylgeranylation is responsible for these effects, since simultaneous treatment with isoprenoid precursors, geranylgeranyl pyrophosphate or farnesyl pyrophosphate, but not a cholesterol precursor squalene, restored the viability of ATL cells. Simvastatin inhibited geranylgeranylation of small GTPases Rab5B and Rac1 in ATL cells, and a geranylgeranyl transferase inhibitor GGTI-298 reduced ATL cell viability more efficiently than a farnesyl transferase inhibitor FTI-277. These results not only unveil an important role for protein geranylgeranylation in ATL cell survival, but also implicate therapeutic potentials of statins in the treatment of ATL.

  14. Histomorphometric study on blood cells in male adult ostrich

    PubMed Central

    Tadjalli, Mina; Nazifi, Saeed; Marzban Abbasabadi, Behrokh; Majidi, Banafsheh

    2013-01-01

    In order to perform a histomorphometric study of blood cells in male adult ostrich, blood samples were obtained from jugular vein of 10 clinically healthy male adult ostriches (2 - 3 years old). The slides were stained with the Giemsa methods and the smears were evaluated for cellular morphology, with cellular size being determined by micrometry. The findings of this study revealed that the shape of the cell, cytoplasm and nucleus of erythrocytes in male adult ostriches were similar to those in other birds such as quails, chickens, Iranian green-head ducks. PMID:25653798

  15. Unipotent, Atoh1+ progenitors maintain the Merkel cell population in embryonic and adult mice.

    PubMed

    Wright, Margaret C; Reed-Geaghan, Erin G; Bolock, Alexa M; Fujiyama, Tomoyuki; Hoshino, Mikio; Maricich, Stephen M

    2015-02-01

    Resident progenitor cells in mammalian skin generate new cells as a part of tissue homeostasis. We sought to identify the progenitors of Merkel cells, a unique skin cell type that plays critical roles in mechanosensation. We found that some Atoh1-expressing cells in the hairy skin and whisker follicles are mitotically active at embryonic and postnatal ages. Genetic fate-mapping revealed that these Atoh1-expressing cells give rise solely to Merkel cells. Furthermore, selective ablation of Atoh1(+) skin cells in adult mice led to a permanent reduction in Merkel cell numbers, demonstrating that other stem cell populations are incapable of producing Merkel cells. These data identify a novel, unipotent progenitor population in the skin that gives rise to Merkel cells both during development and adulthood.

  16. Islet transplantation versus stem cells for the cell therapy of type 1 diabetes mellitus.

    PubMed

    Basta, G; Montanucci, P; Calafiore, R

    2015-12-01

    Pancreatic islet cell transplantation has represented the mainstay of cell therapy for the potential, final cure of type 1 diabetes mellitus (T1D), along the past two decades. Unfortunately, the restricted availability of cadaveric human donor pancreases coupled with heavy side effects of the recipient's general immunosuppression, have severely crippled progress of this approach into clinical trials. Only a few excellence centers, worldwide, have thus far accrued still quite marginal clinical success. In an attempt to overcome the limits of islet transplantation new technologies for use of several stem cell lineages are being under investigation, with initial experimental evidence of success. Essentially, the actual lines of research involve attempts to either activate native endogenous stem cells that replace diseased/dead cells, by a cell regeneration process, or condition other stem cells to acquire the functional properties of the targeted cells to be substituted (i.e., beta-cell-like elements associated with insulin secretory competence). A wide array of stem cells may fulfill this task, from embryonic (whose use still faces strong ethical barriers), to adult, to induced pluripotent stem cells. Mesenchymal adult stem cells, retrievable from many different sites, including adipose tissue, bone marrow and post-partum umbilical cord Wharton Jelly, seem to couple plastic to immunoregulatory properties that might greatly help progress for the disease cure.

  17. Falls and Balance Impairments in Older Adults with Type 2 Diabetes: Thinking Beyond Diabetic Peripheral Neuropathy.

    PubMed

    Hewston, Patricia; Deshpande, Nandini

    2016-02-01

    Older adults with type 2 diabetes have significantly higher incidence of falls than those without type 2 diabetes. The devastating consequences of falls include declines in mobility, activity avoidance, institutionalization and mortality. One of the most commonly identified risk factors associated with falls is impaired balance. Balance impairments and subsequent increased fall risk in older adults with type 2 diabetes are most commonly associated with diabetic peripheral neuropathy (DPN). Consequently, DPN has been the central focus of falls prevention research and interventions for older adults with type 2 diabetes. However, isolated studies have identified adults with type 2 diabetes without overt complications of DPN to also be at increased fall risk. It is known that the ability to maintain balance is a complex skill that requires the integration of multiple sensorimotor and cognitive processes. Emerging evidence suggests that diabetes-related subtle declines in sensory functions (somatosensory, visual and vestibular), metabolic muscle function and executive functions may also contribute to increased fall risk in older adults with type 2 diabetes. Knowledge of these type 2 diabetes-related sensorimotor and cognitive deficits may help to broaden approaches to falls prevention in older adults with type 2 diabetes. Therefore, the purpose of this mini review is to describe the impact of type 2 diabetes on sensorimotor and cognitive systems that may contribute to increased fall risk in older adults with type 2 diabetes.

  18. Adult retinal pigment epithelium cells express neural progenitor properties and the neuronal precursor protein doublecortin.

    PubMed

    Engelhardt, Maren; Bogdahn, Ulrich; Aigner, Ludwig

    2005-04-01

    The adult mammalian retina is devoid of any detectable neurogenesis. However, different cell types have been suggested to potentially act as neural progenitors in the adult mammalian retina in vitro, such as ciliary body (CB), Muller glia, and retinal pigment epithelium (RPE) cells. In rodents and humans, strong evidence for neural stem or progenitor properties exists only for CB-derived cells, but not for other retinal cell types. Here, we provide a comparative analysis of adult rat CB- and RPE-derived cells suggesting that the two cell types share certain neural progenitor properties in vitro. CB and RPE cells expressed neural progenitor markers such as Nestin, Flk-1, Hes1, and Musashi. They proliferated under adherent and neurosphere conditions and showed limited self-renewal. Moreover, they differentiated into neuronal and glial cells based on the expression of differentiation markers such as the young neuronal marker beta-III tubulin and the glial and progenitor markers GFAP and NG2. Expression of beta-III tubulin was found in cells with neuronal and non-neuronal morphology. A subpopulation of RPE- and CB-derived progenitor cells expressed the neurogenesis-specific protein doublecortin (DCX). Interestingly, DCX expression defined a beta-III tubulin-positive CB and RPE fraction with a distinct neuronal morphology. In summary, the data suggest that RPE cells share with CB cells the potential to de-differentiate into a cell type with neural progenitor-like identity. In addition, DCX expression might define the neuronal-differentiating RPE- and CB-derived progenitor population. PMID:15804431

  19. 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

  20. An Adult Case of Bartter Syndrome Type III Presenting with Proteinuria

    PubMed Central

    Cha, Eun Jung; Hwang, Won Min; Yun, Sung-Ro; Park, Moon Hyang

    2016-01-01

    Bartter syndrome (BS) I–IV is a rare autosomal recessive disorder affecting salt reabsorption in the thick ascending limb of the loop of Henle. This report highlights clinicopathological findings and genetic studies of classic BS in a 22-year-old female patient who presented with persistent mild proteinuria for 2 years. A renal biopsy demonstrated a mild to moderate increase in the mesangial cells and matrix of most glomeruli, along with marked juxtaglomerular cell hyperplasia. These findings suggested BS associated with mild IgA nephropathy. Focal tubular atrophy, interstitial fibrosis, and lymphocytic infiltration were also observed. A genetic study of the patient and her parents revealed a mutation of the CLCNKB genes. The patient was diagnosed with BS, type III. This case represents an atypical presentation of classic BS in an adult patient. Pathologic findings of renal biopsy combined with genetic analysis and clinicolaboratory findings are important in making an accurate diagnosis. PMID:26755355

  1. GATAe regulates intestinal stem cell maintenance and differentiation in Drosophila adult midgut.

    PubMed

    Okumura, Takashi; Takeda, Koji; Kuchiki, Megumi; Akaishi, Marie; Taniguchi, Kiichiro; Adachi-Yamada, Takashi

    2016-02-01

    Adult intestinal tissues, exposed to the external environment, play important roles including barrier and nutrient-absorption functions. These functions are ensured by adequately controlled rapid-cell metabolism. GATA transcription factors play essential roles in the development and maintenance of adult intestinal tissues both in vertebrates and invertebrates. We investigated the roles of GATAe, the Drosophila intestinal GATA factor, in adult midgut homeostasis with its first-generated knock-out mutant as well as cell type-specific RNAi and overexpression experiments. Our results indicate that GATAe is essential for proliferation and maintenance of intestinal stem cells (ISCs). Also, GATAe is involved in the differentiation of enterocyte (EC) and enteroendocrine (ee) cells in both Notch (N)-dependent and -independent manner. The results also indicate that GATAe has pivotal roles in maintaining normal epithelial homeostasis of the Drosophila adult midgut through interaction of N signaling. Since recent reports showed that mammalian GATA-6 regulates normal and cancer stem cells in the adult intestinal tract, our data also provide information on the evolutionally conserved roles of GATA factors in stem-cell regulation. PMID:26719127

  2. Adult T-Cell Leukemia: A Review of Epidemiological Evidence

    PubMed Central

    Iwanaga, Masako; Watanabe, Toshiki; Yamaguchi, Kazunari

    2012-01-01

    Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type I (HTLV-1) infection and often occurs in HTLV-1-endemic areas, such as southwestern Japan, the Caribbean islands, Central and South America, Intertropical Africa, and Middle East. To date, many epidemiological studies have been conducted to investigate the incidence of ATL among general population or HTLV-1 carriers and to identify a variety of laboratory, molecular, and host-specific markers to be possible predictive factors for developing ATL because HTLV-1 infection alone is not sufficient to develop ATL. This literature review focuses on the epidemiology of ATL and the risk factors for the development of ATL from HTLV-1 carriers, while keeping information on the epidemiology of HTLV-1 to a minimum. The main lines of epidemiological evidence are: (1) ATL occurs mostly in adults, at least 20–30 years after the HTLV-1 infection, (2) age at onset differs across geographic areas: the average age in the Central and South America (around 40 years old) is younger than that in Japan (around 60 years old), (3) ATL occurs in those infected in childhood, but seldom occurs in those infected in adulthood, (4) male carriers have about a three- to fivefold higher risk of developing ATL than female, (5) the estimated lifetime risk of developing ATL in HTLV-1 carriers is 6–7% for men and 2–3% for women in Japan, (6) a low anti-Tax reactivity, a high soluble interleukin-2 receptor level, a high anti-HTLV-1 titer, and high levels of circulating abnormal lymphocytes and white blood cell count are accepted risk factors for the development of ATL, and (7) a higher proviral load (more than 4 copies/100 peripheral blood mononuclear cells) is an independent risk factor for progression of ATL. Nevertheless, the current epidemiological evidence is insufficient to fully understand the oncogenesis of ATL. Further well-designed epidemiological studies are needed. PMID

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

    PubMed

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

    2003-03-31

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

  4. Cell proliferation and neurogenesis in adult mouse brain.

    PubMed

    Bordiuk, Olivia L; Smith, Karen; Morin, Peter J; Semënov, Mikhail V

    2014-01-01

    Neurogenesis, the formation of new neurons, can be observed in the adult brain of many mammalian species, including humans. Despite significant progress in our understanding of adult neurogenesis, we are still missing data about the extent and location of production of neural precursors in the adult mammalian brain. We used 5-ethynyl-2'-deoxyuridine (EdU) to map the location of proliferating cells throughout the entire adult mouse brain and found that neurogenesis occurs at two locations in the mouse brain. The larger one we define as the main proliferative zone (MPZ), and the smaller one corresponds to the subgranular zone of the hippocampus. The MPZ can be divided into three parts. The caudate migratory stream (CMS) occupies the middle part of the MPZ. The cable of proliferating cells emanating from the most anterior part of the CMS toward the olfactory bulbs forms the rostral migratory stream. The thin layer of proliferating cells extending posteriorly from the CMS forms the midlayer. We have not found any additional aggregations of proliferating cells in the adult mouse brain that could suggest the existence of other major neurogenic zones in the adult mouse brain.

  5. Cell proliferation and neurogenesis in adult mouse brain.

    PubMed

    Bordiuk, Olivia L; Smith, Karen; Morin, Peter J; Semënov, Mikhail V

    2014-01-01

    Neurogenesis, the formation of new neurons, can be observed in the adult brain of many mammalian species, including humans. Despite significant progress in our understanding of adult neurogenesis, we are still missing data about the extent and location of production of neural precursors in the adult mammalian brain. We used 5-ethynyl-2'-deoxyuridine (EdU) to map the location of proliferating cells throughout the entire adult mouse brain and found that neurogenesis occurs at two locations in the mouse brain. The larger one we define as the main proliferative zone (MPZ), and the smaller one corresponds to the subgranular zone of the hippocampus. The MPZ can be divided into three parts. The caudate migratory stream (CMS) occupies the middle part of the MPZ. The cable of proliferating cells emanating from the most anterior part of the CMS toward the olfactory bulbs forms the rostral migratory stream. The thin layer of proliferating cells extending posteriorly from the CMS forms the midlayer. We have not found any additional aggregations of proliferating cells in the adult mouse brain that could suggest the existence of other major neurogenic zones in the adult mouse brain. PMID:25375658

  6. Stem Cell-Mediated Regeneration of the Adult Brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury of the adult mammalian brain is often associated with persistent functional deficits as its potential for regeneration and capacity to rebuild lost neural structures is limited. However, the discovery that neural stem cells (NSCs) persist throughout life in discrete regions of the brain, novel approaches to induce the formation of neuronal and glial cells, and recently developed strategies to generate tissue for exogenous cell replacement strategies opened novel perspectives how to regenerate the adult brain. Here, we will review recently developed approaches for brain repair and discuss future perspectives that may eventually allow for developing novel treatment strategies in acute and chronic brain injury. PMID:27781019

  7. Multiple skin tumors of indeterminate cells in an adult.

    PubMed

    Kolde, G; Bröcker, E B

    1986-10-01

    An adult patient with multiple unusual histiocytic tumors of the skin is described. As shown by immunohistologic study, electron microscopy, and immunoelectron microscopy, the tumors represent circumscribed proliferations of the Langerhans cell-related indeterminate dendritic cells of the skin. This distinct cutaneous histiocytosis may represent a paraneoplastic syndrome.

  8. Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer.

    PubMed

    Sung, Li-Ying; Gao, Shaorong; Shen, Hongmei; Yu, Hui; Song, Yifang; Smith, Sadie L; Chang, Ching-Chien; Inoue, Kimiko; Kuo, Lynn; Lian, Jin; Li, Ao; Tian, X Cindy; Tuck, David P; Weissman, Sherman M; Yang, Xiangzhong; Cheng, Tao

    2006-11-01

    Since the creation of Dolly via somatic cell nuclear transfer (SCNT), more than a dozen species of mammals have been cloned using this technology. One hypothesis for the limited success of cloning via SCNT (1%-5%) is that the clones are likely to be derived from adult stem cells. Support for this hypothesis comes from the findings that the reproductive cloning efficiency for embryonic stem cells is five to ten times higher than that for somatic cells as donors and that cloned pups cannot be produced directly from cloned embryos derived from differentiated B and T cells or neuronal cells. The question remains as to whether SCNT-derived animal clones can be derived from truly differentiated somatic cells. We tested this hypothesis with mouse hematopoietic cells at different differentiation stages: hematopoietic stem cells, progenitor cells and granulocytes. We found that cloning efficiency increases over the differentiation hierarchy, and terminally differentiated postmitotic granulocytes yield cloned pups with the greatest cloning efficiency.

  9. NK Cells and Type 1 Diabetes

    PubMed Central

    Rodacki, Melanie; Milech, Adolpho; de Oliveira, José Egídio Paulo

    2006-01-01

    Type 1 diabetes (T1D) is characterized by an immuno-mediated progressive destruction of the pancreatic β cells. Due to the ability of NK cells to kill target cells as well as to interact with antigen-presenting and T cells, it has been suggested that they could be involved in one or multiple steps of the immune-mediated attack that leads to T1D. Abnormalities in the frequency and activity of NK cells have been described both in animal models and patients with T1D. Some of these alterations are linked to its onset while others seem to be a consequence of the disease. Here, we discuss the main characteristics of NK cells and review the studies that investigated the role of NK cells in T1D, both in mouse models and humans. PMID:17162353

  10. Recents patents for isolating, delivering and tracking adult stem cells in regenerative medicine.

    PubMed

    Fierabracci, Alessandra

    2010-06-01

    The field of regenerative medicine offers nowadays the potential to significantly impact a wide spectrum of healthcare issues, from insulin-dependent diabetes mellitus (Type 1 diabetes, T1D) to cardiovascular disease. In tissue engineering biomaterials, biological factors, regeneration competent cells are used in the process of creating functional tissue. Regarding the type of stem or progenitor cells which represents the best candidate for therapy, embryonic stem cells have been considered the master cells capable of differentiating into every type of cells either in vitro or in vivo, in spite of serious ethical concerns. Nevertheless experimental evidence suggests that adult stem cells and even terminally differentiated somatic cells under appropriate microenvironmental treatments can be reprogrammed and contribute to a much wider spectrum of differentiated progeny than previously anticipated. One of the main goals is to exploit novel technologies aiming to isolate, expand and enrich sources of regeneration competent cells, especially adult somatic stem cells. Researchers are also trying to develop innovative strategies for effectively delivering regenerative cell populations and to implement 'tracking' tools to verify their engraftment and destiny in vivo. Here we review recent patents on the field issued over the past five years.

  11. Neural stem cells in the adult human brain

    PubMed Central

    Gonzalez-Perez, Oscar

    2012-01-01

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

  12. DNA damage response in adult stem cells.

    PubMed

    Insinga, Alessandra; Cicalese, Angelo; Pelicci, Pier Giuseppe

    2014-04-01

    This review discusses the processes of DNA-damage-response and DNA-damage repair in stem and progenitor cells of several tissues. The long life-span of stem cells suggests that they may respond differently to DNA damage than their downstream progeny and, indeed, studies have begun to elucidate the unique stem cell response mechanisms to DNA damage. Because the DNA damage responses in stem cells and progenitor cells are distinctly different, stem and progenitor cells should be considered as two different entities from this point of view. Hematopoietic and mammary stem cells display a unique DNA-damage response, which involves active inhibition of apoptosis, entry into the cell-cycle, symmetric division, partial DNA repair and maintenance of self-renewal. Each of these biological events depends on the up-regulation of the cell-cycle inhibitor p21. Moreover, inhibition of apoptosis and symmetric stem cell division are the consequence of the down-regulation of the tumor suppressor p53, as a direct result of p21 up-regulation. A deeper understanding of these processes is required before these findings can be translated into human anti-aging and anti-cancer therapies. One needs to clarify and dissect the pathways that control p21 regulation in normal and cancer stem cells and define (a) how p21 blocks p53 functions in stem cells and (b) how p21 promotes DNA repair in stem cells. Is this effect dependent on p21s ability to inhibit p53? Such molecular knowledge may pave the way to methods for maintaining short-term tissue reconstitution while retaining long-term cellular and genomic integrity.

  13. The molecular nature of very small embryonic-like stem cells in adult tissues.

    PubMed

    Kim, YongHwan; Jeong, Jaeho; Kang, Hyunsook; Lim, Jisun; Heo, Jinbeom; Ratajczak, Janina; Ratajczak, Mariusz Z; Shin, Dong-Myung

    2014-11-01

    Pluripotent stem cells (PSCs) have been considered as the most important cells in regenerative medicine as they are able to differentiate into all types of cells in the human body. PSCs have been established from several sources of embryo tissue or by reprogramming of terminally differentiated adult tissue by transduction of so-called Yamanaka factors (Oct4, Sox2, Klf4, and cMyc). Interestingly, accumulating evidence has demonstrated the residence of PSCs in adult tissue and with the ability to differentiate into multiple types of tissue-committed stem cells (TCSCs). We also recently demonstrated that a population of pluripotent Oct4(+) SSEA-1(+)Sca-1(+)Lin(-)CD45(-) very small embryonic-like stem cells (VSELs) resides in the adult murine bone marrow (BM) and in other murine tissue. These very small (∼3-6 μm) cells express pluripotent markers such as Oct4, Nanog, and SSEA-1. VSELs could be specified into several tissue-residing TCSCs in response to tissue/organ injury, and thus suggesting that these cells have a physiological role in the rejuvenation of a pool of TCSCs under steady-state conditions. In this review article, we discuss the molecular nature of the rare population of VSELs which have a crucial role in regulating the pluripotency, proliferation, differentiation, and aging of these cells. PMID:25473442

  14. Markers of Epidermal Stem Cell Subpopulations in Adult Mammalian Skin

    PubMed Central

    Kretzschmar, Kai; Watt, Fiona M.

    2014-01-01

    The epidermis is the outermost layer of mammalian skin and comprises a multilayered epithelium, the interfollicular epidermis, with associated hair follicles, sebaceous glands, and eccrine sweat glands. As in other epithelia, adult stem cells within the epidermis maintain tissue homeostasis and contribute to repair of tissue damage. The bulge of hair follicles, where DNA-label-retaining cells reside, was traditionally regarded as the sole epidermal stem cell compartment. However, in recent years multiple stem cell populations have been identified. In this review, we discuss the different stem cell compartments of adult murine and human epidermis, the markers that they express, and the assays that are used to characterize epidermal stem cell properties. PMID:24993676

  15. β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells.

    PubMed

    Corritore, Elisa; Lee, Yong-Syu; Sokal, Etienne M; Lysy, Philippe A

    2016-08-01

    Thorough research on the capacity of human islet transplantation to cure type 1 diabetes led to the achievement of 3- to 5-year-long insulin independence in nearly half of transplanted patients. Yet, translation of this technique to clinical routine is limited by organ shortage and the need for long-term immunosuppression, restricting its use to adults with unstable disease. The production of new bona fide β cells in vitro was thus investigated and finally achieved with human pluripotent stem cells (PSCs). Besides ethical concerns about the use of human embryos, studies are now evaluating the possibility of circumventing the spontaneous tumor formation associated with transplantation of PSCs. These issues fueled the search for cell candidates for β-cell engineering with safe profiles for clinical translation. In vivo studies revealed the regeneration capacity of the exocrine pancreas after injury that depends at least partially on facultative progenitors in the ductal compartment. These stimulated subpopulations of pancreatic ductal cells (PDCs) underwent β-cell transdifferentiation through reactivation of embryonic signaling pathways. In vitro models for expansion and differentiation of purified PDCs toward insulin-producing cells were described using cocktails of growth factors, extracellular-matrix proteins and transcription factor overexpression. In this review, we will describe the latest findings in pancreatic β-cell mass regeneration due to adult ductal progenitor cells. We will further describe recent advances in human PDC transdifferentiation to insulin-producing cells with potential for clinical translational studies.

  16. β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells.

    PubMed

    Corritore, Elisa; Lee, Yong-Syu; Sokal, Etienne M; Lysy, Philippe A

    2016-08-01

    Thorough research on the capacity of human islet transplantation to cure type 1 diabetes led to the achievement of 3- to 5-year-long insulin independence in nearly half of transplanted patients. Yet, translation of this technique to clinical routine is limited by organ shortage and the need for long-term immunosuppression, restricting its use to adults with unstable disease. The production of new bona fide β cells in vitro was thus investigated and finally achieved with human pluripotent stem cells (PSCs). Besides ethical concerns about the use of human embryos, studies are now evaluating the possibility of circumventing the spontaneous tumor formation associated with transplantation of PSCs. These issues fueled the search for cell candidates for β-cell engineering with safe profiles for clinical translation. In vivo studies revealed the regeneration capacity of the exocrine pancreas after injury that depends at least partially on facultative progenitors in the ductal compartment. These stimulated subpopulations of pancreatic ductal cells (PDCs) underwent β-cell transdifferentiation through reactivation of embryonic signaling pathways. In vitro models for expansion and differentiation of purified PDCs toward insulin-producing cells were described using cocktails of growth factors, extracellular-matrix proteins and transcription factor overexpression. In this review, we will describe the latest findings in pancreatic β-cell mass regeneration due to adult ductal progenitor cells. We will further describe recent advances in human PDC transdifferentiation to insulin-producing cells with potential for clinical translational studies. PMID:27540464

  17. β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells

    PubMed Central

    Corritore, Elisa; Lee, Yong-Syu; Sokal, Etienne M.; Lysy, Philippe A.

    2016-01-01

    Thorough research on the capacity of human islet transplantation to cure type 1 diabetes led to the achievement of 3- to 5-year-long insulin independence in nearly half of transplanted patients. Yet, translation of this technique to clinical routine is limited by organ shortage and the need for long-term immunosuppression, restricting its use to adults with unstable disease. The production of new bona fide β cells in vitro was thus investigated and finally achieved with human pluripotent stem cells (PSCs). Besides ethical concerns about the use of human embryos, studies are now evaluating the possibility of circumventing the spontaneous tumor formation associated with transplantation of PSCs. These issues fueled the search for cell candidates for β-cell engineering with safe profiles for clinical translation. In vivo studies revealed the regeneration capacity of the exocrine pancreas after injury that depends at least partially on facultative progenitors in the ductal compartment. These stimulated subpopulations of pancreatic ductal cells (PDCs) underwent β-cell transdifferentiation through reactivation of embryonic signaling pathways. In vitro models for expansion and differentiation of purified PDCs toward insulin-producing cells were described using cocktails of growth factors, extracellular-matrix proteins and transcription factor overexpression. In this review, we will describe the latest findings in pancreatic β-cell mass regeneration due to adult ductal progenitor cells. We will further describe recent advances in human PDC transdifferentiation to insulin-producing cells with potential for clinical translational studies. PMID:27540464

  18. Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest.

    PubMed

    Vickaryous, Matthew K; Hall, Brian K

    2006-08-01

    Metazoans are composed of a finite number of recognisable cell types. Similar to the relationship between species and ecosystems, knowledge of cell type diversity contributes to studies of complexity and evolution. However, as with other units of evolution, the cell type often resists definition. This review proposes guidelines for characterising cell types and discusses cell homology and the various developmental pathways by which cell types arise, including germ layers, blastemata (secondary development/neurulation), stem cells, and transdifferentiation. An updated list of cell types is presented for a familiar, albeit overlooked model taxon, adult Homo sapiens, with 411 cell types, including 145 types of neurons, recognised. Two methods for organising these cell types are explored. One is the artificial classification technique, clustering cells using commonly accepted criteria of similarity. The second approach, an empirical method modeled after cladistics, resolves the classification in terms of shared features rather than overall similarity. While the results of each scheme differ, both methods address important questions. The artificial classification provides compelling (and independent) support for the neural crest as the fourth germ layer, while the cladistic approach permits the evaluation of cell type evolution. Using the cladistic approach we observe a correlation between the developmental and evolutionary origin of a cell, suggesting that this method is useful for predicting which cell types share common (multipotential) progenitors. Whereas the current effort is restricted by the availability of phenotypic details for most cell types, the present study demonstrates that a comprehensive cladistic classification is practical, attainable, and warranted. The use of cell types and cell type comparative classification schemes has the potential to offer new and alternative models for therapeutic evaluation. PMID:16790079

  19. Adult equine bone marrow stromal cells produce a cartilage-like ECM mechanically superior to animal-matched adult chondrocytes.

    PubMed

    Kopesky, P W; Lee, H-Y; Vanderploeg, E J; Kisiday, J D; Frisbie, D D; Plaas, A H K; Ortiz, C; Grodzinsky, A J

    2010-06-01

    Our objective was to evaluate the age-dependent mechanical phenotype of bone marrow stromal cell- (BMSC-) and chondrocyte-produced cartilage-like neo-tissue and to elucidate the matrix-associated mechanisms which generate this phenotype. Cells from both immature (2-4 month-old foals) and skeletally-mature (2-5 year-old adults) mixed-breed horses were isolated from animal-matched bone marrow and cartilage tissue, encapsulated in self-assembling-peptide hydrogels, and cultured with and without TGF-beta1 supplementation. BMSCs and chondrocytes from both donor ages were encapsulated with high viability. BMSCs from both ages produced neo-tissue with higher mechanical stiffness than that produced by either young or adult chondrocytes. Young, but not adult, chondrocytes proliferated in response to TGF-beta1 while BMSCs from both age groups proliferated with TGF-beta1. Young chondrocytes stimulated by TGF-beta1 accumulated ECM with 10-fold higher sulfated-glycosaminoglycan content than adult chondrocytes and 2-3-fold higher than BMSCs of either age. The opposite trend was observed for hydroxyproline content, with BMSCs accumulating 2-3-fold more than chondrocytes, independent of age. Size-exclusion chromatography of extracted proteoglycans showed that an aggrecan-like peak was the predominant sulfated proteoglycan for all cell types. Direct measurement of aggrecan core protein length and chondroitin sulfate chain length by single molecule atomic force microscopy imaging revealed that, independent of age, BMSCs produced longer core protein and longer chondroitin sulfate chains, and fewer short core protein molecules than chondrocytes, suggesting that the BMSC-produced aggrecan has a phenotype more characteristic of young tissue than chondrocyte-produced aggrecan. Aggrecan ultrastructure, ECM composition, and cellular proliferation combine to suggest a mechanism by which BMSCs produce a superior cartilage-like neo-tissue than either young or adult chondrocytes. PMID:20153827

  20. Localization and osteoblastic differentiation potential of neural crest-derived cells in oral tissues of adult mice.

    PubMed

    Ono, Miki; Suzawa, Tetsuo; Takami, Masamichi; Yamamoto, Gou; Hosono, Tomohiko; Yamada, Atsushi; Suzuki, Dai; Yoshimura, Kentaro; Watahiki, Junichi; Hayashi, Ryuhei; Arata, Satoru; Mishima, Kenji; Nishida, Kohji; Osumi, Noriko; Maki, Koutaro; Kamijo, Ryutaro

    2015-09-01

    In embryos, neural crest cells emerge from the dorsal region of the fusing neural tube and migrate throughout tissues to differentiate into various types of cells including osteoblasts. In adults, subsets of neural crest-derived cells (NCDCs) reside as stem cells and are considered to be useful cell sources for regenerative medicine strategies. Numerous studies have suggested that stem cells with a neural crest origin persist into adulthood, especially those within the mammalian craniofacial compartment. However, their distribution as well as capacity to differentiate into osteoblasts in adults is not fully understood. To analyze the precise distribution and characteristics of NCDCs in adult oral tissues, we utilized an established line of double transgenic (P0-Cre/CAG-CAT-EGFP) mice in which NCDCs express green fluorescent protein (GFP) throughout their life. GFP-positive cells were scattered like islands throughout tissues of the palate, gingiva, tongue, and buccal mucosa in adult mice, with those isolated from the latter shown to form spheres, typical cell clusters composed of stem cells, under low-adherent conditions. Furthermore, GFP-positive cells had markedly increased alkaline phosphatase (a marker enzyme of osteoblast differentiation) activity and mineralization as shown by alizarin red staining, in the presence of bone morphogenetic protein (BMP)-2. These results suggest that NCDCs reside in various adult oral tissues and possess potential to differentiate into osteoblastic cells. NCDCs in adults may be a useful cell source for bone regeneration strategies.

  1. Effects of Neuroendocrine CB1 Activity on Adult Leydig Cells

    PubMed Central

    Cobellis, Gilda; Meccariello, Rosaria; Chianese, Rosanna; Chioccarelli, Teresa; Fasano, Silvia; Pierantoni, Riccardo

    2016-01-01

    Endocannabinoids control male reproduction acting at central and local level via cannabinoid receptors. The cannabinoid receptor CB1 has been characterized in the testis, in somatic and germ cells of mammalian and non-mammalian animal models, and its activity related to Leydig cell differentiation, steroidogenesis, spermiogenesis, sperm quality, and maturation. In this short review, we provide a summary of the insights concerning neuroendocrine CB1 activity in male reproduction focusing on adult Leydig cell ontogenesis and steroid biosynthesis. PMID:27375550

  2. Langerhans cells increase in the dermal lesions of adult T cell leukaemia in Japan

    PubMed Central

    Shamoto, M

    1983-01-01

    In cases of adult T cell leukaemia neoplastic T cell infiltration in the skin was accompanied by an increase in Langerhans cells. This is in keeping with the view that Langerhans cells may induce antigen-specific and allogenic T cell activation. Images PMID:6600750

  3. Liver repopulation and correction of metabolic liver disease by transplanted adult mouse pancreatic cells.

    PubMed

    Wang, X; Al-Dhalimy, M; Lagasse, E; Finegold, M; Grompe, M

    2001-02-01

    The emergence of cells with hepatocellular properties in the adult pancreas has been described in several experimental models. To determine whether adult pancreas contains cells that can give rise to therapeutically useful and biochemically normal hepatocytes, we transplanted suspensions of wild-type mouse pancreatic cells into syngeneic recipients deficient in fumarylacetoacetate hydrolase and manifesting tyrosinemia. Four of 34 (12%) mutant mice analyzed were fully rescued by donor-derived cells and had normal liver function. Ten additional mice (29%) showed histological evidence of donor-derived hepatocytes in the liver. Previous work has suggested that pancreatic liver precursors reside within or close to pancreatic ducts. We therefore performed additional transplantations using either primary cell suspensions enriched for ducts or cultured ducts. Forty-four mutant mice were transplanted with cells enriched for pancreatic duct cells, but only three of the 34 (9%) recipients analyzed displayed donor-derived hepatocytes. In addition, 28 of the fumarylacetoacetate hydrolase-deficient mice were transplanted with cultured pancreatic duct cells, but no donor-derived hepatocytes were observed. Our results demonstrate for the first time that adult mouse pancreas contains hepatocyte progenitor cells capable of significant therapeutic liver reconstitution. However, contrary to previous reports, we were unable to detect these cells within the duct compartment. PMID:11159194

  4. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq.

    PubMed

    Zeisel, Amit; Muñoz-Manchado, Ana B; Codeluppi, Simone; Lönnerberg, Peter; La Manno, Gioele; Juréus, Anna; Marques, Sueli; Munguba, Hermany; He, Liqun; Betsholtz, Christer; Rolny, Charlotte; Castelo-Branco, Gonçalo; Hjerling-Leffler, Jens; Linnarsson, Sten

    2015-03-01

    The mammalian cerebral cortex supports cognitive functions such as sensorimotor integration, memory, and social behaviors. Normal brain function relies on a diverse set of differentiated cell types, including neurons, glia, and vasculature. Here, we have used large-scale single-cell RNA sequencing (RNA-seq) to classify cells in the mouse somatosensory cortex and hippocampal CA1 region. We found 47 molecularly distinct subclasses, comprising all known major cell types in the cortex. We identified numerous marker genes, which allowed alignment with known cell types, morphology, and location. We found a layer I interneuron expressing Pax6 and a distinct postmitotic oligodendrocyte subclass marked by Itpr2. Across the diversity of cortical cell types, transcription factors formed a complex, layered regulatory code, suggesting a mechanism for the maintenance of adult cell type identity.

  5. Cell culture models using rat primary alveolar type I cells

    PubMed Central

    Downs, Charles A.; Montgomery, David W.; Merkle, Carrie J.

    2011-01-01

    There is a lack of cell culture models using primary alveolar type I (AT I) cells. The purpose of this study was to develop cell culture models using rat AT I cells and microvascular endothelial cells from the lung (MVECL). Two types of model systems were developed: single and co-culture systems; additionally a 3-dimensional model system was developed. Pure AT I cell (96.3 ±2.7%) and MVECL (97.9 ±1.1 %) preparations were used. AT I cell morphology, mitochondrial number and distribution, actin filament arrangement and number of apoptotic cells at confluence, and telomere attrition were characterized. AT I cells maintained their morphometric characteristics through at least population doubling (PD) 35, while demonstrating telomere attrition through at least PD 100. Furthermore, AT I cells maintained the expression of their specific markers, T1α and AQ-5, through PD 42. For the co-cultures, AT I cells were grown on the top and MVECL were grown on the bottom of fibronectin coated 24 well Transwell Fluroblok™ filter inserts. Neither cell type transmigrated the 1 micron pores. Additionally AT I cells were grown in a thick layer of Matrigel® to create a 3-dimensional model in which primary AT I cells form ring-like structures that resemble an alveolus. The development of these model systems offers the opportunities to investigate AT I cell cells and their interactions with MVECL in response to pharmacological interventions and in the processes of disease, repair and regeneration. PMID:21624488

  6. Cell elasticity with altered cytoskeletal architectures across multiple cell types.

    PubMed

    Grady, Martha E; Composto, Russell J; Eckmann, David M

    2016-08-01

    The cytoskeleton is primarily responsible for providing structural support, localization and transport of organelles, and intracellular trafficking. The structural support is supplied by actin filaments, microtubules, and intermediate filaments, which contribute to overall cell elasticity to varying degrees. We evaluate cell elasticity in five different cell types with drug-induced cytoskeletal derangements to probe how actin filaments and microtubules contribute to cell elasticity and whether it is conserved across cell type. Specifically, we measure elastic stiffness in primary chondrocytes, fibroblasts, endothelial cells (HUVEC), hepatocellular carcinoma cells (HUH-7), and fibrosarcoma cells (HT 1080) subjected to two cytoskeletal destabilizers: cytochalasin D and nocodazole, which disrupt actin and microtubule polymerization, respectively. Elastic stiffness is measured by atomic force microscopy (AFM) and the disruption of the cytoskeleton is confirmed using fluorescence microscopy. The two cancer cell lines showed significantly reduced elastic moduli values (~0.5kPa) when compared to the three healthy cell lines (~2kPa). Non-cancer cells whose actin filaments were disrupted using cytochalasin D showed a decrease of 60-80% in moduli values compared to untreated cells of the same origin, whereas the nocodazole-treated cells showed no change in elasticity. Overall, we demonstrate actin filaments contribute more to elastic stiffness than microtubules but this result is cell type dependent. Cancer cells behaved differently, exhibiting increased stiffness as well as stiffness variability when subjected to nocodazole. We show that disruption of microtubule dynamics affects cancer cell elasticity, suggesting therapeutic drugs targeting microtubules be monitored for significant elastic changes. PMID:26874250

  7. Adult granulosa cell tumor of the testis masquerading as hydrocele

    PubMed Central

    Vallonthaiel, Archana George; Kakkar, Aanchal; Singh, Animesh; Dogra, Prem N; Ray, Ruma

    2015-01-01

    ABSTRACT Adult testicular granulosa cell tumor is a rare, potentially malignant sex cord-stromal tumor, of which 30 cases have been described to date. We report the case of a 43-year-old male who complained of a left testicular swelling. Scrotal ultrasound showed a cystic lesion, suggestive of hydrocele. However, due to a clinical suspicion of a solid-cystic neoplasm, a high inguinal orchidectomy was performed, which, on pathological examination, was diagnosed as adult granulosa cell tumor. Adult testicular granulosa cell tumors have aggressive behaviour as compared to their ovarian counterparts. They may rarely be predominantly cystic and present as hydrocele. Lymph node and distant metastases have been reported in few cases. Role of MIB-1 labelling index in prognostication is not well defined. Therefore, their recognition and documentation of their behaviour is important from a diagnostic, prognostic and therapeutic point of view. PMID:26742984

  8. Interneuron cell types are fit to function.

    PubMed

    Kepecs, Adam; Fishell, Gordon

    2014-01-16

    Understanding brain circuits begins with an appreciation of their component parts - the cells. Although GABAergic interneurons are a minority population within the brain, they are crucial for the control of inhibition. Determining the diversity of these interneurons has been a central goal of neurobiologists, but this amazing cell type has so far defied a generalized classification system. Interneuron complexity within the telencephalon could be simplified by viewing them as elaborations of a much more finite group of developmentally specified cardinal classes that become further specialized as they mature. Our perspective emphasizes that the ultimate goal is to dispense with classification criteria and directly define interneuron types by function. PMID:24429630

  9. YAP Regulates Cell Proliferation, Migration, and Steroidogenesis in Adult Granulosa Cell Tumors

    PubMed Central

    Fu, David; Lv, Xiangmin; Hua, Guohua; He, Chunbo; Dong, Jixin; Lele, Subodh M.; Li, David Wan-Cheng; Zhai, Qiongli; Davis, John S.; Wang, Cheng

    2014-01-01

    The Hippo signaling pathway has been implicated as a conserved regulator of organ size in both Drosophila and mammals. Yes associated protein (YAP), the central component of the Hippo signaling cascade, functions as an oncogene in several malignancies. Ovarian granulosa cell tumors (GCT) are characterized by enlargement of ovary, excess production of estrogen, high frequency of recurrence and potential of malignancy and metastasis. Whether the Hippo pathway plays a role in the pathogenesis of GCT is unknown. This study was conducted to examine the expression of YAP in human adult GCTs and to determine the role of YAP in the proliferation and steroidogenesis of GCT cells. Compared with age-matched normal human ovaries, GCT tissues exhibited higher levels of YAP expression. YAP protein was predominantly expressed in the nucleus of tumor cells, whereas the non-tumor ovarian stromal cells expressed very low levels of YAP. YAP was also expressed in cultured primary human granulosa cells and in KGN and COV434 GCT cell lines. siRNA-mediated knockdown of YAP in KGN cells resulted in a significant reduction in cell proliferation (P<0.001). Conversely, overexpression of wild-type YAP or a constitutively active YAP mutant resulted in a significant increase in KGN cell proliferation and migration. Moreover, YAP knockdown reduced FSH-induced aromatase (CYP19A1) protein expression and estrogen production in KGN cells. These results demonstrate that YAP plays an important role in regulating GCT cell proliferation, migration and steroidogenesis. Targeting the Hippo/YAP pathway may provide a novel therapeutic approach for GCT. PMID:24389730

  10. 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

  11. Walking stability during cell phone use in healthy adults.

    PubMed

    Kao, Pei-Chun; Higginson, Christopher I; Seymour, Kelly; Kamerdze, Morgan; Higginson, Jill S

    2015-05-01

    The number of falls and/or accidental injuries associated with cellular phone use during walking is growing rapidly. Understanding the effects of concurrent cell phone use on human gait may help develop safety guidelines for pedestrians. It was shown previously that older adults had more pronounced dual-task interferences than younger adults when concurrent cognitive task required visual information processing. Thus, cell phone use might have greater impact on walking stability in older than in younger adults. This study examined gait stability and variability during a cell phone dialing task (phone) and two classic cognitive tasks, the Paced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT). Nine older and seven younger healthy adults walked on a treadmill at four different conditions: walking only, PASAT, phone, and SDMT. We computed short-term local divergence exponent (LDE) of the trunk motion (local stability), dynamic margins of stability (MOS), step spatiotemporal measures, and kinematic variability. Older and younger adults had similar values of short-term LDE during all conditions, indicating that local stability was not affected by the dual-task. Compared to walking only, older and younger adults walked with significantly greater average mediolateral MOS during phone and SDMT conditions but significantly less ankle angle variability during all dual-tasks and less knee angle variability during PASAT. The current findings demonstrate that healthy adults may try to control foot placement and joint kinematics during cell phone use or another cognitive task with a visual component to ensure sufficient dynamic margins of stability and maintain local stability.

  12. Walking Stability during Cell Phone Use in Healthy Adults

    PubMed Central

    Kao, Pei-Chun; Higginson, Christopher I.; Seymour, Kelly; Kamerdze, Morgan; Higginson, Jill S.

    2015-01-01

    The number of falls and/or accidental injuries associated with cellular phone use during walking is growing rapidly. Understanding the effects of concurrent cell phone use on human gait may help develop safety guidelines for pedestrians. It was shown previously that older adults had more pronounced dual-task interferences than younger adults when concurrent cognitive task required visual information processing. Thus, cell phone use might have greater impact on walking stability in older than in younger adults. This study examined gait stability and variability during a cell phone dialing task (phone) and two classic cognitive tasks, the Paced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT). Nine older and seven younger healthy adults walked on a treadmill at four different conditions: walking only, PASAT, phone, and SDMT. We computed short-term local divergence exponent (LDE) of the trunk motion (local stability), dynamic margins of stability (MOS), step spatiotemporal measures, and kinematic variability. Older and younger adults had similar values of short-term LDE during all conditions, indicating that local stability was not affected by the dual-task. Compared to walking only, older and younger adults walked with significantly greater average mediolateral MOS during phone and SDMT conditions but significantly less ankle angle variability during all dual-tasks and less knee angle variability during PASAT. The current findings demonstrate that healthy adults may try to control foot placement and joint kinematics during cell phone use or another cognitive task with a visual component to ensure sufficient dynamic margins of stability and maintain local stability. PMID:25890490

  13. Serum uric acid and hypertension in adults: a paradoxical relationship in type 1 diabetes.

    PubMed

    Bjornstad, Petter; Paul Wadwa, R; Sirota, Jeffrey C; Snell-Bergeon, Janet K; McFann, Kimberly; Rewers, Marian; Rivard, Christopher J; Jalal, Diana; Chonchol, Michel B; Johnson, Richard J; Maahs, David M

    2014-04-01

    Adults with type 1 diabetes have lower serum uric acid levels compared with nondiabetic adults. Little is known about the relationship between serum uric acid and blood pressure in type 1 diabetes and whether it differs from the positive relationship found in nondiabetic adults. The authors assessed the cross-sectional and longitudinal relationships over 6 years between serum uric acid and blood pressure in adults with (35±9 years [n=393]) and without (38±9 years [n=685]) type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes study. In nondiabetic adults, serum uric acid was associated with systolic blood pressure in multivariable models adjusted for cardiovascular risk factors. In adults with type 1 diabetes, a negative association was observed between serum uric acid and systolic blood pressure after multivariable adjustments. A positive association was observed between serum uric acid and systolic blood pressure in nondiabetic adults. In contrast, an inverse relationship was demonstrated after multivariable adjustments in type 1 diabetes. PMID:24667019

  14. Writing in a Digital World: Self-Correction While Typing in Younger and Older Adults.

    PubMed

    Kalman, Yoram M; Kavé, Gitit; Umanski, Daniil

    2015-10-13

    This study examined how younger and older adults approach simple and complex computerized writing tasks. Nineteen younger adults (age range 21-31, mean age 26.1) and 19 older adults (age range 65-83, mean age 72.1) participated in the study. Typing speed, quantitative measures of outcome and process, and self-corrections were recorded. Younger adults spent a lower share of their time on actual typing, and demonstrated more prevalent use of delete keys than did older adults. Within the older group, there was no correlation between the total time spent on the entire task and the number of corrections, but increased typing speed was related to more errors. The results suggest that the approach to the task was different across age groups, either because of age or because of cohort effects. We discuss the interplay of speed and accuracy with regard to digital writing, and its implications for the design of human-computer interactions.

  15. Combinations of differentiation markers distinguish subpopulations of alveolar epithelial cells in adult lung.

    PubMed

    Liebler, Janice M; Marconett, Crystal N; Juul, Nicholas; Wang, Hongjun; Liu, Yixin; Flodby, Per; Laird-Offringa, Ite A; Minoo, Parviz; Zhou, Beiyun

    2016-01-15

    Distal lung epithelium is maintained by proliferation of alveolar type II (AT2) cells and, for some daughter AT2 cells, transdifferentiation into alveolar type I (AT1) cells. We investigated if subpopulations of alveolar epithelial cells (AEC) exist that represent various stages in transdifferentiation from AT2 to AT1 cell phenotypes in normal adult lung and if they can be identified using combinations of cell-specific markers. Immunofluorescence microscopy showed that, in distal rat and mouse lungs, ∼ 20-30% of NKX2.1(+) (or thyroid transcription factor 1(+)) cells did not colocalize with pro-surfactant protein C (pro-SP-C), a highly specific AT2 cell marker. In distal rat lung, NKX2.1(+) cells coexpressed either pro-SP-C or the AT1 cell marker homeodomain only protein x (HOPX). Not all HOPX(+) cells colocalize with the AT1 cell marker aquaporin 5 (AQP5), and some AQP5(+) cells were NKX2.1(+). HOPX was expressed earlier than AQP5 during transdifferentiation in rat AEC primary culture, with robust expression of both by day 7. We speculate that NKX2.1 and pro-SP-C colocalize in AT2 cells, NKX2.1 and HOPX or AQP5 colocalize in intermediate or transitional cells, and HOPX and AQP5 are expressed without NKX2.1 in AT1 cells. These findings suggest marked heterogeneity among cells previously identified as exclusively AT1 or AT2 cells, implying the presence of subpopulations of intermediate or transitional AEC in normal adult lung. PMID:26545903

  16. Neural cell adhesion molecule (NCAM) marks adult myogenic cells committed to differentiation

    SciTech Connect

    Capkovic, Katie L.; Stevenson, Severin; Johnson, Marc C.; Thelen, Jay J.; Cornelison, D.D.W.

    2008-04-15

    Although recent advances in broad-scale gene expression analysis have dramatically increased our knowledge of the repertoire of mRNAs present in multiple cell types, it has become increasingly clear that examination of the expression, localization, and associations of the encoded proteins will be critical for determining their functional significance. In particular, many signaling receptors, transducers, and effectors have been proposed to act in higher-order complexes associated with physically distinct areas of the plasma membrane. Adult muscle stem cells (satellite cells) must, upon injury, respond appropriately to a wide range of extracellular stimuli: the role of such signaling scaffolds is therefore a potentially important area of inquiry. To address this question, we first isolated detergent-resistant membrane fractions from primary satellite cells, then analyzed their component proteins using liquid chromatography-tandem mass spectrometry. Transmembrane and juxtamembrane components of adhesion-mediated signaling pathways made up the largest group of identified proteins; in particular, neural cell adhesion molecule (NCAM), a multifunctional cell-surface protein that has previously been associated with muscle regeneration, was significant. Immunohistochemical analysis revealed that not only is NCAM localized to discrete areas of the plasma membrane, it is also a very early marker of commitment to terminal differentiation. Using flow cytometry, we have sorted physically homogeneous myogenic cultures into proliferating and differentiating fractions based solely upon NCAM expression.

  17. Versatile UHV compatible Knudsen type effusion cell

    SciTech Connect

    Shukla, A.K.; Banik, S.; Dhaka, R.S.; Biswas, C.; Barman, S.R.; Haak, H.

    2004-11-01

    A versatile Knudsen type effusion cell has been fabricated for growing nanostructures and epitaxial layers of metals and semiconductors. The cell provides excellent vacuum compatibility (10{sup -10} mbar range during operation), efficient water cooling, uniform heating, and moderate input power consumption (100 W at 1000 deg. C). The thermal properties of the cell have been determined. The performance of the cell has been assessed by x-ray photoemission spectroscopy (XPS) for Mn adlayer growth on Al(111). We find that this Knudsen cell has a stable deposition rate of 0.17 monolayer per minute at 550 deg. C. From the XPS spectra, we show that the Mn adlayers are completely clean, i.e., devoid of any surface contamination.

  18. Stem Cells

    MedlinePlus

    Stem cells are cells with the potential to develop into many different types of cells in the body. They serve as a repair ... body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  19. Exploring the Psychosocial and Behavioral Adjustment Outcomes of Multi-Type Abuse among Homeless Young Adults

    ERIC Educational Resources Information Center

    Ferguson, Kristin M.

    2009-01-01

    This article explores the psychosocial and behavioral adjustment outcomes associated with verbal, emotional, physical, and sexual abuse among homeless young adults as well as the associations among abuse types. Convenience sampling was used to select 28 homeless young adults (ages 18 to 24) from one drop-in center. Overall, subjects experienced…

  20. In Vivo Dedifferentiation of Adult Adipose Cells

    PubMed Central

    Lu, Feng; Dong, Ziqing; Chang, Qiang; Gao, Jianhua

    2015-01-01

    Introduction Adipocytes can dedifferentiate into fibroblast-like cells in vitro and thereby acquire proliferation and multipotent capacities to participate in the repair of various organs and tissues. Whether dedifferentiation occurs under physiological or pathological conditions in vivo is unknown. Methods A tissue expander was placed under the inguinal fat pads of rats and gradually expanded by injection of water. Samples were collected at various time points, and morphological, histological, cytological, ultrastructural, and gene expression analyses were conducted. In a separate experiment, purified green fluorescent protein+ adipocytes were transplanted into C57 mice and collected at various time points. The transplanted adipocytes were assessed by bioluminescence imaging and whole-mount staining. Results The expanded fat pad was obviously thinner than the untreated fat pad on the opposite side. It was also tougher in texture and with more blood vessels attached. Hematoxylin and eosin staining and transmission electron microscopy indicated there were fewer monolocular adipocytes in the expanded fat pad and the morphology of these cells was altered, most notably their lipid content was discarded. Immunohistochemistry showed that the expanded fat pad contained an increased number of proliferative cells, which may have been derived from adipocytes. Following removal of the tissue expander, many small adipocytes were observed. Bioluminescence imaging suggested that some adipocytes survived when transplanted into an ischemic-hypoxic environment. Whole-mount staining revealed that surviving adipocytes underwent a process similar to adipocyte dedifferentiation in vitro. Monolocular adipocytes became multilocular adipocytes and then fibroblast-like cells. Conclusions Mature adipocytes may be able to dedifferentiate in vivo, and this may be an adipose tissue self-repair mechanism. The capacity of adipocytes to dedifferentiate into stem cell-like cells may also have a

  1. EMPOWERING ADULT STEM CELLS FOR MYOCARDIAL REGENERATION

    PubMed Central

    Mohsin, Sadia; Siddiqi, Sailay; Collins, Brett; Sussman, Mark A.

    2012-01-01

    Treatment strategies for heart failure remain a high priority for ongoing research due to the profound unmet need in clinical disease coupled with lack of significant translational progress. The underlying issue is the same whether the cause is acute damage, chronic stress from disease, or aging: progressive loss of functional cardiomyocytes and diminished hemodynamic output. To stave off cardiomyocyte losses, a number of strategic approaches have been embraced in recent years involving both molecular and cellular approaches to augment myocardial structure and performance. Resultant excitement surrounding regenerative medicine in the heart has been tempered by realizations that reparative processes in the heart are insufficient to restore damaged myocardium to normal functional capacity and that cellular cardiomyoplasty is hampered by poor survival, proliferation, engraftment and differentiation of the donated population. To overcome these limitations, a combination of molecular and cellular approaches needs to be adopted involving use of genetic engineering to enhance resistance to cell death and increase regenerative capacity. This review will highlight biological properties of approached to potentiate stem cell-mediated regeneration to promote enhanced myocardial regeneration, persistence of donated cells, and long lasting tissue repair. Optimizing cell delivery and harnessing the power of survival signaling cascades for ex vivo genetic modification of stem cells prior to reintroduction into the patient will be critical to enhance the efficacy of cellular cardiomyoplasty. Once this goal is achieved, then cell-based therapy has great promise for treatment of heart failure to combat the loss of cardiac structure and function associated with acute damage, chronic disease or aging. PMID:22158649

  2. Mesenchymal stem cell-based therapy for type 1 diabetes.

    PubMed

    Wu, Hao; Mahato, Ram I

    2014-03-01

    Diabetes has increasingly become a worldwide health problem, causing huge burden on healthcare system and economy. Type 1 diabetes (T1D), traditionally termed "juvenile diabetes" because of an early onset age, is affecting 5-10% of total diabetic population. Insulin injection, the predominant treatment for T1D, is effective to ameliorate the hyperglycemia but incompetent to relieve the autoimmunity and to regenerate lost islets. Islet transplantation, an experimental treatment for T1D, also suffers from limited supply of human islets and poor immunosuppression. The recent progress in regenerative medicine, especially stem cell therapy, has suggested several novel and potential cures for T1D. Mesenchymal stem cell (MSC) based cell therapy is among one of them. MSCs are a type of adult stem cells residing in bone marrow, adipose tissue, umbilical cord blood, and many other tissues. MSCs, with self-renewal potential and transdifferentiation capability, can be expanded in vitro and directed to various cell lineages with relatively less efforts. MSCs have well-characterized hypoimmunogenicity and immunomodulatory effect. All these features make MSCs attractive for treating T1D. Here, we review the properties of MSCs and some of the recent progress using MSCs as a new therapeutic in the treatment of T1D. We also discuss the strength and limitations of using MSC therapy in human trials.

  3. Intestinal stem cells in the adult Drosophila midgut

    SciTech Connect

    Jiang, Huaqi; Edgar, Bruce A.

    2011-11-15

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights: Black-Right-Pointing-Pointer The homeostasis and regeneration of adult fly midguts are mediated by ISCs. Black-Right-Pointing-Pointer Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). Black-Right-Pointing-Pointer EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. Black-Right-Pointing-Pointer Notch signaling regulates ISC self-renewal and differentiation.

  4. Renal histology in two adult patients with type I glycogen storage disease.

    PubMed

    Obara, K; Saito, T; Sato, H; Ogawa, M; Igarashi, Y; Yoshinaga, K

    1993-02-01

    Two adult patients with type I glycogen storage disease (I-GSD) had chronic renal disease with heavy proteinuria. Renal biopsies showed focal glomerular sclerosis, interstitial fibrosis, tubular atrophy or vacuolation, and prominent arteriosclerosis. Marked glomerular hypertrophy was demonstrated histometrically. Oil red O staining in one patient revealed numerous lipid deposits in the glomerular mesangium, tubular epithelial cells and interstitium. Electron microscopy in the other patient revealed diffuse thickening of the glomerular basement membrane (GBM) and lipid droplets within the mesangium. The glomerular hypertrophy, thickening of the GBM, and subsequent sclerosis were similar to those in insulin-dependent diabetes mellitus. These findings may explain the similarities between the natural histories of renal involvement in the two disorders. Particularly, glomerular hypertrophy may be a key step leading to glomerular sclerosis, which is the predominant finding I-GSD. Hyperlipidemia, which is commonly seen in I-GSD, may also accelerate the glomerular sclerosing process.

  5. Stirred bioreactors for the expansion of adult pancreatic stem cells.

    PubMed

    Serra, Margarida; Brito, Catarina; Leite, Sofia B; Gorjup, Erwin; von Briesen, Hagen; Carrondo, Manuel J T; Alves, Paula M

    2009-01-01

    Adult pluripotent stem cells are a cellular resource representing unprecedented potential for cell therapy and tissue engineering. Complementary to this promise, there is a need for efficient bioprocesses for their large scale expansion and/or differentiation. With this goal in mind, our work focused on the development of three-dimensional (3-D) culture systems for controlled expansion of adult pancreatic stem cells (PSCs). For this purpose, two different culturing strategies were evaluated, using spinner vessels: cell aggregated cultures versus microcarrier technology. The use of microcarrier supports (Cytodex 1 and Cytodex 3) rendered expanded cell populations which retained their self-renewal ability, cell marker, and the potential to differentiate into adipocytes. This strategy surmounted the drawbacks of aggregates in culture which were demonstrably unfeasible as cells clumped together did not proliferate and lost PSC marker expression. Furthermore, the results obtained showed that although both microcarriers tested here were suitable for sustaining cell expansion, Cytodex 3 provided a better substrate for the promotion of cell adherence and growth. For the latter approach, the potential of bioreactor technology was combined with the efficient Cytodex 3 strategy under controlled environmental conditions (pH-7.2, pO2-30% and temperature-37 degrees C); cell growth was more efficient, as shown by faster doubling time, higher growth rate and higher fold increase in cell concentration, when compared to spinner cultures. This study describes a robust bioprocess for the controlled expansion of adult PSC, representing an efficient starting point for the development of novel technologies for cell therapy.

  6. Liver stem cell-derived β-cell surrogates for treatment of type 1 diabetes☆

    PubMed Central

    Yang, Li-Jun

    2012-01-01

    Consistent with the common embryonic origin of liver and pancreas as well the similar glucose-sensing systems in hepatocytes and pancreatic β-cells, it should not be surprising that liver stem cells/hepatocytes can transdifferentiate into insulin-producing cells under high-glucose culture conditions or by genetic reprogramming. Persistent expression of the pancreatic duodenal homeobox-1 (Pdx1) transcription factor or its super-active form Pdx1-VP16 fusion protein in hepatic cells reprograms these cells into pancreatic β-cell precursors. In vitro culture at elevated glucose concentrations or in vivo exposure to a hyperglycemia are required for further differentiation and maturation of liver-derived pancreatic β-cell precursor into functional insulin-producing pancreatic β-like cells. Under appropriate conditions, multiple pancreatic transcription factors can work in concert to reprogram liver stem/adult liver cells into functional insulin-producing cells. If such autologous liver-derived insulin-producing cells can be made to escape the type 1 diabetes-associated autoimmunity, they may serve as a valuable cell source for future cell replacement therapy without the need for life-long immunosuppression. PMID:16890895

  7. New Nerve Cells for the Adult Brain.

    ERIC Educational Resources Information Center

    Kempermann, Gerd; Gage, Fred H.

    1999-01-01

    Contrary to dogma, the human brain does produce new nerve cells in adulthood. The mature human brain spawns neurons routinely in the hippocampus, an area important to memory and learning. This research can make it possible to ease any number of disorders involving neurological damage and death. (CCM)

  8. Serum Uric Acid and Hypertension in Adults: a Paradoxical Relationship in Type 1 Diabetes

    PubMed Central

    Bjornstad, Petter; Wadwa, R. Paul; Sirota, Jeffrey C.; Snell-Bergeon, Janet K.; McFann, Kimberly; Rewers, Marian; Rivard, Christopher J.; Jalal, Diana; Chonchol, Michel B.; Johnson, Richard J.; Maahs, David M.

    2014-01-01

    Adults with type 1 diabetes have lower serum uric acid levels compared to non-diabetic adults. Little is known about the relationship between serum uric acid and blood pressure in type 1 diabetes and whether it differs from the positive relationship found in non-diabetic adults. We assessed the cross-sectional and longitudinal relationships over 6-years between serum uric acid and blood pressure in adults with (35±9 years, n=393) and without (38±9 years n=685) T1D in the Coronary Artery Calcification in Type 1 Diabetes study. In non-diabetic adults, serum uric acid was associated with systolic blood pressure in multivariable-models adjusted for cardiovascular risk-factors. In adults with type 1 diabetes, a negative association was observed between serum uric acid and systolic blood pressure after multivariable-adjustments. A positive association was observed between serum uric acid and systolic blood pressure in non-diabetic adults. In contrast, an inverse relationship was demonstrated after multivariable-adjustments in type 1 diabetes. PMID:24667019

  9. Ocular-side lateralization of adult-type chromatophore precursors: development of pigment asymmetry in metamorphosing flounder larvae.

    PubMed

    Washio, Youhei; Aritaki, Masato; Fujinami, Yuichiro; Shimizu, Daisuke; Yokoi, Hayato; Suzuki, Tohru

    2013-05-01

    The adult-type chromatophores of flounder differentiate at metamorphosis in the skin of ocular side to establish asymmetric pigmentation. In young larva and before metamorphosis, adult-type melanophores that migrate to the ocular side during metamorphosis reside at the base of the dorsal fin as latent precursors. However, the migration route taken by these precursor cells and the mechanisms by which lateralization and asymmetric pigmentation develop on the ocular side are unknown. To further investigate this migration and lateralization, we used in situ hybridization with gch2 probe, a marker for melanoblasts and xanthoblasts (precursors of adult type chromatophores), to examine the distribution of chromatophore precursors in metamorphosing larvae. The gch2-positive precursors were present in the myoseptum as well as in the skin. This finding indicated that these precursors migrated from the dorsal part of the fin to the skin via the myoseptum. Additionally, there were much fewer gch2-positive cells in the myoseptum of the blind side than in the skin and myoseptum of the ocular side, and this finding indicated either that migration of the precursor cells into the myoseptum of blind side was inhibited or that the precursors were eliminated from the myoseptum of the blind side. Therefore, we propose that the signals responsible for development of asymmetric pigmentation in flounder reside not only in the skin but on a larger scale and in multiple tissues throughout the lateral half of the trunk.

  10. SKPs derive from hair follicle precursors and exhibit properties of adult dermal stem cells.

    PubMed

    Biernaskie, Jeffrey; Paris, Maryline; Morozova, Olena; Fagan, B Matthew; Marra, Marco; Pevny, Larysa; Miller, Freda D

    2009-12-01

    Despite the remarkable regenerative capacity of mammalian skin, an adult dermal stem cell has not yet been identified. Here, we investigated whether skin-derived precursors (SKPs) might fulfill such a role. We show that SKPs derive from Sox2(+) hair follicle dermal cells and that these two cell populations are similar with regard to their transcriptome and functional properties. Both clonal SKPs and endogenous Sox2(+) cells induce hair morphogenesis, differentiate into dermal cell types, and home to a hair follicle niche upon transplantation. Moreover, hair follicle-derived SKPs self-renew, maintain their multipotency, and serially reconstitute hair follicles. Finally, grafting experiments show that follicle-associated dermal cells move out of their niche to contribute cells for dermal maintenance and wound-healing. Thus, SKPs derive from Sox2(+) follicle-associated dermal precursors and display functional properties predicted of a dermal stem cell, contributing to dermal maintenance, wound-healing, and hair follicle morphogenesis.

  11. Isolation, culture and analysis of adult subependymal neural stem cells.

    PubMed

    Belenguer, Germán; Domingo-Muelas, Ana; Ferrón, Sacri R; Morante-Redolat, José Manuel; Fariñas, Isabel

    2016-01-01

    Individual cells dissected from the subependymal neurogenic niche of the adult mouse brain proliferate in medium containing basic fibroblast growth factor (bFGF) and/or epidermal growth factor (EGF) as mitogens, to produce multipotent clonal aggregates called neurospheres. These cultures constitute a powerful tool for the study of neural stem cells (NSCs) provided that they allow the analysis of their features and potential capacity in a controlled environment that can be modulated and monitored more accurately than in vivo. Clonogenic and population analyses under mitogen addition or withdrawal allow the quantification of the self-renewing and multilineage potency of these cells and the identification of the mechanisms involved in these properties. Here, we describe a set of procedures developed and/or modified by our group including several experimental options that can be used either independently or in combination for the ex vivo assessment of cell properties of NSCs obtained from the adult subependymal niche. PMID:27016251

  12. High-efficiency immunomagnetic isolation of solid tissue-originated integrin-expressing adult stem cells.

    PubMed

    Palmon, Aaron; David, Ran; Neumann, Yoav; Stiubea-Cohen, Raluca; Krief, Guy; Aframian, Doron J

    2012-02-01

    Isolation of highly pure specific cell types is crucial for successful adult stem cell-based therapy. As the number of such cells in adult tissue is low, an extremely efficient method is needed for their isolation. Here, we describe cell-separation methodologies based on magnetic-affinity cell sorting (MACS) MicroBeads with monoclonal antibodies against specific membrane proteins conjugated to superparamagnetic particles. Cells labeled with MACS MicroBeads are retained in a magnetic field within a MACS column placed in a MACS separator, allowing fast and efficient separation. Both positively labeled and non-labeled fractions can be used directly for downstream applications as the separated cell fractions remain viable with no functional impairment. As immunomagnetic separation depends on the interaction between a cell's membrane and the magnetically labeled antibody, separation of specific cells originating from solid tissues is more complex and demands a cell-dissociating pretreatment. In this paper, we detail the use of immunomagnetic separation for the purpose of regenerating damaged salivary gland (SG) function in animal and human models of irradiated head and neck cancer. Each year 500,000 new cases of head and neck cancer occur worldwide. Most of these patients lose SG function following irradiation therapy. SGs contain integrin α6β1-expressing epithelial stem cells. We hypothesized that these cells can be isolated, multiplied in culture and auto-implanted into the irradiated SGs to regenerate damaged SG function.

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

    PubMed Central

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

    2004-01-01

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

  14. 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

  15. 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

  16. Distinct cell tropism of canine distemper virus strains to adult olfactory ensheathing cells and Schwann cells in vitro.

    PubMed

    Techangamsuwan, Somporn; Haas, Ludwig; Rohn, Karl; Baumgärtner, Wolfgang; Wewetzer, Konstantin

    2009-09-01

    Canine distemper virus (CDV) can enter the brain via infection of olfactory neurons. Whether olfactory ensheathing cells (OECs) are also infected by CDV, and if yes, how they respond to the virus has remained enigmatic. Here, we exposed adult canine OECs in vitro to several attenuated (CDV-2544, CDV-R252, CDV-Ond, CDV-OndeGFP) and one virulent CDV strain (CDV-5804PeGFP) and studied their susceptibility compared to Schwann cells, a closely related cell type sharing the phagocytizing activity. We show that OECs and Schwann cells were infected by CDV strains albeit to different levels. Ten days post-infection (dpi), a mild to severe cytopathic effect ranging from single cell necrosis to layer detachment was noted. The percentage of infection increased during 10 dpi and viral progenies were detected in each culture using virus titration. Interestingly, CDV-2544, CDV-OndeGFP, and CDV-5804PeGFP predominantly infected OECs, while CDV-Ond targeted Schwann cells. No significant differences were found between the virulent and attenuated CDV strains. The observation of a CDV strain-specific cell tropism is evidence for significant molecular differences between OECs and Schwann cells. Whether these differences are either related to strain-specific distemper pathogenesis or support a role of OECs during CDV infection and virus spread needs to be addressed in future studies.

  17. Union Type and Depressive Symptoms among Mexican Adults

    ERIC Educational Resources Information Center

    Schmeer, Kammi K.; Kroeger, Rhiannon A.

    2011-01-01

    Diversity in union type is increasing around the world as cohabitation and higher order unions become more prevalent in developing and developed countries. This necessitates a more nuanced understanding of how different union types relate to individual well-being across social settings. In this study, the authors analyze nationally-representative…

  18. Running rescues defective adult neurogenesis by shortening the length of the cell cycle of neural stem and progenitor cells.

    PubMed

    Farioli-Vecchioli, Stefano; Mattera, Andrea; Micheli, Laura; Ceccarelli, Manuela; Leonardi, Luca; Saraulli, Daniele; Costanzi, Marco; Cestari, Vincenzo; Rouault, Jean-Pierre; Tirone, Felice

    2014-07-01

    Physical exercise increases the generation of new neurons in adult neurogenesis. However, only few studies have investigated the beneficial effects of physical exercise in paradigms of impaired neurogenesis. Here, we demonstrate that running fully reverses the deficient adult neurogenesis within the hippocampus and subventricular zone of the lateral ventricle, observed in mice lacking the antiproliferative gene Btg1. We also evaluated for the first time how running influences the cell cycle kinetics of stem and precursor subpopulations of wild-type and Btg1-null mice, using a new method to determine the cell cycle length. Our data show that in wild-type mice running leads to a cell cycle shortening only of NeuroD1-positive progenitor cells. In contrast, in Btg1-null mice, physical exercise fully reactivates the defective hippocampal neurogenesis, by shortening the S-phase length and the overall cell cycle duration of both neural stem (glial fibrillary acidic protein(+) and Sox2(+)) and progenitor (NeuroD1(+)) cells. These events are sufficient and necessary to reactivate the hyperproliferation observed in Btg1-null early-postnatal mice and to expand the pool of adult neural stem and progenitor cells. Such a sustained increase of cell proliferation in Btg1-null mice after running provides a long-lasting increment of proliferation, differentiation, and production of newborn neurons, which rescues the impaired pattern separation previously identified in Btg1-null mice. This study shows that running positively affects the cell cycle kinetics of specific subpopulations of newly generated neurons and suggests that the plasticity of neural stem cells without cell cycle inhibitory control is reactivated by running, with implications for the long-term modulation of neurogenesis.

  19. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    PubMed Central

    Webb, Carol F.; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

    2015-01-01

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. PMID:26111446

  20. Recent Advances in Therapeutic Approaches for Adult T-cell Leukemia/Lymphoma

    PubMed Central

    Kato, Koji; Akashi, Koichi

    2015-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by human T-cell leukemia/lymphoma virus type 1 (HTLV-1). ATLL occurs in approximately 3%–5% of HTLV-1 carriers during their lifetime and follows a heterogeneous clinical course. The Shimoyama classification has been frequently used for treatment decisions in ATLL patients, and antiviral therapy has been reportedly promising, particularly in patients with indolent type ATLL; however, the prognosis continues to be dismal for patients with aggressive-type ATLL. Recent efforts to improve treatment outcomes have been focused on the development of prognostic stratification and improved dosage, timing, and combination of therapeutic modalities, such as antiviral therapy, chemotherapy, allogeneic hematopoietic stem cell transplantation, and molecular targeted therapy. PMID:26694446

  1. Intraganglionic interactions between satellite cells and adult sensory neurons.

    PubMed

    Christie, Kimberly; Koshy, Dilip; Cheng, Chu; Guo, GuiFang; Martinez, Jose A; Duraikannu, Arul; Zochodne, Douglas W

    2015-07-01

    Perineuronal satellite cells have an intimate anatomical relationship with sensory neurons that suggests close functional collaboration and mutual support. We examined several facets of this relationship in adult sensory dorsal root ganglia (DRG). Collaboration included the support of process outgrowth by clustering of satellite cells, induction of distal branching behavior by soma signaling, the capacity of satellite cells to respond to distal axon injury of its neighboring neurons, and evidence of direct neuron-satellite cell exchange. In vitro, closely adherent coharvested satellite cells routinely clustered around new outgrowing processes and groups of satellite cells attracted neurite processes. Similar clustering was encountered in the pseudounipolar processes of intact sensory neurons within intact DRG in vivo. While short term exposure of distal growth cones of unselected adult sensory neurons to transient gradients of a PTEN inhibitor had negligible impacts on their behavior, exposure of the soma induced early and substantial growth of their distant neurites and branches, an example of local soma signaling. In turn, satellite cells sensed when distal neuronal axons were injured by enlarging and proliferating. We also observed that satellite cells were capable of internalizing and expressing a neuron fluorochrome label, diamidino yellow, applied remotely to distal injured axons of the neuron and retrogradely transported to dorsal root ganglia sensory neurons. The findings illustrate a robust interaction between intranganglionic neurons and glial cells that involve two way signals, features that may be critical for both regenerative responses and ongoing maintenance. PMID:25979201

  2. Intraganglionic interactions between satellite cells and adult sensory neurons.

    PubMed

    Christie, Kimberly; Koshy, Dilip; Cheng, Chu; Guo, GuiFang; Martinez, Jose A; Duraikannu, Arul; Zochodne, Douglas W

    2015-07-01

    Perineuronal satellite cells have an intimate anatomical relationship with sensory neurons that suggests close functional collaboration and mutual support. We examined several facets of this relationship in adult sensory dorsal root ganglia (DRG). Collaboration included the support of process outgrowth by clustering of satellite cells, induction of distal branching behavior by soma signaling, the capacity of satellite cells to respond to distal axon injury of its neighboring neurons, and evidence of direct neuron-satellite cell exchange. In vitro, closely adherent coharvested satellite cells routinely clustered around new outgrowing processes and groups of satellite cells attracted neurite processes. Similar clustering was encountered in the pseudounipolar processes of intact sensory neurons within intact DRG in vivo. While short term exposure of distal growth cones of unselected adult sensory neurons to transient gradients of a PTEN inhibitor had negligible impacts on their behavior, exposure of the soma induced early and substantial growth of their distant neurites and branches, an example of local soma signaling. In turn, satellite cells sensed when distal neuronal axons were injured by enlarging and proliferating. We also observed that satellite cells were capable of internalizing and expressing a neuron fluorochrome label, diamidino yellow, applied remotely to distal injured axons of the neuron and retrogradely transported to dorsal root ganglia sensory neurons. The findings illustrate a robust interaction between intranganglionic neurons and glial cells that involve two way signals, features that may be critical for both regenerative responses and ongoing maintenance.

  3. Wnt signaling in adult intestinal stem cells and cancer.

    PubMed

    Krausova, Michaela; Korinek, Vladimir

    2014-03-01

    Signaling initiated by secreted glycoproteins of the Wnt family regulates many aspects of embryonic development and it is involved in homeostasis of adult tissues. In the gastrointestinal (GI) tract the Wnt pathway maintains the self-renewal capacity of epithelial stem cells. The stem cell attributes are conferred by mutual interactions of the stem cell with its local microenvironment, the stem cell niche. The niche ensures that the threshold of Wnt signaling in the stem cell is kept in physiological range. In addition, the Wnt pathway involves various feedback loops that balance the opposing processes of cell proliferation and differentiation. Today, we have compelling evidence that mutations causing aberrant activation of the Wnt pathway promote expansion of undifferentiated progenitors and lead to cancer. The review summarizes recent advances in characterization of adult epithelial stem cells in the gut. We mainly focus on discoveries related to molecular mechanisms regulating the output of the Wnt pathway. Moreover, we present novel experimental approaches utilized to investigate the epithelial cell signaling circuitry in vivo and in vitro. Pivotal aspects of tissue homeostasis are often deduced from studies of tumor cells; therefore, we also discuss some latest results gleaned from the deep genome sequencing studies of human carcinomas of the colon and rectum. PMID:24308963

  4. Identification and enrichment of colony-forming cells from the adult murine pituitary

    SciTech Connect

    Lepore, D.A.; Roeszler, K.; Wagner, J.; Ross, S.A.; Bauer, K.; Thomas, P.Q. , E-Mail: paul.thomas@mcri.edu.au

    2005-08-01

    Stem and progenitor cells have been identified in many adult tissues including bone marrow, the central nervous system, and skin. While there is direct evidence to indicate the activity of a progenitor cell population in the pituitary gland, this putative subpopulation has not yet been identified. Herein we describe the isolation and characterization of a novel clonogenic cell type in the adult murine pituitary, which we have termed Pituitary Colony-Forming Cells (PCFCs). PCFCs constitute 0.2% of pituitary cells, and generate heterogeneous colonies from single cells. PCFCs exhibit variable proliferative potential, and may exceed 11 population doublings in 14 days. Enrichment of PCFCs to 61.5-fold with 100% recovery can be obtained through the active uptake of the fluorescent dipeptide, {beta}-Ala-Lys-N{epsilon}-AMCA. PCFCs are mostly contained within the large, agranular subpopulation of AMCA{sup +} cells, and constitute 28% of this fraction, corresponding to 140.5-fold enrichment. Interestingly, the AMCA{sup +} population contains rare cells that are GH{sup +} or PRL{sup +}. GH{sup +} cells were also identified in PCFC single cell colonies, suggesting that PCFCs have the potential to differentiate into GH{sup +} cells. Together, these data show that the pituitary contains a rare clonogenic population which may correspond to the somatotrope/lactotrope progenitors suggested by previous experiments.

  5. Satellite cell proliferation in adult skeletal muscle

    NASA Technical Reports Server (NTRS)

    Booth, Frank W. (Inventor); Thomason, Donald B. (Inventor); Morrison, Paul R. (Inventor); Stancel, George M. (Inventor)

    1995-01-01

    Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

  6. The regional association of rising type 2 diabetes incidence with magnesium in drinking water among young adults.

    PubMed

    Kousa, Anne; Puustinen, Niina; Karvonen, Marjatta; Moltchanova, Elena

    2012-01-01

    The incidence of type 2 diabetes is increasing among Finnish young adults. A slightly increased risk in men was found in the north-east and western part of the country. The higher risk areas in women were found in the western coastal area and in eastern Finland. The present register-based study aimed to evaluate the regional association of the incidence of type 2 diabetes among young adults with the concentration of magnesium in local ground water. The association was evaluated using Bayesian modeling of geo-referenced data aggregated into a regular 10 km × 10 km grid cells. No marked association was found, although suggestive findings were detected for magnesium in well water and diabetes in young adult women. The results of this register-based study did not completely rule out the association of well water magnesium with the geographical variation of type 2 diabetes. The incidence of type 2 diabetes was much higher among individuals aged 40 or over. These suggestive findings indicate that the association between magnesium and type 2 diabetes would also be worth examining among individuals over 40 years of age.

  7. Fetal and adult liver stem cells for liver regeneration and tissue engineering.

    PubMed

    Fiegel, H C; Lange, Claudia; Kneser, U; Lambrecht, W; Zander, A R; Rogiers, X; Kluth, D

    2006-01-01

    For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches.

  8. Axonal control of the adult neural stem cell niche.

    PubMed

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D; Tecott, Laurence H; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-04-01

    The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSCs) in the walls of the lateral ventricles of the adult brain. How the adult brain's neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  9. Axonal Control of the Adult Neural Stem Cell Niche

    PubMed Central

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D.; Tecott, Laurence H.; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-01-01

    SUMMARY The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSC) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  10. Direct transcriptional reprogramming of adult cells to embryonic nephron progenitors.

    PubMed

    Hendry, Caroline E; Vanslambrouck, Jessica M; Ineson, Jessica; Suhaimi, Norseha; Takasato, Minoru; Rae, Fiona; Little, Melissa H

    2013-09-01

    Direct reprogramming involves the enforced re-expression of key transcription factors to redefine a cellular state. The nephron progenitor population of the embryonic kidney gives rise to all cells within the nephron other than the collecting duct through a mesenchyme-to-epithelial transition, but this population is exhausted around the time of birth. Here, we sought to identify the conditions under which adult proximal tubule cells could be directly transcriptionally reprogrammed to nephron progenitors. Using a combinatorial screen for lineage-instructive transcription factors, we identified a pool of six genes (SIX1, SIX2, OSR1, EYA1, HOXA11, and SNAI2) that activated a network of genes consistent with a cap mesenchyme/nephron progenitor phenotype in the adult proximal tubule (HK2) cell line. Consistent with these reprogrammed cells being nephron progenitors, we observed differential contribution of the reprogrammed population into the Six2(+) nephron progenitor fields of an embryonic kidney explant. Dereplication of the pool suggested that SNAI2 can suppress E-CADHERIN, presumably assisting in the epithelial-to-mesenchymal transition (EMT) required to form nephron progenitors. However, neither TGFβ-induced EMT nor SNAI2 overexpression alone was sufficient to create this phenotype, suggesting that additional factors are required. In conclusion, these results suggest that reinitiation of kidney development from a population of adult cells by generating embryonic progenitors may be feasible, opening the way for additional cellular and bioengineering approaches to renal repair and regeneration.

  11. Adult stem cells applied to tissue engineering and regenerative medicine.

    PubMed

    Cuenca-López, M D; Zamora-Navas, P; García-Herrera, J M; Godino, M; López-Puertas, J M; Guerado, E; Becerra, J; Andrades, J A

    2008-01-01

    Regeneration takes place in the body at a moment or another throughout life. Bone, cartilage, and tendons (the key components of the structure and articulation in the body) have a limited capacity for self-repair and, after traumatic injury or disease, the regenerative power of adult tissue is often insufficient. When organs or tissues are irreparably damaged, they may be replaced by an artificial device or by a donor organ. However, the number of available donor organs is considerably limited. Generation of tissue-engineered replacement organs by extracting stem cells from the patient, growing them and modifying them in clinical conditions after re-introduction in the body represents an ideal source for corrective treatment. Mesenchymal stem cells (MSCs) are the multipotential progenitors that give rise to skeletal cells, vascular smooth muscle cells, muscle (skeletal and cardiac muscle), adipocytes (fat tissue) and hematopoietic (blood)-supportive stromal cells. MSCs are found in multiple connective tissues, in adult bone marrow, skeletal muscles and fat pads. The wide representation in adult tissues may be related to the existence of a circulating blood pool or that MSCs are associated to the vascular system.

  12. Biology of the adult enteric neural stem cell.

    PubMed

    Estrada-Mondaca, Sandino; Carreón-Rodríguez, Alfonso; Belkind-Gerson, Jaime

    2007-01-01

    An increasing body of evidence has accumulated in recent years supporting the existence of neural stem cells in the adult gut. There are at least three groups that have obtained them using different methodologies and have described them in vitro. There is a growing amount of knowledge on their biology, but many questions are yet unanswered. Among these questions is whether these cells are part of a permanent undifferentiated pool or are recruited in a regular basis; in addition, the factors and genes involved in their survival, proliferation, migration, and differentiation are largely unknown. Finally, with between 10 and 20% of adults suffering from diseases involving the enteric nervous system, most notably irritable bowel syndrome and gastroesophageal reflux, what is the possible role of enteric nervous stem cells in health and disease?

  13. Recent advances in bone regeneration using adult stem cells.

    PubMed

    Zigdon-Giladi, Hadar; Rudich, Utai; Michaeli Geller, Gal; Evron, Ayelet

    2015-04-26

    Bone is a highly vascularized tissue reliant on the close spatial and temporal association between blood vessels and bone cells. Therefore, cells that participate in vasculogenesis and osteogenesis play a pivotal role in bone formation during prenatal and postnatal periods. Nevertheless, spontaneous healing of bone fracture is occasionally impaired due to insufficient blood and cellular supply to the site of injury. In these cases, bone regeneration process is interrupted, which might result in delayed union or even nonunion of the fracture. Nonunion fracture is difficult to treat and have a high financial impact. In the last decade, numerous technological advancements in bone tissue engineering and cell-therapy opened new horizon in the field of bone regeneration. This review starts with presentation of the biological processes involved in bone development, bone remodeling, fracture healing process and the microenvironment at bone healing sites. Then, we discuss the rationale for using adult stem cells and listed the characteristics of the available cells for bone regeneration. The mechanism of action and epigenetic regulations for osteogenic differentiation are also described. Finally, we review the literature for translational and clinical trials that investigated the use of adult stem cells (mesenchymal stem cells, endothelial progenitor cells and CD34(+) blood progenitors) for bone regeneration.

  14. Wildtype adult stem cells, unlike tumor cells, are resistant to cellular damages in Drosophila.

    PubMed

    Ma, Meifang; Zhao, Hang; Zhao, Hanfei; Binari, Richard; Perrimon, Norbert; Li, Zhouhua

    2016-03-15

    Adult stem cells or residential progenitor cells are critical to maintain the structure and function of adult tissues (homeostasis) throughout the lifetime of an individual. Mis-regulation of stem cell proliferation and differentiation often leads to diseases including cancer, however, how wildtype adult stem cells and cancer cells respond to cellular damages remains unclear. We find that in the adult Drosophila midgut, intestinal stem cells (ISCs), unlike tumor intestinal cells, are resistant to various cellular damages. Tumor intestinal cells, unlike wildtype ISCs, are easily eliminated by apoptosis. Further, their proliferation is inhibited upon autophagy induction, and autophagy-mediated tumor inhibition is independent of caspase-dependent apoptosis. Interestingly, inhibition of tumorigenesis by autophagy is likely through the sequestration and degradation of mitochondria, as compromising mitochondria activity in these tumor models mimics the induction of autophagy and increasing the production of mitochondria alleviates the tumor-suppression capacity of autophagy. Together, these data demonstrate that wildtype adult stem cells and tumor cells show dramatic differences in sensitivity to cellular damages, thus providing potential therapeutic implications targeting tumorigenesis. PMID:26845534

  15. Cell type-specific bipolar cell input to ganglion cells in the mouse retina.

    PubMed

    Neumann, S; Hüser, L; Ondreka, K; Auler, N; Haverkamp, S

    2016-03-01

    Many distinct ganglion cell types, which are the output elements of the retina, were found to encode for specific features of a visual scene such as contrast, color information or movement. The detailed composition of retinal circuits leading to this tuning of retinal ganglion cells, however, is apart from some prominent examples, largely unknown. Here we aimed to investigate if ganglion cell types in the mouse retina receive selective input from specific bipolar cell types or if they sample their synaptic input non-selectively from all bipolar cell types stratifying within their dendritic tree. To address this question we took an anatomical approach and immunolabeled retinae of two transgenic mouse lines (GFP-O and JAM-B) with markers for ribbon synapses and type 2 bipolar cells. We morphologically identified all green fluorescent protein (GFP)-expressing ganglion cell types, which co-stratified with type 2 bipolar cells and assessed the total number of bipolar input synapses and the proportion of synapses deriving from type 2 bipolar cells. Only JAM-B ganglion cells received synaptic input preferentially from bipolar cell types other than type 2 bipolar cells whereas the other analyzed ganglion cell types sampled their bipolar input most likely from all bipolar cell terminals within their dendritic arbor.

  16. Haploidentical Stem Cell Transplantation in Adult Haematological Malignancies

    PubMed Central

    Parmesar, Kevon; Raj, Kavita

    2016-01-01

    Haematopoietic stem cell transplantation is a well-established treatment option for both hematological malignancies and nonmalignant conditions such as aplastic anemia and haemoglobinopathies. For those patients lacking a suitable matched sibling or matched unrelated donor, haploidentical donors are an alternative expedient donor pool. Historically, haploidentical transplantation led to high rates of graft rejection and GVHD. Strategies to circumvent these issues include T cell depletion and management of complications thereof or T replete transplants with GVHD prophylaxis. This review is an overview of these strategies and contemporaneous outcomes for hematological malignancies in adult haploidentical stem cell transplant recipients. PMID:27313619

  17. The 1993 cell typings of the International Cell Exchange.

    PubMed

    Lau, M; Terasaki, P I; Park, M S

    1993-01-01

    1. This is a summary of the typings for 40 cells for Class I antigens and 20 cultured cell lines for Class II antigens through the International Cell Exchange. Serological typings were compared with DNA typing reports for Class II specificities. Presently, 283 laboratories participate in the monthly Class I exchange. Class II results were received from 124 serology labs and 81 DNA labs on a monthly basis. 2. In 1993, 12 A-locus antigens were typed and 8 specificities reached levels of 95% or greater average detection. Thirteen of the 33 B-locus antigens showed 95% or better mean agreement levels. There was an improvement in detection of B76 and B7801. 3. Discrepancy rates of 7 A-locus and 9 B-locus antigens typed 3 or more times were compared with the overall rates for each respective locus. The discrepancy rate of false negatives, ie, how often the antigen was missed for the recognized B-locus specificities, continued to be greater than those for the A-locus antigens. The discrepancy rates, especially the percent false-positive, decreased for A33 during the recent 6-year period. 4. We showed the number of labs with their total of false-negatives and false-positives. Twelve labs attained a final total of no misses for all antigens. In 1993, 11 labs achieved impressive perfect records (zero false negative and false positive) for all analyzed antigens. 5. Retyping results of 2 donors showed improved antigen detection, particularly of A2403, B70, and B76. 6. Eleven cells typed in previous cell exchanges as having new or rare variants were sequenced recently. The B*5102 and B*5901 cells were retyped as reference cells. A new A-locus variant detected in previous exchanges was recently confirmed by sequence work as A*8001. New variants of B5 and B22 were discussed. 7. In addition to the mean detection rates, the low and high levels were determined for 15 broad (11 DR & 4 DQ) specificities by serology and compared with those attained for the respective generic (low

  18. Adult stem cell plasticity: will engineered tissues be rejected?

    PubMed Central

    Fang, Te-Chao; Alison, Malcolm R; Wright, Nicholas A; Poulsom, Richard

    2004-01-01

    The dogma that adult tissue-specific stem cells remain committed to supporting only their own tissue has been challenged; a new hypothesis, that adult stem cells demonstrate plasticity in their repertoires, is being tested. This is important because it seems possible that haematopoietic stem cells, for example, could be exploited to generate and perhaps deliver cell-based therapies deep within existing nonhaematopoietic organs. Much of the evidence for plasticity derives from histological studies of tissues from patients or animals that have received grafts of cells or whole organs, from a donor bearing (or lacking) a definitive marker. Detection in the recipient of appropriately differentiated cells bearing the donor marker is indicative of a switch in phenotype of a stem cell or a member of a transit amplifying population or of a differentiated cell. In this review, we discuss evidence for these changes occurring but do not consider the molecular basis of cell commitment. In general, the extent of engraftment is low but may be increased if tissues are damaged. In model systems of liver regeneration, the repeated application of a selection pressure increases levels of engraftment considerably; how this occurs is unclear. Cell fusion plays a part in regeneration and remodelling of the liver, skeletal muscle and even regions of the brain. Genetic disease may be amenable to some forms of cell therapy, yet immune rejection will present challenges. Graft-vs.-host disease will continue to present problems, although this may be avoided if the cells were derived from the recipient or they were tolerized. Despite great expectations for cellular therapies, there are indications that attempts to replace missing proteins could be confounded simply by the development of specific immunity that rejects the new phenotype. PMID:15255965

  19. Plant single-cell and single-cell-type metabolomics.

    PubMed

    Misra, Biswapriya B; Assmann, Sarah M; Chen, Sixue

    2014-10-01

    In conjunction with genomics, transcriptomics, and proteomics, plant metabolomics is providing large data sets that are paving the way towards a comprehensive and holistic understanding of plant growth, development, defense, and productivity. However, dilution effects from organ- and tissue-based sampling of metabolomes have limited our understanding of the intricate regulation of metabolic pathways and networks at the cellular level. Recent advances in metabolomics methodologies, along with the post-genomic expansion of bioinformatics knowledge and functional genomics tools, have allowed the gathering of enriched information on individual cells and single cell types. Here we review progress, current status, opportunities, and challenges presented by single cell-based metabolomics research in plants.

  20. Type of Multimorbidity and Complementary and Alternative Medicine Use among Adults

    PubMed Central

    Alwhaibi, Monira; Sambamoorthi, Usha

    2015-01-01

    Objective. To examine the association between type of multimorbidity and CAM use among adults with multimorbidity. Methods. The current study used a cross-sectional design with retrospective data from 2012 National Health Interview Survey. Multimorbidity was classified into two groups: (1) adults with coexisting physical and mental illnesses and (2) adults with two or more chronic physical illnesses only. CAM use was measured using a set of 18 variables. Logistic regression and multinomial logistic regressions were used to assess the association between the type of multimorbidity and ever used CAM, CAM use in the past 12 months, and type of CAM. Results. Overall, 31.2% of adults with coexisting physical and mental illnesses and 20.1% of adults with only physical illnesses used CAM in the past 12 months. Adults with coexisting physical and mental illnesses were more likely to ever use CAM (AOR = 1.68, 95% CI = 1.49, 1.90), use CAM in the past 12 months (AOR = 1.32, 95% CI = 1.15, 1.52), and use mind-body therapies in the past 12 months (AOR = 1.36, 95% CI = 1.16, 1.59) compared to adults with only physical illnesses. Conclusion. Multimorbidity of chronic physical and mental illnesses was associated with higher CAM use. PMID:25648169

  1. Cells of renin lineage are adult pluripotent progenitors in experimental glomerular disease

    PubMed Central

    Kaverina, Natalya V.; Eng, Diana G.; Krofft, Ronald D.; Glenn, Sean T.; Duffield, Jeremy S.; Gross, Kenneth W.; Shankland, Stuart J.

    2015-01-01

    Modified vascular smooth muscle cells of the kidney afferent arterioles have recently been shown to serve as progenitors for glomerular epithelial cells in response to glomerular injury. To determine whether such cells of renin lineage (CoRL) serve as progenitors for other cells in kidney disease characterized by both glomerular and tubulointerstitial injury, permanent genetic cell fate mapping of adult CoRL using Ren1cCreER × Rs-tdTomato-R reporter mice was performed. TdTomato-labeled CoRL were almost completely restricted to the juxtaglomerular compartment in healthy kidneys. Following 2 wk of antibody-mediated focal segmental glomerulosclerosis (FSGS) or 16 wk of ⅚ nephrectomy-induced chronic kidney diseases, tdTomato-mapped CoRL were identified in both interstitial and glomerular compartments. In the interstitium, PDGFβ receptor (R)-expressing cells significantly increased, and a portion of these expressed tdTomato. This was accompanied by a decrease in native pericyte number, but an increase in the number of tdTomato cells that coexpressed the pericyte markers PDGFβ-R and NG2. These cells surrounded vessels and coexpressed the pericyte markers CD73 and CD146, but not the endothelial marker ERG. Within glomeruli of reporter mice with the ⅚ nephrectomy model, a subset of labeled CoRL migrated to the glomerular tuft and coexpressed podocin and synaptopodin. By contrast, labeled CoRL were not detected in glomerular or interstitial compartments following uninephrectomy. These observations indicate that in addition to supplying new adult podocytes to glomeruli, CoRL have the capacity to become new adult pericytes in the setting of interstitial disease. We conclude that CoRL have the potential to function as progenitors for multiple adult cell types in kidney disease. PMID:26062877

  2. Considering Personality Type in Adult Learning: Using the Myers-Briggs Type Indicator in Instructor Preparation at PricewaterhouseCoopers

    ERIC Educational Resources Information Center

    Daisley, Richard J.

    2011-01-01

    This article explores the feasibility of using the Myers-Briggs Type Indicator (MBTI) as a framework for instructor development in a professional services training environment. It explores the consistency of MBTI with common adult learning theory, addresses questions on MBTI's reliability and validity, and explores the applicability of MBTI to the…

  3. 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

  4. Type 1 diabetes immunotherapy using polyclonal regulatory T cells.

    PubMed

    Bluestone, Jeffrey A; Buckner, Jane H; Fitch, Mark; Gitelman, Stephen E; Gupta, Shipra; Hellerstein, Marc K; Herold, Kevan C; Lares, Angela; Lee, Michael R; Li, Kelvin; Liu, Weihong; Long, S Alice; Masiello, Lisa M; Nguyen, Vinh; Putnam, Amy L; Rieck, Mary; Sayre, Peter H; Tang, Qizhi

    2015-11-25

    Type 1 diabetes (T1D) is an autoimmune disease that occurs in genetically susceptible individuals. Regulatory T cells (Tregs) have been shown to be defective in the autoimmune disease setting. Thus, efforts to repair or replace Tregs in T1D may reverse autoimmunity and protect the remaining insulin-producing β cells. On the basis of this premise, a robust technique has been developed to isolate and expand Tregs from patients with T1D. The expanded Tregs retained their T cell receptor diversity and demonstrated enhanced functional activity. We report on a phase 1 trial to assess safety of Treg adoptive immunotherapy in T1D. Fourteen adult subjects with T1D, in four dosing cohorts, received ex vivo-expanded autologous CD4(+)CD127(lo/-)CD25(+) polyclonal Tregs (0.05 × 10(8) to 26 × 10(8) cells). A subset of the adoptively transferred Tregs was long-lived, with up to 25% of the peak level remaining in the circulation at 1 year after transfer. Immune studies showed transient increases in Tregs in recipients and retained a broad Treg FOXP3(+)CD4(+)CD25(hi)CD127(lo) phenotype long-term. There were no infusion reactions or cell therapy-related high-grade adverse events. C-peptide levels persisted out to 2+ years after transfer in several individuals. These results support the development of a phase 2 trial to test efficacy of the Treg therapy. PMID:26606968

  5. First cloned swamp buffalo produced from adult ear fibroblast cell.

    PubMed

    Tasripoo, K; Suthikrai, W; Sophon, S; Jintana, R; Nualchuen, W; Usawang, S; Bintvihok, A; Techakumphu, M; Srisakwattana, K

    2014-07-01

    The world's first cloned swamp buffalo (Bubalus bubalis) derived from adult ear skin fibroblast has been reported. Donor fibroblast cells were produced from biopsies taken from adult male ear skin and in vitro matured oocytes obtained from a slaughterhouse were used as cytoplasts. A total of 39 blastocysts and 19 morulae fresh embryos were transferred into 12 recipient buffaloes. Progesterone assays indicated establishment of pregnancy in 10 of the 12 buffaloes (83.3%) after 45 days, with six animals still pregnant at 3 months. One recipient maintained pregnancy to term and naturally delivered a 40 kg male calf after 326 days of gestation. DNA analysis showed that the cloned calf was genetically identical to the donor cells. Genotype analyses, using 12 buffalo microsatellite markers, confirmed that the cloned calf was derived from the donor cell lines. In conclusion, the present study reports, for the first time, the establishment of pregnancy and birth of the first cloned Thai swamp buffalo derived from adult ear skin fibroblast cells.

  6. Defining cell types and states with single-cell genomics

    PubMed Central

    Trapnell, Cole

    2015-01-01

    A revolution in cellular measurement technology is under way: For the first time, we have the ability to monitor global gene regulation in thousands of individual cells in a single experiment. Such experiments will allow us to discover new cell types and states and trace their developmental origins. They overcome fundamental limitations inherent in measurements of bulk cell population that have frustrated efforts to resolve cellular states. Single-cell genomics and proteomics enable not only precise characterization of cell state, but also provide a stunningly high-resolution view of transitions between states. These measurements may finally make explicit the metaphor that C.H. Waddington posed nearly 60 years ago to explain cellular plasticity: Cells are residents of a vast “landscape” of possible states, over which they travel during development and in disease. Single-cell technology helps not only locate cells on this landscape, but illuminates the molecular mechanisms that shape the landscape itself. However, single-cell genomics is a field in its infancy, with many experimental and computational advances needed to fully realize its full potential. PMID:26430159

  7. [Therapeutic use of stem cells. II. Adult stem cells].

    PubMed

    Uzan, Georges

    2004-09-30

    Many degenerative diseases are not curable by means of classical medicine. The long term objective of cell therapy is to treat the patients with their own stem cells that could be either purified from the diseased organ or from "reservoirs" of stem cells such as that constituted by the bone marrow. The existence of stem cells in the organs or reservoirs is now established in vitro and in some cases, in animal models. Numbers of technical problems linked to the scarcity of these cells still delay the clinical use of purified stem cells. However, clinical protocols using heterogeneous cell populations have already started to treat a growing number of diseases. In some case, autologous cells can be used, as it is the case for bone marrow transplantation in blood diseases. Mesenchymal cells, also purified from the bone marrow are currently used in orthopaedic diseases. Because these cells reveal a broad differentiation potential, active research programs explore their possible use for treatment of other diseases. Bone marrow also contains vascular stem cells that could be active in reappearing defective vessels responsible for ischaemic diseases. Indeed, clinical trials in which bone marrow cells are injected in the cardiac muscle of patients with myocardial infarction or in the leg muscle (gastrocnemius) of patients with hind limb ischaemia have already started. Artificial skin prepared from skin biopsies is used for the reconstitution of the derma of severely burned patients. Clinical trials have also started, using allogenic cells. The patients must be treated by immunosuppressive drugs. Neurodegenerative diseases such as Parkinson have been successfully treated by intra-cerebral injection of foetal neurones. Pancreatic islets implanted in the liver have shown to re-establish a normal glycaemia in diabetic patients. However, all these clinical trials use differentiated cells or at least progenitors which display differentiation potential and lifetime much more

  8. An opposite effect of the CDK inhibitor, p18(INK4c) on embryonic stem cells compared with tumor and adult stem cells.

    PubMed

    Li, Yanxin; Pal, Rekha; Sung, Li-Ying; Feng, Haizhong; Miao, Weimin; Cheng, Shi-Yuan; Tian, Cindy; Cheng, Tao

    2012-01-01

    Self-renewal is a feature common to both adult and embryonic stem (ES) cells, as well as tumor stem cells (TSCs). The cyclin-dependent kinase inhibitor, p18(INK4c), is a known tumor suppressor that can inhibit self-renewal of tumor cells or adult stem cells. Here, we demonstrate an opposite effect of p18 on ES cells in comparison with teratoma cells. Our results unexpectedly showed that overexpression of p18 accelerated the growth of mouse ES cells and embryonic bodies (EB); on the contrary, inhibited the growth of late stage teratoma. Up-regulation of ES cell markers (i.e., Oct4, Nanog, Sox2, and Rex1) were detected in both ES and EB cells, while concomitant down-regulation of various differentiation markers was observed in EB cells. These results demonstrate that p18 has an opposite effect on ES cells as compared with tumor cells and adult stem cells. Mechanistically, expression of CDK4 was significantly increased with overexpression of p18 in ES cells, likely leading to a release of CDK2 from the inhibition by p21 and p27. As a result, self-renewal of ES cells was enhanced. Our current study suggests that targeting p18 in different cell types may yield different outcomes, thereby having implications for therapeutic manipulations of cell cycle machinery in stem cells. PMID:23049777

  9. Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

    PubMed

    Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

    2016-03-15

    Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life.

  10. Intestinal type of lung adenocarcinoma in younger adults.

    PubMed

    Stojsic, Jelena; Kontic, Milica; Subotic, Dragan; Popovic, Marko; Tomasevic, Dragana; Lukic, Jelena

    2014-01-01

    Intestinal type of lung adenocarcinoma (ILADC) was initially described by Tsao and Fraser in 1991. Morphology and immunophenotype of ILADC are the same as in colorectal adenocarcinoma. Rectocolonoscopy must be performed to exclude colorectal origin of adenocarcinoma. Colorectal adenocarcinoma claimed to be genetically similar to an ILADC. Patients. We describe 24- and 26-year-old patients of both genders who went under surgery because of a lung tumor mass detected on CT scan. ILADC was diagnosed on resected lung specimens. According to positivity of Cytokeratin20, CDX-2, and Villin, respectively, and negativity of Cytokeratin7, TTF-1, Napsin-A, SurfactantB, MUC-1, and MUC-2, respectively, ILADC was diagnosed. KRAS mutation was detected in tumor tissue of the male patient. Conclusion. Rectocolonoscopy is the only relevant method for distinguishing the intestinal type of lung adenocarcinoma from metastatic colorectal carcinoma because immunohistochemistry and detection of mutation status are frequently the same in both types of adenocarcinoma. More investigations are needed for further understanding of ILADC in purpose of personalized lung carcinoma therapy particularly introducing detection of mutation status, especially in younger patients. PMID:24782938

  11. Immunological properties of embryonic and adult stem cells

    PubMed Central

    Bifari, Francesco; Pacelli, Luciano; Krampera, Mauro

    2010-01-01

    The possibility of treating degenerative diseases by stem cell-based approaches is a promising therapeutical option. Among major concerns for the clinical application of stem cells, some derive from the possibility that stem cells may be rejected by the immune system as a consequence of histoincompatibility and that stem cells themselves may interfere with the normal functions of host immune response. Therefore, the immunogenicity and the immunomodulatory properties of stem cells must be carefully addressed. Although these properties are common features of different stem cell types, some peculiarities can be recognized and characterized for their proper clinical use. PMID:21607122

  12. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    SciTech Connect

    Webb, Carol F.; Ratliff, Michelle L.; Powell, Rebecca; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

    2015-08-07

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

  13. Cell secretion from the adult lamprey supraneural body tissues possesses cytocidal activity against tumor cells.

    PubMed

    Pang, Yue; Wang, Shiyue; Ba, Wei; Li, Qingwei

    2015-01-01

    The supraneural body was identified in the adult lamprey, and its secretions induced the death of a variety of tumor cells but had no effect on normal cells. The cell secretions from different lamprey tissues were separated, and these secretions killed human tumor cells to varying degrees. The cell secretions induced remarkable cell morphological alterations such as cell blebbing, and the plasma membrane was destroyed by the secretions. In addition, the secretions induced morphological alterations of the mitochondria, cytoskeletal structure, and endoplasmic reticulum, eventually leading to cell death. These observations suggest the presence of a novel protein in the lamprey and the possibility of new applications for the protein in the medical field.

  14. Adult Langerhans Cell Histiocytosis with Hepatic and Pulmonary Involvement

    PubMed Central

    Araujo, Bruno; Costa, Francisco; Lopes, Joanne; Castro, Ricardo

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of Langerhans cells of unknown etiology. It can involve multiple organ systems with different clinical presentation, which complicates the diagnosis. It can range from isolated to multisystem disease with different prognosis. Although common among children, liver involvement is relatively rare in adults and frequently overlooked. Natural history of liver LCH fits into two stages: an early stage with infiltration by histiocytes and a late stage with sclerosis of the biliary tree. Pulmonary findings are more common and include multiple nodules in different stages of cavitation, predominantly in the upper lobes. We present a case of adult LCH with pulmonary and biopsy proven liver involvement with resolution of the hepatic findings after treatment. PMID:25977828

  15. Mesenchymal stem cells instruct oligodendrogenic fate decision on adult neural stem cells.

    PubMed

    Rivera, Francisco J; Couillard-Despres, Sebastien; Pedre, Xiomara; Ploetz, Sonja; Caioni, Massimiliano; Lois, Carlos; Bogdahn, Ulrich; Aigner, Ludwig

    2006-10-01

    Adult stem cells reside in different tissues and organs of the adult organism. Among these cells are MSCs that are located in the adult bone marrow and NSCs that exist in the adult central nervous system (CNS). In transplantation experiments, MSCs demonstrated neuroprotective and neuroregenerative effects that were associated with functional improvements. The underlying mechanisms are largely unidentified. Here, we reveal that the interactions between adult MSCs and NSCs, mediated by soluble factors, induce oligodendrogenic fate decision in NSCs at the expense of astrogenesis. This was demonstrated (a) by an increase in the percentage of cells expressing the oligodendrocyte markers GalC and myelin basic protein, (b) by a reduction in the percentage of glial fibrillary acidic protein (GFAP)-expressing cells, and (c) by the expression pattern of cell fate determinants specific for oligodendrogenic differentiation. Thus, it involved enhanced expression of the oligodendrogenic transcription factors Olig1, Olig2, and Nkx2.2 and diminished expression of Id2, an inhibitor of oligodendrogenic differentiation. Results of (a) 5-bromo-2'-deoxyuridine pulse-labeling of cells, (b) cell fate analysis, and (c) cell death/survival analysis suggested an inductive mechanism and excluded a selection process. A candidate factor screen excluded a number of growth factors, cytokines, and neurotrophins that have previously been shown to influence neurogenesis and neural differentiation from the oligodendrogenic activity derived from the MSCs. This work might have major implications for the development of future transplantation strategies for the treatment of degenerative diseases in the CNS. PMID:16763198

  16. Physical skill training increases the number of surviving new cells in the adult hippocampus.

    PubMed

    Curlik, Daniel M; Maeng, Lisa Y; Agarwal, Prateek R; Shors, Tracey J

    2013-01-01

    The dentate gyrus is a major site of plasticity in the adult brain, giving rise to thousands of new neurons every day, through the process of adult neurogenesis. Although the majority of these cells die within two weeks of their birth, they can be rescued from death by various forms of learning. Successful acquisition of select types of associative and spatial memories increases the number of these cells that survive. Here, we investigated the possibility that an entirely different form of learning, physical skill learning, could rescue new hippocampal cells from death. To test this possibility, rats were trained with a physically-demanding and technically-difficult version of a rotarod procedure. Acquisition of the physical skill greatly increased the number of new hippocampal cells that survived. The number of surviving cells positively correlated with performance on the task. Only animals that successfully mastered the task retained the cells that would have otherwise died. Animals that failed to learn, and those that did not learn well did not retain any more cells than those that were untrained. Importantly, acute voluntary exercise in activity wheels did not increase the number of surviving cells. These data suggest that acquisition of a physical skill can increase the number of surviving hippocampal cells. Moreover, learning an easier version of the task did not increase cell survival. These results are consistent with previous reports revealing that learning only rescues new neurons from death when acquisition is sufficiently difficult to achieve. Finally, complete hippocampal lesions did not disrupt acquisition of this physical skill. Therefore, physical skill training that does not depend on the hippocampus can effectively increase the number of surviving cells in the adult hippocampus, the vast majority of which become mature neurons.

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

    PubMed

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

    2014-02-01

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

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

    PubMed

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

    2006-01-01

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

  19. Adult progenitor cell transplantation influences contractile performance and calcium handling of recipient cardiomyocytes.

    PubMed

    Lee, Joon; Stagg, Mark A; Fukushima, Satsuki; Soppa, Gopal K R; Siedlecka, Urszula; Youssef, Samuel J; Suzuki, Ken; Yacoub, Magdi H; Terracciano, Cesare M N

    2009-04-01

    Adult progenitor cell transplantation has been proposed for the treatment of heart failure, but the mechanisms effecting functional improvements remain unknown. The aim of this study was to test the hypothesis that, in failing hearts treated with cell transplantation, the mechanical properties and excitation-contraction coupling of recipient cardiomyocytes are altered. Adult rats underwent coronary artery ligation, leading to myocardial infarction and chronic heart failure. After 3 wk, they received intramyocardial injections of either 10(7) green fluorescence protein (GFP)-positive bone marrow mononuclear cells or 5 x 10(6) GFP-positive skeletal myoblasts. Four weeks after injection, both cell types increased ejection fraction and reduced cardiomyocyte size. The contractility of isolated GFP-negative cardiomyocytes was monitored by sarcomere shortening assessment, Ca(2+) handling by indo-1 and fluo-4 fluorescence, and electrophysiology by patch-clamping techniques. Injection of either bone marrow cells or skeletal myoblasts normalized the impaired contractile performance and the prolonged time to peak of the Ca(2+) transient observed in failing cardiomyocytes. The smaller and slower L-type Ca(2+) current observed in heart failure normalized after skeletal myoblast, but not bone marrow cell, transplantation. Measurement of Ca(2+) sparks suggested a normalization of sarcoplasmic reticulum Ca(2+) leak after skeletal myoblast transplantation. The increased Ca(2+) wave frequency observed in failing myocytes was reduced by either bone marrow cells or skeletal myoblasts. In conclusion, the morphology, contractile performance, and excitation-contraction coupling of individual recipient cardiomyocytes are altered in failing hearts treated with adult progenitor cell transplantation. PMID:19181964

  20. 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

  1. TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia/lymphoma

    PubMed Central

    Horlad, Hasita; Ohnishi, Koji; Ma, Chaoya; Fujiwara, Yukio; Niino, Daisuke; Ohshima, Koichi; Jinushi, Masahisa; Matsuoka, Masao; Takeya, Motohiro; Komohara, Yoshihiro

    2016-01-01

    Adult T-cell leukemia/lymphoma (ATLL), an aggressive type of malignant lymphoma, is highly resistant to chemotherapy. However, the detailed mechanisms of the chemoresistance of ATLL have never been elucidated. We previously demonstrated that direct cell-cell interaction between macrophages and lymphoma cells was significantly associated with lymphoma progression in patients with ATLL. The present study aimed to further analyze the effects of cell-cell interaction between macrophages and ATLL cells by means of cell culture studies and immunohistochemical analysis using human ATLL samples. It was found that direct co-culture with macrophages induced chemoresistance in the ATLL ATN-1 cell line, but not in other cell lines, including TL-Mor, ED and ATL-2S. It was also found that expression of the T cell Ig and mucin domain-containing molecule-3 (TIM-3) was induced in ATN-1 cells by their long-term co-culture with macrophages. TIM-3 gene transfection induced chemoresistance in the ATN-1 cells. Immunostaining of ATLL tissues showed TIM-3 expression in 25 out of 58 ATLL cases. Although TIM-3 expression was not associated with overall survival or T classification, it was associated with resistance to chemotherapy. TIM-3 expression is therefore considered to be a marker for predicting the efficacy of chemotherapy, and TIM-3-associated signals may be a therapeutic target for patients with ATLL. PMID:27446463

  2. Adult presentation of Bartter syndrome type IV with erythrocytosis

    PubMed Central

    Heilberg, Ita Pfeferman; Tótoli, Cláudia; Calado, Joaquim Tomaz

    2015-01-01

    Abstract Bartter syndrome comprises a group of rare autosomal-recessive salt-losing disorders with distinct phenotypes, but one unifying pathophysiology consisting of severe reductions of sodium reabsorption caused by mutations in five genes expressed in the thick ascending limb of Henle, coupled with increased urinary excretion of potassium and hydrogen, which leads to hypokalemic alkalosis. Bartter syndrome type IV, caused by loss-of-function mutations in barttin, a subunit of chloride channel CLC-Kb expressed in the kidney and inner ear, usually occurs in the antenatal-neonatal period. We report an unusual case of late onset presentation of Bartter syndrome IV and mild phenotype in a 20 years-old man who had hypokalemia, deafness, secondary hyperparathyroidism and erythrocytosis. PMID:26537508

  3. Neural stem/progenitor cell properties of glial cells in the adult mouse auditory nerve

    PubMed Central

    Lang, Hainan; Xing, Yazhi; Brown, LaShardai N.; Samuvel, Devadoss J.; Panganiban, Clarisse H.; Havens, Luke T.; Balasubramanian, Sundaravadivel; Wegner, Michael; Krug, Edward L.; Barth, Jeremy L.

    2015-01-01

    The auditory nerve is the primary conveyor of hearing information from sensory hair cells to the brain. It has been believed that loss of the auditory nerve is irreversible in the adult mammalian ear, resulting in sensorineural hearing loss. We examined the regenerative potential of the auditory nerve in a mouse model of auditory neuropathy. Following neuronal degeneration, quiescent glial cells converted to an activated state showing a decrease in nuclear chromatin condensation, altered histone deacetylase expression and up-regulation of numerous genes associated with neurogenesis or development. Neurosphere formation assays showed that adult auditory nerves contain neural stem/progenitor cells (NSPs) that were within a Sox2-positive glial population. Production of neurospheres from auditory nerve cells was stimulated by acute neuronal injury and hypoxic conditioning. These results demonstrate that a subset of glial cells in the adult auditory nerve exhibit several characteristics of NSPs and are therefore potential targets for promoting auditory nerve regeneration. PMID:26307538

  4. Differential expression of id genes and their potential regulator znf238 in zebrafish adult neural progenitor cells and neurons suggests distinct functions in adult neurogenesis.

    PubMed

    Diotel, Nicolas; Beil, Tanja; Strähle, Uwe; Rastegar, Sepand

    2015-01-01

    Teleost fish display a remarkable ability to generate new neurons and to repair brain lesions during adulthood. They are, therefore, a very popular model to investigate the molecular mechanisms of constitutive and induced neurogenesis in adult vertebrates. In this study, we investigated the expression patterns of inhibitor of DNA binding (id) genes and of their potential transcriptional repressor, znf238, in the whole brain of adult zebrafish. We show that while id1 is exclusively expressed in ventricular cells in the whole brain, id2a, id3 and id4 genes are expressed in broader areas. Interestingly, znf238 was also detected in these regions, its expression overlapping with id2a, id3 and id4 expression. Further detailed characterization of the id-expressing cells demonstrated that (a) id1 is expressed in type 1 and type 2 neural progenitors as previously published, (b) id2a in type 1, 2 and 3 neural progenitors, (c) id3 in type 3 neural progenitors and (d) id4 in postmitotic neurons. Our data provide a detailed map of id and znf238 expression in the brain of adult zebrafish, supplying a framework for studies of id genes function during adult neurogenesis and brain regeneration in the zebrafish.

  5. Progressive deterioration of beta-cell function in obese youth with type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In adults, type 2 diabetes (T2DM) is characterized with progressive deterioration in insulin secretion. Data are scanty in youth. We investigated prospectively the change in ß-cell function and in insulin sensitivity in youth with T2DM. Six adolescents with T2DM [hemoglobin A1c (HbA1c) 6.6 +/- 1.0%]...

  6. Prevalence of vitamin D deficiency in adults with sickle cell disease.

    PubMed

    Goodman, B Mitchell; Artz, Nicole; Radford, Barbera; Chen, Ian A

    2010-04-01

    Vitamin D deficiency has been linked to fracture risk and chronic musculoskeletal pain. Adults with sickle cell disease have a high prevalence of low bone density and chronic pain with poorly defined etiologies. We recognized that vitamin D deficiency may represent a treatable etiology and sought to determine the prevalence of vitamin D deficiency in adults with sickle cell. We measured 25-hydroxy vitamin D levels in adults at 2 university-based sickle cell disease-management programs. Regression was performed in 142 patients to identify predictors of low vitamin D. Mean vitamin D levels were 9.0 ng/mL at Eastern Virginia Medical School and 12.8 ng/mL at University of Chicago; 139 of 142 (98%) had suboptimal levels (<30 ng/mL) and 85/142 (60%) were severely deficient (<10 ng/mL). Vitamin D level was not related to age, sex, hydroxyurea use, sickle cell type, or date of lab draw. Vitamin D deficiency was, therefore, nearly ubiquitous in our patient population, with a majority being severely deficient. Further studies are warranted to evaluate the effects of vitamin D repletion on clinical outcomes such as bone density, chronic musculoskeletal pain, and functional status. Clinicians caring for patients with sickle cell disease should be aware of and screen for this important clinical state.

  7. Adult spinal cord ependymal layer: a promising pool of quiescent stem cells to treat spinal cord injury.

    PubMed

    Panayiotou, Elena; Malas, Stavros

    2013-11-28

    Spinal cord injury (SCI) is a major health burden and currently there is no effective medical intervention. Research performed over the last decade revealed that cells surrounding the central canal of the adult spinal cord and forming the ependymal layer acquire stem cell properties either in vitro or in response to injury. Following SCI activated ependymal cells generate progeny cells which migrate to the injury site but fail to produce the appropriate type of cells in sufficient number to limit the damage, rendering this physiological response mainly ineffective. Research is now focusing on the manipulation of ependymal cells to produce cells of the oligodendrocyte lineage which are primarily lost in such a situation leading to secondary neuronal degeneration. Thus, there is a need for a more focused approach to understand the molecular properties of adult ependymal cells in greater detail and develop effective strategies for guiding their response during SCI.

  8. Adult human neural stem cell therapeutics: Current developmental status and prospect

    PubMed Central

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

    2015-01-01

    Over the past two decades, regenerative therapies using stem cell technologies have been developed for various neurological diseases. Although stem cell therapy is an attractive option to reverse neural tissue damage and to recover neurological deficits, it is still under development so as not to show significant treatment effects in clinical settings. In this review, we discuss the scientific and clinical basics of adult neural stem cells (aNSCs), and their current developmental status as cell therapeutics for neurological disease. Compared with other types of stem cells, aNSCs have clinical advantages, such as limited proliferation, inborn differentiation potential into functional neural cells, and no ethical issues. In spite of the merits of aNSCs, difficulties in the isolation from the normal brain, and in the in vitro expansion, have blocked preclinical and clinical study using aNSCs. However, several groups have recently developed novel techniques to isolate and expand aNSCs from normal adult brains, and showed successful applications of aNSCs to neurological diseases. With new technologies for aNSCs and their clinical strengths, previous hurdles in stem cell therapies for neurological diseases could be overcome, to realize clinically efficacious regenerative stem cell therapeutics. PMID:25621112

  9. Adult human neural stem cell therapeutics: Current developmental status and prospect.

    PubMed

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

    2015-01-26

    Over the past two decades, regenerative therapies using stem cell technologies have been developed for various neurological diseases. Although stem cell therapy is an attractive option to reverse neural tissue damage and to recover neurological deficits, it is still under development so as not to show significant treatment effects in clinical settings. In this review, we discuss the scientific and clinical basics of adult neural stem cells (aNSCs), and their current developmental status as cell therapeutics for neurological disease. Compared with other types of stem cells, aNSCs have clinical advantages, such as limited proliferation, inborn differentiation potential into functional neural cells, and no ethical issues. In spite of the merits of aNSCs, difficulties in the isolation from the normal brain, and in the in vitro expansion, have blocked preclinical and clinical study using aNSCs. However, several groups have recently developed novel techniques to isolate and expand aNSCs from normal adult brains, and showed successful applications of aNSCs to neurological diseases. With new technologies for aNSCs and their clinical strengths, previous hurdles in stem cell therapies for neurological diseases could be overcome, to realize clinically efficacious regenerative stem cell therapeutics.

  10. Relations of Behavioral Autonomy to Health Outcomes Among Emerging Adults With and Without Type 1 Diabetes

    PubMed Central

    Reynolds, Kerry A.; Becker, Dorothy; Escobar, Oscar; Siminerio, Linda

    2014-01-01

    Objective To examine the relation of behavioral autonomy to psychological, behavioral, and physical health among emerging adults with and without type 1 diabetes. Methods High school seniors with (n = 118) and without type 1 diabetes (n = 122) completed online questionnaires for three consecutive years. Behavioral autonomy, psychological health, risk behaviors, and diabetes outcomes were assessed. Regression analyses were conducted to predict Time 2 and 3 outcomes, controlling for Time 1 outcomes. Results There were no group differences in behavioral autonomy. Behavioral autonomy predicted better psychological health but only for emerging adults without diabetes. Behavioral autonomy was related to increased risk behavior for both groups. Behavioral autonomy was unrelated to self-care but predicted better glycemic control for females. Conclusions Behavioral autonomy may be beneficial for psychological health, but is related to increased risk behavior. The implications of behavioral autonomy for emerging adults with type 1 diabetes require careful consideration. PMID:25157070

  11. Adult stem cells therapy for urine incontinence in women.

    PubMed

    Stangel-Wójcikiewicz, Klaudia; Majka, Marcin; Basta, Antoni; Stec, Małgorzata; Pabian, Wojciech; Piwowar, Monika; Chancellor, Michael B

    2010-05-01

    The past few years brought high development in obtaining and culturing autologous adult stem cells. In this paper we review publications of experimental investigations and clinical trials of the muscle-derived cells and the application in the treatment of stress urinary incontinence among women. Mesenchymal stem cells (MSCs) can be obtained from bone marrow but it is associated with a painful biopsy procedure. Collection of muscle-derived stem cells (MDSCs) is less harmful because the skeletal muscle biopsy is performed with a small caliber needle in local anesthesia. The stem-based therapy could be the next step in the treatment of urinary incontinence. There are still many elements of therapy such as effectiveness or long-term side effects which need to be researched.

  12. Serum uric acid and insulin sensitivity in adolescents and adults with and without type 1 diabetes

    PubMed Central

    Bjornstad, Petter; Snell-Bergeon, Janet K.; McFann, Kimberly; Wadwa, R. Paul; Rewers, Marian; Rivard, Christopher J.; Jalal, Diana; Chonchol, Michel B.; Johnson, Richard J.; Maahs, David M.

    2014-01-01

    Hypothesis Decreased insulin sensitivity (IS) exists in type 1 diabetes. Serum uric acid (SUA), whose concentration is related to renal clearance, predicts vascular complications in type 1 diabetes. SUA is also inversely associated with IS in non-diabetics, but has not been examined in type 1 diabetes. We hypothesized SUA would be associated with reduced IS in adolescents and adults with type 1 diabetes. Methods The cross-sectional and longitudinal associations of SUA with IS was investigated in 254 adolescents with type 1 diabetes and 70 without in the Determinants of Macrovascular Disease in Adolescents with Type 1 Diabetes Study, and in 471 adults with type 1 diabetes and 571 without in the Coronary Artery Calcification in Type 1 diabetes (CACTI) study. Results SUA was lower in subjects with type 1 diabetes (p<0.0001), but still remained inversely associated with IS after multivariable adjustments- in adolescents (β±SE: −1.99±0.62, p=0.001, R2=2%) and adults (β±SE:−0.91±0.33, p=0.006, R2=6%) with type 1 diabetes, though less strongly than in non-diabetic controls (adolescents: β±SE: −2.70±1.19, p=0.03, R2=15%, adults: β±SE:−5.99±0.75, p<0.0001, R2=39%). Conclusion We demonstrated a significantly weaker relationship between SUA and reduced IS in subjects with type 1 diabetes than non-diabetic controls. PMID:24461546

  13. Transgenic Expression of a Single Transcription Factor Pdx1 Induces Transdifferentiation of Pancreatic Acinar Cells to Endocrine Cells in Adult Mice.

    PubMed

    Miyazaki, Satsuki; Tashiro, Fumi; Miyazaki, Jun-Ichi

    2016-01-01

    A promising approach to new diabetes therapies is to generate β cells from other differentiated pancreatic cells in vivo. Because the acinar cells represent the most abundant cell type in the pancreas, an attractive possibility is to reprogram acinar cells into β cells. The transcription factor Pdx1 (Pancreas/duodenum homeobox protein 1) is essential for pancreatic development and cell lineage determination. Our objective is to examine whether exogenous expression of Pdx1 in acinar cells of adult mice might induce reprogramming of acinar cells into β cells. We established a transgenic mouse line in which Pdx1 and EGFP (enhanced green fluorescent protein) could be inducibly expressed in the acinar cells. After induction of Pdx1, we followed the acinar cells for their expression of exocrine and endocrine markers using cell-lineage tracing with EGFP. The acinar cell-specific expression of Pdx1 in adult mice reprogrammed the acinar cells as endocrine precursor cells, which migrated into the pancreatic islets and differentiated into insulin-, somatostatin-, or PP (pancreatic polypeptide)-producing endocrine cells, but not into glucagon-producing cells. When the mice undergoing such pancreatic reprogramming were treated with streptozotocin (STZ), the newly generated insulin-producing cells were able to ameliorate STZ-induced diabetes. This paradigm of in vivo reprogramming indicates that acinar cells hold promise as a source for new islet cells in regenerative therapies for diabetes. PMID:27526291

  14. Transgenic Expression of a Single Transcription Factor Pdx1 Induces Transdifferentiation of Pancreatic Acinar Cells to Endocrine Cells in Adult Mice

    PubMed Central

    Miyazaki, Satsuki; Tashiro, Fumi; Miyazaki, Jun-ichi

    2016-01-01

    A promising approach to new diabetes therapies is to generate β cells from other differentiated pancreatic cells in vivo. Because the acinar cells represent the most abundant cell type in the pancreas, an attractive possibility is to reprogram acinar cells into β cells. The transcription factor Pdx1 (Pancreas/duodenum homeobox protein 1) is essential for pancreatic development and cell lineage determination. Our objective is to examine whether exogenous expression of Pdx1 in acinar cells of adult mice might induce reprogramming of acinar cells into β cells. We established a transgenic mouse line in which Pdx1 and EGFP (enhanced green fluorescent protein) could be inducibly expressed in the acinar cells. After induction of Pdx1, we followed the acinar cells for their expression of exocrine and endocrine markers using cell-lineage tracing with EGFP. The acinar cell-specific expression of Pdx1 in adult mice reprogrammed the acinar cells as endocrine precursor cells, which migrated into the pancreatic islets and differentiated into insulin-, somatostatin-, or PP (pancreatic polypeptide)-producing endocrine cells, but not into glucagon-producing cells. When the mice undergoing such pancreatic reprogramming were treated with streptozotocin (STZ), the newly generated insulin-producing cells were able to ameliorate STZ-induced diabetes. This paradigm of in vivo reprogramming indicates that acinar cells hold promise as a source for new islet cells in regenerative therapies for diabetes. PMID:27526291

  15. Distribution of angiotensin type-1 receptor messenger RNA expression in the adult rat brain.

    PubMed

    Lenkei, Z; Palkovits, M; Corvol, P; Llorens-Cortes, C

    1998-02-01

    Angiotensin II and angiotensin III in the brain exert their various effects by acting on two pharmacologically well-defined receptors, the type-1 (AT1) and the type-2 (AT2) receptors. Receptor binding autoradiography has revealed the dominant presence of AT1 in brain nuclei involved in cardiovascular, body fluid and neuroendocrine control. The cloning of the AT1 complementary DNA has revealed the existence of two receptor subtypes in rodents, AT1A and AT1B. Using specific riboprobes for in situ hybridization, we have previously shown that the AT1A messenger RNA is predominantly expressed in the rat forebrain; in contrast the AT1B subtype predominates in the anterior pituitary. Using a similar technical approach, the aim of the present study was to establish the precise anatomical localization of cells synthetising the AT1A receptor in the adult rat brain. High AT1A messenger RNA expression was found in the vascular organ of the lamina terminalis, the median preoptic nucleus, the subfornical organ, the hypothalamic periventricular nucleus, the parvocellular parts of the paraventricular nucleus, the nucleus of the solitary tract and the area postrema, in agreement with previous autoradiographic studies, describing a high density of AT1 binding sites in these nuclei. In addition, AT1A messenger RNA expression was detected in several brain areas, where no AT1 binding was reported previously. Thus, we identify strong expression of AT1A messenger RNA expression in scattered cells of the lateral parts of the preoptic region, the lateral hypothalamus and several brainstem nuclei. In none of these structures was the AT1B messenger RNA detectable at the microscopic level. In conclusion, it is suggested that angiotensins may exert their central effects on body fluid and cardiovascular homeostasis mainly via the AT1A receptor subtype. PMID:9483539

  16. Are there differential relationships between different types of childhood maltreatment and different types of adult personality pathology?

    PubMed

    Cohen, Lisa Janet; Tanis, Thachell; Bhattacharjee, Reetuparna; Nesci, Christina; Halmi, Winter; Galynker, Igor

    2014-01-30

    While considerable data support the relationship between childhood trauma and adult personality pathology in general, there is little research investigating the specific relationships between different types of childhood maltreatment and adult personality disorders. The present study tested a model incorporating five a priori hypotheses regarding the association between distinct forms of childhood maltreatment and personality pathology in 231 psychiatric patients using multiple self-report measures (Personality Diagnostic Questionnaire-4th Edition, Child Trauma Questionnaire, Conflict in Tactics Scale Parent-Child Child-Adult, and Multidimensional Neglectful Behavior Scale). Step-wise linear regressions supported three out of five hypotheses, suggesting independent relationships between: physical abuse and antisocial personality disorder traits; emotional abuse and Cluster C personality disorder traits; and maternal neglect and Cluster A personality disorder traits after controlling for co-occurring maltreatment types and personality disorder traits. Results did not support an independent relationship between sexual abuse and borderline personality traits nor between emotional abuse and narcissistic personality disorder traits. Additionally, there were three unexpected findings: physical abuse was independently and positively associated with narcissistic and paranoid traits and negatively associated with Cluster C traits. These findings can help refine our understanding of adult personality pathology and support the future development of clinical tools for survivors of childhood maltreatment.

  17. A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking.

    PubMed

    Ratajczak, M Z

    2015-04-01

    This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of the complement cascade as a trigger for egress of hematopoietic stem cells from bone marrow into blood as well as the emerging role of novel homing factors and priming mechanisms that support stromal-derived factor 1-mediated homing of hematopoietic stem/progenitor cells after transplantation.

  18. A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking

    PubMed Central

    Ratajczak, M Z

    2015-01-01

    This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of the complement cascade as a trigger for egress of hematopoietic stem cells from bone marrow into blood as well as the emerging role of novel homing factors and priming mechanisms that support stromal-derived factor 1-mediated homing of hematopoietic stem/progenitor cells after transplantation. PMID:25486871

  19. Robust G2 pausing of adult stem cells in Hydra.

    PubMed

    Buzgariu, Wanda; Crescenzi, Marco; Galliot, Brigitte

    2014-01-01

    Hydra is a freshwater hydrozoan polyp that constantly renews its two tissue layers thanks to three distinct stem cell populations that cannot replace each other, epithelial ectodermal, epithelial endodermal, and multipotent interstitial. These adult stem cells, located in the central body column, exhibit different cycling paces, slow for the epithelial, fast for the interstitial. To monitor the changes in cell cycling in Hydra, we established a fast and efficient flow cytometry procedure, which we validated by confirming previous findings, as the Nocodazole-induced reversible arrest of cell cycling in G2/M, and the mitogenic signal provided by feeding. Then to dissect the cycling and differentiation behaviors of the interstitial stem cells, we used the AEP_cnnos1 and AEP_Icy1 transgenic lines that constitutively express GFP in this lineage. For the epithelial lineages we used the sf-1 strain that rapidly eliminates the fast cycling cells upon heat-shock and progressively becomes epithelial. This study evidences similar cycling patterns for the interstitial and epithelial stem cells, which all alternate between the G2 and S-phases traversing a minimal G1-phase. We also found interstitial progenitors with a shorter G2 that pause in G1/G0. At the animal extremities, most cells no longer cycle, the epithelial cells terminally differentiate in G2 and the interstitial progenitors in G1/G0. At the apical pole ~80% cells are post-mitotic differentiated cells, reflecting the higher density of neurons and nematocytes in this region. We discuss how the robust G2 pausing of stem cells, maintained over weeks of starvation, may contribute to regeneration.

  20. Inflammatory cues acting on the adult intestinal stem cells and the early onset of cancer (Review)

    PubMed Central

    DE LERMA BARBARO, A.; PERLETTI, G.; BONAPACE, I.M.; MONTI, E.

    2014-01-01

    The observation that cancer often arises at sites of chronic inflammation has prompted the idea that carcinogenesis and inflammation are deeply interwoven. In fact, the current literature highlights a role for chronic inflammation in virtually all the steps of carcinogenesis, including tumor initiation, promotion and progression. The aim of the present article is to review the current literature on the involvement of chronic inflammation in the initiation step and in the very early phases of tumorigenesis, in a type of cancer where adult stem cells are assumed to be the cells of origin of neoplasia. Since the gastrointestinal tract is regarded as the best-established model system to address the liaison between chronic inflammation and neoplasia, the focus of this article will be on intestinal cancer. In fact, the anatomy of the intestinal epithelial lining is uniquely suited to study adult stem cells in their niche, and the bowel crypt is an ideal developmental biology system, as proliferation, differentiation and cell migration are all distributed linearly along the long axis of the crypt. Moreover, crypt stem cells are regarded today as the most likely targets of neoplastic transformation in bowel cancer. More specifically, the present review addresses the molecular mechanisms whereby a state of chronic inflammation could trigger the neoplastic process in the intestine, focusing on the generation of inflammatory cues evoking enhanced proliferation in cells not initiated but at risk of neoplastic transformation because of their stemness. Novel experimental approaches, based on triggering an inflammatory stimulus in the neighbourhood of adult intestinal stem cells, are warranted to address some as yet unanswered questions. A possible approach, the targeted transgenesis of Paneth cells, may be aimed at ‘hijacking’ the crypt stem cell niche from a status characterized by the maintenance of homeostasis to local chronic inflammation, with the prospect of initiating

  1. HTLV-1 and associated adult T-cell leukemia/lymphoma.

    PubMed

    Mahieux, Renaud; Gessain, Antoine

    2003-12-01

    Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infects 15-20 millions individuals worldwide. This oncoretrovirus can be transmitted through 3 ways: horizontally, vertically (mother to child) and via blood transfusion. HTLV-1 causes 2 major diseases: adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1-associated myelopathy. Tax is a 40-kDa phosphoprotein that is encoded by the pX region of the virus. Several lines of evidence have demonstrated a central role for this protein in the immortalization or transformation of the HTLV-1 infected cells. Apart from its ability to drive transcription from the viral promoter, it also deregulates the cell cycle, inhibits apoptosis, has an effect on the maintenance of the genomic stability and induces the production of several cytokines. In addition, several arguments strongly suggest the existence of host genetic factors, that could be involved in the HTLV-1 infection as well as in the development of ATLL among HTLV-1 infected individuals. ATLL can be classified into 4 major subtypes: a smoldering type, a chronic type, a lymphoma type and a leukemic type. The demonstration by Southern blot analysis of the clonal integration of an HTLV-1 provirus in the tumoral cells represents the gold-standard to define biologically ATLL. The survival rate of ATLL patients, especially those who develop the acute leukemic or lymphomas forms, is very poor, and such clonal malignant CD4 expansion remains one of the most severe lymphoproliferations.

  2. Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells

    PubMed Central

    Zhang, Yiqiang; Zhong, Jiang F; Qiu, Hongyu; Robb MacLellan, W.; Marbán, Eduardo; Wang, Charles

    2015-01-01

    It has been believed that mammalian adult cardiomyocytes (ACMs) are terminally-differentiated and are unable to proliferate. Recently, using a bi-transgenic ACM fate mapping mouse model and an in vitro culture system, we demonstrated that adult mouse cardiomyocytes were able to dedifferentiate into cardiac progenitor-like cells (CPCs). However, little is known about the molecular basis of their intrinsic cellular plasticity. Here we integrate single-cell transcriptome and whole-genome DNA methylation analyses to unravel the molecular mechanisms underlying the dedifferentiation and cell cycle reentry of mouse ACMs. Compared to parental cardiomyocytes, dedifferentiated mouse cardiomyocyte-derived CPCs (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlated well with the methylome, our transcriptomic data showed that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. In addition, implantation of mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. Our study demonstrates that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. PMID:26657817

  3. Rat alveolar type I cells proliferate, express OCT-4, and exhibit phenotypic plasticity in vitro.

    PubMed

    Gonzalez, Robert F; Allen, Lennell; Dobbs, Leland G

    2009-12-01

    Alveolar type I (TI) cells are large, squamous cells that cover 95-99% of the internal surface area of the lung. Although TI cells are believed to be terminally differentiated, incapable of either proliferation or phenotypic plasticity, TI cells in vitro both proliferate and express phenotypic markers of other differentiated cell types. Rat TI cells isolated in purities of >99% proliferate in culture, with a sixfold increase in cell number before the cells reach confluence; >50% of the cultured TI cells are Ki67+. At cell densities of 1-2 cells/well, approximately 50% of the cells had the capacity to form colonies. Under the same conditions, type II cells do not proliferate. Cultured TI cells express RTI40 and aquaporin 5, phenotypic markers of the TI cell phenotype. By immunofluorescence, Western blotting, and Q-PCR, TI cells express OCT-4A (POU5F1), a transcription factor associated with maintenance of the pluripotent state in stem cells. Based on the expression patterns of various marker proteins, TI cells are distinct from either of two recently described putative pulmonary multipotent cell populations, the bronchoalveolar stem cell or the OCT-4+ stem/progenitor cell. Although TI cells in adult rat lung tissue do not express either surfactant protein C (SP-C) or CC10, respective markers of the TII and Clara cell phenotypes, in culture TI cells can be induced to express both SP-C and CC10. Together, the findings that TI cells proliferate and exhibit phenotypic plasticity in vitro raise the possibility that TI cells may have similar properties in vivo. PMID:19717550

  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. Writing in a Digital World: Self-Correction While Typing in Younger and Older Adults

    PubMed Central

    Kalman, Yoram M.; Kavé, Gitit; Umanski, Daniil

    2015-01-01

    This study examined how younger and older adults approach simple and complex computerized writing tasks. Nineteen younger adults (age range 21–31, mean age 26.1) and 19 older adults (age range 65–83, mean age 72.1) participated in the study. Typing speed, quantitative measures of outcome and process, and self-corrections were recorded. Younger adults spent a lower share of their time on actual typing, and demonstrated more prevalent use of delete keys than did older adults. Within the older group, there was no correlation between the total time spent on the entire task and the number of corrections, but increased typing speed was related to more errors. The results suggest that the approach to the task was different across age groups, either because of age or because of cohort effects. We discuss the interplay of speed and accuracy with regard to digital writing, and its implications for the design of human-computer interactions. PMID:26473904

  6. Secondary prevention of type 1 diabetes mellitus: stopping immune destruction and promoting beta-cell regeneration.

    PubMed

    Couri, C E B; Foss, M C; Voltarelli, J C

    2006-10-01

    Type 1 diabetes mellitus results from a cell-mediated autoimmune attack against pancreatic beta-cells. Traditional treatments involve numerous daily insulin dosages/injections and rigorous glucose control. Many efforts toward the identification of beta-cell precursors have been made not only with the aim of understanding the physiology of islet regeneration, but also as an alternative way to produce beta-cells to be used in protocols of islet transplantation. In this review, we summarize the most recent studies related to precursor cells implicated in the regeneration process. These include embryonic stem cells, pancreas-derived multipotent precursors, pancreatic ductal cells, hematopoietic stem cells, mesenchymal stem cells, hepatic oval cells, and mature beta-cells. There is controversial evidence of the potential of these cell sources to regenerate beta-cell mass in diabetic patients. However, clinical trials using embryonic stem cells, umbilical cord blood or adult bone marrow stem cells are under way. The results of various immunosuppressive regimens aiming at blocking autoimmunity against pancreatic beta-cells and promoting beta-cell preservation are also analyzed. Most of these regimens provide transient and partial effect on insulin requirements, but new regimens are beginning to be tested. Our own clinical trial combines a high dose immunosuppression with mobilized peripheral blood hematopoietic stem cell transplantation in early-onset type 1 diabetes mellitus.

  7. Mitochondrial DNA heteroplasmy in cloned cattle produced by fetal and adult cell cloning.

    PubMed

    Steinborn, R; Schinogl, P; Zakhartchenko, V; Achmann, R; Schernthaner, W; Stojkovic, M; Wolf, E; Müller, M; Brem, G

    2000-07-01

    Mammals have been cloned from adult donor cells. Here we report the first cases of mitochondrial DNA (mtDNA) heteroplasmy in adult mammalian clones generated from fetal and adult donor cells. The heteroplasmic clones included a healthy cattle equivalent of the sheep Dolly, for which a lack of heteroplasmy was reported.

  8. Mitochondrial DNA heteroplasmy in cloned cattle produced by fetal and adult cell cloning.

    PubMed

    Steinborn, R; Schinogl, P; Zakhartchenko, V; Achmann, R; Schernthaner, W; Stojkovic, M; Wolf, E; Müller, M; Brem, G

    2000-07-01

    Mammals have been cloned from adult donor cells. Here we report the first cases of mitochondrial DNA (mtDNA) heteroplasmy in adult mammalian clones generated from fetal and adult donor cells. The heteroplasmic clones included a healthy cattle equivalent of the sheep Dolly, for which a lack of heteroplasmy was reported. PMID:10888867

  9. Prenatal cocaine exposure alters progenitor cell markers in the subventricular zone of the adult rat brain

    PubMed Central

    Patel, Dhyanesh Arvind; Booze, Rosemarie M.; Mactutus, Charles F.

    2013-01-01

    Long-term consequences of early developmental exposure to drugs of abuse may have deleterious effects on the proliferative plasticity of the brain. The purpose of this study was to examine the long-term effects of prenatal exposure to cocaine, using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, on the proliferative cell types of the subventricular zones (SVZ) in the adult (180 days-old) rat brain. Employing immunocytochemistry, the expression of GFAP+ (type B cells) and nestin+(GFAP−) (Type C and A cells) staining was quantified in the subcallosal area of the SVZ. GFAP+ expression was significantly different between the prenatal cocaine treated group and the vehicle (saline) control group. The prenatal cocaine treated group possessed significantly lower GFAP+ expression relative to the vehicle control group, suggesting that prenatal cocaine exposure significantly reduced the expression of type B neural stem cells of the SVZ. In addition, there was a significant sex difference in nestin+ expression with females showing approximately 8–13% higher nestin+ expression compared to the males. More importantly, a significant prenatal treatment condition (prenatal cocaine, control) by sex interaction in nestin+ expression was confirmed, indicating different effects of cocaine based on sex of the animal. Specifically, prenatal cocaine exposure eliminated the basal difference between the sexes. Collectively, the present findings suggest that prenatal exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, can selectively alter the major proliferative cell types in the subcallosal area of the SVZ in an adult rat brain, and does so differently for males and females. PMID:22119286

  10. Screen printed SIS-type solar cells

    NASA Astrophysics Data System (ADS)

    Avaritsiotis, J. N.; Caroubalos, C.; Campbell, D. S.

    Experimentation was performed on the formation of an SIS junction on n-type monocrystalling Si wafers using thick film techniques and an indium-tin oxide thick film paste. A SiO layer 20 A thick grew on the optically smooth side of monocrystalline wafers during the firing of a screen printed Au back contact. An ITO film 2000 A thick was grown on the oxidized surface and a silver front thick-film grid was fired on the other side. Various firing temperatures were examined to test the effects on the open circuit voltage and the current density. The best samples displayed an open circuit voltage of 293 mV for an illumination of 55-90 mW/sq cm, after which the short circuit current fell off. The best cell efficiencies were less than one, although the performance degraded less than 10 pct in 6 mos.

  11. Alveolar epithelial type I cells contain transport proteins and transport sodium, supporting an active role for type I cells in regulation of lung liquid homeostasis

    PubMed Central

    Johnson, Meshell D.; Widdicombe, Jonathan H.; Allen, Lennell; Barbry, Pascal; Dobbs, Leland G.

    2002-01-01

    Transport of lung liquid is essential for both normal pulmonary physiologic processes and for resolution of pathologic processes. The large internal surface area of the lung is lined by alveolar epithelial type I (TI) and type II (TII) cells; TI cells line >95% of this surface, TII cells <5%. Fluid transport is regulated by ion transport, with water movement following passively. Current concepts are that TII cells are the main sites of ion transport in the lung. TI cells have been thought to provide only passive barrier, rather than active, functions. Because TI cells line most of the internal surface area of the lung, we hypothesized that TI cells could be important in the regulation of lung liquid homeostasis. We measured both Na+ and K+ (Rb+) transport in TI cells isolated from adult rat lungs and compared the results to those of concomitant experiments with isolated TII cells. TI cells take up Na+ in an amiloride-inhibitable fashion, suggesting the presence of Na+ channels; TI cell Na+ uptake, per microgram of protein, is ≈2.5 times that of TII cells. Rb+ uptake in TI cells was ≈3 times that in TII cells and was inhibited by 10−4 M ouabain, the latter observation suggesting that TI cells exhibit Na+-, K+-ATPase activity. By immunocytochemical methods, TI cells contain all three subunits (α, β, and γ) of the epithelial sodium channel ENaC and two subunits of Na+-, K+-ATPase. By Western blot analysis, TI cells contain ≈3 times the amount of αENaC/μg protein of TII cells. Taken together, these studies demonstrate that TI cells not only contain molecular machinery necessary for active ion transport, but also transport ions. These results modify some basic concepts about lung liquid transport, suggesting that TI cells may contribute significantly in maintaining alveolar fluid balance and in resolving airspace edema. PMID:11842214

  12. Arnold-Chiari Type I malformation: a look at two cases in the adult

    PubMed Central

    McArthur, Ross A

    1994-01-01

    This paper reviews the varied presentations of Arnold-Chiari Malformation (ACM) in terms of anatomy, clinical presentation, diagnostic workup, and therapeutic considerations. Emphasis is placed on the Type I condition as it appears in the adult. ACM is a developmental anomaly in which the cerebellar tonsils and portions of the posterior fossa structures herniate through the foramen magnum. It is frequently accompanied by a broad spectrum of additional anatomical variations and can present clinically in a variety of ways. Two cases of ACM Type I in the adult are presented. Both patients were treated initially by conservative measures before MRI could be obtained to establish the diagnosis. Neither one of these patients showed improvement with such a therapeutic regimen. It is important for practitioners to be aware of the varied presentations of ACM in the adult. ImagesFigure 1Figure 2Figure 3

  13. Optimizing Management of Patients with Adult T Cell Leukemia-Lymphoma

    PubMed Central

    Yared, Jean A.; Kimball, Amy S.

    2015-01-01

    Adult T cell leukemia-lymphoma is a rare disease with a high mortality rate, and is challenging for the clinician. Early allogeneic stem cell transplant can confer durable remission. As novel therapeutic agents become available to treat T cell malignancies, it is increasingly important that medical oncologists, hematologists, and hematopathologists recognize and accurately diagnose adult T cell leukemia-lymphoma. There is no uniform standard of treatment of adult T cell leukemia-lymphoma, and clinical trials remain critical to improving outcomes. Here we present one management approach based on the recent advances in treatment for adult T cell leukemia-lymphoma patients. PMID:26610571

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

    PubMed Central

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

    2011-01-01

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

  15. Different cryopreservation requirements in foetal versus adult skin cells from an endangered mammal, the Iberian lynx (Lynx pardinus).

    PubMed

    León-Quinto, Trinidad; Simón, Miguel A; Cadenas, Rafael; Martínez, Africa; Serna, Arturo

    2014-04-01

    Cryobanking somatic foetal cells acquire much relevance in endangered species for biodiversity conservation purposes. Such cells could be later used to reintroduce the lost genes into the breeding pool, by inducing pluripotency and/or nuclear transfer if necessary. Since requirements for preserving foetal cells are not always the same as for adult ones, we evaluated the cryosensitivity of foetal skin cells in comparison with adult ones from the critically endangered Iberian lynx. Responses to cryoinjury were analyzed in both thawed cell types by means of cell viability and functionality (by analyzing their membrane integrity, metabolic activity, glycosaminoglycan content and proliferative activity). Freezing media included the permeating cryoprotectant Me2SO, either alone or along with the non-permeating cryoprotectant sucrose at 0.1 or 0.2M. When Me2SO was the only cryoprotectant, survival rate fell in thawed foetal cells to 54±4% (against 89±6% for thawed adult ones) and both proliferative and metabolic activities remained significantly lower than values for thawed adult cells. However, the combination of sucrose (both 0.1 as 0.2) and Me2SO in foetal cells significantly increased their survival rates (to 71±4% and 73±5%, respectively), proliferative activities (partially at day 7 and completely at day 14 after thawing) and metabolic activities. Our findings clearly show a difference between foetal and adult cells concerning their cryopreservation sensitivity and requirements, as well as their recovery time after thawing. These results are of relevance for the cryopreservation of foetal and adult cells from the Iberian lynx and could be also useful for other mammals.

  16. Abacavir, an anti–HIV-1 drug, targets TDP1-deficient adult T cell leukemia

    PubMed Central

    Tada, Kohei; Kobayashi, Masayuki; Takiuchi, Yoko; Iwai, Fumie; Sakamoto, Takashi; Nagata, Kayoko; Shinohara, Masanobu; Io, Katsuhiro; Shirakawa, Kotaro; Hishizawa, Masakatsu; Shindo, Keisuke; Kadowaki, Norimitsu; Hirota, Kouji; Yamamoto, Junpei; Iwai, Shigenori; Sasanuma, Hiroyuki; Takeda, Shunichi; Takaori-Kondo, Akifumi

    2015-01-01

    Adult T cell leukemia (ATL) is an aggressive T cell malignancy caused by human T cell leukemia virus type 1 (HTLV-1) and has a poor prognosis. We analyzed the cytotoxic effects of various nucleoside analog reverse transcriptase inhibitors (NRTIs) for HIV-1 on ATL cells and found that abacavir potently and selectively kills ATL cells. Although NRTIs have minimal genotoxicities on host cells, the therapeutic concentration of abacavir induced numerous DNA double-strand breaks (DSBs) in the chromosomal DNA of ATL cells. DSBs persisted over time in ATL cells but not in other cell lines, suggesting impaired DNA repair. We found that the reduced expression of tyrosyl-DNA phosphodiesterase 1 (TDP1), a repair enzyme, is attributable to the cytotoxic effect of abacavir on ATL cells. We also showed that TDP1 removes abacavir from DNA ends in vitro. These results suggest a model in which ATL cells with reduced TDP1 expression are unable to excise abacavir incorporated into genomic DNA, leading to irreparable DSBs. On the basis of the above mechanism, we propose abacavir as a promising chemotherapeutic agent for ATL. PMID:26601161

  17. Activation of Type II Cells into Regenerative Stem Cell Antigen-1+ Cells during Alveolar Repair

    PubMed Central

    Kumar, Varsha Suresh; Zhang, Wei; Rehman, Jalees; Malik, Asrar B.

    2015-01-01

    The alveolar epithelium is composed of two cell types: type I cells comprise 95% of the gas exchange surface area, whereas type II cells secrete surfactant, while retaining the ability to convert into type I cells to induce alveolar repair. Using lineage-tracing analyses in the mouse model of Pseudomonas aeruginosa–induced lung injury, we identified a population of stem cell antigen (Sca)-1–expressing type II cells with progenitor cell properties that mediate alveolar repair. These cells were shown to be distinct from previously reported Sca-1–expressing bronchioalveolar stem cells. Microarray and Wnt reporter studies showed that surfactant protein (Sp)-C+Sca-1+ cells expressed Wnt signaling pathway genes, and inhibiting Wnt/β-catenin signaling prevented the regenerative function of Sp-C+Sca-1+ cells in vitro. Thus, P. aeruginosa–mediated lung injury induces the generation of a Sca-1+ subset of type II cells. The progenitor phenotype of the Sp-C+Sca-1+ cells that mediates alveolar epithelial repair might involve Wnt signaling. PMID:25474582

  18. Microarray analysis of gene expression in adult retinal ganglion cells.

    PubMed

    Ivanov, Dmitry; Dvoriantchikova, Galina; Nathanson, Lubov; McKinnon, Stuart J; Shestopalov, Valery I

    2006-01-01

    Retinal ganglion cells (RGCs) transfer visual information to the brain and are known to be susceptible to selective degeneration in various neuropathies such as glaucoma. This selective vulnerability suggests that these highly specialized neurons possess a distinct gene expression profile that becomes altered by neuropathy-associated stresses, which lead to the RGC death. In this study, to identify genes expressed predominantly in adult RGCs, a global transcriptional profile of purified primary RGCs has been compared to that of the whole retina. To avoid alterations of the original gene expression profile by cell culture conditions, we isolated RNA directly from adult RGCs purified by immunopanning without prior sub-cultivation. Genes expressed predominantly in RGCs included: Nrg1, Rgn, 14-3-3 family (Ywhah, Ywhaz, Ywhab), Nrn1, Gap43, Vsnl1, Rgs4. Some of these genes may serve as novel markers for these neurons. Our analysis revealed enrichment in genes controlling the pro-survival pathways in RGCs as compared to other retinal cells. PMID:16376886

  19. Adults Living with Type 2 Diabetes: Kept Personal Health Information Items as Expressions of Need

    ERIC Educational Resources Information Center

    Whetstone, Melinda

    2013-01-01

    This study investigated personal information behavior and information needs that 21 adults managing life with Type 2 diabetes identify explicitly and implicitly during discussions of item acquisition and use of health information items that are kept in their homes. Research drew upon a naturalistic lens, in that semi-structured interviews were…

  20. Volunteering among Older Spanish Adults: Does the Type of Organization Matter?

    ERIC Educational Resources Information Center

    Celdran, Montserrat; Villar, Feliciano

    2007-01-01

    This study in Spain explored three aspects of older adult volunteering (motivations, satisfaction, and perceptions of benefits and drawbacks) and examines to what extent these aspects are influenced by the type of organization and other factors (sociodemographic variables and level of volunteering). The sample consisted of 88 older adults…

  1. Chronic ethanol consumption transiently reduces adult neural progenitor cell proliferation.

    PubMed

    Rice, Ann C; Bullock, M Ross; Shelton, Keith L

    2004-06-11

    Adult neural stem/progenitor cells proliferate throughout the life of the animal in the subependymal zone and the subgranular zone of the dentate gyrus (DG). Treatments such as enriched environment, dietary restriction, running and anti-depressants increase proliferation, however, stress and opiates have been shown to decrease proliferation. While models of binge ethanol drinking decreases proliferation, few studies have characterized the effect chronic ethanol usage has on progenitor cell proliferation. In this study, we have examined changes in the progenitor cell proliferation rate following chronic ethanol consumption. Animals were given a nutritionally balanced liquid diet containing 6.5% v/v ethanol or an isocalorically balanced liquid diet. Bromodeoxyuridine (BrdU) was administered (150 mg/kg x 3) and the animals sacrificed 2 h after the last injection on days 3, 10 or 30 of the ethanol diet. Coronal brain blocks were paraffin embedded and 6 microm sections sliced and immunohistochemically stained for BrdU. Quantitation of the number of BrdU-labeled cells in the subgranular zone of the DG revealed a significant decrease only at the 3-day time-point, with recovery by the 10- and 30-day time-points. Thus, the progenitor cell proliferation rate is transiently decreased by chronic ethanol usage. This data suggests that chronic alcohol use results in a compensatory response that restores the progenitor cell proliferation rate.

  2. Postnatal disappearance of type A intercalated cells in carbonic anhydrase II-deficient mice.

    PubMed

    Brion, L P; Suarez, C; Saenger, P

    2001-06-01

    Despite chronic acidosis, collecting ducts in adult carbonic anhydrase II-deficient (CAD mice) are depleted of intercalated cells, including those of type A, which are acid-secreting cells. We hypothesized that this depletion could occur during postnatal development. Principal cells were identified by immunofluorescence using an antibody to rat aquaporin-2 (AQP-2), and type A intercalated cells using an antibody specific for anion exchanger (AE1). In CAD mice the proportion of AQP2-positive cells, normal at 11 days, increased progressively in the cortical (CCD) and outer medullary collecting duct (OMCD), to reach almost 100% in the OMCD in adults. The percentage of AE1-positive cells in the OMCD of CAD mice decreased by half by 6 weeks of age and further by adulthood. In controls, however, the proportion of AQP2-positive cells and that of AE1-positive cells in the OMCD remained stable after 10 days of age. AE1-positive cells accounted for the majority of intercalated cells in the OMCD. The mechanisms leading to selective postnatal cell depletion in the collecting duct in CAD mice remain to be determined.

  3. The Molecular Profiles of Neural Stem Cell Niche in the Adult Subventricular Zone

    PubMed Central

    Lee, Cheol; Hu, Jingqiong; Ralls, Sherry; Kitamura, Toshio; Loh, Y. Peng; Yang, Yanqin; Mukouyama, Yoh-suke; Ahn, Sohyun

    2012-01-01

    Neural stem cells (NSCs) reside in a unique microenvironment called the neurogenic niche and generate functional new neurons. The neurogenic niche contains several distinct types of cells and interacts with the NSCs in the subventricular zone (SVZ) of the lateral ventricle. While several molecules produced by the niche cells have been identified to regulate adult neurogenesis, a systematic profiling of autocrine/paracrine signaling molecules in the neurogenic regions involved in maintenance, self-renewal, proliferation, and differentiation of NSCs has not been done. We took advantage of the genetic inducible fate mapping system (GIFM) and transgenic mice to isolate the SVZ niche cells including NSCs, transit-amplifying progenitors (TAPs), astrocytes, ependymal cells, and vascular endothelial cells. From the isolated cells and microdissected choroid plexus, we obtained the secretory molecule expression profiling (SMEP) of each cell type using the Signal Sequence Trap method. We identified a total of 151 genes encoding secretory or membrane proteins. In addition, we obtained the potential SMEP of NSCs using cDNA microarray technology. Through the combination of multiple screening approaches, we identified a number of candidate genes with a potential relevance for regulating the NSC behaviors, which provide new insight into the nature of neurogenic niche signals. PMID:23209762

  4. The simplest method for in vitro β-cell production from human adult stem cells.

    PubMed

    Bhandari, Dilli Ram; Seo, Kwang-Won; Sun, Bo; Seo, Min-Soo; Kim, Hyung-Sik; Seo, Yoo-Jin; Marcin, Jurga; Forraz, Nicolas; Roy, Helene Le; Larry, Denner; Colin, McGuckin; Kang, Kyung-Sun

    2011-10-01

    Diabetes mellitus is a challenging autoimmune disease. Biomedical researchers are currently exploring efficient and effective ways to solve this challenge. The potential of stem cell therapies for treating diabetes represents one of the major focuses of current research on diabetes treatment. Here, we have attempted to differentiate adult stem cells from umbilical cord blood-derived mesenchymal cells (UCB-MSC), Wharton's jelly-derived mesenchymal stem cells (WJ-MSC) and amniotic epithelial stem cells (AE-SC) into insulin-producing cells. The serum-free protocol developed in this study resulted in the differentiation of cells into definitive endoderm, pancreatic foregut, pancreatic endoderm and, finally, pancreatic endocrine cells, which expressed the marker genes SOX17, PDX1, NGN3, NKX6.1, INS, GCG, and PPY, respectively. Detection of the expression of the gap junction-related gene connexin-36 (CX36) using RT-PCR provided conclusive evidence for insulin-producing cell differentiation. In addition to this RT-PCR result, insulin and C-peptide protein were detected by immunohistochemistry and ELISA. Glucose stimulation test results showed that significantly greater amounts of C-peptide and insulin were released from differentiated cells than from undifferentiated cells. In conclusion, the methods investigated in this study can be considered an effective and efficient means of obtaining insulin-producing cells from adult stem cells within a week.

  5. Recent advances in the treatment of adult T-cell leukemia-lymphomas

    PubMed Central

    Utsunomiya, Atae; Choi, Ilseung; Chihara, Dai; Seto, Masao

    2015-01-01

    Recent advances in treatment for adult T-cell leukemia-lymphoma (ATL) are reviewed herein. It is currently possible to select a therapeutic strategy for ATL and predict prognosis by classification of patients by clinical subtypes and clinicopathological factors. Although the overall survival (OS) of patients with ATL has increased marginally because of advances in chemotherapy, further prolongation of survival might be difficult with conventional chemotherapy alone. Promising results have been reported for antiviral therapy using zidovudine and interferon-α, and, indeed, antiviral therapy is currently the standard treatment for patients with ATL in western countries. Remarkably, the 5-year OS rates are 100% for both the smoldering-type and chronic-type ATL. Recently, treatments for ATL have included allogeneic hematopoietic stem cell transplantation and molecular targeted therapies. Furthermore, the anti-CCR4 monoclonal antibody mogamulizumab has been shown to have marked cytotoxic effects on ATL cells, especially in the leukemic type of ATL. In the lymphoma type of ATL, the response rate may be improved by combining mogamulizumab with chemotherapy. It should be recognized that prevention of infection from carriers of human T-cell leukemia virus type-I and transfer of the virus from mother to infant are crucial issues for the eradication of ATL. PMID:25613789

  6. T cell subset profile in healthy Zambian adults at the University Teaching Hospital

    PubMed Central

    Chisenga, Caroline Cleopatra; Kelly, Paul

    2016-01-01

    Introduction Symptom-free human immunodeficiency virus antibody-negative Zambian adults (51 subjects, aged 20 to 62 years, 33.3% women and 66.7% men) were studied to establish T cell subset reference ranges. Methods We carried out across sectional study at the University Teaching Hospital, Lusaka. Blood samples were collected from healthy donor volunteers from hospital health care staff, between February and March 2015. Immunopheno typing was undertaken to characterize Tcell subsets using the markers CD3, CD4, CD8, α4β7, Ki67, CD25, CCR7, CD54RA, CD57, CD28, CD27 and HLA-DR. Results Among 51 volunteers, Women had significantly higher absolute CD4 count (median 1042; IQR 864, 1270) than in men (671; 545, 899) (p=0.003). Women also had more CD4 cells expressing homing, naïve, effector and effector memory T cell subsets compared to men. However, in the CD8 population, only the effector cells were significantly different with women expressing more than the males. Conclusion We provide early reference range for T cell subsets in Zambian adults and conclude that among the African women some T cell subsets are higher than men. PMID:27231509

  7. [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.

  8. Telomere-to-centromere ratio of bovine clones, embryos, gametes, fetal cells, and adult cells.

    PubMed

    Meerdo, Lora N; Reed, William A; White, Kenneth L

    2005-01-01

    In 1997, Dolly, the first animal cloned from an adult cell, was born. It was announced in 1999 that Dolly might be aging faster than normal because her telomeres were shorter than age-matched control sheep. Telomeres, a repeated DNA sequence located at the ends of linear chromosomes, allow for base pair loss during DNA replication. Telomere shortening acts as a "mitotic clock," leading to replicative senescence. By using whole cell lysate and slot-blot analysis, we determined the telomere-to-centromere ratio (T/C) for bovine gametes, embryos, fetal tissues (brain, heart, lung, kidney, uterus, ovary, and skin), adult donor cells, and cloned embryos. Our data indicates a consistency in T/C among the various fetal tissues. The T/C of sperm is significantly lower than in oocytes. The T/C decreases from the oocyte to the 2-8-cell stage embryo, increases dramatically at the morula stage, and decreases at the blastocyst stage. Our data shows no significant difference in T/C between cloned embryos and in vitro fertilized (IVF) embryos, but there is a significant difference between cloned embryos and adult donor cells. In conclusion, the enucleated bovine oocyte has the ability to reestablish the telomere length of adult somatic cell donor nuclei. PMID:15996118

  9. The types of endocrine cells in the pancreas of Sunda porcupine (Hystrix javanica)

    PubMed Central

    Budipitojo, Teguh; Fibrianto, Yuda Heru; Mulyani, Guntari Titik

    2016-01-01

    Aim: To identify the types of endocrine cells in the pancreas of the Sunda porcupine (Hystrix javanica) and its immunolocalization. Materials and Methods: Five adult H. javanica were used without sexual distinction. The presences of endocrine cells (glucagon, insulin, somatostatin, and pancreatic polypeptide [PP]) in pancreatic tissues were detected using the avidin-biotin-peroxidase complex method. Results: The fusiform, round, and oval form endocrine cells were detected in the islets of Langerhans and exocrine parts. Most of the insulin cells were found in the central area, glucagon cells were identified in the central and peripheral areas, and somatostatin and PP cells were detected in the mantle area of the islets of Langerhans. Glucagon and somatostatin cells were also detected in smaller numbers of peripheral parts of the islet. In all of the islet parts, glucagon endocrine cells were most prevalent cell type and then, somatostatin, insulin, and PP. In the exocrine parts, PP, somatostatin, glucagon, and insulin endocrine cells were found in the inter-acinus part with moderate, moderate, a few and rare numbers, in that order. In the pancreatic duct, glucagon and somatostatin cells were found between epithelial cells in rare numbers. Conclusion: The pancreas of Sunda porcupine (H. javanica) contains four types of major pancreatic endocrine cells with approximately similar distribution patterns to the other rodents, except for abundant glucagon cells in the peripheral area of the islets of Langerhans. PMID:27397977

  10. Social network types and the health of older adults: exploring reciprocal associations.

    PubMed

    Li, Ting; Zhang, Yanlong

    2015-04-01

    Social network types have been proved to have significant impacts on older population's health outcomes. However, the existing discoveries are still inconsistent, which may be attributed largely to the heterogeneous measures and methods scholars used and to the unidirectional causalities presumed in most research. This study addresses these gaps by using more-refined measures to explore whether the network types have differential impacts on older adults' health outcomes, and whether a reverse causal relationship exists between older adults' health conditions and the network types they adopted. Using data from three recent waves (2005, 2008, and 2012) of the Chinese Longitudinal Healthy Longevity Survey (n = 4190), we constructed four network types using the K-means clustering method (i.e., diverse, friend, family, and restricted), and examined their impacts on a variety of health outcomes (i.e., physical, cognitive, psychological, and overall well-being). Our results demonstrate that there are strong reciprocal associations between these two factors. On the one hand, a diverse network type yielded the most beneficial health outcomes as measured by multiple health indicators, and the friend-focused network type is more beneficial than the family-focused network type in physical outcomes but not in psychological outcomes. On the other hand, we found that a decrease in all health indicators leads to withdrawal from more-beneficial network types such as a diversified network type, and a shift to less-beneficial network types such as family-focused or restricted networks. The understanding of this reciprocal association could encourage programs designed to enhance healthy aging to focus on improving the bridging social capital of older adults so that they can break the vicious cycle between network isolation and poor health conditions.

  11. Identification of Adeno-Associated Viral Vectors That Target Neonatal and Adult Mammalian Inner Ear Cell Subtypes.

    PubMed

    Shu, Yilai; Tao, Yong; Wang, Zhengmin; Tang, Yong; Li, Huawei; Dai, Pu; Gao, Guangping; Chen, Zheng-Yi

    2016-09-01

    The mammalian inner ear consists of diverse cell types with important functions. Gene mutations in these diverse cell types have been found to underlie different forms of genetic hearing loss. Targeting these mutations for gene therapy development represents a future therapeutic strategy to treat hearing loss. Adeno-associated viral (AAV) vectors have become the vector of choice for gene delivery in animal models in vivo. To identify AAV vectors that target inner ear cell subtypes, we systemically screened 12 AAV vectors with different serotypes (AAV1, 2, 5, 6, 6.2, 7, 8, 9, rh.8, rh.10, rh.39, and rh.43) that carry a reporter gene GFP in neonatal and adult mice by microinjection in vivo. We found that most AAVs infect both neonatal and adult inner ear, with different specificities and expression levels. The inner ear cochlear sensory epithelial region, which includes auditory hair cells and supporting cells, is most frequently targeted for gene delivery. Expression of the transgene is sustained, and neonatal inner ear delivery does not adversely affect hearing. Adult inner ear injection of AAV has a similar infection pattern as the younger inner ear, with the exception that outer hair cell death caused by the injection procedure can lead to hearing loss. In the adult, more so than in the neonatal mice, cell types infected and efficiency of infection are correlated with the site of injection. Most infected cells survive in neonatal and adult inner ears. The study adds to the list of AAV vectors that transduce the mammalian inner ear efficiently, providing the tools that are important to study inner ear gene function and for the development of gene therapy to treat hearing loss. PMID:27342665

  12. Type I collagen aging impairs discoidin domain receptor 2-mediated tumor cell growth suppression

    PubMed Central

    Saby, Charles; Buache, Emilie; Brassart-Pasco, Sylvie; El Btaouri, Hassan; Courageot, Marie-Pierre; Van Gulick, Laurence; Garnotel, Roselyne; Jeannesson, Pierre; Morjani, Hamid

    2016-01-01

    Tumor cells are confronted to a type I collagen rich environment which regulates cell proliferation and invasion. Biological aging has been associated with structural changes of type I collagen. Here, we address the effect of collagen aging on cell proliferation in a three-dimensional context (3D). We provide evidence for an inhibitory effect of adult collagen, but not of the old one, on proliferation of human fibrosarcoma HT-1080 cells. This effect involves both the activation of the tyrosine kinase Discoidin Domain Receptor 2 (DDR2) and the tyrosine phosphatase SHP-2. DDR2 and SHP-2 were less activated in old collagen. DDR2 inhibition decreased SHP-2 phosphorylation in adult collagen and increased cell proliferation to a level similar to that observed in old collagen. In the presence of old collagen, a high level of JAK2 and ERK1/2 phosphorylation was observed while expression of the cell cycle negative regulator p21CIP1 was decreased. Inhibition of DDR2 kinase function also led to an increase in ERK1/2 phosphorylation and a decrease in p21CIP1 expression. Similar signaling profile was observed when DDR2 was inhibited in adult collagen. Altogether, these data suggest that biological collagen aging could increase tumor cell proliferation by reducingthe activation of the key matrix sensor DDR2. PMID:27121132

  13. Type I collagen aging impairs discoidin domain receptor 2-mediated tumor cell growth suppression.

    PubMed

    Saby, Charles; Buache, Emilie; Brassart-Pasco, Sylvie; El Btaouri, Hassan; Courageot, Marie-Pierre; Van Gulick, Laurence; Garnotel, Roselyne; Jeannesson, Pierre; Morjani, Hamid

    2016-05-01

    Tumor cells are confronted to a type I collagen rich environment which regulates cell proliferation and invasion. Biological aging has been associated with structural changes of type I collagen. Here, we address the effect of collagen aging on cell proliferation in a three-dimensional context (3D).We provide evidence for an inhibitory effect of adult collagen, but not of the old one, on proliferation of human fibrosarcoma HT-1080 cells. This effect involves both the activation of the tyrosine kinase Discoidin Domain Receptor 2 (DDR2) and the tyrosine phosphatase SHP-2. DDR2 and SHP-2 were less activated in old collagen. DDR2 inhibition decreased SHP-2 phosphorylation in adult collagen and increased cell proliferation to a level similar to that observed in old collagen.In the presence of old collagen, a high level of JAK2 and ERK1/2 phosphorylation was observed while expression of the cell cycle negative regulator p21CIP1 was decreased. Inhibition of DDR2 kinase function also led to an increase in ERK1/2 phosphorylation and a decrease in p21CIP1 expression. Similar signaling profile was observed when DDR2 was inhibited in adult collagen. Altogether, these data suggest that biological collagen aging could increase tumor cell proliferation by reducingthe activation of the key matrix sensor DDR2. PMID:27121132

  14. Alternate protein kinase A activity identifies a unique population of stromal cells in adult bone.

    PubMed

    Tsang, Kit Man; Starost, Matthew F; Nesterova, Maria; Boikos, Sosipatros A; Watkins, Tonya; Almeida, Madson Q; Harran, Michelle; Li, Andrew; Collins, Michael T; Cheadle, Christopher; Mertz, Edward L; Leikin, Sergey; Kirschner, Lawrence S; Robey, Pamela; Stratakis, Constantine A

    2010-05-11

    A population of stromal cells that retains osteogenic capacity in adult bone (adult bone stromal cells or aBSCs) exists and is under intense investigation. Mice heterozygous for a null allele of prkar1a (Prkar1a(+/-)), the primary receptor for cyclic adenosine monophosphate (cAMP) and regulator of protein kinase A (PKA) activity, developed bone lesions that were derived from cAMP-responsive osteogenic cells and resembled fibrous dysplasia (FD). Prkar1a(+/-) mice were crossed with mice that were heterozygous for catalytic subunit Calpha (Prkaca(+/-)), the main PKA activity-mediating molecule, to generate a mouse model with double heterozygosity for prkar1a and prkaca (Prkar1a(+/-)Prkaca(+/-)). Unexpectedly, Prkar1a(+/-)Prkaca(+/-) mice developed a greater number of osseous lesions starting at 3 months of age that varied from the rare chondromas in the long bones and the ubiquitous osteochondrodysplasia of vertebral bodies to the occasional sarcoma in older animals. Cells from these lesions originated from an area proximal to the growth plate, expressed osteogenic cell markers, and showed higher PKA activity that was mostly type II (PKA-II) mediated by an alternate pattern of catalytic subunit expression. Gene expression profiling confirmed a preosteoblastic nature for these cells but also showed a signature that was indicative of mesenchymal-to-epithelial transition and increased Wnt signaling. These studies show that a specific subpopulation of aBSCs can be stimulated in adult bone by alternate PKA and catalytic subunit activity; abnormal proliferation of these cells leads to skeletal lesions that have similarities to human FD and bone tumors. PMID:20421483

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

    PubMed Central

    Schmelzer, Eva; Over, Patrick; Nettleship, Ian; Gerlach, Joerg C.

    2016-01-01

    Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium-based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three-dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale-up of hepatic three-dimensional culture models for regenerative medicine applications. PMID:27403430

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

    PubMed

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

    2016-01-01

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

  17. Development of Adult-Generated Cell Connectivity with Excitatory and Inhibitory Cell Populations in the Hippocampus.

    PubMed

    Restivo, Leonardo; Niibori, Yosuke; Mercaldo, Valentina; Josselyn, Sheena A; Frankland, Paul W

    2015-07-22

    New neurons are generated continuously in the subgranular zone of the hippocampus and integrate into existing hippocampal circuits throughout adulthood. Although the addition of these new neurons may facilitate the formation of new memories, as they integrate, they provide additional excitatory drive to CA3 pyramidal neurons. During development, to maintain homeostasis, new neurons form preferential contacts with local inhibitory circuits. Using retroviral and transgenic approaches to label adult-generated granule cells, we first asked whether a comparable process occurs in the adult hippocampus in mice. Similar to development, we found that, during adulthood, new neurons form connections with inhibitory cells in the dentate gyrus, hilus, and CA3 regions as they integrate into hippocampal circuits. In particular, en passant bouton and filopodia connections with CA3 interneurons peak when adult-generated dentate granule cells (DGCs) are ∼4 weeks of age, a time point when these cells are most excitable. Consistent with this, optical stimulation of 4-week-old (but not 6- or 8-week-old) adult-generated DGCs strongly activated CA3 interneurons. Finally, we found that CA3 interneurons were activated robustly during learning and that their activity was strongly coupled with activity of 4-week-old (but not older) adult-generated DGCs. These data indicate that, as adult-generated neurons integrate into hippocampal circuits, they transiently form strong anatomical, effective, and functional connections with local inhibitory circuits in CA3. Significance statement: New neurons are generated continuously in the subgranular zone of the hippocampus and integrate into existing hippocampal circuits throughout adulthood. Understanding how these cells integrate within well formed circuits will increase our knowledge about the basic principles governing circuit assembly in the adult hippocampus. This study uses a combined connectivity analysis (anatomical, functional, and effective

  18. Conditionally reprogrammed cells represent a stem-like state of adult epithelial cells

    PubMed Central

    Suprynowicz, Frank A.; Upadhyay, Geeta; Krawczyk, Ewa; Kramer, Sarah C.; Hebert, Jess D.; Liu, Xuefeng; Yuan, Hang; Cheluvaraju, Chaitra; Clapp, Phillip W.; Boucher, Richard C.; Kamonjoh, Christopher M.; Randell, Scott H.; Schlegel, Richard

    2012-01-01

    The combination of irradiated fibroblast feeder cells and Rho kinase inhibitor, Y-27632, conditionally induces an indefinite proliferative state in primary mammalian epithelial cells. These conditionally reprogrammed cells (CRCs) are karyotype-stable and nontumorigenic. Because self-renewal is a recognized property of stem cells, we investigated whether Y-27632 and feeder cells induced a stem-like phenotype. We found that CRCs share characteristics of adult stem cells and exhibit up-regulated expression of α6 and β1 integrins, ΔNp63α, CD44, and telomerase reverse transcriptase, as well as decreased Notch signaling and an increased level of nuclear β-catenin. The induction of CRCs is rapid (occurs within 2 d) and results from reprogramming of the entire cell population rather than the selection of a minor subpopulation. CRCs do not overexpress the transcription factor sets characteristic of embryonic or induced pluripotent stem cells (e.g., Sox2, Oct4, Nanog, or Klf4). The induction of CRCs is also reversible, and removal of Y-27632 and feeders allows the cells to differentiate normally. Thus, when CRCs from ectocervical epithelium or tracheal epithelium are placed in an air–liquid interface culture system, the cervical cells form a well differentiated stratified squamous epithelium, whereas the tracheal cells form a ciliated airway epithelium. We discuss the diagnostic and therapeutic opportunities afforded by a method that can generate adult stem-like cells in vitro without genetic manipulation. PMID:23169653

  19. Cell type-specific transcriptome profiling in mammalian brains

    PubMed Central

    LoVerso, Peter R.; Cui, Feng

    2016-01-01

    A mammalian brain contains numerous types of cells. Advances in neuroscience in the past decade allow us to identify and isolate neural cells of interest from mammalian brains. Recent developments in high-throughput technologies, such as microarrays and next-generation sequencing (NGS), provide detailed information on gene expression in pooled cells on a genomic scale. As a result, many novel genes have been found critical in cell type-specific transcriptional regulation. These differentially expressed genes can be used as molecular signatures, unique to a particular class of neural cells. Use of this gene expression-based approach can further differentiate neural cell types into subtypes, potentially linking some of them with neurological diseases. In this article, experimental techniques used to purify neural cells are described, followed by a review on recent microarray- or NGS-based transcriptomic studies of common neural cell types. The future prospects of cell type-specific research are also discussed. PMID:27100485

  20. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells.

    PubMed

    Wakao, Shohei; Kuroda, Yasumasa; Ogura, Fumitaka; Shigemoto, Taeko; Dezawa, Mari

    2012-11-08

    Mesenchymal stem cells (MSCs) are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse) cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine.

  1. Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

    PubMed Central

    Klings, Elizabeth S.; Wyszynski, Diego F.; Nolan, Vikki G.; Steinberg, Martin H.

    2006-01-01

    Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Measurements and Main Results: Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 ± 14.7% predicted) and DlCO (64.5 ± 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DlCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Conclusions: Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function. PMID:16556694

  2. Contribution of Bone Marrow Hematopoietic Stem Cells to Adult Mouse Inner Ear: Mesenchymal Cells and Fibrocytes

    PubMed Central

    Lang, Hainan; Ebihara, Yasuhiro; Schmiedt, Richard A.; Minamiguchi, Hitoshi; Zhou, Daohong; Smythe, Nancy; Liu, Liya; Ogawa, Makio; Schulte, Bradley A.

    2008-01-01

    Bone marrow (BM)-derived stem cells have shown plasticity with a capacity to differentiate into a variety of specialized cells. To test the hypothesis that some cells in the inner ear are derived from BM, we transplanted either isolated whole BM cells or clonally expanded hematopoietic stem cells (HSCs) prepared from transgenic mice expressing enhanced green fluorescent protein (EGFP) into irradiated adult mice. Isolated GFP+ BM cells also were transplanted into conditioned newborn mice derived from pregnant mice injected with busulfan (which ablates HSCs in the newborns). Quantification of GFP+ cells was performed 3-20 months after transplant. GFP+ cells were found in the inner ear with all transplant conditions. They were most abundant within the spiral ligament but were also found in other locations normally occupied by fibrocytes and mesenchymal cells. No GFP+ neurons or hair cells were observed in inner ears of transplanted mice. Dual immunofluorescence assays demonstrated that most of the GFP+ cells were negative for CD45, a macrophage and hematopoietic cell marker. A portion of the GFP+ cells in the spiral ligament expressed immunoreactive Na, K-ATPase or the Na-K-Cl transporter (NKCC), proteins used as markers for specialized ion transport fibrocytes. Phenotypic studies indicated that the GFP+ cells did not arise from fusion of donor cells with endogenous cells. This study provides the first evidence for the origin of inner ear cells from BM and more specifically from HSCs. The results suggest that mesenchymal cells, including fibrocytes in the adult inner ear, may be derived continuously from HSCs. PMID:16538683

  3. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine.

    PubMed

    Caplan, Arnold I

    2007-11-01

    Adult mesenchymal stem cells (MSCs) can be isolated from bone marrow or marrow aspirates and because they are culture-dish adherent, they can be expanded in culture while maintaining their multipotency. The MSCs have been used in preclinical models for tissue engineering of bone, cartilage, muscle, marrow stroma, tendon, fat, and other connective tissues. These tissue-engineered materials show considerable promise for use in rebuilding damaged or diseased mesenchymal tissues. Unanticipated is the realization that the MSCs secrete a large spectrum of bioactive molecules. These molecules are immunosuppressive, especially for T-cells and, thus, allogeneic MSCs can be considered for therapeutic use. In this context, the secreted bioactive molecules provide a regenerative microenvironment for a variety of injured adult tissues to limit the area of damage and to mount a self-regulated regenerative response. This regenerative microenvironment is referred to as trophic activity and, therefore, MSCs appear to be valuable mediators for tissue repair and regeneration. The natural titers of MSCs that are drawn to sites of tissue injury can be augmented by allogeneic MSCs delivered via the bloodstream. Indeed, human clinical trials are now under way to use allogeneic MSCs for treatment of myocardial infarcts, graft-versus-host disease, Crohn's Disease, cartilage and meniscus repair, stroke, and spinal cord injury. This review summarizes the biological basis for the in vivo functioning of MSCs through development and aging. PMID:17620285

  4. Heterogeneity of stromal cells in the human splenic white pulp. Fibroblastic reticulum cells, follicular dendritic cells and a third superficial stromal cell type

    PubMed Central

    Steiniger, Birte S; Wilhelmi, Verena; Seiler, Anja; Lampp, Katrin; Stachniss, Vitus

    2014-01-01

    At least three phenotypically and morphologically distinguishable types of branched stromal cells are revealed in the human splenic white pulp by subtractive immunohistological double-staining. CD271 is expressed in fibroblastic reticulum cells of T-cell zones and in follicular dendritic cells of follicles. In addition, there is a third CD271− and CD271+/− stromal cell population surrounding T-cell zones and follicles. At the surface of follicles the third population consists of individually variable partially overlapping shells of stromal cells exhibiting CD90 (Thy-1), MAdCAM-1, CD105 (endoglin), CD141 (thrombomodulin) and smooth muscle α-actin (SMA) with expression of CD90 characterizing the broadest shell and SMA the smallest. In addition, CXCL12, CXCL13 and CCL21 are also present in third-population stromal cells and/or along fibres. Not only CD27+ and switched B lymphocytes, but also scattered IgD++ B lymphocytes and variable numbers of CD4+ T lymphocytes often occur close to the third stromal cell population or one of its subpopulations at the surface of the follicles. In contrast to human lymph nodes, neither podoplanin nor RANKL (CD254) were detected in adult human splenic white pulp stromal cells. The superficial stromal cells of the human splenic white pulp belong to a widespread cell type, which is also found at the surface of red pulp arterioles surrounded by a mixed T-cell/B-cell population. Superficial white pulp stromal cells differ from fibroblastic reticulum cells and follicular dendritic cells not only in humans, but apparently also in mice and perhaps in rats. However, the phenotype of white pulp stromal cells is species-specific and more heterogeneous than described so far. PMID:24890772

  5. TAp63 prevents premature aging by promoting adult stem cell maintenance

    PubMed Central

    Su, Xiaohua; Paris, Maryline; Gi, Young Jin; Tsai, Kenneth Y.; Cho, Min Soon; Lin, Yu-Li; Biernaskie, Jeffrey A.; Sinha, Satrajit; Prives, Carol; Pevny, Larysa H.; Miller, Freda D.; Flores, Elsa R.

    2012-01-01

    SUMMARY The cellular mechanisms that regulate the maintenance of adult tissue stem cells are still largely unknown. We show here that the p53 family member, TAp63, is essential for maintenance of epidermal and dermal precursors and that, in its absence, these precursors senesce and skin ages prematurely. Specifically, we have developed a TAp63 conditional knockout mouse and used it to ablate TAp63 in the germline (TAp63−/−) or in K14-expressing cells in the basal layer of the epidermis (TAp63fl/fl;K14cre+). TAp63−/− mice age prematurely and develop blisters, skin ulcerations, senescence of hair follicle-associated dermal and epidermal cells, and decreased hair morphogenesis. These phenotypes are likely due to loss of TAp63 in dermal and epidermal precursors since both cell types show defective proliferation, early senescence, and genomic instability. These data indicate that TAp63 serves to maintain adult skin stem cells by regulating cellular senescence and genomic stability, thereby preventing premature tissue aging. PMID:19570515

  6. Regulation of antiviral T cell responses by type I interferons.

    PubMed

    Crouse, Josh; Kalinke, Ulrich; Oxenius, Annette

    2015-04-01

    Type I interferons (IFNs) are pro-inflammatory cytokines that are rapidly induced in different cell types during viral infections. The consequences of type I IFN signalling include direct antiviral activity, innate immune cell activation and regulation of adaptive immune responses. In this Review, we discuss recent conceptual advances in our understanding of indirect and direct regulation of T cell immunity by type I IFNs, which can either promote or inhibit T cell activation, proliferation, differentiation and survival. This regulation depends, to a large extent, on the timing of type I IFN exposure relative to T cell receptor signalling. Type I IFNs also provide activated T cells with resistance to natural killer cell-mediated elimination. PMID:25790790

  7. Screening for coeliac disease in adult patients with type 1 diabetes mellitus: myths, facts and controversy.

    PubMed

    Bakker, Sjoerd F; Tushuizen, Maarten E; von Blomberg, Boudewina M E; Bontkes, Hetty J; Mulder, Chris J; Simsek, Suat

    2016-01-01

    This review aims at summarizing the present knowledge on the clinical consequences of concomitant coeliac disease (CD) in adult patients with type 1 diabetes mellitus (T1DM). The cause of the increased prevalence of CD in T1DM patients is a combination of genetic and environmental factors. Current screening guidelines for CD in adult T1DM patients are not uniform. Based on the current evidence of effects of CD on bone mineral density, diabetic complications, quality of life, morbidity and mortality in patients with T1DM, we advise periodic screening for CD in adult T1DM patients to prevent delay in CD diagnosis and subsequent CD and/or T1DM related complications. PMID:27478507

  8. Type III tibial avulsion fracture with associated anterior cruciate ligament injury: Report of two cases in adults.

    PubMed

    Levy, H J; Fowble, V A

    2001-05-01

    Tibial spine avulsion fractures are more common in children than adults. Many reports have provided classification and treatment options, including fixation for displaced type III fractures. However, long-term follow-up on injury to the anterior cruciate ligament and knee joint stability in adults is not well documented. We present 2 cases of type III tibial avulsion fractures in adults with associated interstitial injury to the anterior cruciate ligament. Primary anterior cruciate ligament reconstruction was performed in both patients.

  9. Pubertal and adult Leydig cell function in Mullerian inhibiting substance-deficient mice.

    PubMed

    Wu, Xiufeng; Arumugam, Ramamani; Baker, Stephen P; Lee, Mary M

    2005-02-01

    Mullerian inhibiting substance (MIS) causes Mullerian duct regression during sexual differentiation and regulates postnatal Leydig cell development. MIS knockout (MIS-KO) mice with targeted deletions of MIS develop Leydig cell hyperplasia, but their circulating androgen concentrations are reportedly unaltered. We compared reproductive hormone profiles, androgen biosynthesis, and the expression of key steroidogenic and metabolic enzymes in MIS-KO and wild-type (WT) mice at puberty (36 d) and sexual maturity (60 d). In pubertal animals, basal testosterone and LH concentrations in plasma were lower in MIS-KO than WT mice, whereas human chorionic gonadotropin-stimulated testosterone concentrations were similar. In adults, basal LH, and both basal and human chorionic gonadotropin (hCG)-stimulated testosterone concentrations were similar. Purified Leydig cells from pubertal MIS-KO mice had lower testosterone but higher androstanediol and androstenedione production rates. In contrast, testosterone, androstanediol, and androstenedione production rates were all lower in adult MIS-KO Leydig cells. Steroidogenic acute regulatory protein expression was lower in pubertal MIS-KO mice compared with WT, whereas 17beta-hydroxy-steroid dehydrogenase and 5alpha-reductase were greater, and P450c17 and P450scc were similar. The expression of steroidogenic acute regulatory protein and 17beta-hydroxysteroid dehydrogenase was lower in adult MIS-KO mice, whereas that of 5alpha-reductase, P450c17, and P450scc was similar. Collectively, these results suggest that in the absence of MIS, Leydig cells remain less differentiated, causing an altered intratesticular androgen milieu that may contribute to the infertility of MIS-KO mice. In immature mice, this deficit in steroidogenic capacity appears to be mediated by a direct loss of MIS action in Leydig cells as well as by indirect effects via the hypothalamic-pituitary-gonadal axis.

  10. Reduced transcription of TCOF1 in adult cells of Treacher Collins syndrome patients

    PubMed Central

    2009-01-01

    Background Treacher Collins syndrome (TCS) is an autosomal dominant craniofacial disorder caused by frameshift deletions or duplications in the TCOF1 gene. These mutations cause premature termination codons, which are predicted to lead to mRNA degradation by nonsense mediated mRNA decay (NMD). Haploinsufficiency of the gene product (treacle) during embryonic development is the proposed molecular mechanism underlying TCS. However, it is still unknown if TCOF1 expression levels are decreased in post-embryonic human cells. Methods We have estimated TCOF1 transcript levels through real time PCR in mRNA obtained from leucocytes and mesenchymal cells of TCS patients (n = 23) and controls (n = 18). Mutational screening and analysis of NMD were performed by direct sequencing of gDNA and cDNA, respectively. Results All the 23 patients had typical clinical features of the syndrome and pathogenic mutations were detected in 19 of them. We demonstrated that the expression level of TCOF1 is 18-31% lower in patients than in controls (p < 0.05), even if we exclude the patients in whom we did not detect the pathogenic mutation. We also observed that the mutant allele is usually less abundant than the wild type one in mesenchymal cells. Conclusions This is the first study to report decreased expression levels of TCOF1 in TCS adult human cells, but it is still unknown if this finding is associated to any phenotype in adulthood. In addition, as we demonstrated that alleles harboring the pathogenic mutations have lower expression, we herein corroborate the current hypothesis of NMD of the mutant transcript as the explanation for diminished levels of TCOF1 expression. Further, considering that TCOF1 deficiency in adult cells could be associated to pathologic clinical findings, it will be important to verify if TCS patients have an impairment in adult stem cell properties, as this can reduce the efficiency of plastic surgery results during rehabilitation of these patients. PMID:20003452

  11. Can thymic epithelial cells be infected by human T-lymphotropic virus type 1?

    PubMed

    Moreira-Ramos, Klaysa; Castro, Flávia Madeira Monteiro de; Linhares-Lacerda, Leandra; Savino, Wilson

    2011-09-01

    The human T-lymphotropic virus type-1 (HTLV-1) is the cause of adult T cell leukaemias/lymphoma. Because thymic epithelial cells (TEC) express recently defined receptors for the virus, it seemed conceivable that these cells might be a target for HTLV-1 infection. We developed an in vitro co-culture system comprising HTLV-1+-infected T cells and human TECs. Infected T cells did adhere to TECs and, after 24 h, the viral proteins gp46 and p19 were observed in TECs. After incubating TECs with culture supernatants from HTLV-1+-infected T cells, we detected gp46 on TEC membranes and the HTLV-1 tax gene integrated in the TEC genome. In conclusion, the human thymic epithelium can be infected in vitro by HTLV-1, not only via cell-cell contact, but also via exposure to virus-containing medium. PMID:22012233

  12. Comparative study of the chondrogenic potential of human bone marrow stromal cells, neonatal chondrocytes and adult chondrocytes

    SciTech Connect

    Saha, Sushmita; Kirkham, Jennifer; Wood, David; Curran, Stephen; Yang, Xuebin

    2010-10-22

    Research highlights: {yields} This study has characterised three different cell types under conditions similar to those used for autologous chondrocyte implantation (ACI) for applications in cartilage repair/regeneration. {yields} Compared for the first time the chondrogenic potential of neonatal chondrocytes with human bone marrow stromal cells (HBMSCs) and adult chondrocytes. {yields} Demonstrated that adult chondrocytes hold greatest potential for use in ACI based on their higher proliferation rates, lower alkaline phosphatise activity and enhanced expression of chondrogenic genes. {yields} Demonstrated the need for chondroinduction as a necessary pre-requisite to efficient chondrogenesis in vitro and, by extrapolation, for cell based therapy (e.g. ACI or cartilage tissue engineering). -- Abstract: Cartilage tissue engineering is still a major clinical challenge with optimisation of a suitable source of cells for cartilage repair/regeneration not yet fully addressed. The aims of this study were to compare and contrast the differences in chondrogenic behaviour between human bone marrow stromal cells (HBMSCs), human neonatal and adult chondrocytes to further our understanding of chondroinduction relative to cell maturity and to identify factors that promote chondrogenesis and maintain functional homoeostasis. Cells were cultured in monolayer in either chondrogenic or basal medium, recapitulating procedures used in existing clinical procedures for cell-based therapies. Cell doubling time, morphology and alkaline phosphatase specific activity (ALPSA) were determined at different time points. Expression of chondrogenic markers (SOX9, ACAN and COL2A1) was compared via real time polymerase chain reaction. Amongst the three cell types studied, HBMSCs had the highest ALPSA in basal culture and lowest ALPSA in chondrogenic media. Neonatal chondrocytes were the most proliferative and adult chondrocytes had the lowest ALPSA in basal media. Gene expression analysis revealed

  13. Comparison of Types of Cell Death: Apoptosis and Necrosis.

    ERIC Educational Resources Information Center

    Manning, Francis; Zuzel, Katherine

    2003-01-01

    Cell death is an essential factor in many biological processes including development. Discusses two types of cell death: (1) necrosis (induced by sodium azide); and (2) apoptosis (induced by sodium chromate). Illustrates key features that differ between these two types of cells death including loss of membrane integrity and internucleosomal DNA…

  14. Physical activity related information sources predict physical activity behaviors in adults with type 2 diabetes.

    PubMed

    Plotnikoff, Ronald C; Johnson, Steven T; Karunamuni, Nandini; Boule, Normand G

    2010-12-01

    Physical activity (PA) is a key management strategy for type 2 diabetes. Despite the known benefits, PA levels are low. Whether the low level of PA is related to lack of knowledge or support is not fully understood. This study was conducted to describe where and how often adults with type 2 diabetes receive and seek information related to PA and examine the relationships between the source and quality of PA information with PA behaviors. A series of questions related to the source and quality of PA information were added to a baseline survey distributed to the participants (N = 244) of the Canadian Aerobic and Resistance Training in Diabetes (CARED) study. Physicians and television were found to be the main sources of PA-related information. In our cross-sectional model, sources of PA-related information other than that from health care professionals explained 14% (p = .05) and 16% (p < .05) of the variance for aerobic-based and resistance training behaviors and 22% (p < .01) and 15% (p < .05) for these behaviors in our longitudinal model. Physical activity (PA)-related information is widely available to adults with type 2 diabetes. Neither the quantity nor the quality of the PA information provided by health care professionals predicted PA behavior. These data provide further insight into the modes with which PA can be promoted to adults with type 2 diabetes. PMID:21170787

  15. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process

    PubMed Central

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix–only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications

  16. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process.

    PubMed

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix-only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications. PMID

  17. Functional Expression of T-Type Ca2+ Channels in Spinal Motoneurons of the Adult Turtle

    PubMed Central

    Canto-Bustos, Martha; Loeza-Alcocer, Emanuel; González-Ramírez, Ricardo; Gandini, María A.; Delgado-Lezama, Rodolfo; Felix, Ricardo

    2014-01-01

    Voltage-gated Ca2+ (CaV) channels are transmembrane proteins comprising three subfamilies named CaV1, CaV2 and CaV3. The CaV3 channel subfamily groups the low-voltage activated Ca2+ channels (LVA or T-type) a significant role in regulating neuronal excitability. CaV3 channel activity may lead to the generation of complex patterns of action potential firing such as the postinhibitory rebound (PIR). In the adult spinal cord, these channels have been found in dorsal horn interneurons where they control physiological events near the resting potential and participate in determining excitability. In motoneurons, CaV3 channels have been found during development, but their functional expression has not yet been reported in adult animals. Here, we show evidence for the presence of CaV3 channel-mediated PIR in motoneurons of the adult turtle spinal cord. Our results indicate that Ni2+ and NNC55-0396, two antagonists of CaV3 channel activity, inhibited PIR in the adult turtle spinal cord. Molecular biology and biochemical assays revealed the expression of the CaV3.1 channel isotype and its localization in motoneurons. Together, these results provide evidence for the expression of CaV3.1 channels in the spinal cord of adult animals and show also that these channels may contribute to determine the excitability of motoneurons. PMID:25255145

  18. Multipotent stem cells in the Malpighian tubules of adult Drosophila melanogaster

    PubMed Central

    Singh, Shree Ram; Hou, Steven X.

    2009-01-01

    Summary Excretion is an essential process of an organism's removal of the waste products of metabolism to maintain a constant chemical composition of the body fluids despite changes in the external environment. Excretion is performed by the kidneys in vertebrates and by Malpighian tubules (MTs) in Drosophila. The kidney serves as an excellent model organ to investigate the cellular and molecular mechanisms underlying organogenesis. Mammals and Drosophila share common principles of renal development. Tissue homeostasis, which is accomplished through self-renewal or differentiation of stem cells, is critical for the maintenance of adult tissues throughout the lifetime of an animal. Growing evidence suggests that stem cell self-renewal and differentiation is controlled by both intrinsic and extrinsic factors. Deregulation of stem cell behavior results in cancer formation, tissue degeneration, and premature aging. The mammalian kidney has a low rate of cellular turnover but has a great capacity for tissue regeneration following an ischemic injury. However, there is an ongoing controversy about the source of regenerating cells in the adult kidney that repopulate injured renal tissues. Recently, we identified multipotent stem cells in the MTs of adult Drosophila and found that these stem cells are able to proliferate and differentiate in several types of cells in MTs. Furthermore, we demonstrated that an autocrine JAK-STAT (Janus kinase–signal transducers and activators of transcription) signaling regulates stem cell self-renewal or differentiation of renal stem cells. The Drosophila MTs provide an excellent in vivo system for studying the renal stem cells at cellular and molecular levels. Understanding the molecular mechanisms governing stem cell self-renewal or differentiation in vivo is not only crucial to using stem cells for future regenerative medicine and gene therapy, but it also will increase our understanding of the mechanisms underlying cancer formation

  19. Naturally Acquired Antibodies against Haemophilus influenzae Type a in Aboriginal Adults, Canada

    PubMed Central

    Nix, Eli B.; Williams, Kylie; Cox, Andrew D.; St. Michael, Frank; Romero-Steiner, Sandra; Schmidt, Daniel S.; McCready, William G.

    2015-01-01

    In the post-Haemophilus influenzae type b (Hib) vaccine era that began in the 1980's, H. influenzae type a (Hia) emerged as a prominent cause of invasive disease in North American Aboriginal populations. To test whether a lack of naturally acquired antibodies may underlie increased rates of invasive Hia disease, we compared serum bactericidal activity against Hia and Hib and IgG and IgM against capsular polysaccharide between Canadian Aboriginal and non-Aboriginal healthy and immunocompromised adults. Both healthy and immunocompromised Aboriginal adults exhibited significantly higher bactericidal antibody titers against Hia than did non-Aboriginal adults (p = 0.042 and 0.045 respectively), with no difference in functional antibody activity against Hib. IgM concentrations against Hia were higher than IgG in most study groups; the inverse was true for antibody concentrations against Hib. Our results indicate that Aboriginal adults possess substantial serum bactericidal activity against Hia that is mostly due to IgM antibodies. The presence of sustained IgM against Hia suggests recent Hia exposure. PMID:25626129

  20. Yoga for Adults with Type 2 Diabetes: A Systematic Review of Controlled Trials

    PubMed Central

    Innes, Kim E.; Selfe, Terry Kit

    2016-01-01

    A growing body of evidence suggests yogic practices may benefit adults with type 2 diabetes (DM2). In this systematic review, we evaluate available evidence from prospective controlled trials regarding the effects of yoga-based programs on specific health outcomes pertinent to DM2 management. To identify qualifying studies, we searched nine databases and scanned bibliographies of relevant review papers and all identified articles. Controlled trials that did not target adults with diabetes, included only adults with type 1 diabetes, were under two-week duration, or did not include quantitative outcome data were excluded. Study quality was evaluated using the PEDro scale. Thirty-three papers reporting findings from 25 controlled trials (13 nonrandomized, 12 randomized) met our inclusion criteria (N = 2170 participants). Collectively, findings suggest that yogic practices may promote significant improvements in several indices of importance in DM2 management, including glycemic control, lipid levels, and body composition. More limited data suggest that yoga may also lower oxidative stress and blood pressure; enhance pulmonary and autonomic function, mood, sleep, and quality of life; and reduce medication use in adults with DM2. However, given the methodological limitations of existing studies, additional high-quality investigations are required to confirm and further elucidate the potential benefits of yoga programs in populations with DM2. PMID:26788520

  1. Yoga for Adults with Type 2 Diabetes: A Systematic Review of Controlled Trials.

    PubMed

    Innes, Kim E; Selfe, Terry Kit

    2016-01-01

    A growing body of evidence suggests yogic practices may benefit adults with type 2 diabetes (DM2). In this systematic review, we evaluate available evidence from prospective controlled trials regarding the effects of yoga-based programs on specific health outcomes pertinent to DM2 management. To identify qualifying studies, we searched nine databases and scanned bibliographies of relevant review papers and all identified articles. Controlled trials that did not target adults with diabetes, included only adults with type 1 diabetes, were under two-week duration, or did not include quantitative outcome data were excluded. Study quality was evaluated using the PEDro scale. Thirty-three papers reporting findings from 25 controlled trials (13 nonrandomized, 12 randomized) met our inclusion criteria (N = 2170 participants). Collectively, findings suggest that yogic practices may promote significant improvements in several indices of importance in DM2 management, including glycemic control, lipid levels, and body composition. More limited data suggest that yoga may also lower oxidative stress and blood pressure; enhance pulmonary and autonomic function, mood, sleep, and quality of life; and reduce medication use in adults with DM2. However, given the methodological limitations of existing studies, additional high-quality investigations are required to confirm and further elucidate the potential benefits of yoga programs in populations with DM2.

  2. Yoga for Adults with Type 2 Diabetes: A Systematic Review of Controlled Trials.

    PubMed

    Innes, Kim E; Selfe, Terry Kit

    2016-01-01

    A growing body of evidence suggests yogic practices may benefit adults with type 2 diabetes (DM2). In this systematic review, we evaluate available evidence from prospective controlled trials regarding the effects of yoga-based programs on specific health outcomes pertinent to DM2 management. To identify qualifying studies, we searched nine databases and scanned bibliographies of relevant review papers and all identified articles. Controlled trials that did not target adults with diabetes, included only adults with type 1 diabetes, were under two-week duration, or did not include quantitative outcome data were excluded. Study quality was evaluated using the PEDro scale. Thirty-three papers reporting findings from 25 controlled trials (13 nonrandomized, 12 randomized) met our inclusion criteria (N = 2170 participants). Collectively, findings suggest that yogic practices may promote significant improvements in several indices of importance in DM2 management, including glycemic control, lipid levels, and body composition. More limited data suggest that yoga may also lower oxidative stress and blood pressure; enhance pulmonary and autonomic function, mood, sleep, and quality of life; and reduce medication use in adults with DM2. However, given the methodological limitations of existing studies, additional high-quality investigations are required to confirm and further elucidate the potential benefits of yoga programs in populations with DM2. PMID:26788520

  3. Adult bone marrow: which stem cells for cellular therapy protocols in neurodegenerative disorders?

    PubMed

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Rogister, Bernard

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy.

  4. Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

    PubMed Central

    West, John D; Dorà, Natalie J; Collinson, J Martin

    2015-01-01

    In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell (LESC) hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient (or transit) amplifying cells (TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell (CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed

  5. Cell-permeable p38 MAP kinase promotes migration of adult neural stem/progenitor cells

    PubMed Central

    Hamanoue, Makoto; Morioka, Kazuhito; Ohsawa, Ikuroh; Ohsawa, Keiko; Kobayashi, Masaaki; Tsuburaya, Kayo; Akasaka, Yoshikiyo; Mikami, Tetsuo; Ogata, Toru; Takamatsu, Ken

    2016-01-01

    Endogenous neural stem/progenitor cells (NPCs) can migrate toward sites of injury, but the migration activity of NPCs is insufficient to regenerate damaged brain tissue. In this study, we showed that p38 MAP kinase (p38) is expressed in doublecortin-positive adult NPCs. Experiments using the p38 inhibitor SB203580 revealed that endogenous p38 participates in NPC migration. To enhance NPC migration, we generated a cell-permeable wild-type p38 protein (PTD-p38WT) in which the HIV protein transduction domain (PTD) was fused to the N-terminus of p38. Treatment with PTD-p38WT significantly promoted the random migration of adult NPCs without affecting cell survival or differentiation; this effect depended on the cell permeability and kinase activity of the fusion protein. These findings indicate that PTD-p38WT is a novel and useful tool for unraveling the roles of p38, and that this protein provides a reasonable approach for regenerating the injured brain by enhancing NPC migration. PMID:27067799

  6. Type and Intensity of Negative Life Events Are Associated With Depression in Adults With Intellectual Disabilities.

    PubMed

    Hove, Oddbjørn; Assmus, Jörg; Havik, Odd E

    2016-09-01

    This study investigated the associations between types and intensity of life events and symptoms of depression among adults with intellectual disabilities. A community sample (N = 593) was screened for current depression and exposure to life events (i.e., loss, illness, change, and bullying) during the previous 12 months. Symptoms of depression were measured using the Psychopathology Checklists for Adults With Intellectual Disabilities. Exposure to three of the four types of life events studied (loss, illness, and bullying) and the intensity of the events were associated with depression, particularly in the cases of loss of relatives and bullying. Quality of care moderated the association between bullying and depression and may buffer the adverse consequences of bullying. PMID:27611352

  7. Identifying Mobility Types in Cognitively Heterogeneous Older Adults Based on GPS-Tracking: What Discriminates Best?

    PubMed

    Wettstein, Markus; Wahl, Hans-Werner; Shoval, Noam; Auslander, Gail; Oswald, Frank; Heinik, Jeremia

    2015-12-01

    Heterogeneity in older adults' mobility and its correlates have rarely been investigated based on objective mobility data and in samples including cognitively impaired individuals. We analyzed mobility profiles within a cognitively heterogeneous sample of N = 257 older adults from Israel and Germany based on GPS tracking technology. Participants were aged between 59 and 91 years (M = 72.9; SD = 6.4) and were either cognitively healthy (CH, n = 146), mildly cognitively impaired (MCI, n = 76), or diagnosed with an early-stage dementia of the Alzheimer's type (DAT, n = 35). Based on cluster analysis, we identified three mobility types ("Mobility restricted," "Outdoor oriented," "Walkers"), which could be predicted based on socio-demographic indicators, activity, health, and cognitive impairment status using discriminant analysis. Particularly demented individuals and persons with worse health exhibited restrictions in mobility. Our findings contribute to a better understanding of heterogeneity in mobility in old age.

  8. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits.

    PubMed

    Dennie, Donnahue; Louboutin, Jean-Pierre; Strayer, David S

    2016-04-26

    Neurogenesis takes place in the adult mammalian brain in three areas: Subgranular zone of the dentate gyrus (DG); subventricular zone of the lateral ventricle; olfactory bulb. Different molecular markers can be used to characterize the cells involved in adult neurogenesis. It has been recently suggested that a population of bone marrow (BM) progenitor cells may migrate to the brain and differentiate into neuronal lineage. To explore this hypothesis, we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells. Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells, then after several months in mature neurons and microglial cells, and thus without central nervous system (CNS) lesion. Most of transgene-expressing cells expressed NeuN, a marker of mature neurons. Thus, BM-derived cells may function as progenitors of CNS cells in adult animals. The mechanism by which the cells from the BM come to be neurons remains to be determined. Although the observed gradual increase in transgene-expressing neurons over 16 mo suggests that the pathway involved differentiation of BM-resident cells into neurons, cell fusion as the principal route cannot be totally ruled out. Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons. Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector. In addition to cells expressing markers of mature neurons, transgene-positive cells were also positive for nestin and doublecortin, molecules expressed by developing neuronal cells. These cells were actively proliferating, as shown by short term BrdU incorporation studies. Inducing seizures by using kainic acid increased the number of BM progenitor cells

  9. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits

    PubMed Central

    Dennie, Donnahue; Louboutin, Jean-Pierre; Strayer, David S

    2016-01-01

    Neurogenesis takes place in the adult mammalian brain in three areas: Subgranular zone of the dentate gyrus (DG); subventricular zone of the lateral ventricle; olfactory bulb. Different molecular markers can be used to characterize the cells involved in adult neurogenesis. It has been recently suggested that a population of bone marrow (BM) progenitor cells may migrate to the brain and differentiate into neuronal lineage. To explore this hypothesis, we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells. Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells, then after several months in mature neurons and microglial cells, and thus without central nervous system (CNS) lesion. Most of transgene-expressing cells expressed NeuN, a marker of mature neurons. Thus, BM-derived cells may function as progenitors of CNS cells in adult animals. The mechanism by which the cells from the BM come to be neurons remains to be determined. Although the observed gradual increase in transgene-expressing neurons over 16 mo suggests that the pathway involved differentiation of BM-resident cells into neurons, cell fusion as the principal route cannot be totally ruled out. Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons. Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector. In addition to cells expressing markers of mature neurons, transgene-positive cells were also positive for nestin and doublecortin, molecules expressed by developing neuronal cells. These cells were actively proliferating, as shown by short term BrdU incorporation studies. Inducing seizures by using kainic acid increased the number of BM progenitor cells

  10. Sex-typed personality traits and gender identity as predictors of young adults' career interests.

    PubMed

    Dinella, Lisa M; Fulcher, Megan; Weisgram, Erica S

    2014-04-01

    Gender segregation of careers is still prominent in the U.S. workforce. The current study was designed to investigate the role of sex-typed personality traits and gender identity in predicting emerging adults' interests in sex-typed careers. Participants included 586 university students (185 males, 401 females). Participants reported their sex-typed personality traits (masculine and feminine traits), gender identities (gender typicality, contentment, felt pressure to conform, and intergroup bias), and interests in sex-typed careers. Results indicated both sex-typed personality traits and gender identity were important predictors of young adults' career interests, but in varying degrees and differentially for men and women. Men's sex-typed personality traits and gender typicality were predictive of their masculine career interests even more so when the interaction of their masculine traits and gender typicality were considered. When gender typicality and sex-typed personality traits were considered simultaneously, gender typicality was negatively related to men's feminine career interests and gender typicality was the only significant predictor of men's feminine career interests. For women, sex-typed personality traits and gender typicality were predictive of their sex-typed career interests. The level of pressure they felt to conform to their gender also positively predicted interest in feminine careers. The interaction of sex-typed personality traits and gender typicality did not predict women's career interests more than when these variables were considered as main effects. Results of the multidimensional assessment of gender identity confirmed that various dimensions of gender identity played different roles in predicting career interests and gender typicality was the strongest predictor of career interests.

  11. Feasibility Study of a Bio-inspired Artificial Pancreas in Adults with Type 1 Diabetes

    PubMed Central

    Herrero, Pau; El Sharkawy, Mohamed; Pesl, Peter; Jugnee, Narvada; Thomson, Hazel; Pavitt, Darrell; Toumazou, Christofer; Johnston, Desmond; Georgiou, Pantelis; Oliver, Nick

    2014-01-01

    Abstract Background: This study assesses proof of concept and safety of a novel bio-inspired artificial pancreas (BiAP) system in adults with type 1 diabetes during fasting, overnight, and postprandial conditions. In contrast to existing glucose controllers in artificial pancreas systems, the BiAP uses a control algorithm based on a mathematical model of β-cell physiology. The algorithm is implemented on a miniature silicon microchip within a portable hand-held device that interfaces the components of the artificial pancreas. Materials and Methods: In this nonrandomized open-label study each subject attended for a 6-h fasting study followed by a 13-h overnight and post-breakfast study on a separate occasion. During both study sessions the BiAP system was used, and microboluses of insulin were recommended every 5 min by the control algorithm according to subcutaneous sensor glucose levels. The primary outcome was percentage time spent in the glucose target range (3.9–10.0 mmol/L). Results: Twenty subjects (55% male; mean [SD] age, 44 [10] years; duration of diabetes, 22 [12] years; glycosylated hemoglobin, 7.4% [0.7%] [57 (7) mmol/mol]; body mass index, 25 [4] kg/m2) participated in the fasting study, and the median (interquartile range) percentage time in target range was 98.0% (90.8–100.0%). Seventeen of these subjects then participated in the overnight/postprandial study, where 70.7% (63.9–77.4%) of time was spent in the target range and, reassuringly, 0.0% (0.0–2.3%) of time was spent in hypoglycemia (<3.9 mmol/L). Conclusions: The BiAP achieves safe glycemic control during fasting, overnight, and postprandial conditions. PMID:24801544

  12. Neuronal cell types and connectivity: lessons from the retina

    PubMed Central

    Seung, H. Sebastian; Sümbül, Uygar

    2014-01-01

    We describe recent progress towards defining neuronal cell types in the mouse retina, and attempt to extract lessons that may be generally useful in the mammalian brain. Achieving a comprehensive catalog of retinal cell types now appears within reach, because researchers have achieved consensus concerning two fundamental challenges. The first is accuracy—defining pure cell types rather than settling for neuronal classes that are mixtures of types. The second is completeness—developing methods guaranteed to eventually identify all cell types, as well as criteria for determining when all types have been found. Case studies illustrate how these two challenges are handled by combining state-of-the-art molecular, anatomical and physiological techniques. Progress is also being made in observing and modeling connectivity between cell types. Scaling up to larger brain regions, such as the cortex, will require not only technical advances but careful consideration of the challenges of accuracy and completeness. PMID:25233310

  13. Neonatal infection with neurotropic influenza A virus affects working memory and expression of type III Nrg1 in adult mice.

    PubMed

    Asp, Linnéa; Beraki, Simret; Kristensson, Krister; Ogren, Sven Ove; Karlsson, Håkan

    2009-08-01

    Epidemiological studies suggest that early life infections may contribute to the development of psychiatric disorders characterized by cognitive deficits. Here, we studied the effects of a neonatal influenza A/WSN/33 virus infection on locomotor activity, working memory and emotional behavior in adult mice. In addition to wild type mice, immunodeficient (Tap1(-/-)) mice lacking functional CD8(+) T cells, were included in the study to model the potential influence of a genetic deficit relating to virus clearance. Three to four months after the infection, infected Tap1(-/-) mice, but not wild type mice, exhibited deficits in working memory as well as increased rearing activity and anxiety. In the medial prefrontal cortices of these infected Tap1(-/-) mice reduced levels of type III Nrg1 transcripts were observed supporting a role for neuregulin 1 signaling in neuronal circuits involved in working memory. Virus replication, distribution or clearance did not differ between the two genotypes. The lack of CD8(+) T cells, however, appeared to contribute to a more pronounced glia response in Tap1(-/-) than in wild type mice. Thus, the present study suggest that the risk of developing deficits in cognitive and emotional behavior following a CNS infection during brain development is influenced by genetic variation in genes involved in the immune response.

  14. Morphologic evidence for differentiation of pinealocytes from photoreceptor cells in the adult noctule bat (Nyctalus noctula, Schreber).

    PubMed

    Pevet, P; Ariëns Kappers, J; Voûte, A M

    1977-07-26

    An electron microscopical investigation of the pineal gland of the adult noctule bat revealed the presence of some peculiar ciliary derivatives, similar to the club-shaped outer segment of rudimentary photoreceptor cells in the pineal organ of nonmammalian vertebrates. The pinealocytes of population I can be classified in several morphological types, one of them displaying morphological features resembling those of rudimentary photoreceptor cells. These results reconfirm the concept of the sensory cell line in the vertebrate pineal organ. The question whether the pinealocytes of population II belong to the same sensory cell line is discussed.

  15. Label-Retaining Cells in the Adult Murine Salivary Glands Possess Characteristics of Adult Progenitor Cells

    PubMed Central

    Chibly, Alejandro M.; Querin, Lauren; Harris, Zoey; Limesand, Kirsten H.

    2014-01-01

    Radiotherapy is the primary treatment for patients with head and neck cancer, which account for roughly 500,000 annual cases worldwide. Dysfunction of the salivary glands and associated conditions like xerostomia and dysphagia are often developed by these patients, greatly diminishing their life quality. Current preventative and palliative care fail to deliver an improvement in the quality of life, thus accentuating the need for regenerative therapies. In this study, a model of label retaining cells (LRCs) in murine salivary glands was developed, in which LRCs demonstrated proliferative potential and possessed markers of putative salivary progenitors. Mice were labeled with 5-Ethynyl-2′-deoxyuridine (EdU) at postnatal day 10 and chased for 8 weeks. Tissue sections from salivary glands obtained at the end of chase demonstrated co-localization between LRCs and the salivary progenitor markers keratin 5 and keratin 14, as well as kit mRNA, indicating that LRCs encompass a heterogeneous population of salivary progenitors. Proliferative potential of LRCs was demonstrated by a sphere assay, in which LRCs were found in primary and secondary spheres and they co-localized with the proliferation marker Ki67 throughout sphere formation. Surprisingly, LRCs were shown to be radio-resistant and evade apoptosis following radiation treatment. The clinical significance of these findings lie in the potential of this model to study the mechanisms that prevent salivary progenitors from maintaining homeostasis upon exposure to radiation, which will in turn facilitate the development of regenerative therapies for salivary gland dysfunction. PMID:25238060

  16. Label-retaining cells in the adult murine salivary glands possess characteristics of adult progenitor cells.

    PubMed

    Chibly, Alejandro M; Querin, Lauren; Harris, Zoey; Limesand, Kirsten H

    2014-01-01

    Radiotherapy is the primary treatment for patients with head and neck cancer, which account for roughly 500,000 annual cases worldwide. Dysfunction of the salivary glands and associated conditions like xerostomia and dysphagia are often developed by these patients, greatly diminishing their life quality. Current preventative and palliative care fail to deliver an improvement in the quality of life, thus accentuating the need for regenerative therapies. In this study, a model of label retaining cells (LRCs) in murine salivary glands was developed, in which LRCs demonstrated proliferative potential and possessed markers of putative salivary progenitors. Mice were labeled with 5-Ethynyl-2'-deoxyuridine (EdU) at postnatal day 10 and chased for 8 weeks. Tissue sections from salivary glands obtained at the end of chase demonstrated co-localization between LRCs and the salivary progenitor markers keratin 5 and keratin 14, as well as kit mRNA, indicating that LRCs encompass a heterogeneous population of salivary progenitors. Proliferative potential of LRCs was demonstrated by a sphere assay, in which LRCs were found in primary and secondary spheres and they co-localized with the proliferation marker Ki67 throughout sphere formation. Surprisingly, LRCs were shown to be radio-resistant and evade apoptosis following radiation treatment. The clinical significance of these findings lie in the potential of this model to study the mechanisms that prevent salivary progenitors from maintaining homeostasis upon exposure to radiation, which will in turn facilitate the development of regenerative therapies for salivary gland dysfunction.

  17. Characterizing Newly Repopulated Microglia in the Adult Mouse: Impacts on Animal Behavior, Cell Morphology, and Neuroinflammation

    PubMed Central

    Elmore, Monica R. P.; Lee, Rafael J.; West, Brian L.; Green, Kim N.

    2015-01-01

    Microglia are the primary immune cell in the brain and are postulated to play important roles outside of immunity. Administration of the dual colony-stimulating factor 1 receptor (CSF1R)/c-Kit kinase inhibitor, PLX3397, to adult mice results in the elimination of ~99% of microglia, which remain eliminated for as long as treatment continues. Upon removal of the inhibitor, microglia rapidly repopulate the entire adult brain, stemming from a central nervous system (CNS) resident progenitor cell. Using this method of microglial elimination and repopulation, the role of microglia in both healthy and diseased states can be explored. Here, we examine the responsiveness of newly repopulated microglia to an inflammatory stimulus, as well as determine the impact of these cells on behavior, cognition, and neuroinflammation. Two month-old wild-type mice were placed on either control or PLX3397 diet for 21 d to eliminate microglia. PLX3397 diet was then removed in a subset of animals to allow microglia to repopulate and behavioral testing conducted beginning at 14 d repopulation. Finally, inflammatory profiling of the microglia-repopulated brain in response to lipopolysaccharide (LPS; 0.25 mg/kg) or phosphate buffered saline (PBS) was determined 21 d after inhibitor removal using quantitative real time polymerase chain reaction (RT-PCR), as well as detailed analyses of microglial morphologies. We find mice with repopulated microglia to perform similarly to controls by measures of behavior, cognition, and motor function. Compared to control/resident microglia, repopulated microglia had larger cell bodies and less complex branching in their processes, which resolved over time after inhibitor removal. Inflammatory profiling revealed that the mRNA gene expression of repopulated microglia was similar to normal resident microglia and that these new cells appear functional and responsive to LPS. Overall, these data demonstrate that newly repopulated microglia function similarly to the

  18. Characterizing newly repopulated microglia in the adult mouse: impacts on animal behavior, cell morphology, and neuroinflammation.

    PubMed

    Elmore, Monica R P; Lee, Rafael J; West, Brian L; Green, Kim N

    2015-01-01

    Microglia are the primary immune cell in the brain and are postulated to play important roles outside of immunity. Administration of the dual colony-stimulating factor 1 receptor (CSF1R)/c-Kit kinase inhibitor, PLX3397, to adult mice results in the elimination of ~99% of microglia, which remain eliminated for as long as treatment continues. Upon removal of the inhibitor, microglia rapidly repopulate the entire adult brain, stemming from a central nervous system (CNS) resident progenitor cell. Using this method of microglial elimination and repopulation, the role of microglia in both healthy and diseased states can be explored. Here, we examine the responsiveness of newly repopulated microglia to an inflammatory stimulus, as well as determine the impact of these cells on behavior, cognition, and neuroinflammation. Two month-old wild-type mice were placed on either control or PLX3397 diet for 21 d to eliminate microglia. PLX3397 diet was then removed in a subset of animals to allow microglia to repopulate and behavioral testing conducted beginning at 14 d repopulation. Finally, inflammatory profiling of the microglia-repopulated brain in response to lipopolysaccharide (LPS; 0.25 mg/kg) or phosphate buffered saline (PBS) was determined 21 d after inhibitor removal using quantitative real time polymerase chain reaction (RT-PCR), as well as detailed analyses of microglial morphologies. We find mice with repopulated microglia to perform similarly to controls by measures of behavior, cognition, and motor function. Compared to control/resident microglia, repopulated microglia had larger cell bodies and less complex branching in their processes, which resolved over time after inhibitor removal. Inflammatory profiling revealed that the mRNA gene expression of repopulated microglia was similar to normal resident microglia and that these new cells appear functional and responsive to LPS. Overall, these data demonstrate that newly repopulated microglia function similarly to the

  19. Reduced physical activity in adults at risk for type 2 diabetes who curtail their sleep

    PubMed Central

    Booth, J.N.; Bromley, L.E.; Darukhanavala, A.P.; Whitmore, H.R.; Imperial, J.G.; Penev, P.D.

    2011-01-01

    Adults with parental history of type 2 diabetes have high metabolic morbidity, which is exacerbated by physical inactivity. Self-reported sleep <6 h/day is associated with increased incidence of obesity and diabetes, which may be mediated in part by sleep-loss-related reduction in physical activity. We examined the relationship between habitual sleep curtailment and physical activity in adults with parental history of type 2 diabetes. Forty-eight young urban adults with parental history of type 2 diabetes (27F/21M; mean [SD] age 26 [4] y; BMI 23.8 [2.5] kg/m2) each completed 13 [2] days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Laboratory polysomnography was used to screen for sleep disorders. The primary outcome of the study was the comparison of total daily activity counts between participants with habitual sleep <6 vs. ≥6 h/night. Secondary measures included daily time spent sedentary and in light, moderate, and vigorous physical activity. Short sleepers had no sleep abnormalities and showed signs of increased sleep pressure consistent with a behavioral pattern of habitual sleep curtailment. Compared to participants who slept ≥6 h/night, short sleepers had 27% fewer daily activity counts (P=0.042), spent less time in moderate-plus-vigorous physical activity (−43 min/day; P=0.010), and remained more sedentary (+69 min/day; P=0.026). Our results indicate that young urban adults with parental history of type 2 diabetes who habitually curtail their sleep have less daily physical activity and more sedentary living, which may enhance their metabolic risk. PMID:21996665

  20. Topography of Purkinje cells and other calbindin-immunoreactive cells within adult and hatchling turtle cerebellum.

    PubMed

    Ariel, Michael; Ward, Kyle C; Tolbert, Daniel L

    2009-12-01

    The turtle's cerebellum (Cb) is an unfoliated sheet, so the topography of its entire cortex can be easily studied physiologically by optical recordings. However, unlike the mammalian Cb, little is known about the topography of turtle Purkinje cells (PCs). Here, topography was examined using calbindin-D(28K) immunohistochemistry of adult and hatchling turtles (Trachemys scripta elegans, 2.5-15 cm carapace length). Each Cb was flattened between two Sylgard sheets and fixed in paraformaldehyde. Sections (52 microm thick) were cut parallel to the flattened cortex (tangential), resulting in calbindin-immunolabeled PCs being localized to three to six sections for each turtle. PC position and size were quantified using Neurolucida Image Analysis system. Although hatchling Cb were medial-laterally narrower (3.0 vs. 6.5 mm) and rostral-caudally shorter (2.5 vs. 5.5 mm) than adult Cb, both averaged near 15,000 PCs distributed uniformly. Hatchling PCs were smaller than adult PCs (178 vs. 551 microm(2)) and more densely packed (2,180 vs. 625 cells/mm(2)). Calbindin immunoreactivity also labeled non-PCs along the Cb's marginal rim and its caudal pole. Many of these were very small (22.9 microm(2)) ovoid-shaped cells clustered together, possibly proliferating external granule layer cells. Other labeled cells were larger and fusiform-shaped (12.6 x 33.4 microm) adjacent to inner granule cells along the marginal rim, suggestive of migrating cells. It is not known whether these are new neurons being generated within the adult and hatchling Cb and if they connect to efferent and afferent paths. Based on these anatomical findings, we suggest that unique physiological features may exist along the rim of the turtle Cb.

  1. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    SciTech Connect

    Kheradmand, Arash; Dezfoulian, Omid; Alirezaei, Masoud; Rasoulian, Bahram

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  2. Severe adult malaria is associated with specific PfEMP1 adhesion types and high parasite biomass

    PubMed Central

    Bernabeu, Maria; Danziger, Samuel A.; Avril, Marion; Vaz, Marina; Babar, Prasad H.; Brazier, Andrew J.; Herricks, Thurston; Maki, Jennifer N.; Pereira, Ligia; Mascarenhas, Anjali; Gomes, Edwin; Chery, Laura; Aitchison, John D.; Rathod, Pradipsinh K.; Smith, Joseph D.

    2016-01-01

    The interplay between cellular and molecular determinants that lead to severe malaria in adults is unexplored. Here, we analyzed parasite virulence factors in an infected adult population in India and investigated whether severe malaria isolates impair endothelial protein C receptor (EPCR), a protein involved in coagulation and endothelial barrier permeability. Severe malaria isolates overexpressed specific members of the Plasmodium falciparum var gene/PfEMP1 (P. falciparum erythrocyte membrane protein 1) family that bind EPCR, including DC8 var genes that have previously been linked to severe pediatric malaria. Machine learning analysis revealed that DC6- and DC8-encoding var transcripts in combination with high parasite biomass were the strongest indicators of patient hospitalization and disease severity. We found that DC8 CIDRα1 domains from severe malaria isolates had substantial differences in EPCR binding affinity and blockade activity for its ligand activated protein C. Additionally, even a low level of inhibition exhibited by domains from two cerebral malaria isolates was sufficient to interfere with activated protein C-barrier protective activities in human brain endothelial cells. Our findings demonstrate an interplay between parasite biomass and specific PfEMP1 adhesion types in the development of adult severe malaria, and indicate that low impairment of EPCR function may contribute to parasite virulence. PMID:27185931

  3. Embryonic and adult stem cells as a source for cell therapy in Parkinson's disease.

    PubMed

    Levy, Yossef S; Stroomza, Merav; Melamed, Eldad; Offen, Daniel

    2004-01-01

    The rationale behind the use of cells as therapeutic modalities for neurodegenerative diseases in general, and in Parkinson's disease (PD) in particular, is that they will improve patient's functioning by replacing the damaged cell population. It is reasoned that these cells will survive, grow neurites, establish functional synapses, integrate best and durably with the host tissue mainly in the striatum, renew the impaired wiring, and lead to meaningful clinical improvement. To increase the generation of dopamine, researchers have already transplanted non-neuronal cells, without any genetic manipulation or after introduction of genes such as tyrosine hydroxylase, in animal models of PD. Because these cells were not of neuronal origin, they developed without control, did not integrate well into the brain parenchyma, and their survival rates were low. Clinical experiments using cell transplantation as a therapy for PD have been conducted since the 1980s. Most of these experiments used fetal dopaminergic cells originating in the ventral mesencephalic tissue obtained from fetuses. Although it was shown that the transplanted cells survived and some patients benefited from this treatment, others suffered from severe dyskinesia, probably caused by the graft's excessive and uncontrolled production and release of dopamine. It is now recognized that cell-replacement strategy will be effective in PD only if the transplanted cells have the same abilities, such as dopamine synthesis and control release, reuptake, and metabolizing dopamine, as the original dopaminergic neurons. Recent studies on embryonic and adult stem cells have demonstrated that cells are able to both self-renew and produce differentiated tissues, including dopaminergic neurons. These new methods offer real hope for tissue replacement in a wide range of diseases, especially PD. In this review we summarize the evidence of dopaminergic neuron generation from embryonic and adult stem cells, and discuss their

  4. Social cognitive theory correlates of moderate-intensity exercise among adults with type 2 diabetes.

    PubMed

    Heiss, Valerie J; Petosa, R L

    2016-01-01

    The purpose of this study was to identify social cognitive theory (SCT) correlates of moderate- to vigorous-intensity exercise (MVPA) among adults with type 2 diabetes. Adults with type 2 diabetes (N = 181) participated in the study. Participants were recruited through ResearchMatch.org to complete an online survey. The survey used previously validated instruments to measure dimensions of self-efficacy, self-regulation, social support, outcome expectations, the physical environment, and minutes of MVPA per week. Spearman Rank Correlations were used to determine the relationship between SCT variables and MVPA. Classification and Regression Analysis using a decision tree model was used to determine the amount of variance in MVPA explained by SCT variables. Due to low levels of vigorous activity, only moderate-intensity exercise (MIE) was analyzed. SCT variables explained 42.4% of the variance in MIE. Self-monitoring, social support from family, social support from friends, and self-evaluative outcome expectations all contributed to the variability in MIE. Other contributing variables included self-reward, task self-efficacy, social outcome expectations, overcoming barriers, and self-efficacy for making time for exercise. SCT is a useful theory for identifying correlates of MIE among adults with type 2 diabetes. The SCT correlates can be used to refine diabetes education programs to target the adoption and maintenance of regular exercise.

  5. Quantification of HIV-based lentiviral vectors: influence of several cell type parameters on vector infectivity.

    PubMed

    Gay, Virginie; Moreau, Karen; Hong, Saw-See; Ronfort, Corinne

    2012-02-01

    A human immunodeficiency virus type (HIV-1)-based lentiviral vector pseudotyped with the vesicular stomatitis virus envelope glycoprotein and encoding the GFP reporter gene was used to evaluate different methods of lentiviral vector titration. GFP expression, viral DNA quantification and the efficiency of vector DNA integration were assayed after infection of conventional HIV-1-permissive cell lines and human primary adult fibroblasts with the vector. We found that vector titers based on GFP expression determined by flow cytometry may vary by more than 50-fold depending on the cell type and the promoter-cell combination used. Interestingly, we observed that the viral integration process in primary HDFa cells was significantly more efficient compared to that in SupT1 or 293T cells. We propose that determination of the amount of integrated viral DNA by quantitative PCR be used in combination with the reporter gene expression assay.

  6. Star cell type core configuration for structural sandwich materials

    DOEpatents

    Christensen, Richard M.

    1995-01-01

    A new pattern for cellular core material used in sandwich type structural materials. The new pattern involves star shaped cells intermixed with hexagonal shaped cells. The new patterned cellular core material includes star shaped cells interconnected at points thereof and having hexagonal shape cells positioned adjacent the star points. The new pattern allows more flexibility and can conform more easily to curved shapes.

  7. Freedom of expression: cell-type-specific gene profiling.

    PubMed

    Otsuki, Leo; Cheetham, Seth W; Brand, Andrea H

    2014-01-01

    Cell fate and behavior are results of differential gene regulation, making techniques to profile gene expression in specific cell types highly desirable. Many methods now enable investigation at the DNA, RNA and protein level. This review introduces the most recent and popular techniques, and discusses key issues influencing the choice between these such as ease, cost and applicability of information gained. Interdisciplinary collaborations will no doubt contribute further advances, including not just in single cell type but single-cell expression profiling.

  8. Early postnatal GFAP-expressing cells produce multilineage progeny in cerebrum and astrocytes in cerebellum of adult mice.

    PubMed

    Guo, Zhibao; Wang, Xijuan; Xiao, Jun; Wang, Yihui; Lu, Hong; Teng, Junfang; Wang, Wei

    2013-09-26

    Early postnatal GFAP-expressing cells are thought to be immature astrocytes. However, it is not clear if they possess multilineage capacity and if they can generate different lineages (astrocytes, neurons and oligodendrocytes) in the brain of adult mice. In order to identify the fate of astroglial cells in the postnatal brain, hGFAP-Cre-ER(T2) transgenic mice were crossed with the R26R Cre reporter mouse strains which exhibit constitutive expression of β-galactosidase (β-gal). Mice carrying the hGFAP-Cre-ER(T2)/R26R transgene were treated with Tamoxifen to induce Cre recombination in astroglial cells at postnatal (P) day 6 and Cre recombinase-expressing cells were identified by X-gal staining. Immunohistochemical staining was used to identify the type(s) of these reporter-tagged cells. Sixty days after recombination, X-gal-positive cells in different cerebral regions of the adult mice expressed the astroglial markers Blbp and GFAP, the neuronal marker NeuN, the oligodendrocyte precursor cell marker NG2 and the mature oligodendrocyte marker CC1. X-gal-positive cells in the cerebellum coexpressed the astroglial marker Blbp, but not the granule cell marker NeuN, Purkinje cell marker Calbindin or oligodendrocyte precursor cell marker NG2. Our genetic fate mapping data demonstrated that early postnatal GFAP-positive cells possessed multilineage potential and eventually differentiated into neurons, astrocytes, and oligodendrocyte precursor cells in the cerebrum and into astrocytes (including Bergmann glia) in the cerebellum of adult mice.

  9. Initial manifestation of primary hyperoxaluria type I in adults-- recognition, diagnosis, and management.

    PubMed Central

    Kuiper, J J

    1996-01-01

    Primary hyperoxaluria type I may initially manifest as urolithiasis, renal insufficiency, or symptoms of systemic oxalosis. This hereditary disorder was fatal until effective therapies evolved during the past two decades. Difficulty in recognizing and diagnosing this disorder in adults is illustrated in a report of a patient eventually restored to good health by high-flux dialysis and combined renal and hepatic transplantation. I explore the molecular processes of the genetic defect and discuss clinical indicators of primary hyperoxaluria type I, manifestations of oxalosis, the pathogenesis of chronic oxalate nephropathy, and the diagnosis and management of this disease. Images Figure 2. Figure 3. Figure 4. PMID:8779202

  10. Intertwining extracellular nucleotides and their receptors with Ca2+ in determining adult neural stem cell survival, proliferation and final fate.

    PubMed

    Lecca, Davide; Fumagalli, Marta; Ceruti, Stefania; Abbracchio, Maria P

    2016-08-01

    In the central nervous system (CNS), during both brain and spinal cord development, purinergic and pyrimidinergic signalling molecules (ATP, UTP and adenosine) act synergistically with peptidic growth factors in regulating the synchronized proliferation and final specification of multipotent neural stem cells (NSCs) to neurons, astrocytes or oligodendrocytes, the myelin-forming cells. Some NSCs still persist throughout adulthood in both specific 'neurogenic' areas and in brain and spinal cord parenchyma, retaining the potentiality to generate all the three main types of adult CNS cells. Once CNS anatomical structures are defined, purinergic molecules participate in calcium-dependent neuron-to-glia communication and also control the behaviour of adult NSCs. After development, some purinergic mechanisms are silenced, but can be resumed after injury, suggesting a role for purinergic signalling in regeneration and self-repair also via the reactivation of adult NSCs. In this respect, at least three different types of adult NSCs participate in the response of the adult brain and spinal cord to insults: stem-like cells residing in classical neurogenic niches, in particular, in the ventricular-subventricular zone (V-SVZ), parenchymal oligodendrocyte precursor cells (OPCs, also known as NG2-glia) and parenchymal injury-activated astrocytes (reactive astrocytes). Here, we shall review and discuss the purinergic regulation of these three main adult NSCs, with particular focus on how and to what extent modulation of intracellular calcium levels by purinoceptors is mandatory to determine their survival, proliferation and final fate.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377726

  11. [Dendritic cells and interaction with other cell types. Immune tolerance].

    PubMed

    Guerder, S

    2001-07-01

    T cell tolerance to self antigen is mainly established in the thymus were self-reactive T cells are deleted. Interdigitating dendritic cells and medulary epithelial cells are directly involved in the deletion process. Some self-reactive T cells escape, however this thymic censorship and enter the peripheral pool of naive T cells. Multiple mechanisms are also at play in the periphery to control this potentially armfull T cells, this include deletion and immune deviation.

  12. Social network types and functional dependency in older adults in Mexico

    PubMed Central

    2010-01-01

    Background Social networks play a key role in caring for older adults. A better understanding of the characteristics of different social networks types (TSNs) in a given community provides useful information for designing policies to care for this age group. Therefore this study has three objectives: 1) To derive the TSNs among older adults affiliated with the Mexican Institute of Social Security; 2) To describe the main characteristics of the older adults in each TSN, including the instrumental and economic support they receive and their satisfaction with the network; 3) To determine the association between functional dependency and the type of social network. Methods Secondary data analysis of the 2006 Survey of Autonomy and Dependency (N = 3,348). The TSNs were identified using the structural approach and cluster analysis. The association between functional dependency and the TSNs was evaluated with Poisson regression with robust variance analysis in which socio-demographic characteristics, lifestyle and medical history covariates were included. Results We identified five TSNs: diverse with community participation (12.1%), diverse without community participation (44.3%); widowed (32.0%); nonfriends-restricted (7.6%); nonfamily-restricted (4.0%). Older adults belonging to widowed and restricted networks showed a higher proportion of dependency, negative self-rated health and depression. Older adults with functional dependency more likely belonged to a widowed network (adjusted prevalence ratio 1.5; 95%CI: 1.1-2.1). Conclusion The derived TSNs were similar to those described in developed countries. However, we identified the existence of a diverse network without community participation and a widowed network that have not been previously described. These TSNs and restricted networks represent a potential unmet need of social security affiliates. PMID:20187973

  13. Robust regeneration of adult zebrafish lateral line hair cells reflects continued precursor pool maintenance.

    PubMed

    Cruz, Ivan A; Kappedal, Ryan; Mackenzie, Scott M; Hailey, Dale W; Hoffman, Trevor L; Schilling, Thomas F; Raible, David W

    2015-06-15

    We have examined lateral line hair cell and support cell maintenance in adult zebrafish when growth is largely complete. We demonstrate that adult zebrafish not only replenish hair cells after a single instance of hair cell damage, but also maintain hair cells and support cells after multiple rounds of damage and regeneration. We find that hair cells undergo continuous turnover in adult zebrafish in the absence of damage. We identify mitotically-distinct support cell populations and show that hair cells regenerate from underlying support cells in a region-specific manner. Our results demonstrate that there are two distinct support cell populations in the lateral line, which may help explain why zebrafish hair cell regeneration is extremely robust, retained throughout life, and potentially unlimited in regenerative capacity.

  14. Robust regeneration of adult zebrafish lateral line hair cells reflects continued precursor pool maintenance

    PubMed Central

    Cruz, Ivan A.; Kappedal, Ryan; Mackenzie, Scott M.; Hailey, Dale W.; Hoffman, Trevor L.; Schilling, Thomas F.; Raible, David W.

    2015-01-01

    We have examined lateral line hair cell and support cell maintenance in adult zebrafish when growth is largely complete. We demonstrate that adult zebrafish not only replenish hair cells after a single instance of hair cell damage, but also maintain hair cells and support cells after multiple rounds of damage and regeneration. We find that hair cells undergo continuous turnover in adult zebrafish in the absence of damage. We identify mitotically-distinct support cell populations and show that hair cells regenerate from underlying support cells in a region-specific manner. Our results demonstrate that there are two distinct support cell populations in the lateral line, which may help explain why zebrafish hair cell regeneration is extremely robust, retained throughout life, and potentially unlimited in regenerative capacity. PMID:25869855

  15. A single cell bioengineering approach to elucidate mechanisms of adult stem cell self-renewal.

    PubMed

    Gilbert, Penney M; Corbel, Stephane; Doyonnas, Regis; Havenstrite, Karen; Magnusson, Klas E G; Blau, Helen M

    2012-04-01

    The goal of regenerative medicine is to restore form and function to damaged and aging tissues. Adult stem cells, present in tissues such as skeletal muscle, comprise a reservoir of cells with a remarkable capacity to proliferate and repair tissue damage. Muscle stem cells, known as satellite cells, reside in a quiescent state in an anatomically distinct compartment, or niche, ensheathed between the membrane of the myofiber and the basal lamina. Recently, procedures for isolating satellite cells were developed and experiments testing their function upon transplantation into muscles revealed an extraordinary potential to contribute to muscle fibers and access and replenish the satellite cell compartment. However, these properties are rapidly lost once satellite cells are plated in culture. Accordingly, elucidating the role of extrinsic factors in controlling muscle stem cell fate, in particular self-renewal, is critical. Through careful design of bioengineered culture platforms, analysis of specific proteins presented to stem cells is possible. Critical to the success of the approach is single cell analysis, as more rapidly proliferating progenitors may mask the behavior of stem cells that proliferate slowly. Bioengineering approaches provide a potent means of gaining insight into the role of extrinsic factors in the stem cell microenvironment on stem cell function and the mechanisms that control their diverse fates. Ultimately, the multidisciplinary approach presented here will lead to novel therapeutic strategies for degenerative diseases. PMID:22327505

  16. Exenatide Treatment for 6 Months Improves Insulin Sensitivity in Adults With Type 1 Diabetes

    PubMed Central

    Sarkar, Gayatri; Alattar, May; Brown, Rebecca J.; Quon, Michael J.; Harlan, David M.; Rother, Kristina I.

    2014-01-01

    OBJECTIVE Exenatide treatment improves glycemia in adults with type 2 diabetes and has been shown to reduce postprandial hyperglycemia in adolescents with type 1 diabetes. We studied the effects of exenatide on glucose homeostasis in adults with long-standing type 1 diabetes. RESEARCH DESIGN AND METHODS Fourteen patients with type 1 diabetes participated in a crossover study of 6 months' duration on exenatide (10 μg four times a day) and 6 months off exenatide. We assessed changes in fasting and postprandial blood glucose and changes in insulin sensitivity before and after each study period. RESULTS High-dose exenatide therapy reduced postprandial blood glucose but was associated with higher fasting glucose concentrations without net changes in hemoglobin A1c. Exenatide increased insulin sensitivity beyond the effects expected as a result of weight reduction. CONCLUSIONS Exenatide is a promising adjunctive agent to insulin therapy because of its beneficial effects on postprandial blood glucose and insulin sensitivity in patients with type 1 diabetes. PMID:24194508

  17. Inhibition of proliferation by agricultural plant extracts in seven human adult T-cell leukaemia (ATL)-related cell lines.

    PubMed

    Kai, Hisahiro; Akamatsu, Ena; Torii, Eri; Kodama, Hiroko; Yukizaki, Chizuko; Sakakibara, Yoichi; Suiko, Masahito; Morishita, Kazuhiro; Kataoka, Hiroaki; Matsuno, Koji

    2011-07-01

    Adult T-cell leukaemia (ATL) is caused by human T-cell leukaemia virus type I (HTLV-I) infection and is resistant to conventional chemotherapy. We evaluated the inhibitory effects of agricultural plants on the proliferation of seven ATL-related human leukaemia cells, using three ATL cell lines (ED, Su9T01 and S1T), two human T-cell lines transformed by HTLV-I infection (HUT-102 and MT-2) and two HTLV-I-negative human T-cell acute lymphoblastic leukaemia cell lines (Jurkat and MOLT-4). A total of 52 samples of 80% ethanol extracts obtained from 30 types of agricultural plants were examined. On the basis of IC(50) values, we selected samples with greater activity than genistein, which was used as a positive control. The highest inhibitory effect was observed with extracts from leaves of Vaccinium virgatum Aiton (blueberry) on four cell lines (ED, Su9T01, HUT-102 and Jurkat); seeds of Momordica charantia L. (bitter gourd) exhibited the second highest activity. The bitter gourd seeds suppressed the proliferation of three cell lines (Su9T01, HUT-102 and Jurkat). The extracts from edible parts of Ipomea batatas LAM. (sweet potato), edible parts of Colocasia esculenta (L.) Schott (taro), skin of taro and seeds of Prunus mume Sieb. et Zucc. (mume) showed markedly greater inhibitory effects on Su9T01 than genistein. These findings suggest that ATL-preventative bioactive compounds may exist in these agricultural plants, which are considered to be functional foods. PMID:21293936

  18. Endothelial juxtaposition of distinct adult stem cells activates angiogenesis signaling molecules in endothelial cells.

    PubMed

    Mohammadi, Elham; Nassiri, Seyed Mahdi; Rahbarghazi, Reza; Siavashi, Vahid; Araghi, Atefeh

    2015-12-01

    Efficacy of therapeutic angiogenesis needs a comprehensive understanding of endothelial cell (EC) function and biological factors and cells that interplay with ECs. Stem cells are considered the key components of pro- and anti-angiogenic milieu in a wide variety of physiopathological states, and interactions of EC-stem cells have been the subject of controversy in recent years. In this study, the potential effects of three tissue-specific adult stem cells, namely rat marrow-derived mesenchymal stem cells (rBMSCs), rat adipose-derived stem cells (rADSCs) and rat muscle-derived satellite cells (rSCs), on the endothelial activation of key angiogenic signaling molecules, including VEGF, Ang-2, VEGFR-2, Tie-2, and Tie2-pho, were investigated. Human umbilical vein endothelial cells (HUVECs) and rat lung microvascular endothelial cells (RLMECs) were cocultured with the stem cells or incubated with the stem cell-derived conditioned media on Matrigel. Following HUVEC-stem cell coculture, CD31-positive ECs were flow sorted and subjected to western blotting to analyze potential changes in the expression of the pro-angiogenic signaling molecules. Elongation and co-alignment of the stem cells were seen along the EC tubes in the EC-stem cell cocultures on Matrigel, with cell-to-cell dye communication in the EC-rBMSC cocultures. Moreover, rBMSCs and rADSCs significantly improved endothelial tubulogenesis in both juxtacrine and paracrine manners. These two latter stem cells dynamically up-regulated VEGF, Ang-2, VREGR-2, and Tie-2 but down-regulated Tie2-pho and the Tie2-pho/Tie-2 ratio in HUVECs. Induction of pro-angiogenic signaling in ECs by marrow- and adipose-derived MSCs further indicates the significance of stem cell milieu in angiogenesis dynamics. PMID:26068799

  19. Early life trauma predicts self-reported levels of depressive and anxiety symptoms in nonclinical community adults: relative contributions of early life stressor types and adult trauma exposure.

    PubMed

    Chu, Denise A; Williams, Leanne M; Harris, Anthony W F; Bryant, Richard A; Gatt, Justine M

    2013-01-01

    Exposure to early life trauma is a known risk factor for depression and anxiety disorders in adulthood. This study aimed to evaluate the relative contributions of early life versus adult trauma in predicting levels of depressive and anxiety symptoms in nonclinical community adults. 1209 nonclinical community adults (18-70 years; 45% male) were assessed for mental health status, early life stressors, lifetime trauma exposure, and self-reported levels of depressive and anxiety symptoms. A subset of the full sample subjected to group comparisons (n = 1088) indicated that early life stressor exposure primarily accounted for significantly higher depressive and anxiety symptom scores when compared against adults reporting to be free of childhood stressor or adult trauma exposure. Subsequent hierarchical multiple regression analyses of this subset using five distinct early life stressor types, namely 'Interpersonal violation', 'Family breakup', 'Disasters/war', 'Familial health trauma/death' and 'Personal health trauma' derived from principal component analysis of a wide range of self-reported early stressor events in the full sample, showed childhood 'Interpersonal violation' differentially predicted higher self-reported depressive and anxiety symptom scores in both males and females. Adult trauma exposure did not significantly predict these symptom scores. These findings underline the relative importance of exposure to 'interpersonal violation' relative to other types of early life stressors and adult trauma in the risk of depressive and anxiety symptoms in nonclinical community adults.

  20. EGF induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes

    PubMed Central

    Gonzalez-Perez, Oscar; Romero-Rodriguez, Ricardo; Soriano-Navarro, Mario; Garcia-Verdugo, Jose Manuel; Alvarez-Buylla, Arturo

    2012-01-01

    New neurons and oligodendrocytes are continuously produced in the subventricular zone (SVZ) of adult mammalian brains. Under normal conditions, the SVZ primary precursors (type B1 cells) generate type C cells, the majority of which differentiate into neurons, with a small sub-population giving rise to oligodendrocytes. Epidermal growth factor (EGF) signaling induces dramatic proliferation and migration of SVZ progenitors, a process that could have therapeutic applications. However, the fate of cells derived from adult neural stem cells after EGF stimulation remains unknown. Here, we specifically labeled SVZ B1 cells and followed their progeny after a 7-day intraventricular infusion of EGF. Cells derived from SVZ B1 cells invaded the parenchyma around the SVZ into striatum, septum, corpus callosum, and fimbria-fornix. The majority of these B1-derived cells gave rise to cells in the oligodendrocyte lineage including local NG2+ progenitors, pre-myelinating and myelinating oligodendrocytes. SVZ B1 cells also gave rise to a population of highly branched S100β+/GFAP+ cells in the striatum and septum, but no neuronal differentiation was observed. Interestingly, when demyelination was induced in the corpus callosum by a local injection of lysolecithin, increased number of cells derived from SVZ B1 cells and stimulated to migrate and proliferate by EGF infusion, differentiated into oligodendrocytes at the lesion site. This work indicates that EGF infusion can greatly expand the number of progenitors derived from the SVZ primary progenitors, which migrate and differentiate into oligodendroglial cells. This expanded population could be used for the repair of white matter lesions. PMID:19544429

  1. Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes.

    PubMed

    Li, Xiaoheng; Wang, Zhao; Jiang, Zhenming; Guo, Jingjing; Zhang, Yuxi; Li, Chenhao; Chung, Jinyong; Folmer, Janet; Liu, June; Lian, Qingquan; Ge, Renshan; Zirkin, Barry R; Chen, Haolin

    2016-03-01

    Testicular Leydig cells are the primary source of testosterone in males. Adult Leydig cells have been shown to arise from stem cells present in the neonatal testis. Once established, adult Leydig cells turn over only slowly during adult life, but when these cells are eliminated experimentally from the adult testis, new Leydig cells rapidly reappear. As in the neonatal testis, stem cells in the adult testis are presumed to be the source of the new Leydig cells. As yet, the mechanisms involved in regulating the proliferation and differentiation of these stem cells remain unknown. We developed a unique in vitro system of cultured seminiferous tubules to assess the ability of factors from the seminiferous tubules to regulate the proliferation of the tubule-associated stem cells, and their subsequent entry into the Leydig cell lineage. The proliferation of the stem Leydig cells was stimulated by paracrine factors including Desert hedgehog (DHH), basic fibroblast growth factor (FGF2), platelet-derived growth factor (PDGF), and activin. Suppression of proliferation occurred with transforming growth factor β (TGF-β). The differentiation of the stem cells was regulated positively by DHH, lithium- induced signaling, and activin, and negatively by TGF-β, PDGFBB, and FGF2. DHH functioned as a commitment factor, inducing the transition of stem cells to the progenitor stage and thus into the Leydig cell lineage. Additionally, CD90 (Thy1) was found to be a unique stem cell surface marker that was used to obtain purified stem cells by flow cytometry.

  2. Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes

    PubMed Central

    Li, Xiaoheng; Wang, Zhao; Jiang, Zhenming; Guo, Jingjing; Zhang, Yuxi; Li, Chenhao; Chung, Jinyong; Folmer, Janet; Liu, June; Lian, Qingquan; Ge, Renshan; Zirkin, Barry R.; Chen, Haolin

    2016-01-01

    Testicular Leydig cells are the primary source of testosterone in males. Adult Leydig cells have been shown to arise from stem cells present in the neonatal testis. Once established, adult Leydig cells turn over only slowly during adult life, but when these cells are eliminated experimentally from the adult testis, new Leydig cells rapidly reappear. As in the neonatal testis, stem cells in the adult testis are presumed to be the source of the new Leydig cells. As yet, the mechanisms involved in regulating the proliferation and differentiation of these stem cells remain unknown. We developed a unique in vitro system of cultured seminiferous tubules to assess the ability of factors from the seminiferous tubules to regulate the proliferation of the tubule-associated stem cells, and their subsequent entry into the Leydig cell lineage. The proliferation of the stem Leydig cells was stimulated by paracrine factors including Desert hedgehog (DHH), basic fibroblast growth factor (FGF2), platelet-derived growth factor (PDGF), and activin. Suppression of proliferation occurred with transforming growth factor β (TGF-β). The differentiation of the stem cells was regulated positively by DHH, lithium- induced signaling, and activin, and negatively by TGF-β, PDGFBB, and FGF2. DHH functioned as a commitment factor, inducing the transition of stem cells to the progenitor stage and thus into the Leydig cell lineage. Additionally, CD90 (Thy1) was found to be a unique stem cell surface marker that was used to obtain purified stem cells by flow cytometry. PMID:26929346

  3. Regulatory T Cell Immunotherapy for Type 1 Diabetes: A Step Closer to Success?

    PubMed

    Bayry, Jagadeesh; Gautier, Jean-François

    2016-02-01

    Regulatory T cell (Treg) therapy has shown promises in experimental models of type 1 diabetes (T1D) and other autoimmune diseases. Now, Bluestone et al. (2015) report in a phase 1, dose-escalation study that ex vivo-expanded autologous polyclonal Treg therapy is safe and well tolerated in adult patients with recent-onset T1D. PMID:26863486

  4. Improved fuel-cell-type hydrogen sensor

    NASA Technical Reports Server (NTRS)

    Rudek, F. P.; Rutkowski, M. D.

    1968-01-01

    Modified hydrogen sensor replaces oxygen cathode with a cathode consisting of a sealed paste of gold hydroxide and a pure gold current collector. The net reaction which occurs during cell operation is the reduction of the gold hydroxide to gold and water, with a half-cell potential of 1.4 volts.

  5. Pathogenic memory type Th2 cells in allergic inflammation.

    PubMed

    Endo, Yusuke; Hirahara, Kiyoshi; Yagi, Ryoji; Tumes, Damon J; Nakayama, Toshinori

    2014-02-01

    Immunological memory is a hallmark of adaptive immunity. Memory CD4 T helper (Th) cells are central to acquired immunity, and vaccines for infectious diseases are developed based on this concept. However, memory Th cells also play a critical role in the pathogenesis of various chronic inflammatory diseases, including asthma. We refer to these populations as 'pathogenic memory Th cells.' Here, we review recent developments highlighting the functions and characteristics of several pathogenic memory type Th2 cell subsets in allergic inflammation. Also discussed are the similarities and differences between pathogenic memory Th2 cells and recently identified type 2 innate lymphoid cells (ILC2), focusing on cytokine production and phenotypic profiles.

  6. The Impact of Neurofibromatosis Type 1 on the Health and Wellbeing of Australian Adults.

    PubMed

    Crawford, Hilda A; Barton, Belinda; Wilson, Meredith J; Berman, Yemima; McKelvey-Martin, Valerie J; Morrison, Patrick J; North, Kathryn N

    2015-12-01

    The complications of neurofibromatosis type 1 (NF1) are widespread, unpredictable and variable and each person's experience of this disorder is unique. However, few studies have addressed the impact of NF1 from an individual's perspective. This qualitative study aims to identify the ways in which NF1 impacts upon affected Australian adults. Sixty adults with NF1, with a range of disease severity and visibility participated in a semi-structured interview about the ways in which NF1 impacted upon their life and health. Data were analyzed using grounded theory methodology. Results indicated that NF1 impacts upon affected adults in five major ways: 1) cosmetic burden of disease 2) learning difficulties 3) concerns about the risk of passing NF1 to offspring 4) uncertain disease progression, and 5) pain. Participants identified the aspects of NF1 that bothered them the most, creating a hierarchy of NF1 concerns within the cohort. Importantly, mildly affected adults shared many of the same concerns as those more severely affected. This study enhances our current understanding of the impact of NF1 in adulthood, and augments existing recommendations for the care of these patients.

  7. Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells

    PubMed Central

    Kilcoyne, Karen R.; Smith, Lee B.; Atanassova, Nina; Macpherson, Sheila; McKinnell, Chris; van den Driesche, Sander; Jobling, Matthew S.; Chambers, Thomas J. G.; De Gendt, Karel; Verhoeven, Guido; O’Hara, Laura; Platts, Sophie; Renato de Franca, Luiz; Lara, Nathália L. M.; Anderson, Richard A.; Sharpe, Richard M.

    2014-01-01

    Fetal growth plays a role in programming of adult cardiometabolic disorders, which in men, are associated with lowered testosterone levels. Fetal growth and fetal androgen exposure can also predetermine testosterone levels in men, although how is unknown, because the adult Leydig cells (ALCs) that produce testosterone do not differentiate until puberty. To explain this conundrum, we hypothesized that stem cells for ALCs must be present in the fetal testis and might be susceptible to programming by fetal androgen exposure during masculinization. To address this hypothesis, we used ALC ablation/regeneration to identify that, in rats, ALCs derive from stem/progenitor cells that express chicken ovalbumin upstream promoter transcription factor II. These stem cells are abundant in the fetal testis of humans and rodents, and lineage tracing in mice shows that they develop into ALCs. The stem cells also express androgen receptors (ARs). Reduction in fetal androgen action through AR KO in mice or dibutyl phthalate (DBP) -induced reduction in intratesticular testosterone in rats reduced ALC stem cell number by ∼40% at birth to adulthood and induced compensated ALC failure (low/normal testosterone and elevated luteinizing hormone). In DBP-exposed males, this failure was probably explained by reduced testicular steroidogenic acute regulatory protein expression, which is associated with increased histone methylation (H3K27me3) in the proximal promoter. Accordingly, ALCs and ALC stem cells immunoexpressed increased H3K27me3, a change that was also evident in ALC stem cells in fetal testes. These studies highlight how a key component of male reproductive development can fundamentally reprogram adult hormone production (through an epigenetic change), which might affect lifetime disease risk. PMID:24753613

  8. The immunoregulatory role of type I and type II NKT cells in cancer and other diseases

    PubMed Central

    Terabe, Masaki; Berzofsky, Jay A.

    2014-01-01

    NKT cells are CD1d-restricted T cells that recognize lipid antigens. They also have been shown to play critical roles in the regulation of immune responses. In the immune responses against tumors, two subsets of NKT cells, type I and type II, play opposing roles and cross-regulate each other. As members of both the innate and adaptive immune systems, which form a network of multiple components, they also interact with other immune components. Here we discuss the function of NKT cells in tumor immunity and their interaction with other regulatory cells, especially CD4+CD25+Foxp3+ regulatory T cells. PMID:24384834

  9. Volume-activated Na/H exchange activity in fetal and adult pig red cells: inhibition by cyclic AMP.

    PubMed

    Sergeant, S; Sohn, D H; Kim, H D

    1989-08-01

    Hyposmotic swelling of pig red cells leads to a selective increase in K permeability, whereas hyperosmotic cell shrinkage augments the Na permeability. In this regard, the ouabain-resistant (OR) Na flux of red cells of newborn and adult pigs is characterized in detail. A reduction in cell volume by approximately 18% leads to an increase in the OR Na efflux of fetal and adult cells by 15- and fourfold, respectively. The OR Na influx in both cell types is equally influenced by cell shrinkage. Depletion of cellular K does not influence the volume-activated OR Na efflux. Nor does OR Na influx require external K. Both OR Na efflux and influx activated by shrinkage are inhibited by the diuretics furosemide and amiloride. The rank order of decreasing anion sensitivity for diuretic-sensitive Na efflux was acetate greater than chloride greater than gluconate greater than nitrate. Cell shrinkage induced by the addition of hypertonic salts results in an acidification of the unbuffered and CO2-free media, provided that both Na and DIDS are present. The acidification process can be reversed by either of the diuretic agents. These findings suggest that the shrinkage-activated OR Na flux is primarily mediated by a Na/H exchanger rather than by a Na/K/Cl cotransporter. Once loaded with either cAMP or cGMP, cell swelling can no longer activate the Na/H exchanger. The Na/H exchanger activity is detectable in the fetal cells of normal volume but quiescent in adult cells, indicating that the exchanger undergoes a developmental change during the transition from the fetal to adult stage. PMID:2552123

  10. Autonomous isolation, long-term culture and differentiation potential of adult salivary gland-derived stem/progenitor cells.

    PubMed

    Baek, Hyunjung; Noh, Yoo Hun; Lee, Joo Hee; Yeon, Soo-In; Jeong, Jaemin; Kwon, Heechung

    2014-09-01

    Salivary gland stem/progenitor cells belong to the endodermal lineage and may serve as good candidates to replace their dysfunctional counterparts. The objective of this study was to isolate large numbers of salivary gland tissue-derived stem cells (SGSCs) from adult rats in order to develop a clinically applicable method that does not involve sorting or stem cell induction by duct ligation. We analysed SGSCs isolated from normal rat salivary glands to determine whether they retained the major characteristics of stem cells, self-renewal and multipotency, especially with respect to the various endodermal cell types. SGSCs expressed high levels of integrin α6β1 and c-kit, which are surface markers of SGSCs. In particular, the integrin α6β1(+) /c-kit(+) salivary gland cells maintained the morphology, proliferation activity and multipotency of stem cells for up to 92 passages in 12 months. Furthermore, we analysed the capacity of SGSCs to differentiate into endoderm lineage cell types, such as acinar-like and insulin-secreting cells. When cultured on growth factor reduced matrigel, the morphology of progenitor cells changed to acinar-like structures and these cells expressed the acinar cell-specific marker, α-amylase, and tight junction markers. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) data showed increased expression of pancreatic cell markers, including insulin, Pdx1, pan polypeptide and neurogenin-3, when these cells formed pancreatic clusters in the presence of activin A, exendin-4 and retinoic acid. These data demonstrate that adult salivary stem/progenitor cells may serve as a potential source for cell therapy in salivary gland hypofunction and diabetes.

  11. Associations of HLA-A, -B and -DRB1 Types with Oral Diseases in Swiss Adults

    PubMed Central

    Mauramo, Matti; Ramseier, Adrian Markus; Buser, Andreas; Tiercy, Jean-Marie; Weiger, Roland; Waltimo, Tuomas

    2014-01-01

    Human leukocyte antigens (HLA) are crucial components of host defense against microbial challenge but the associations of HLA types with oral infectious diseases have not been studied in detail. This prospective cross-sectional study examined associations of HLA-A, -B and -DRB1 types with common oral diseases in a healthy Swiss adult population. 257 subjects (107 m, 150 f, mean age: 43.5 yr; range: 21–58 yr) with known HLA-A, -B and -DRB1 profiles and comprehensive medical records were included. A thorough anamnesis was followed by oral examinations including saliva flow measurements, the DMFT score for cariological status, complete periodontal status with plaque and bleeding indexes as well as assessment of mucosal alterations and temporomandibular dysfunction (TMD). Student’s t-test and Pearson chi-square test were utilized to compare the oral diseases between HLA positive and negative subjects. Bonferroni correction for multiple comparisons was used and PBonf<0.05 was considered statistically significant. HLA types -B15 (PBonf = 0.002), -B51 (PBonf = 0.02) and -DRB1*12 (PBonf = 0.02) were associated with less periodontal disease manifestations. HLA-A32 had a positive association with TMD dysfunction (PBonf = 0.012). No other statistically significant associations were observed. In conclusion, HLA types may contribute to the development of oral diseases in generally healthy Caucasian adults. PMID:25072155

  12. Polycomb-dependent epigenetic landscape in adult T-cell leukemia.

    PubMed

    Fujikawa, Dai; Nakagawa, Shota; Hori, Makoto; Kurokawa, Naoya; Soejima, Ai; Nakano, Kazumi; Yamochi, Tadanori; Nakashima, Makoto; Kobayashi, Seiichiro; Tanaka, Yuetsu; Iwanaga, Masako; Utsunomiya, Atae; Uchimaru, Kaoru; Yamagishi, Makoto; Watanabe, Toshiki

    2016-04-01

    Adult T-cell leukemia-lymphoma (ATL) shows global gene expression alterations that confer cellular characteristics and unfavorable prognosis. However, molecular mechanisms of the sustained expression changes are largely unknown, because there is no study addressing the relationship between landscapes of the gene expression and epigenetic modifications. Here, we analyzed ATL epigenome and integrated it with transcriptome from primary ATL cells and those from corresponding normal CD4(+)T cells to decipher ATL-specific "epigenetic code" that was critical for cell identity. We found that polycomb-repressive complex 2 (PRC2)-mediated trimethylation at histone H3Lys27 (H3K27me3) was significantly and frequently reprogrammed at half of genes in ATL cells. A large proportion of the abnormal gene downregulation was detected at the early stage of disease progression and was explained by H3K27me3 accumulation. The global H3K27me3 alterations involved ATL-specific gene expression changes that included several tumor suppressors, transcription factors, epigenetic modifiers, miRNAs, and developmental genes, suggesting diverse outcomes by the PRC2-dependent hierarchical regulation. Interestingly, a key enzyme, EZH2, was sensitive to promiscuous signaling network including the NF-κB pathway and was functionally affected by human T-cell leukemia virus type I (HTLV-1) Tax. The Tax-dependent immortalized cells showed H3K27me3 reprogramming that was significantly similar to that of ATL cells. Of note, a majority of the epigenetic silencing has occurred in leukemic cells from indolent ATL and also in HTLV-1-infected T cells from asymptomatic HTLV-1 carriers. Because pharmacologic inhibition of EZH2 reversed epigenetic disruption and selectively eliminated leukemic and HTLV-1-infected cells, targeting the epigenetic elements will hold great promise in treatment and prevention of the onset of ATL and HTLV-1-related diseases. PMID:26773042

  13. Modes of Human T Cell Leukemia Virus Type 1 Transmission, Replication and Persistence

    PubMed Central

    Carpentier, Alexandre; Barez, Pierre-Yves; Hamaidia, Malik; Gazon, Hélène; de Brogniez, Alix; Perike, Srikanth; Gillet, Nicolas; Willems, Luc

    2015-01-01

    Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes cancer (Adult T cell Leukemia, ATL) and a spectrum of inflammatory diseases (mainly HTLV-associated myelopathy—tropical spastic paraparesis, HAM/TSP). Since virions are particularly unstable, HTLV-1 transmission primarily occurs by transfer of a cell carrying an integrated provirus. After transcription, the viral genomic RNA undergoes reverse transcription and integration into the chromosomal DNA of a cell from the newly infected host. The virus then replicates by either one of two modes: (i) an infectious cycle by virus budding and infection of new targets and (ii) mitotic division of cells harboring an integrated provirus. HTLV-1 replication initiates a series of mechanisms in the host including antiviral immunity and checkpoint control of cell proliferation. HTLV-1 has elaborated strategies to counteract these defense mechanisms allowing continuous persistence in humans. PMID:26198240

  14. Erythropoietin gene expression: developmental-stage specificity, cell-type specificity, and hypoxia inducibility.

    PubMed

    Suzuki, Norio

    2015-01-01

    Erythrocytes play an essential role in the delivery of oxygen from the lung to every organ; a decrease in erythrocytes (anemia) causes hypoxic stress and tissue damage. To maintain oxygen homeostasis in adult mammals, when the kidney senses hypoxia, it secretes an erythroid growth factor, erythropoietin (Epo), which stimulates erythropoiesis in the bone marrow. Recently, studies using genetically modified mice have shown that the in vivo expression profile of the Epo gene changes dramatically during development. The first Epo-producing cells emerge in the neural crest and neuroepithelium of mid-stage embryos and support primitive erythropoiesis in the yolk sac. Subsequently, Epo from the hepatocytes stimulates erythropoiesis in the fetal liver of later stage embryos in a paracrine manner. In fact, erythroid lineage cells comprise the largest cell population in the fetal liver, and hepatocytes are distributed among the erythroid cell clusters. Adult erythropoiesis in the bone marrow requires Epo that is secreted by renal Epo-producing cells (REP cells). REP cells are widely distributed in the renal cortex and outer medulla. Hypoxia-inducible Epo production both in hepatocytes and REP cells is controlled at the gene transcription level that is mainly mediated by the hypoxia-inducible transcription factor (HIF) pathway. These mouse studies further provide insights into the molecular mechanisms of the cell-type specific, hypoxia-inducible expression of the Epo gene, which involves multiple sets of cis- and trans-regulatory elements. PMID:25786542

  15. Latent Classes of Young Adults Based on Use of Multiple Types of Tobacco and Nicotine Products

    PubMed Central

    Lenk, Kathleen M.; Forster, Jean L.

    2014-01-01

    Introduction: New tobacco and nicotine products such as snus, hookah, and electronic cigarettes have risen in popularity in recent years. Use of these products among young adults is of particular interest given that experimentation with new products is common in young adulthood. Methods: We conducted latent class analysis among a population-based sample of young adults to identify separate classes based on use of 6 types of tobacco or nicotine products: snus, hookah, electronic cigarettes, cigarillos, snuff, and cigarettes. We then examined how identified classes differed on demographic characteristics and marijuana and alcohol use. Results: We identified 5 classes: the largest group (60%) was characterized as reporting no or limited use of any of the products, while the smallest group (7%) was characterized by use of many types of products (poly-users). Of the 3 middle classes, 2 were the same size (10%) and were characterized by primarily using 2 of the products: one class used snus and snuff, and the other used cigarillos and hookah; the third class (13%) was characterized by primarily cigarette smoking. Numerous differences were seen across classes, including the poly-users being less likely to be college students/graduates and more likely to be male and use marijuana and alcohol. Conclusions: We found that young adults can be grouped into 5 subgroups based on types of tobacco/nicotine products they do and do not use. A poly-use group that uses all types of tobacco products is concerning, particularly given high levels of marijuana and alcohol use reported in this group. PMID:24604019

  16. Hair follicle dermal stem cells regenerate the dermal sheath, repopulate the dermal papilla, and modulate hair type.

    PubMed

    Rahmani, Waleed; Abbasi, Sepideh; Hagner, Andrew; Raharjo, Eko; Kumar, Ranjan; Hotta, Akitsu; Magness, Scott; Metzger, Daniel; Biernaskie, Jeff

    2014-12-01

    The dermal papilla (DP) provide instructive signals required to activate epithelial progenitors and initiate hair follicle regeneration. DP cell numbers fluctuate over the hair cycle, and hair loss is associated with gradual depletion/atrophy of DP cells. How DP cell numbers are maintained in healthy follicles remains unclear. We performed in vivo fate mapping of adult hair follicle dermal sheath (DS) cells to determine their lineage relationship with DP and found that a subset of DS cells are retained following each hair cycle, exhibit self-renewal, and repopulate the DS and the DP with new cells. Ablating these hair follicle dermal stem cells and their progeny retarded hair regrowth and altered hair type specification, suggesting that they function to modulate normal DP function. This work identifies a bipotent stem cell within the adult hair follicle mesenchyme and has important implications toward restoration of hair growth after injury, disease, and aging.

  17. Exosome-like vesicles derived by Schistosoma japonicum adult worms mediates M1 type immune- activity of macrophage.

    PubMed

    Wang, Lifu; Li, Zhitao; Shen, Jia; Liu, Zhen; Liang, Jinyi; Wu, Xiaoying; Sun, Xi; Wu, Zhongdao

    2015-05-01

    Exosomes are 30-100-nm membrane vesicles of endocytic origin that are released into the extracellular space upon fusion of the multi-vesicular bodies (MVB) with the plasma membrane, while initial studies described that the role of exosomes was a reticulocyte cargo-disposal mechanism allowing remodeling of the plasma membrane during the maturation of reticulocytes to erythrocytes. Recent studies indicate that exosomes are secreted by most cells and pathogens and play an important role in intercellular signaling and exert regulatory function by carrying bioactive molecules. As numerous pathogens, adult worm of Schistosoma japonicum (S. japonicum) reside in mesenteric veins of definitive host including man and mammal animals. It was reported that the worms or the eggs also have specialized secretion systems to export effector proteins or other molecules into host target cells. However, the mechanisms involved remained unclear. This study investigated the isolation of the exosome-like vesicles secreted by S. japonicum adult worms and its immune activity on microphage in vitro. In this report, we identified exosome-based secretion as a new mechanism for protein secretion by S. japonicum. Electron microscopy tomography revealed the previously unidentified ultrastructural detail of exosome-like vesicles with high resolution; they were found to be typical spherical shape and to have a diverse population that varies in size of 30-100 nm. Exosome-like vesicles isolated from S. japonicum contained a significantly different protein compared with debris pelleted and the apoptosis body. We also demonstrate that macrophages were preferentially differentiated into the M1 subtype while being treated with S. japonicum exosome-like vesicles. This study reveals there are exosome-like vesicles derived by S. japonicum adult worms, and the exosome-like vesicles can mediate M1-type immune- activity of macrophage.

  18. High Cell Surface Death Receptor Expression Determines Type I Versus Type II Signaling*

    PubMed Central

    Meng, Xue Wei; Peterson, Kevin L.; Dai, Haiming; Schneider, Paula; Lee, Sun-Hee; Zhang, Jin-San; Koenig, Alexander; Bronk, Steve; Billadeau, Daniel D.; Gores, Gregory J.; Kaufmann, Scott H.

    2011-01-01

    Previous studies have suggested that there are two signaling pathways leading from ligation of the Fas receptor to induction of apoptosis. Type I signaling involves Fas ligand-induced recruitment of large amounts of FADD (FAS-associated death domain protein) and procaspase 8, leading to direct activation of caspase 3, whereas type II signaling involves Bid-mediated mitochondrial perturbation to amplify a more modest death receptor-initiated signal. The biochemical basis for this dichotomy has previously been unclear. Here we show that type I cells have a longer half-life for Fas message and express higher amounts of cell surface Fas, explaining the increased recruitment of FADD and subsequent signaling. Moreover, we demonstrate that cells with type II Fas signaling (Jurkat or HCT-15) can signal through a type I pathway upon forced receptor overexpression and that shRNA-mediated Fas down-regulation converts cells with type I signaling (A498) to type II signaling. Importantly, the same cells can exhibit type I signaling for Fas and type II signaling for TRAIL (TNF-α-related apoptosis-inducing ligand), indicating that the choice of signaling pathway is related to the specific receptor, not some other cellular feature. Additional experiments revealed that up-regulation of cell surface death receptor 5 levels by treatment with 7-ethyl-10-hydroxy-camptothecin converted TRAIL signaling in HCT116 cells from type II to type I. Collectively, these results suggest that the type I/type II dichotomy reflects differences in cell surface death receptor expression. PMID:21865165

  19. [Psychological distress in adults with neurofibromatosis type 1: a longitudinal study].

    PubMed

    Reichardt, Christoph; Scherwath, Angela; Felix Mautner, Victor; Bullinger, Monika; Petersen-Ewert, Corinna

    2013-02-01

    Neurofibromatosis type 1 (NF1) is a rare genetic disorder with an autosomal dominant inheritance. It is a chronic condition that affects mostly the skin and causes it to grow multiple tumors and also affects the nervous system. The clinical picture is complex with highly variable symptoms and clinical severity. This study explores the psychological distress in 129 adult patients with NF1. It turned out that adults with NF1 have a higher level of psychological distress compared to the general population. The psychological distress is stable within a year. Physicians treating patients with NF1 should consider the psychological distress in NF1 patients. Psychotherapy, psychiatric treatment and psychosocial offers are therefore essential. PMID:23408303

  20. Adolescent social defeat disturbs adult aggression-related impulsivity in wild-type rats.

    PubMed

    Coppens, Caroline M; Coolen, Alex; de Boer, Sietse F; Koolhaas, Jaap M

    2014-10-01

    Adolescence is generally considered as a developmental period during which adverse social experiences may have lasting consequences in terms of an increased vulnerability to affective disorders. This study aimed at determining the individual susceptibility to adolescent social stress using a rat model. We used rats of the Wild-type Groningen strain, which are characterized by a broad variation in adult levels of aggression and impulsivity. We hypothesized that experience of social defeat in adolescence results in heightened aggression and impulsivity levels in adulthood. In contrast to our expectation, adolescent social defeat did not lead to a difference in the average adult level of aggression and impulsivity, but the significant correlation between offensive aggression and impulsivity found in control animals was not present in animals defeated during adolescence.

  1. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    SciTech Connect

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.

    1995-12-01

    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  2. Niemann-Pick type C: focus on the adolescent/adult onset form.

    PubMed

    Di Lazzaro, Vincenzo; Marano, Massimo; Florio, Lucia; De Santis, Stefano

    2016-11-01

    Niemann-Pick disease type C (NP-C) is an inherited sphingolipidosis characterized by progressive neurological deterioration and early mortality. The symptomatology and disease progression of NP-C are markedly affected by the age at onset of neurological manifestations, and categorization into early-infantile, late-infantile, juvenile, adolescent/adult neurological onset forms can aid evaluation of disease course and responses to therapy. Here, we review current information on the detection, diagnosis, monitoring and treatment of NP-C, with a focus on the adolescent/adult-onset form. A recent analysis indicated that the combined incidence of NP-C related to NPC1 gene mutations (NPC1) and NP-C related to NPC2 gene mutations (NPC2) is approximately 1 case in every 89 000 live births. In particular, late-onset phenotypes might well provide a greater contribution to the overall incidence than has previously been reported. Some neuropathological features in NP-C are held in common with other advanced age-onset diseases such as Alzheimer's disease. Visceral symptoms such as splenomegaly are frequently asymptomatic in patients with adolescent/adult-onset NP-C, and are only occasionally detected during routine ultrasound assessments. In contrast, most patients with adolescent/adult-onset exhibit some degree of slowly progressive, non-disease-specific movement disorders (e.g. cerebellar ataxia), and/or more pathognomonic neurological signs such as vertical supranuclear gaze palsy. An increasing number of adolescent/adult-onset cases have been reported following initial recognition of cognitive impairment and/or psychiatric signs. The recent development and implementation of new clinical screening tools (e.g. the NP-C suspicion index) and biomarkers (e.g. plasma oxysterols) should help identify patients who warrant further investigation and possible treatment. PMID:26998855

  3. Niemann-Pick type C: focus on the adolescent/adult onset form.

    PubMed

    Di Lazzaro, Vincenzo; Marano, Massimo; Florio, Lucia; De Santis, Stefano

    2016-11-01

    Niemann-Pick disease type C (NP-C) is an inherited sphingolipidosis characterized by progressive neurological deterioration and early mortality. The symptomatology and disease progression of NP-C are markedly affected by the age at onset of neurological manifestations, and categorization into early-infantile, late-infantile, juvenile, adolescent/adult neurological onset forms can aid evaluation of disease course and responses to therapy. Here, we review current information on the detection, diagnosis, monitoring and treatment of NP-C, with a focus on the adolescent/adult-onset form. A recent analysis indicated that the combined incidence of NP-C related to NPC1 gene mutations (NPC1) and NP-C related to NPC2 gene mutations (NPC2) is approximately 1 case in every 89 000 live births. In particular, late-onset phenotypes might well provide a greater contribution to the overall incidence than has previously been reported. Some neuropathological features in NP-C are held in common with other advanced age-onset diseases such as Alzheimer's disease. Visceral symptoms such as splenomegaly are frequently asymptomatic in patients with adolescent/adult-onset NP-C, and are only occasionally detected during routine ultrasound assessments. In contrast, most patients with adolescent/adult-onset exhibit some degree of slowly progressive, non-disease-specific movement disorders (e.g. cerebellar ataxia), and/or more pathognomonic neurological signs such as vertical supranuclear gaze palsy. An increasing number of adolescent/adult-onset cases have been reported following initial recognition of cognitive impairment and/or psychiatric signs. The recent development and implementation of new clinical screening tools (e.g. the NP-C suspicion index) and biomarkers (e.g. plasma oxysterols) should help identify patients who warrant further investigation and possible treatment.

  4. Development of the Adult PedsQL™ Neurofibromatosis Type 1 Module: Initial Feasibility, Reliability and Validity

    PubMed Central

    2013-01-01

    Background Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder with significant impact on health-related quality of life (HRQOL). Research in understanding the pathogenetic mechanisms of neurofibroma development has led to the use of new clinical trials for the treatment of NF1. One of the most important outcomes of a trial is improvement in quality of life, however, no condition specific HRQOL instrument for NF1 exists. The objective of this study was to develop an NF1 HRQOL instrument as a module of PedsQL™ and to test for its initial feasibility, internal consistency reliability and validity in adults with NF1. Methods The NF1 specific HRQOL instrument was developed using a standard method of PedsQL™ module development – literature review, focus group/semi-structured interviews, cognitive interviews and experts’ review of initial draft, pilot testing and field testing. Field testing involved 134 adults with NF1. Feasibility was measured by the percentage of missing responses, internal consistency reliability was measured with Cronbach’s alpha and validity was measured by the known-groups method. Results Feasibility, measured by the percentage of missing responses was 4.8% for all subscales on the adult version of the NF1-specific instrument. Internal consistency reliability for the Total Score (alpha =0.97) and subscale reliabilities ranging from 0.72 to 0.96 were acceptable for group comparisons. The PedsQL™ NF1 module distinguished between NF1 adults with excellent to very good, good, and fair to poor health status. Conclusions The results demonstrate the initial feasibility, reliability and validity of the PedsQL™ NF1 module in adult patients. The PedsQL™ NF1 Module can be used to understand the multidimensional nature of NF1 on the HRQOL patients with this disorder. PMID:23432799

  5. Biology of the Sertoli Cell in the Fetal, Pubertal, and Adult Mammalian Testis.

    PubMed

    Chojnacka, Katarzyna; Zarzycka, Marta; Mruk, Dolores D

    2016-01-01

    A healthy man typically produces between 50 × 10(6) and 200 × 10(6) spermatozoa per day by spermatogenesis; in the absence of Sertoli cells in the male gonad, this individual would be infertile. In the adult testis, Sertoli cells are sustentacular cells that support germ cell development by secreting proteins and other important biomolecules that are essential for germ cell survival and maturation, establishing the blood-testis barrier, and facilitating spermatozoa detachment at spermiation. In the fetal testis, on the other hand, pre-Sertoli cells form the testis cords, the future seminiferous tubules. However, the role of pre-Sertoli cells in this process is much less clear than the function of Sertoli cells in the adult testis. Within this framework, we provide an overview of the biology of the fetal, pubertal, and adult Sertoli cell, highlighting relevant cell biology studies that have expanded our understanding of mammalian spermatogenesis. PMID:27300181

  6. Clinical Trials of Adult Stem Cell Therapy in Patients with Ischemic Stroke.

    PubMed

    Bang, Oh Young

    2016-01-01

    Stem cell therapy is considered a potential regenerative strategy for patients with neurologic deficits. Studies involving animal models of ischemic stroke have shown that stem cells transplanted into the brain can lead to functional improvement. With current advances in the understanding regarding the effects of introducing stem cells and their mechanisms of action, several clinical trials of stem cell therapy have been conducted in patients with stroke since 2005, including studies using mesenchymal stem cells, bone marrow mononuclear cells, and neural stem/progenitor cells. In addition, several clinical trials of the use of adult stem cells to treat ischemic stroke are ongoing. This review presents the status of our understanding of adult stem cells and results from clinical trials, and introduces ongoing clinical studies of adult stem cell therapy in the field of stroke.

  7. The Relationship between Type D Personality and Suicidality in Low-Income, Middle-Aged Adults

    PubMed Central

    Yoon, Dae Hyun; Kim, Seog Ju; Lee, Jong-Ha; Kim, Pyo-Min; Park, Doo-Heum; Ryu, Seung Ho; Yu, Jaehak

    2015-01-01

    Objective Low-income adults are considered to be a group at high risk for suicide. We sought to examine the effect of type D personality and other socio-demographic factors on suicidality in low-income, middle-aged Koreans. Methods In total, 306 low-income, middle-aged Koreans [age: 49.16±5.24 (40-59) years, 156 males, 150 females] were enrolled from the Korean National Basic Livelihood Security System. Socio-demographic data, including employment status, income, health, marital status, and educational attainment, were gathered. Beck's 19-item Scale for Suicidal Ideation (SSI) was applied to evaluate suicidality, and the DS14 was used to assess type D personality. Results Unemployment (p<0.01) and absence of spouse (p=0.03) predicted higher SSI scores independent of other socioeconomic factors. All type D personality scores [i.e., negative affectivity (NA), social inhibition (SI), and total score] predicted higher SSI scores independent of all socioeconomic factors (all, p<0.001). Subjects with type D personality had higher SSI scores (p<0.001), and the association between suicidality and socio-demographic factors (employment or physical health) could be found only in subjects without type D personality. Conclusion Type D personality was a risk factor for suicide in low-income Koreans, independently from socio-economic factors. In addition, the socio-demographic factors were less prominently associated with suicidality in those with type D personality. PMID:25670941

  8. Higher Fibrinogen Levels Predict Progression of Coronary Artery Calcification in Adults with Type 1 Diabetes

    PubMed Central

    Rodrigues, T.C.; Snell-Bergeon, J.K.; Maahs, D.M; Kinney, G.L.; Rewers, M.

    2010-01-01

    Aim To determine whether fibrinogen levels predict independently progression of coronary artery calcification (CAC) in adults with type 1 diabetes. Methods Data from a prospective cohort - the Coronary Artery Calcification in Type 1 Diabetes Study - were evaluated. Fibrinogen levels at baseline were separated into quartiles. CAC was measured twice and averaged at baseline and at follow-up 2.4 ± 0.4 years later. CAC progressors were defined as participants whose square-root transformed CAC volume increased by ≥ 2.53 or development mm of clinical coronary artery disease during the follow-up period. Results Fibrinogen levels were higher in progressors than in non-progressors (276 ± 61 mg/dl versus 259 ± 61 mg/dl, p = 0.0003). CAC progression, adjusted for known cardiovascular risk factors, increased in the highest quartile. Conclusions Higher fibrinogen levels predict CAC progression in type 1 diabetes subjects, independent of standard cardiovascular risk factors. PMID:20079495

  9. Current data with inulin-type fructans and calcium, targeting bone health in adults.

    PubMed

    Coxam, Véronique

    2007-11-01

    In humans, there is increasing evidence that the colon can absorb nutritionally significant amounts of calcium, and this process may be susceptible to dietary manipulation by fermentable substrates, especially inulin-type fructans. Inulin-type fructans can modulate calcium absorption because they are resistant to hydrolysis by mammalian enzymes and are fermented in the large intestine to produce short-chain fatty acids, which in turn reduce luminal pH and modify calcium speciation, and hence solubility, or exert a direct effect on the mucosal transport pathway. Quite a few intervention studies showed an improvement of calcium absorption in adolescents or young adults by inulin-type fructans. In the same way, a positive effect has been reported in older women.

  10. Identification and quantitation of morphological cell types in electrophoretically separated human embryonic kidney cell cultures

    NASA Technical Reports Server (NTRS)

    Williams, K. B.; Kunze, M. E.; Todd, P. W.

    1985-01-01

    Four major cell types were identified by phase microscopy in early passage human embryonic kidney cell cultures. They are small and large epithelioid, domed, and fenestrated cells. Fibroblasts are also present in some explants. The percent of each cell type changes with passage number as any given culture grows. As a general rule, the fraction of small epithelioid cells increases, while the fraction of fenestrated cells, always small, decreases further. When fibroblasts are present, they always increase in percentage of the total cell population. Electrophoretic separation of early passage cells showed that the domed cells have the highest electrophoretic mobility, fibroblasts have an intermediate high mobility, small epithelioid cells have a low mobility, broadly distributed, and fenestrated cells have the lowest mobility. All cell types were broadly distributed among electrophoretic subfractions, which were never pure but only enriched with respect to a given cell type.

  11. Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia.

    PubMed

    Fry, Christopher S; Lee, Jonah D; Mula, Jyothi; Kirby, Tyler J; Jackson, Janna R; Liu, Fujun; Yang, Lin; Mendias, Christopher L; Dupont-Versteegden, Esther E; McCarthy, John J; Peterson, Charlotte A

    2015-01-01

    A key determinant of geriatric frailty is sarcopenia, the age-associated loss of skeletal muscle mass and strength. Although the etiology of sarcopenia is unknown, the correlation during aging between the loss of activity of satellite cells, which are endogenous muscle stem cells, and impaired muscle regenerative capacity has led to the hypothesis that the loss of satellite cell activity is also a cause of sarcopenia. We tested this hypothesis in male sedentary mice by experimentally depleting satellite cells in young adult animals to a degree sufficient to impair regeneration throughout the rest of their lives. A detailed analysis of multiple muscles harvested at various time points during aging in different cohorts of these mice showed that the muscles were of normal size, despite low regenerative capacity, but did have increased fibrosis. These results suggest that lifelong reduction of satellite cells neither accelerated nor exacerbated sarcopenia and that satellite cells did not contribute to the maintenance of muscle size or fiber type composition during aging, but that their loss may contribute to age-related muscle fibrosis.

  12. 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

  13. Asymmetrical cell division in Blepharisma japonicum: difference between daughter cells in mating-type expression.

    PubMed

    Miyake, A; Harumoto, T

    1990-09-01

    In cell division of high-frequency-selfers in the ciliate Blepharisma japonicum, daughter cells are different in mating-type expression. The anterior daughter cell is mating type I. The posterior daughter cell is mating type II at first and then changes to mating type I after about 24 h. The anteroposterior polarity of predivision cells appears to correlate with the asymmetrical cell division. This work introduces a unicellular organism about the size of microscopic metazoa as a model system for the study of asymmetrical cell division, which is particularly important in developmental processes.

  14. Speech-in-Noise Perception Deficit in Adults with Dyslexia: Effects of Background Type and Listening Configuration

    ERIC Educational Resources Information Center

    Dole, Marjorie; Hoen, Michel; Meunier, Fanny

    2012-01-01

    Developmental dyslexia is associated with impaired speech-in-noise perception. The goal of the present research was to further characterize this deficit in dyslexic adults. In order to specify the mechanisms and processing strategies used by adults with dyslexia during speech-in-noise perception, we explored the influence of background type,…

  15. A RANDOMIZED CONTROLLED TRIAL OF RESISTANCE EXERCISE TRAINING TO IMPROVE GLYCEMIC CONTROL IN OLDER ADULTS WITH TYPE 2 DIABETES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE-To determine the efficacy of high-intensity progressive resistance training (PRT) on glycemic control in older adults with type 2 diabetes. RESEARCH DESIGN AND METHODS-We performed a 16-week randomized controlled trial in 62 Latino older adults (40 women and 22 men; mean +/- SE age 66 +/...

  16. NGF induces adult stem Leydig cells to proliferate and differentiate during Leydig cell regeneration

    SciTech Connect

    Zhang, Lei; Wang, Huaxi; Yang, Yan; Liu, Hui; Zhang, Qihao; Xiang, Qi; Ge, Renshan; Su, Zhijian; Huang, Yadong

    2013-06-28

    Highlights: •Nerve growth factor has shown significant changes on mRNA levels during Adult Leydig cells regeneration. •We established the organ culture model of rat seminiferous tubules with ethane dimethyl sulphonate (EDS) treatment. •Nerve growth factor has shown proliferation and differentiation-promoting effects on Adult stem Leydig cells. •Nerve growth factor induces progenitor Leydig cells to proliferate and differentiate and immature Leydig cells to proliferate. -- Abstract: Nerve growth factor (NGF) has been reported to be involved in male reproductive physiology. However, few reports have described the activity of NGF during Leydig cell development. The objective of the present study was to examine the role of NGF during stem-Leydig-cell (SLC) regeneration. We investigated the effects of NGF on Leydig-cell (LC) regeneration by measuring mRNA levels in the adult rat testis after ethane dimethanesulfonate (EDS) treatment. Furthermore, we used the established organ culture model of rat seminiferous tubules to examine the regulation of NGF during SLC proliferation and differentiation using EdU staining, real-time PCR and western blotting. Progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs) were also used to investigate the effects of NGF on LCs at different developmental stages. NGF mRNA levels changed significantly during Leydig-cell regeneration in vivo. In vitro, NGF significantly promoted the proliferation of stem Leydig cells and also induced steroidogenic enzyme gene expression and 3β-HSD protein expression. The data from PLCs and ILCs showed that NGF could increase Cyclin D1 and Hsd 17b3 mRNA levels in PLCs and Cyclin D1 mRNA levels in ILCs. These results indicate that NGF may play an important role during LC regeneration by regulating the proliferation and differentiation of LCs at different developmental stages, from SLCs to PLCs and from PLCs to ILCs. The discovery of this effect of NGF on Leydig cells will provide useful

  17. In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas.

    PubMed

    Tremblay, Jacob R; LeBon, Jeanne M; Luo, Angela; Quijano, Janine C; Wedeken, Lena; Jou, Kevin; Riggs, Arthur D; Tirrell, David A; Ku, H Teresa

    2016-01-01

    Stem and progenitor cells from the adult pancreas could be a potential source of therapeutic beta-like cells for treating patients with type 1 diabetes. However, it is still unknown whether stem and progenitor cells exist in the adult pancreas. Research strategies using cre-lox lineage-tracing in adult mice have yielded results that either support or refute the idea that beta cells can be generated from the ducts, the presumed location where adult pancreatic progenitors may reside. These in vivo cre-lox lineage-tracing methods, however, cannot answer the questions of self-renewal and multi-lineage differentiation-two criteria necessary to define a stem cell. To begin addressing this technical gap, we devised 3-dimensional colony assays for pancreatic progenitors. Soon after our initial publication, other laboratories independently developed a similar, but not identical, method called the organoid assay. Compared to the organoid assay, our method employs methylcellulose, which forms viscous solutions that allow the inclusion of extracellular matrix proteins at low concentrations. The methylcellulose-containing assays permit easier detection and analyses of progenitor cells at the single-cell level, which are critical when progenitors constitute a small sub-population, as is the case for many adult organ stem cells. Together, results from several laboratories demonstrate in vitro self-renewal and multi-lineage differentiation of pancreatic progenitor-like cells from mice. The current protocols describe two methylcellulose-based colony assays to characterize mouse pancreatic progenitors; one contains a commercial preparation of murine extracellular matrix proteins and the other an artificial extracellular matrix protein known as a laminin hydrogel. The techniques shown here are 1) dissociation of the pancreas and sorting of CD133(+)Sox9/EGFP(+) ductal cells from adult mice, 2) single cell manipulation of the sorted cells, 3) single colony analyses using microfluidic q

  18. Cord blood T cells mediate enhanced antitumor effects compared with adult peripheral blood T cells.

    PubMed

    Hiwarkar, Prashant; Qasim, Waseem; Ricciardelli, Ida; Gilmour, Kimberly; Quezada, Sergio; Saudemont, Aurore; Amrolia, Persis; Veys, Paul

    2015-12-24

    Unrelated cord blood transplantation (CBT) without in vivo T-cell depletion is increasingly used to treat high-risk hematologic malignancies. Following T-replete CBT, naïve CB T cells undergo rapid peripheral expansion with memory-effector differentiation. Emerging data suggest that unrelated CBT, particularly in the context of HLA mismatch and a T-replete graft, may reduce leukemic relapse. To study the role of CB T cells in mediating graft-versus-tumor responses and dissect the underlying immune mechanisms for this, we compared the ability of HLA-mismatched CB and adult peripheral blood (PB) T cells to eliminate Epstein-Barr virus (EBV)-driven human B-cell lymphoma in a xenogeneic NOD/SCID/IL2rg(null) mouse model. CB T cells mediated enhanced tumor rejection compared with equal numbers of PB T cells, leading to improved survival in the CB group (P < .0003). Comparison of CB T cells that were autologous vs allogeneic to the lymphoma demonstrated that this antitumor effect was mediated by alloreactive rather than EBV-specific T cells. Analysis of tumor-infiltrating lymphocytes demonstrated that CB T cells mediated this enhanced antitumor effect by rapid infiltration of the tumor with CCR7(+)CD8(+) T cells and prompt induction of cytotoxic CD8(+) and CD4(+) T-helper (Th1) T cells in the tumor microenvironment. In contrast, in the PB group, this antilymphoma effect is impaired because of delayed tumoral infiltration of PB T cells and a relative bias toward suppressive Th2 and T-regulatory cells. Our data suggest that, despite being naturally programmed toward tolerance, reconstituting T cells after unrelated T-replete CBT may provide superior Tc1-Th1 antitumor effects against high-risk hematologic malignancies.

  19. Epigenetic deregulation of Ellis Van Creveld confers robust Hedgehog signaling in adult T-cell leukemia.

    PubMed

    Takahashi, Ryutaro; Yamagishi, Makoto; Nakano, Kazumi; Yamochi, Toshiko; Yamochi, Tadanori; Fujikawa, Dai; Nakashima, Makoto; Tanaka, Yuetsu; Uchimaru, Kaoru; Utsunomiya, Atae; Watanabe, Toshiki

    2014-09-01

    One of the hallmarks of cancer, global gene expression alteration, is closely associated with the development and malignant characteristics associated with adult T-cell leukemia (ATL) as well as other cancers. Here, we show that aberrant overexpression of the Ellis Van Creveld (EVC) family is responsible for cellular Hedgehog (HH) activation, which provides the pro-survival ability of ATL cells. Using microarray, quantitative RT-PCR and immunohistochemistry we have demonstrated that EVC is significantly upregulated in ATL and human T-cell leukemia virus type I (HTLV-1)-infected cells. Epigenetic marks, including histone H3 acetylation and Lys4 trimethylation, are specifically accumulated at the EVC locus in ATL samples. The HTLV-1 Tax participates in the coordination of EVC expression in an epigenetic fashion. The treatment of shRNA targeting EVC, as well as the transcription factors for HH signaling, diminishes the HH activation and leads to apoptotic death in ATL cell lines. We also showed that a HH signaling inhibitor, GANT61, induces strong apoptosis in the established ATL cell lines and patient-derived primary ATL cells. Therefore, our data indicate that HH activation is involved in the regulation of leukemic cell survival. The epigenetically deregulated EVC appears to play an important role for HH activation. The possible use of EVC as a specific cell marker and a novel drug target for HTLV-1-infected T-cells is implicated by these findings. The HH inhibitors are suggested as drug candidates for ATL therapy. Our findings also suggest chromatin rearrangement associated with active histone markers in ATL.

  20. Neuronal Neuregulin 1 type III directs Schwann cell migration

    PubMed Central

    Perlin, Julie R.; Lush, Mark E.; Stephens, W. Zac; Piotrowski, Tatjana; Talbot, William S.

    2011-01-01

    During peripheral nerve development, each segment of a myelinated axon is matched with a single Schwann cell. Tight regulation of Schwann cell movement, proliferation and differentiation is essential to ensure that these glial cells properly associate with axons. ErbB receptors are required for Schwann cell migration, but the operative ligand and its mechanism of action have remained unknown. We demonstrate that zebrafish Neuregulin 1 (Nrg1) type III, which signals through ErbB receptors, controls Schwann cell migration in addition to its previously known roles in proliferation and myelination. Chimera analyses indicate that ErbB receptors are required in all migrating Schwann cells, and that Nrg1 type III is required in neurons for migration. Surprisingly, expression of the ligand in a few axons is sufficient to induce migration along a chimeric nerve constituted largely of nrg1 type III mutant axons. These studies also reveal a mechanism that allows Schwann cells to fasciculate axons regardless of nrg1 type III expression. Time-lapse imaging of transgenic embryos demonstrated that misexpression of human NRG1 type III results in ectopic Schwann cell migration, allowing them to aberrantly enter the central nervous system. These results demonstrate that Nrg1 type III is an essential signal that controls Schwann cell migration to ensure that these glia are present in the correct numbers and positions in developing nerves. PMID:21965611

  1. The transcriptional coactivator Cbp regulates self-renewal and differentiation in adult hematopoietic stem cells.

    PubMed

    Chan, Wai-In; Hannah, Rebecca L; Dawson, Mark A; Pridans, Clare; Foster, Donna; Joshi, Anagha; Göttgens, Berthold; Van Deursen, Jan M; Huntly, Brian J P

    2011-12-01

    The transcriptional coactivator Cbp plays an important role in a wide range of cellular processes, including proliferation, differentiation, and apoptosis. Although studies have shown its requirement for hematopoietic stem cell (HSC) development, its role in adult HSC maintenance, as well as the cellular and molecular mechanisms underlying Cbp function, is not clear. Here, we demonstrate a gradual loss of phenotypic HSCs and differentiation defects following conditional ablation of Cbp during adult homeostasis. In addition, Cbp-deficient HSCs reconstituted hematopoiesis with lower efficiency than their wild-type counterparts, and this response was readily exhausted under replicative stress. This phenotype relates to an alteration in cellular fate decisions for HSCs, with Cbp loss leading to an increase in differentiation, quiescence, and apoptosis. Genome-wide analyses of Cbp occupancy and differential gene expression upon Cbp deletion identified HSC-specific genes regulated by Cbp, providing a molecular basis for the phenotype. Finally, Cbp binding significantly overlapped at genes combinatorially bound by 7 major hematopoietic transcriptional regulators, linking Cbp to a critical HSC transcriptional regulatory network. Our data demonstrate that Cbp plays a role in adult HSC homeostasis by maintaining the balance between different HSC fate decisions, and our findings identify a putative HSC-specific transcriptional network coordinated by Cbp.

  2. Dynamic expression of TrkB receptor protein on proliferating and maturing cells in the adult mouse dentate gyrus

    PubMed Central

    Donovan, Michael H.; Yamaguchi, Masahiro; Eisch, Amelia J.

    2008-01-01

    Brain-derived neurotrophic factor (BDNF) is implicated in regulation of adult hippocampal neurogenesis, presumably via its primary receptor, TrkB, but controversy exists about how BDNF affects neurogenesis (e.g. proliferation vs. survival/differentiation). This controversy arises, in part, due to the lack of information about if and when TrkB is expressed on adult neural precursors in vivo. Using multiple methods to analyze proliferating and maturing cells in the adult mouse subgranular zone (SGZ), we find that the proportion of proliferating cells that are TrkB-IR is low and it remains low for at least one week following BrdU labeling, but increases as neuroblasts mature. Use of the nestin-GFP transgenic mouse revealed the likelihood of being TrkB-IR increased with presumed maturity of the cell type. Stem-like cells, which rarely divide, were likely to express TrkB. However, early progenitors and late progenitors, which are still in the cell cycle had rare TrkB expression. Immature neuroblasts, however, were more likely to express TrkB, especially as their morphology became more mature. Taken together, these findings emphasize that expression of TrkB protein is closely linked to progression towards neuronal maturity. This provides evidence that maturing cells but not proliferating cells in the adult mouse SGZ have the molecular machinery necessary to respond directly to BDNF. Furthermore, these findings lay critical groundwork for further exploration of the role of BDNF-TrkB signaling in regulation of adult hippocampal neurogenesis. PMID:18240316

  3. Expression of reelin in adult mammalian blood, liver, pituitary pars intermedia, and adrenal chromaffin cells.

    PubMed

    Smalheiser, N R; Costa, E; Guidotti, A; Impagnatiello, F; Auta, J; Lacor, P; Kriho, V; Pappas, G D

    2000-02-01

    Reelin regulates telencephalic and cerebellar lamination during mammalian development and is expressed in several structures of the adult brain; however, only traces of reelin were believed to be in peripheral tissues. Because reelin structurally resembles extracellular matrix proteins, and because many of these proteins are expressed in blood, we hypothesized that reelin also might be detectable in the circulation. Reelin (420 kDa) and two reelin-like immunoreactive bands (310 and 160 kDa) are expressed in serum and platelet-poor plasma of rats, mice, and humans, but these three bands were not detectable in serum of homozygous reeler (rl/rl) mice. Reelin plasma levels in heterozygous (rl/+) mice were half of those in wild-type littermates. Western blotting and immunocytochemistry using antireelin mAbs indicated that reelin-like immunoreactivity was expressed in a subset of chromaffin cells within the rat adrenal medulla and in a subset of cells coexpressing alpha-melanocyte-stimulating hormone within the pituitary pars intermedia. However, surgical removal of adrenal or pituitary failed to decrease the amount of reelin (420-kDa band) expressed in serum. Adult liver expressed one-third of the reelin mRNA concentration expressed in adult mouse cerebral cortex. Full-length reelin protein was detectable in liver extracts in situ; acutely isolated liver cells also secreted full-length reelin in vitro. Liver appears to be a prime candidate to produce and maintain the circulating reelin pool. It now becomes relevant to ask whether circulating reelin has a physiologic role on one or more peripheral target tissues.

  4. Expression of reelin in adult mammalian blood, liver, pituitary pars intermedia, and adrenal chromaffin cells

    PubMed Central

    Smalheiser, Neil R.; Costa, Erminio; Guidotti, Alessandro; Impagnatiello, Francesco; Auta, James; Lacor, Pascale; Kriho, Virginia; Pappas, George D.

    2000-01-01

    Reelin regulates telencephalic and cerebellar lamination during mammalian development and is expressed in several structures of the adult brain; however, only traces of reelin were believed to be in peripheral tissues. Because reelin structurally resembles extracellular matrix proteins, and because many of these proteins are expressed in blood, we hypothesized that reelin also might be detectable in the circulation. Reelin (420 kDa) and two reelin-like immunoreactive bands (310 and 160 kDa) are expressed in serum and platelet-poor plasma of rats, mice, and humans, but these three bands were not detectable in serum of homozygous reeler (rl/rl) mice. Reelin plasma levels in heterozygous (rl/+) mice were half of those in wild-type littermates. Western blotting and immunocytochemistry using antireelin mAbs indicated that reelin-like immunoreactivity was expressed in a subset of chromaffin cells within the rat adrenal medulla and in a subset of cells coexpressing α-melanocyte-stimulating hormone within the pituitary pars intermedia. However, surgical removal of adrenal or pituitary failed to decrease the amount of reelin (420-kDa band) expressed in serum. Adult liver expressed one-third of the reelin mRNA concentration expressed in adult mouse cerebral cortex. Full-length reelin protein was detectable in liver extracts in situ; acutely isolated liver cells also secreted full-length reelin in vitro. Liver appears to be a prime candidate to produce and maintain the circulating reelin pool. It now becomes relevant to ask whether circulating reelin has a physiologic role on one or more peripheral target tissues. PMID:10655522

  5. The association between different types of exercise and energy expenditure in young nonoverweight and overweight adults.

    PubMed

    Drenowatz, Clemens; Hand, Gregory A; Shook, Robin P; Jakicic, John M; Hebert, James R; Burgess, Stephanie; Blair, Steven N

    2015-03-01

    With decades of trends for decreasing activity during work and travel, exercise becomes an important contributor to total physical activity (PA) and energy expenditure. The purpose of this study was to examine the contribution of different types of exercise to the variability in energy expenditure and time spent at different PA intensities in young adults. Four hundred and seventeen adults (49.9% male; 46.2 overweight/obese) between 21 and 36 years of age provided valid objective PA and energy expenditure data, assessed via the SenseWear Armband (BodyMedia Inc.). Frequency and duration of participation in various exercise types was self-reported. Weight status was based on body mass index (BMI) (kg/m(2)) with body weight and height being measured according to standard procedures. Eighty-four percent of the participants reported regular exercise engagement with no difference in participation rate by sex or BMI category. Exercise time along with sex and ethnicity explained roughly 60% of the variability in total daily energy expenditure (TDEE) while the association between exercise and time spent in moderate to vigorous PA or being sedentary was low or nonsignificant. Engagement in endurance exercise and sports contributed predominantly to the variability in energy expenditure and PA in nonoverweight participants. In overweight/obese participants engagement in resistance exercise and swimming contributed significantly to variability in TDEE. Current exercise recommendations focus primarily on aerobic exercise, but results of the present study suggest that nonweight-bearing exercises, such as resistance exercise and swimming, contribute significantly to the variability in TDEE in overweight/obese adults, which would make these types of activities viable options for exercise interventions. PMID:25647557

  6. Abuse in Childhood and Adolescence As a Predictor of Type 2 Diabetes in Adult Women

    PubMed Central

    Rich-Edwards, Janet W.; Spiegelman, Donna; Lividoti Hibert, Eileen N.; Jun, Hee-Jin; Todd, Tamarra James; Kawachi, Ichiro; Wright, Rosalind J.

    2010-01-01

    Background Although child abuse is associated with obesity, it is not known whether early abuse increases risk of type 2 diabetes. Purpose To investigate associations of child and adolescent abuse with adult diabetes Methods Proportional hazards models were used to examine associations of lifetime abuse reported in 2001 with risk of diabetes from 1989 to 2005 among 67,853 women in the Nurses Health Study II. Data were analyzed in 2009. Results Child or teen physical abuse was reported by 54% and sexual abuse by 34% of participants. Models were adjusted for age, race, body type at age 5 years, and parental education and history of diabetes. Compared to women who reported no physical abuse, the hazards ratio (HR) was 1.03 (95% CI: 0.91, 1.17) for mild physical abuse, 1.26 (1.14, 1.40) for moderate physical abuse, and 1.54 (1.34, 1.77) for severe physical abuse. Compared with women reporting no sexual abuse in childhood or adolescence, the HR was 1.16 (1.05, 1.29) for unwanted sexual touching, 1.34 (1.13, 1.59) for one episode of forced sexual activity, and 1.69 (1.45, 1.97) for repeated forced sex. Adult BMI accounted for 60% (32%, 87%) of the association of child and adolescent physical abuse and 64% (38%, 91%) of the association of sexual abuse with diabetes. Conclusions Moderate to severe physical and sexual abuse in childhood and adolescence have dose response associations with risk of type 2 diabetes among adult women. This excess risk is partially explained by the higher BMI of women with a history of early abuse. PMID:21084073

  7. Cost-Effectiveness of Increasing Influenza Vaccination Coverage in Adults with Type 2 Diabetes in Turkey

    PubMed Central

    Akın, Levent; Macabéo, Bérengère; Caliskan, Zafer; Altinel, Serdar; Satman, Ilhan

    2016-01-01

    Objective In Turkey, the prevalence of diabetes is high but the influenza vaccination coverage rate (VCR) is low (9.1% in 2014), despite vaccination being recommended and reimbursed. This study evaluated the cost-effectiveness of increasing the influenza VCR of adults with type 2 diabetes in Turkey to 20%. Methods A decision-analytic model was adapted to Turkey using data derived from published sources. Direct medical costs and indirect costs due to productivity loss were included in the societal perspective. The time horizon was set at 1 year to reflect the seasonality of influenza. Results Increasing the VCR for adults with type 2 diabetes to 20% is predicted to avert an additional 19,777 influenza cases, 2376 hospitalizations, and 236 deaths. Associated influenza costs avoided were estimated at more than 8.3 million Turkish Lira (TRY), while the cost of vaccination would be more than TRY 8.4 million. The incremental cost-effectiveness ratio was estimated at TRY 64/quality-adjusted life years, which is below the per capita gross domestic product of TRY 21,511 and therefore very cost-effective according to World Health Organization guidelines. Factors most influencing the incremental cost-effectiveness ratio were the excess hospitalization rate, inpatient cost, vaccine effectiveness against hospitalization, and influenza attack rate. Increasing the VCR to >20% was also estimated to be very cost-effective. Conclusions Increasing the VCR for adults with type 2 diabetes in Turkey to ≥20% would be very cost-effective. PMID:27322384

  8. The Oxygen Environment at Birth Specifies the Population of Alveolar Epithelial Stem Cells in the Adult Lung.

    PubMed

    Yee, Min; Gelein, Robert; Mariani, Thomas J; Lawrence, B Paige; O'Reilly, Michael A

    2016-05-01

    Alveolar epithelial type II cells (AEC2) maintain pulmonary homeostasis by producing surfactant, expressing innate immune molecules, and functioning as adult progenitor cells for themselves and alveolar epithelial type I cells (AEC1). How the proper number of alveolar epithelial cells is determined in the adult lung is not well understood. Here, BrdU labeling, genetic lineage tracing, and targeted expression of the anti-oxidant extracellular superoxide dismutase in AEC2s are used to show how the oxygen environment at birth influences postnatal expansion of AEC2s and AEC1s in mice. Birth into low (12%) or high (≥60%) oxygen stimulated expansion of AEC2s through self-renewal and differentiation of the airway Scgb1a1 + lineage. This non-linear or hormesis response to oxygen was specific for the alveolar epithelium because low oxygen stimulated and high oxygen inhibited angiogenesis as defined by changes in V-cadherin and PECAM (CD31). Although genetic lineage tracing studies confirmed adult AEC2s are stem cells for AEC1s, we found no evidence that postnatal growth of AEC1s were derived from self-renewing Sftpc + or the Scbg1a1 + lineage of AEC2s. Taken together, our results show how a non-linear response to oxygen at birth promotes expansion of AEC2s through two distinct lineages. Since neither lineage contributes to the postnatal expansion of AEC1s, the ability of AEC2s to function as stem cells for AEC1s appears to be restricted to the adult lung. Stem Cells 2016;34:1396-1406. PMID:26891117

  9. The Neurogenic Factor NeuroD1 Is Expressed in Post-Mitotic Cells during Juvenile and Adult Xenopus Neurogenesis and Not in Progenitor or Radial Glial Cells

    PubMed Central

    D'Amico, Laure Anne; Boujard, Daniel; Coumailleau, Pascal

    2013-01-01

    In contrast to mammals that have limited proliferation and neurogenesis capacities, the Xenopus frog exhibit a great potential regarding proliferation and production of new cells in the adult brain. This ability makes Xenopus a useful model for understanding the molecular programs required for adult neurogenesis. Transcriptional factors that control adult neurogenesis in vertebrate species undergoing widespread neurogenesis are unknown. NeuroD1 is a member of the family of proneural genes, which function during embryonic neurogenesis as a potent neuronal differentiation factor. Here, we study in detail the expression of NeuroD1 gene in the juvenile and adult Xenopus brains by in situ hybridization combined with immunodetections for proliferation markers (PCNA, BrdU) or in situ hybridizations for cell type markers (Vimentin, Sox2). We found NeuroD1 gene activity in many brain regions, including olfactory bulbs, pallial regions of cerebral hemispheres, preoptic area, habenula, hypothalamus, cerebellum and medulla oblongata. We also demonstrated by double staining NeuroD1/BrdU experiments, after long post-BrdU administration survival times, that NeuroD1 gene activity was turned on in new born neurons during post-metamorphic neurogenesis. Importantly, we provided evidence that NeuroD1-expressing cells at this brain developmental stage were post-mitotic (PCNA-) cells and not radial glial (Vimentin+) or progenitors (Sox2+) cells. PMID:23799108

  10. Hematopoietic bone marrow cells participate in endothelial, but not epithelial or mesenchymal cell renewal in adult rats

    PubMed Central

    Odörfer, Kathrin I; Egerbacher, Monika; Unger, Nina J; Weber, Karin; Jamnig, Angelika; Lepperdinger, Günter; Kleiter, Miriam; Sandgren, Eric P; Erben, Reinhold G

    2011-01-01

    The extent to which bone marrow (BM) contributes to physiological cell renewal is still controversial. Using the marker human placental alkaline phosphatase (ALPP) which can readily be detected in paraffin and plastic sections by histochemistry or immunohistochemistry, and in ultrathin sections by electron microscopy after pre-embedding staining, we examined the role of endogenous BM in physiological cell renewal by analysing tissues from lethally irradiated wild-type inbred Fischer 344 (F344) rats transplanted (BMT) with unfractionated BM from ALPP-transgenic F344 rats ubiquitously expressing the marker. Histochemical, immunohistochemical and immunoelectron microscopic analysis showed that the proportion of ALPP+ capillary endothelial cells (EC) profoundly increased from 1 until 6 months after BMT in all organs except brain and adrenal medulla. In contrast, pericytes and EC in large blood vessels were ALPP–. Epithelial cells in kidney, liver, pancreas, intestine and brain were recipient-derived at all time-points. Similarly, osteoblasts, chondrocytes, striated muscle and smooth muscle cells were exclusively of recipient origin. The lack of mesenchymal BM-derived cells in peripheral tissues prompted us to examine whether BMT resulted in engraftment of mesenchymal precursors. Four weeks after BMT, all haematopoietic BM cells were of donor origin by flow cytometric analysis, whereas isolation of BM mesenchymal stem cells (MSC) failed to show engraftment of donor MSC. In conclusion, our data show that BM is an important source of physiological renewal of EC in adult rats, but raise doubt whether reconstituted irradiated rats are an apt model for BM-derived regeneration of mesenchymal cells in peripheral tissues. PMID:21091631

  11. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    NASA Astrophysics Data System (ADS)

    van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

    2014-04-01

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

  12. Cell growth characteristics, differentiation frequency, and immunophenotype of adult ear mesenchymal stem cells.

    PubMed

    Staszkiewicz, Jaroslaw; Frazier, Trivia P; Rowan, Brian G; Bunnell, Bruce A; Chiu, Ernest S; Gimble, Jeffrey M; Gawronska-Kozak, Barbara

    2010-01-01

    Ear mesenchymal stem cells (EMSCs) represent a readily accessible population of stem-like cells that are adherent, clonogenic, and have the ability to self-renew. Previously, we have demonstrated that they can be induced to differentiate into adipocyte, osteocyte, chondrocyte, and myocyte lineages. The purpose of the current study was to characterize the growth kinetics of the cells and to determine their ability to form colonies of fibroblasts, adipocytes, osteocytes, and chondrocytes. In addition, the immunophenotypes of freshly isolated and culture-expanded cells were evaluated. From 1 g of tissue, we were able to isolate an average of 7.8 x 10(6) cells exhibiting a cell cycle length of approximately 2-3 days. Colony-forming unit (CFU) assays indicated high proliferation potential, and confirmed previously observed multipotentiality of the cells. Fluorescence-activated cell sorting (FACS) showed that EMSCs were negative for hematopoietic markers (CD4, CD45), proving that they did not derive from circulating hematopoietic cells. The FACS analyses also showed high expression of stem cell antigen-1 (Sca-1) with only a minor population of cells expressing CD117, thus identifying Sca-1 as the more robust stem cell biomarker. Additionally, flow cytometry data revealed that the expression patterns of hematopoietic, stromal, and stem cell markers were maintained in the passaged EMSCs, consistent with the persistence of an undifferentiated state. This study indicates that EMSCs provide an alternative model for in vitro analyses of adult mesenchymal stem cells (MSCs). Further studies will be necessary to determine their utility for tissue engineering and regenerative medical applications. PMID:19400629

  13. Cerebellar stem cells do not produce neurons and astrocytes in adult mouse

    SciTech Connect

    Su, Xin; Guan, Wuqiang; Yu, Yong-Chun; Fu, Yinghui

    2014-07-18

    Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1{sup +} or nestin{sup +} stem cells exist, and most of them are quiescent. • Cell proliferation rate is diversified among cerebellar regions and decreases over time. - Abstract: Although previous studies implied that cerebellar stem cells exist in some adult mammals, little is known about whether these stem cells can produce new neurons and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.) injection, we found that there are abundant BrdU{sup +} cells in adult mouse cerebellum, and their quantity and density decreases significantly over time. We also found cell proliferation rate is diversified in different cerebellar regions. Among these BrdU{sup +} cells, very few are mash1{sup +} or nestin{sup +} stem cells, and the vast majority of cerebellar stem cells are quiescent. Data obtained by in vivo retrovirus injection indicate that stem cells do not produce neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by retrovirus are Iba1{sup +} microglia. These results indicate that very few stem cells exist in adult mouse cerebellum, and none of these stem cells contribute to neurogenesis and astrogenesis under physiological condition.

  14. Perioperative anaesthetic management of penetrating neck injury associated with Rh blood type in a young adult

    PubMed Central

    Wang, Tao; Zhou, Yeting; Shi, Jiaohui; Wang, Zhichun

    2013-01-01

    We describe here a young adult patient with penetrating neck injuries (PNI) with an Rh negative blood type and discuss the perioperative anaesthetic management of single-stage surgical exploration under general anaesthesia and extracorporeal circulation in this patient. The patient had zone II PNI and he was in a haemodynamically progressive unstable state, and the knife penetrated the left internal jugular vein, superior thyroid artery and recurrent laryngeal nerve; the trachea and the oesophagus were swelling at a rapid rate. Eight weeks after operation, the patient was discharged from the hospital without any complications. PMID:23429024

  15. Novel Cell Types, Neurosecretory Cells and Body Plan of the Early-Diverging Metazoan, Trichoplax adhaerens

    PubMed Central

    Smith, Carolyn L.; Varoqueaux, Frédérique; Kittelmann, Maike; Azzam, Rita N.; Cooper, Benjamin; Winters, Christine A.; Eitel, Michael; Fasshauer, Dirk; Reese, Thomas S.

    2014-01-01

    Summary Background Trichoplax adhaerens is the best-known member of the Phylum Placozoa, one of the earliest-diverging metazoan phyla. It is a small disk-shaped animal that glides on surfaces in warm oceans to feed on algae. Prior anatomical studies of Trichoplax revealed that it has a simple three-layered organization with four somatic cell types. Results We reinvestigate the cellular organization of Trichoplax using advanced freezing and microscopy techniques to identify localize and count cells. Six somatic cell types are deployed in stereotyped positions. A thick ventral plate, comprising the majority of the cells, includes ciliated epithelial cells, newly identified lipophil cells packed with large lipid granules, and gland cells. Lipophils project deep into the interior where they alternate with regularly spaced fiber cells whose branches contact all other cell types, including cells of the dorsal and ventral epithelium. Crystal cells, each containing a birefringent crystal, are arrayed around the rim. Gland cells express several proteins typical of neurosecretory cells, and a subset of them, around the rim, also expresses an FMRFamide-like neuropeptide. Conclusions Structural analysis of Trichoplax with significantly improved techniques provides an advance in understanding its cell types and their distributions. We find two previously undetected cell types, lipohil and crystal cells, and an organized body plan in which different cell types are arranged in distinct patterns. The composition of gland cells suggests that they are neurosecretory cells and could control locomotor and feeding behavior. PMID:24954051

  16. Origins of adult pigmentation: diversity in pigment stem cell lineages and implications for pattern evolution

    PubMed Central

    Spiewak, Jessica E.

    2014-01-01

    Summary Teleosts comprise about half of all vertebrate species and exhibit an extraordinary diversity of adult pigment patterns that function in shoaling, camouflage and mate choice and have played important roles in speciation. Here, we review recent studies that have identified several distinct neural crest lineages, with distinct genetic requirements, that give rise to adult pigment cells in fishes. These lineages include post-embryonic, peripheral nerve associated stem cells that generate black melanophores and iridescent iridophores, cells derived directly from embryonic neural crest cells that generate yellow-orange xanthophores, and bipotent stem cells that generate both melanophores and xanthophores. This complexity in adult chromatophore lineages has implications for our understanding of adult traits, melanoma, and the evolutionary diversification of pigment cell lineages and patterns. PMID:25421288

  17. Origins of adult pigmentation: diversity in pigment stem cell lineages and implications for pattern evolution.

    PubMed

    Parichy, David M; Spiewak, Jessica E

    2015-01-01

    Teleosts comprise about half of all vertebrate species and exhibit an extraordinary diversity of adult pigment patterns that function in shoaling, camouflage, and mate choice and have played important roles in speciation. Here, we review studies that have identified several distinct neural crest lineages, with distinct genetic requirements, that give rise to adult pigment cells in fishes. These lineages include post-embryonic, peripheral nerve-associated stem cells that generate black melanophores and iridescent iridophores, cells derived directly from embryonic neural crest cells that generate yellow-orange xanthophores, and bipotent stem cells that generate both melanophores and xanthophores. This complexity in adult chromatophore lineages has implications for our understanding of adult traits, melanoma, and the evolutionary diversification of pigment cell lineages and patterns.

  18. Regulatory focus and adherence to self-care behaviors among adults with type 2 diabetes.

    PubMed

    Avraham, Rinat; Van Dijk, Dina; Simon-Tuval, Tzahit

    2016-09-01

    The aims of this study were, first, to test the association between regulatory focus of adults with type 2 diabetes and their adherence to two types of self-care behaviors - lifestyle change (e.g. physical activity and diet) and medical care regimens (blood-glucose monitoring, foot care and medication usage). Second, to explore whether a fit between the message framing and patients' regulatory focus would improve their intentions to adhere specifically when the type of behavior fits the patients' regulatory focus as well. A cross-sectional study was conducted among 130 adults with type 2 diabetes who were hospitalized in an academic medical center. The patients completed a set of questionnaires that included their diabetes self-care activities, regulatory focus, self-esteem and demographic, socioeconomic and clinical data. In addition, participants were exposed to either a gain-framed or a loss-framed message, and were then asked to indicate their intention to improve adherence to self-care behaviors. A multivariable linear regression model revealed that promoters reported higher adherence to lifestyle change behaviors than preventers did (B = .60, p = .028). However, no effect of regulatory focus on adherence to medical care regimens was found (B = .46, p = .114). In addition, preventers reported higher intentions to adhere to medical care behaviors when the message framing was congruent with prevention focus (B = 1.16, p = .023). However, promoters did not report higher intentions to adhere to lifestyle behaviors when the message framing was congruent with promotion focus (B = -.16, p = .765). These findings justify the need to develop tailor-made interventions that are adjusted to both patients' regulatory focus and type of health behavior. PMID:26576471

  19. Age-associated Failure to Adjust Type I Interferon Receptor Signaling Thresholds after T-cell Activation1

    PubMed Central

    Li, Guangjin; Ju, Jihang; Weyand, Cornelia M.; Goronzy, Jörg J.

    2015-01-01

    With increasing age, naïve CD4 T cells acquire intrinsic defects that compromise their ability to respond and differentiate. Type I IFNs, pervasive constituents of the environment in which adaptive immune responses occur, are known to regulate T cell differentiation and survival. Activated naïve CD4 T cells from older individuals have reduced responses to type I IFN, a defect that develops during activation and is not observed in quiescent naïve CD4 T cells. Naïve CD4 T cells from young adults upregulate the expression of STAT1 and STAT5 after activation, lowering their threshold to respond to type I IFN stimulation. The heightened STAT signaling is critical to maintain the expression of CD69 that regulates lymphocyte egress and the ability to produce IL-2 and to survive. Although activation of T cells from older adults also induces transcription of STAT1 and STAT5, failure to exclude SHP1 to the signaling complex blunts their type I IFN response. In summary, our data show that type I IFN signaling thresholds in naïve CD4 T cells after activation are dynamically regulated to respond environmental cues for clonal expansion and memory cell differentiation. Naïve CD4 T cells from older adults have a defect in this threshold calibration. Restoring their ability to respond to type I IFN emerges as a promising target to restore T cell responses and improve the induction of T cell memory. PMID:26091718

  20. Everyday Living with Diabetes Described by Family Members of Adult People with Type 1 Diabetes

    PubMed Central

    Paavilainen, Eija; Åstedt-Kurki, Päivi

    2013-01-01

    The aim of this study was to explore family members' experiences of everyday life in families with adult people living with type 1 diabetes. The grounded theory method was used to gather and analyse data from the interviews of nineteen family members. Six concepts describing the family members' views on everyday living with diabetes were generated on the basis of the data. Everyday life with diabetes is described as being intertwined with hypoglycemia. Becoming acquainted with diabetes takes place little by little. Being involved in the management and watching self-management from the sidelines are concepts describing family members' participation in the daily management of diabetes. The family members are also integrating diabetes into everyday life. Living on an emotional roller-coaster tells about the thoughts and feelings that family members experience. Family members of adult people with diabetes are involved in the management of the diabetes in many ways and experience many concerns. The family members' point of view is important to take into consideration when developing education for adults with diabetes. PMID:24455251

  1. Everyday living with diabetes described by family members of adult people with type 1 diabetes.

    PubMed

    Rintala, Tuula-Maria; Paavilainen, Eija; Astedt-Kurki, Päivi

    2013-01-01

    The aim of this study was to explore family members' experiences of everyday life in families with adult people living with type 1 diabetes. The grounded theory method was used to gather and analyse data from the interviews of nineteen family members. Six concepts describing the family members' views on everyday living with diabetes were generated on the basis of the data. Everyday life with diabetes is described as being intertwined with hypoglycemia. Becoming acquainted with diabetes takes place little by little. Being involved in the management and watching self-management from the sidelines are concepts describing family members' participation in the daily management of diabetes. The family members are also integrating diabetes into everyday life. Living on an emotional roller-coaster tells about the thoughts and feelings that family members experience. Family members of adult people with diabetes are involved in the management of the diabetes in many ways and experience many concerns. The family members' point of view is important to take into consideration when developing education for adults with diabetes. PMID:24455251

  2. How do different types of childhood maltreatment relate to adult personality pathology?

    PubMed

    Cohen, Lisa J; Foster, Michelle; Nesci, Cristina; Tanis, Thachell; Halmi, Winter; Galynker, Igor

    2013-03-01

    There are insufficient data investigating the relative associations between different kinds of childhood maltreatment and the severity of adult personality pathology. Personality pathology and childhood maltreatment (sexual, physical, and emotional abuse and neglect) were assessed in 156 nonpsychotic psychiatric patients. Measures included the Personality Diagnostic Questionnaire for DSM-IV (PDQ-4+), the Childhood Trauma Questionnaire (CTQ), the Multidimensional Neglectful Behavior Scale (MNBS), and the Conflict Tactics Scales Parent-Child version (CTSPC-CA). Bivariate logistic regression analyses revealed each maltreatment type to significantly correlate with adult personality pathology. However, in multivariate logistic analyses controlling for education, neglect and emotional abuse were the only significant predictors of adult personality pathology (adjusted odds ratio [AOR] for MNBS neglect, 3.60; AOR for CTQ emotional abuse, 3.81). Analysis of the CTSPC-CA yielded a strong effect on maternal (AOR, 3.71) but not paternal neglect. These data suggest that clinicians should routinely evaluate for histories of neglect and emotional abuse, particularly in patients with marked personality pathology.

  3. Strong associations between the pesticide hexachlorocyclohexane and type 2 diabetes in Saudi adults.

    PubMed

    Al-Othman, Abdulaziz; Yakout, Sobhy; Abd-Alrahman, Sherif H; Al-Daghri, Nasser M

    2014-08-29

    Pesticide exposure has been implicated as an environmental risk factor for the development of type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the association of the body burden of the pesticide hexachlorocyclohexane (HCH) with the risk of T2DM in a sample of adults from Saudi Arabia. Serum samples were obtained from 280 adult subjects. Hexachlorocyclohexane isomer residues were measured by high-resolution gas chromatography-mass spectrometry. Data on lifestyle, dietary habits, and health status were gathered. Associations between exposure and T2DM were analyzed by logistic regression. Around 49% of adults enrolled in this study were diagnosed with T2DM. Among various HCH isomers, serum concentrations of the pesticides β and γ-HCH were most strongly and consistently linked to T2DM in our studied subjects. Associations of HCH varied across five components of the metabolic syndrome. It positively and significantly associated with four out of the five components, especially elevated triglycerides, high fasting glucose, high blood pressure and HOMA-IR but negatively and significantly with HDL-cholesterol. This study in line with earlier ones about diabetes associated with HCH pesticide exposure and proposes possible hormonal pathways worthy of further investigation.

  4. Cell type-dependent Erk-Akt pathway crosstalk regulates the proliferation of fetal neural progenitor cells.

    PubMed

    Rhim, Ji Heon; Luo, Xiangjian; Gao, Dongbing; Xu, Xiaoyun; Zhou, Tieling; Li, Fuhai; Wang, Ping; Wong, Stephen T C; Xia, Xiaofeng

    2016-01-01

    Neural progenitor (NP) cells are the multipotent cells that produce neurons and glia in the central nervous system. Compounds regulating their proliferation are key to both understanding brain development and unlocking their potential in regenerative repair. We discuss a chemical screen that unexpectedly identified inhibitors of Erk signaling potently promoting the self-renewing divisions of fetal NP cells. This occurred through crosstalk between Erk and Akt signaling cascades. The crosstalk mechanism is cell type-specific, and is not detected in adult NP cells as well as brain tumor cells. The mechanism was also shown to be independent from the GSK-3 signaling pathway, which has been reported to be a major regulator of NP cell homeostasis and inhibitors to which were also identified in the screen. In vitro Erk inhibition led to the prolonged rapid expansion of fetal NP cells while retaining their multipotency. In vivo inhibitor administration significantly inhibited the neuronal differentiation, and resulted in increased proliferative progenitor cells in the ventricular/subventricular zone (VZ/SVZ) of the embryonic cortex. Our results uncovered a novel regulating pathway for NP cell proliferation in the developing brain. The discovery provides a pharmacological basis for in vitro expansion and in vivo manipulation of NP cells. PMID:27211495

  5. Cell type-dependent Erk-Akt pathway crosstalk regulates the proliferation of fetal neural progenitor cells

    PubMed Central

    Rhim, Ji heon; Luo, Xiangjian; Gao, Dongbing; Xu, Xiaoyun; Zhou, Tieling; Li, Fuhai; Wang, Ping; Wong, Stephen T. C.; Xia, Xiaofeng

    2016-01-01

    Neural progenitor (NP) cells are the multipotent cells that produce neurons and glia in the central nervous system. Compounds regulating their proliferation are key to both understanding brain development and unlocking their potential in regenerative repair. We discuss a chemical screen that unexpectedly identified inhibitors of Erk signaling potently promoting the self-renewing divisions of fetal NP cells. This occurred through crosstalk between Erk and Akt signaling cascades. The crosstalk mechanism is cell type-specific, and is not detected in adult NP cells as well as brain tumor cells. The mechanism was also shown to be independent from the GSK-3 signaling pathway, which has been reported to be a major regulator of NP cell homeostasis and inhibitors to which were also identified in the screen. In vitro Erk inhibition led to the prolonged rapid expansion of fetal NP cells while retaining their multipotency. In vivo inhibitor administration significantly inhibited the neuronal differentiation, and resulted in increased proliferative progenitor cells in the ventricular/subventricular zone (VZ/SVZ) of the embryonic cortex. Our results uncovered a novel regulating pathway for NP cell proliferation in the developing brain. The discovery provides a pharmacological basis for in vitro expansion and in vivo manipulation of NP cells. PMID:27211495

  6. Cloning adult farm animals: a review of the possibilities and problems associated with somatic cell nuclear transfer.

    PubMed

    Edwards, J L; Schrick, F N; McCracken, M D; van Amstel, S R; Hopkins, F M; Welborn, M G; Davies, C J

    2003-08-01

    In 1997, Wilmut et al. announced the birth of Dolly, the first ever clone of an adult animal. To date, adult sheep, goats, cattle, mice, pigs, cats and rabbits have been cloned using somatic cell nuclear transfer. The ultimate challenge of cloning procedures is to reprogram the somatic cell nucleus for development of the early embryo. The cell type of choice for reprogramming the somatic nucleus is an enucleated oocyte. Given that somatic cells are easily obtained from adult animals, cultured in the laboratory and then genetically modified, cloning procedures are ideal for introducing specific genetic modifications in farm animals. Genetic modification of farm animals provides a means of studying genes involved in a variety of biological systems and disease processes. Moreover, genetically modified farm animals have created a new form of 'pharming' whereby farm animals serve as bioreactors for production of pharmaceuticals or organ donors. A major limitation of cloning procedures is the extreme inefficiency for producing live offspring. Dolly was the only live offspring produced after 277 attempts. Similar inefficiencies for cloning adult animals of other species have been described by others. Many factors related to cloning procedures and culture environment contribute to the death of clones, both in the embryonic and fetal periods as well as during neonatal life. Extreme inefficiencies of this magnitude, along with the fact that death of the surrogate may occur, continue to raise great concerns with cloning humans.

  7. Cloning adult farm animals: a review of the possibilities and problems associated with somatic cell nuclear transfer.

    PubMed

    Edwards, J L; Schrick, F N; McCracken, M D; van Amstel, S R; Hopkins, F M; Welborn, M G; Davies, C J

    2003-08-01

    In 1997, Wilmut et al. announced the birth of Dolly, the first ever clone of an adult animal. To date, adult sheep, goats, cattle, mice, pigs, cats and rabbits have been cloned using somatic cell nuclear transfer. The ultimate challenge of cloning procedures is to reprogram the somatic cell nucleus for development of the early embryo. The cell type of choice for reprogramming the somatic nucleus is an enucleated oocyte. Given that somatic cells are easily obtained from adult animals, cultured in the laboratory and then genetically modified, cloning procedures are ideal for introducing specific genetic modifications in farm animals. Genetic modification of farm animals provides a means of studying genes involved in a variety of biological systems and disease processes. Moreover, genetically modified farm animals have created a new form of 'pharming' whereby farm animals serve as bioreactors for production of pharmaceuticals or organ donors. A major limitation of cloning procedures is the extreme inefficiency for producing live offspring. Dolly was the only live offspring produced after 277 attempts. Similar inefficiencies for cloning adult animals of other species have been described by others. Many factors related to cloning procedures and culture environment contribute to the death of clones, both in the embryonic and fetal periods as well as during neonatal life. Extreme inefficiencies of this magnitude, along with the fact that death of the surrogate may occur, continue to raise great concerns with cloning humans. PMID:12846674

  8. Abnormal centrosome amplification in cells through the targeting of Ran-binding protein-1 by the human T cell leukemia virus type-1 Tax oncoprotein

    PubMed Central

    Peloponese, Jean-Marie; Haller, Kerstin; Miyazato, Akiko; Jeang, Kuan-Teh

    2005-01-01

    Human T cell leukemia virus type-1 (HTLV-1) is an oncogenic retrovirus etiologically causal of adult T cell leukemia. The virus encodes a Tax oncoprotein that functions in transcriptional regulation, cell cycle control, and transformation. Because adult T cell leukemia like many other human cancers is a disease of genomic instability with frequent gains and losses of chromosomes, to understand this disease it is important to comprehend how HTLV-1 engenders aneuploidy in host cells. In this regard, loss of cell cycle checkpoints permits tolerance of aneuploidy but does not explain how aneuploidy is created. We show here that HTLV-1 Tax causes abnormal centrosome fragmentation in the mitotic phase of the cell cycle. We report that Tax directly binds Ran and Ran-binding protein-1, locates to centrosomes/spindle poles, and causes supernumerary centrosomes. PMID:16365316

  9. Overlap of genetic susceptibility to type 1 diabetes, type 2 diabetes, and latent autoimmune diabetes in adults.

    PubMed

    Basile, Kevin J; Guy, Vanessa C; Schwartz, Stanley; Grant, Struan F A

    2014-01-01

    Despite the notion that there is a degree of commonality to the biological etiology of type 1 diabetes (T1D) and type 2 diabetes (T2D), the lack of overlap in the genetic factors underpinning each of them suggests very distinct mechanisms. A disorder considered to be at the "intersection" of these two diseases is "latent autoimmune diabetes in adults" (LADA). Interestingly, genetic signals from both T1D and T2D are also seen in LADA, including the key HLA and transcription factor 7-like 2 (TCF7L2) loci, but the magnitudes of these effects are more complex than just pointing to LADA as being a simple admixture of T1D and T2D. We review the current status of the understanding of the genetics of LADA and place it in the context of what is known about the genetics of its better-studied "cousins," T1D and T2D, especially with respect to the myriad of discoveries made over the last decade through genome-wide association studies.

  10. Star cell type core configuration for structural sandwich materials

    DOEpatents

    Christensen, R.M.

    1995-08-01

    A new pattern for cellular core material used in sandwich type structural materials is disclosed. The new pattern involves star shaped cells intermixed with hexagonal shaped cells. The new patterned cellular core material includes star shaped cells interconnected at points thereof and having hexagonal shape cells positioned adjacent the star points. The new pattern allows more flexibility and can conform more easily to curved shapes. 3 figs.

  11. Altered regulatory T cell phenotype in latent autoimmune diabetes of the adults (LADA).

    PubMed

    Radenkovic, M; Silver, C; Arvastsson, J; Lynch, K; Lernmark, Å; Harris, R A; Agardh, C-D; Cilio, C M

    2016-10-01

    Latent autoimmune diabetes of the adults (LADA) accounts for up to 12% of all patients with diabetes. Initially the disease resembles type 2 diabetes (T2D); however, the typical presence of β cell autoantibodies indicates an autoimmune basis of LADA. While dysfunctional regulatory T cells (Tregs ) have been implicated in autoimmune diabetes, these cells have been scarcely studied in LADA. The aim of this study was to investigate the frequency and phenotype of circulating Tregs in LADA patients early during disease progression. Flow cytometric analysis was performed on whole blood and peripheral mononuclear cells (PBMC) from patients diagnosed with LADA prior to insulin deficiency (n = 39) and from healthy volunteers (n = 20). Overall, we found the frequency and activation status of peripheral putative Tregs to be altered in LADA patients compared to healthy controls. While total T cells and CD4(+) T cells expressing high levels of CD25 (CD4(+) CD25(hi) ) were unchanged, the frequency and total numbers of CD4(+) T cells expressing an intermediate level of CD25 (CD4(+) CD25(int) ) were decreased in LADA patients. Interestingly, the expression of the Treg -specific marker forkhead box protein 3 (FoxP3), as well as the activation and memory makers CD69, cytotoxic T lymphocyte associated antigen 4 (CTLA-4), CCR4 and CD45RO were increased in CD4(+) CD25(+) T cells of the patients. Our data depict phenotypical changes in T cells of LADA patients that may reflect a derangement in peripheral immune regulation contributing to the slow process leading to insulin-dependent diabetes in these patients.

  12. Generation and characterization of LIF-dependent canine induced pluripotent stem cells from adult dermal fibroblasts.

    PubMed

    Whitworth, Deanne J; Ovchinnikov, Dmitry A; Wolvetang, Ernst J

    2012-08-10

    Dogs provide a more clinically relevant model of human disease than rodents, particularly with respect to hereditary diseases. Thus, the availability of canine stem cells will greatly facilitate the use of the dog in the development of stem cell-based gene therapies and regenerative medicine. In this study we describe the production of canine induced pluripotent stem cells (ciPSCs) from adult dermal fibroblasts. These cells have a morphology resembling previously described canine embryonic stem cells, a normal karyotype, and express pluripotency markers including alkaline phosphatase, Nanog, Oct4, Telomerase, SSEA1, SSEA4, TRA1-60, TRA1-81, and Rex1. Furthermore, the inactive X chromosome is reactivated indicating a ground-state pluripotency. In culture they readily form embryoid bodies, which in turn give rise to cell types from all 3 embryonic germ layers, as indicated by expression of the definitive endoderm markers Cxcr4 and α-fetoprotein, mesoderm markers Collagen IIA and Gata2, and ectoderm markers βIII-tubulin, Enolase, and Nestin. Of particular significance is the observation that these ciPSCs are dependent only on leukemia inhibitory factor (LIF), making them similar to mouse and canine embryonic stem cells, but strikingly unlike the ciPSCs recently described in two other studies, which were dependent on both basic fibroblast growth factor and LIF in order to maintain their pluripotency. Thus, our ciPSCs closely resemble mouse ESCs derived from the inner cell mass of preimplantation embryos, while the previously described ciPSCs appear to be more representative of cells from the epiblast of mouse postimplantation embryos.

  13. Altered regulatory T cell phenotype in latent autoimmune diabetes of the adults (LADA).

    PubMed

    Radenkovic, M; Silver, C; Arvastsson, J; Lynch, K; Lernmark, Å; Harris, R A; Agardh, C-D; Cilio, C M

    2016-10-01

    Latent autoimmune diabetes of the adults (LADA) accounts for up to 12% of all patients with diabetes. Initially the disease resembles type 2 diabetes (T2D); however, the typical presence of β cell autoantibodies indicates an autoimmune basis of LADA. While dysfunctional regulatory T cells (Tregs ) have been implicated in autoimmune diabetes, these cells have been scarcely studied in LADA. The aim of this study was to investigate the frequency and phenotype of circulating Tregs in LADA patients early during disease progression. Flow cytometric analysis was performed on whole blood and peripheral mononuclear cells (PBMC) from patients diagnosed with LADA prior to insulin deficiency (n = 39) and from healthy volunteers (n = 20). Overall, we found the frequency and activation status of peripheral putative Tregs to be altered in LADA patients compared to healthy controls. While total T cells and CD4(+) T cells expressing high levels of CD25 (CD4(+) CD25(hi) ) were unchanged, the frequency and total numbers of CD4(+) T cells expressing an intermediate level of CD25 (CD4(+) CD25(int) ) were decreased in LADA patients. Interestingly, the expression of the Treg -specific marker forkhead box protein 3 (FoxP3), as well as the activation and memory makers CD69, cytotoxic T lymphocyte associated antigen 4 (CTLA-4), CCR4 and CD45RO were increased in CD4(+) CD25(+) T cells of the patients. Our data depict phenotypical changes in T cells of LADA patients that may reflect a derangement in peripheral immune regulation contributing to the slow process leading to insulin-dependent diabetes in these patients. PMID:27357431

  14. Characterization of a Unique Cell Population Marked by Transgene Expression in the Adult Cochlea of Nestin-CreERT2/tdTomato-Reporter Mice

    PubMed Central

    Chow, Cynthia L.; Guo, Weixiang; Trivedi, Parul; Zhao, Xinyu; Gubbels, Samuel P.

    2015-01-01

    Hair cells in the adult mammalian cochlea cannot spontaneously regenerate after damage resulting in the permanency of hearing loss. Stem cells have been found to be present in the cochlea of young rodents; however, there has been little evidence for their existence into adulthood. We used nestin-CreERT2/tdTomato-reporter mice to trace the lineage of putative nestin-expressing cells and their progeny in the cochleae of adult mice. Nestin, an intermediate filament found in neural progenitor cells during early development and adulthood, is regarded as a multi-potent and neural stem cell marker. Other investigators have reported its presence in postnatal and young adult rodents; however, there are discrepancies amongst these reports. Using lineage tracing, we documented a robust population of tdTomato-expressing cells and evaluated these cells at a series of adult time points. Upon activation of the nestin promoter, tdTomato was observed just below and medial to the inner hair cell layer. All cells co-localized with the stem cell and cochlear-supporting-cell marker Sox2 as well as the supporting cell and Schwann cell marker Sox10; however, they did not co-localize with the Schwann cell marker Krox20, spiral ganglion marker NF200, or GFAP-expressing supporting cell marker. The cellular identity of this unique population of tdTomato-expressing cells in the adult cochlea of nestin-CreERT2/tdTomato mice remains unclear however these cells may represent a type of supporting cell on the neural aspect of the inner hair cell layer. PMID:25611038

  15. Characterization of a unique cell population marked by transgene expression in the adult cochlea of nestin-CreER(T2)/tdTomato-reporter mice.

    PubMed

    Chow, Cynthia L; Guo, Weixiang; Trivedi, Parul; Zhao, Xinyu; Gubbels, Samuel P

    2015-07-01

    Hair cells in the adult mammalian cochlea cannot spontaneously regenerate after damage, resulting in the permanency of hearing loss. Stem cells have been found to be present in the cochlea of young rodents; however, there has been little evidence for their existence into adulthood. We used nestin-CreER(T2)/tdTomato-reporter mice to trace the lineage of putative nestin-expressing cells and their progeny in the cochleae of adult mice. Nestin, an intermediate filament found in neural progenitor cells during early development and adulthood, is regarded as a multipotent and neural stem cell marker. Other investigators have reported its presence in postnatal and young adult rodents; however, there are discrepancies among these reports. Using lineage tracing, we documented a robust population of tdTomato-expressing cells and evaluated these cells at a series of adult time points. Upon activation of the nestin promoter, tdTomato was observed just below and medial to the inner hair cell layer. All cells colocalized with the stem cell and cochlear-supporting-cell marker Sox2 as well as the supporting cell and Schwann cell marker Sox10; however, they did not colocalize with the Schwann cell marker Krox20, spiral ganglion marker NF200, nor glial fibrillary acidic acid (GFAP)-expressing supporting cell marker. The cellular identity of this unique population of tdTomato-expressing cells in the adult cochlea of nestin-CreER(T2)/tdTomato mice remains unclear; however, these cells may represent a type of supporting cell on the neural aspect of the inner hair cell layer. PMID:25611038

  16. Changes seen on computed tomography of the chest in mildly symptomatic adult patients with sickle cell disease*

    PubMed Central

    Alves, Ursula David; Lopes, Agnaldo José; Maioli, Maria Christina Paixão; Soares, Andrea Ribeiro; de Melo, Pedro Lopes; Mogami, Roberto

    2016-01-01

    Objective To describe and quantify the main changes seen on computed tomography of the chest in mildly symptomatic adult patients with sickle cell disease, as well as to evaluate the radiologist accuracy in determining the type of hemoglobinopathy. Materials and Methods A prospective study involving 44 adult patients with sickle cell disease who underwent inspiration and expiration computed tomography of the chest. The frequency of tomography findings and the extent of involvement are reported. We also calculated radiologist accuracy in determining the type of hemoglobinopathy by analyzing the pulmonary alterations and morphology of the spleen. Results The changes found on computed tomography scans, in descending order of frequency, were as follows: fibrotic opacities (81.8%); mosaic attenuation (56.8%); architectural distortion (31.8%); cardiomegaly (25.0%); lobar volume reduction (18.2%); and increased caliber of peripheral pulmonary arteries (9.1%). For most of the findings, the involvement was considered mild, five or fewer lung segments being affected. The accuracy in determining the type of hemoglobinopathy (HbSS group versus not HbSS group) was 72.7%. Conclusion In adult patients with sickle cell disease, the main tomography findings reflect fibrotic changes. In addition, computed tomography can be helpful in differentiating among hemoglobinopathies. PMID:27777473

  17. Why do young adults with Type 1 diabetes find it difficult to manage diabetes in the workplace?

    PubMed

    Balfe, Myles; Brugha, Ruairi; Smith, Diarmuid; Sreenan, Seamus; Doyle, Frank; Conroy, Ronan

    2014-03-01

    This article explores how and why workplace environments impact diabetes management for adults people with Type 1 diabetes, 23-30 years of age. Interviews were conducted with 35 young adults, 29 women and 6 men. The majority of these interviewees worked in sectors such as banking, technology and administration. Young adults found it difficult to manage diabetes in the workplace for two main reasons: work-related time pressures and the non-routine nature of interviewees' work and working environment. Young adults also found it difficult to get the time to exercise both inside and outside of work. Young adults with Type 1 diabetes need to be provided with the tools and technologies that they need to manage diabetes in modern flexible workplaces.

  18. Wt1 dictates the fate of fetal and adult Leydig cells during development in the mouse testis.

    PubMed

    Wen, Qing; Zheng, Qiao-Song; Li, Xi-Xia; Hu, Zhao-Yuan; Gao, Fei; Cheng, C Yan; Liu, Yi-Xun

    2014-12-15

    Wilms' tumor 1 (Wt1) is a tumor suppressor gene encoding ∼24 zinc finger transcription factors. In the mammalian testis, Wt1 is expressed mostly by Sertoli cells (SCs) involved in testis development, spermatogenesis, and adult Leydig cell (ALC) steroidogenesis. Global knockout (KO) of Wt1 is lethal in mice due to defects in embryogenesis. Herein, we showed that Wt1 is involved in regulating fetal Leydig cell (FLC) degeneration and ALC differentiation during testicular development. Using Wt1(-/flox);Amh-Cre mice that specifically deleted Wt1 in the SC vs. age-matched wild-type (WT) controls, FLC-like-clusters were found in Wt1-deficient testes that remained mitotically active from postnatal day 1 (P1) to P56, and no ALC was detected at these ages. Leydig cells in mutant adult testes displayed morphological features of FLC. Also, FLC-like cells in adult mutant testes had reduced expression in ALC-associated genes Ptgds, Sult1e1, Vcam1, Hsd11b1, Hsd3b6, and Hsd17b3 but high expression of FLC-associated genes Thbs2 and Hsd3b1. Whereas serum LH and testosterone level in mutant mice were not different from controls, intratesticular testosterone level was significantly reduced. Deletion of Wt1 gene also perturbed the expression of steroidogenic enzymes Star, P450c17, Hsd3b6, Hsd3b1, Hsd17b1, and Hsd17b3. FLCs in adult mutant testes failed to convert androstenedione to testosterone due to a lack of Hsd17b3, and this defect was rescued by coculturing with fetal SCs. In summary, FLC-like cells in mutant testes are putative FLCs that remain mitotically active in adult mice, illustrating that Wt1 dictates the fate of FLC and ALC during postnatal testis development.

  19. Barrier Epithelial Cells and the Control of Type 2 Immunity.

    PubMed

    Hammad, Hamida; Lambrecht, Bart N

    2015-07-21

    Type-2-cell-mediated immunity, rich in eosinophils, basophils, mast cells, CD4(+) T helper 2 (Th2) cells, and type 2 innate lymphoid cells (ILC2s), protects the host from helminth infection but also drives chronic allergic diseases like asthma and atopic dermatitis. Barrier epithelial cells (ECs) represent the very first line of defense and express pattern recognition receptors to recognize type-2-cell-mediated immune insults like proteolytic allergens or helminths. These ECs mount a prototypical response made up of chemokines, innate cytokines such as interleukin-1 (IL-1), IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), as well as the alarmins uric acid, ATP, HMGB1, and S100 proteins. These signals program dendritic cells (DCs) to mount Th2-cell-mediated immunity and in so doing boost ILC2, basophil, and mast cell function. Here we review the general mechanisms of how different stimuli trigger type-2-cell-mediated immunity at mucosal barriers and how this leads to protection or disease.

  20. The Satellite Cell in Male and Female, Developing and Adult Mouse Muscle: Distinct Stem Cells for Growth and Regeneration

    PubMed Central

    Neal, Alice; Boldrin, Luisa; Morgan, Jennifer Elizabeth

    2012-01-01

    Satellite cells are myogenic cells found between the basal lamina and the sarcolemma of the muscle fibre. Satellite cells are the source of new myofibres; as such, satellite cell transplantation holds promise as a treatment for muscular dystrophies. We have investigated age and sex differences between mouse satellite cells in vitro and assessed the importance of these factors as mediators of donor cell engraftment in an in vivo model of satellite cell transplantation. We found that satellite cell numbers are increased in growing compared to adult and in male compared to female adult mice. We saw no difference in the expression of the myogenic regulatory factors between male and female mice, but distinct profiles were observed according to developmental stage. We show that, in contrast to adult mice, the majority of satellite cells from two week old mice are proliferating to facilitate myofibre growth; however a small proportion of these cells are quiescent and not contributing to this growth programme. Despite observed changes in satellite cell populations, there is no difference in engraftment efficiency either between satellite cells derived from adult or pre-weaned donor mice, male or female donor cells, or between male and female host muscle environments. We suggest there exist two distinct satellite cell populations: one for muscle growth and maintenance and one for muscle regeneration. PMID:22662253

  1. Enrichment of a bipotent hepatic progenitor cell from naive adult liver tissue

    SciTech Connect

    Wright, Natasha; Samuelson, Lisa; Walkup, Maggie H.; Chandrasekaran, Prakash; Gerber, David A.

    2008-02-08

    Background/Aim: Recent interest in the liver stem cell field has led to the identification and characterization of several hepatic progenitor cell populations from fetal and adult tissues. We isolated a hepatic progenitor cell from naive adult liver and the current studies focus on differentiation and growth. Results: A Sca-1{sup +} hepatic progenitor cell was identified within the liver parenchyma. This cell expresses numerous liver related genes and transcription found in the developing and/or adult liver. It is located in the peri-portal region and expresses markers associated with undifferentiated hepatic cell populations, mature hepatocytes and biliary cells which distinguish it from the Sca-1{sup -} fraction. Conclusion: This hepatic progenitor cell from uninjured liver has features of both hepatocytic and biliary populations and demonstrates proliferative potential. Further studies will focus on sca-HPC subsets and conditions that regulate differentiation towards hepatic or biliary lineages.

  2. Adult acute lymphoblastic leukemia with a rare b3a3 type BCR/ABL1 fusion transcript.

    PubMed

    Kurita, Daisuke; Hatta, Yoshihiro; Hojo, Atsuko; Kura, Yoshimasa; Sawada, Umihiko; Kanda, Yoshinobu; Takei, Masami

    2016-04-01

    The Philadelphia chromosome (Ph) is the most frequent chromosomal abnormality detected in adult acute lymphoblastic leukemia (ALL). This chromosome forms the BCR/ABL1 fusion gene; thus, ABL1 exon a2 is generally used as a primer-binding region for the detection of the fusion transcript via reverse transcription polymerase chain reaction (RT-PCR). We observed a rare case of adult Ph-positive (Ph(+)) ALL, in which the BCR/ABL1 fusion transcript was not detected using the ABL1 exon a2 region primer. However, we were able to isolate a PCR product by RT-PCR with the BCR exon 13 (b2) and ABL1 exon a3 primers. Analysis of the sequence of the RT-PCR product revealed that the fusion point was between BCR exon 14 (b3) and ABL1 exon a3, and that the transcript lacked ABL1 exon a2. The patient achieved cytogenetic remission through combination chemotherapies, but relapse occurred before hematopoietic stem cell transplantation and the patient died 11 months after the initialization of chemotherapies. If the BCR/ABL1 fusion transcript is undetected with the ABL1 exon a2 region primer in Ph(+) ALL cases, an RT-PCR analysis that can detect the b3a3 type BCR/ABL1 fusion transcript should be considered to improve diagnosis. PMID:26854094

  3. Shorter adult height is associated with poorer cognitive performance in elderly men with type II diabetes.

    PubMed

    West, Rebecca K; Ravona-Springer, Ramit; Heymann, Anthony; Schmeidler, James; Leroith, Derek; Koifman, Keren; Guerrero-Berroa, Elizabeth; Preiss, Rachel; Hoffman, Hadas; Silverman, Jeremy M; Beeri, Michal Schnaider

    2015-01-01

    We studied the relationship of adult body height with five cognitive outcomes (executive functioning, semantic categorization, attention/working memory, episodic memory, and an overall cognition measure) in 897 cognitively normal elderly with type 2 diabetes. Regression analyses controlling for sociodemographic, cardiovascular, and diabetes-related risk factors and depression demonstrated that in males, shorter stature was associated with poorer executive functioning (p = 0.001), attention/working memory (p = 0.007), and overall cognition (p = 0.016), but not with episodic memory (p = 0.715) or semantic categorization (p = 0.948). No relationship between height and cognition was found for females. In cognitively normal type 2 diabetes male subjects, shorter stature, a surrogate for early-life stress and poor nutrition, was associated with cognitive functions. PMID:25374105

  4. Resolution of Type 2 Diabetes Following Bariatric Surgery: Implications for Adults and Adolescents

    PubMed Central

    Nandagopal, Radha; Brown, Rebecca J.

    2010-01-01

    Abstract Bariatric surgery is now widely reported to ameliorate or resolve type 2 diabetes mellitus in adults. Some clinical investigators even suggest its use as an early therapeutic intervention for type 2 diabetes in patients not meeting standard criteria for bariatric surgery. However, little is known about the exact mechanisms explaining the metabolic consequences, and much active investigation is underway to identify hormonal changes leading to diabetes resolution. This review includes a detailed description of various bariatric surgical procedures, including the latest less-invasive techniques, and a summary of current data providing insight into the short- and long-term metabolic effects. We outline current hypotheses regarding the mechanisms by which these surgical procedures affect diabetes and report on morbidity and mortality. Finally, we discuss the available data on bariatric surgery in adolescent patients, including special considerations in this potentially vulnerable population. PMID:20615109

  5. Lifestyle and cardiometabolic risk in adults with type 1 diabetes: a review.

    PubMed

    Leroux, Catherine; Brazeau, Anne-Sophie; Gingras, Véronique; Desjardins, Katherine; Strychar, Irene; Rabasa-Lhoret, Rémi

    2014-02-01

    Over the past decades, there has been a major upward shift in the prevalence of cardiometabolic risk (CMR) factors (central obesity, insulin resistance, hypertension and dyslipidemia) in patients with type 1 diabetes, which could have either an additive or a synergistic effect on risk for cardiovascular disease. These metabolic changes are occurring in parallel to the worldwide obesity epidemic and the widespread use of intensive insulin therapy. Poor lifestyle habits (poor diet quality, sedentary behaviours and smoking) are known to be driving factors for increased CMR factors in the general population. The objective of this review is to explore the lifestyle habits of adults with type 1 diabetes and its potential association with CMR factors. Evidence suggests that adherence to dietary guidelines is low in subjects with type 1 diabetes with a high prevalence of patients consuming an atherogenic diet. Sedentary habits are also more prevalent than in the general population, possibly because of the additional contribution of exercise-induced hypoglycemic fear. Moreover, the prevalence of smokers is still significant in the population with type 1 diabetes. All of these behaviours could trigger a cascade of metabolic anomalies that may contribute to increased CMR factors in patients with type 1 diabetes. The intensification of insulin treatment leading to new daily challenges (e.g. carbohydrates counting, increase of hypoglycemia) could contribute to the adoption of poor lifestyle habits. Preventive measures, such as identification of patients at high risk and promotion of lifestyle changes, should be encouraged. The most appropriate therapeutic measures remain to be established.

  6. Benign mast cell hyperplasia and atypical mast cell infiltrates in penile lichen planus in adult men.

    PubMed

    Regauer, Sigrid; Beham-Schmid, Christine

    2014-08-01

    Introduction. Lichen planus (LP) is a chronic cytokine-mediated disease of possible auto-immune etiology. 25% of men have anogenital manifestations. Erosive penile LP causes a scarring phimosis of the foreskin in uncircumcised men. Mast cells as potent immune modulators have been implicated in a number of autoimmune and chronic inflammatory diseases, but have not been investigated in LP. Material and Methods. Formalin-fixed tissues of 117 circumcision specimens of adult men affected by LP were evaluated for the extent of mast cell and lymphocyte infiltrates, characterized immunohistochemically with antibodies to CD 3, 4, 8, 20, 21, 25, 30, 117c and human mast cell tryptase. Specimens with dense mast cell infiltrates were analyzed for point mutations of the c-kit gene (D816V). Results. Unaffected skin and modified mucosa of foreskins contained ⟨5 mast cells/mm². The inflammatory infiltrate of LP-lesions displayed ⟨15 mast cells/mm² in 33/117 foreskins, 16-40 mast cells/mm² in 22/117 and ⟩40 mast cells/mm² (average 70, range 40-100) in 62/117 foreskins. Lesional mast cells of 29/117 (24%) foreskins showed aberrant CD25-expression and/or spindled morphology, with 11/29 men having erosive LP, 13/29 a lymphocytic vasculitis and 1/28 a systemic mastocytosis. Neither CD30-expression nor c-kit mutations were identified. Atypical mast cell infiltrates in LP correlated with high disease activity, erosive LP and presence of lymphocytic vasculitis Conclusions. Increased mast cells in penile LP, mostly representing a benign hyperplasia/activation syndrome, suggests them as targets for innovative therapy options for symptomatic LP-patients not responding to corticosteroid therapy. Presently, the biological implications of atypical mast cell infiltrates in penile LP are unknown. PMID:24402730

  7. Acute Hypoglycemia Impairs Executive Cognitive Function in Adults With and Without Type 1 Diabetes

    PubMed Central

    Graveling, Alex J.; Deary, Ian J.; Frier, Brian M.

    2013-01-01

    OBJECTIVE Acute hypoglycemia impairs cognitive function in several domains. Executive cognitive function governs organization of thoughts, prioritization of tasks, and time management. This study examined the effect of acute hypoglycemia on executive function in adults with and without diabetes. RESEARCH DESIGN AND METHODS Thirty-two adults with and without type 1 diabetes with no vascular complications or impaired awareness of hypoglycemia were studied. Two hyperinsulinemic glucose clamps were performed at least 2 weeks apart in a single-blind, counterbalanced order, maintaining blood glucose at 4.5 mmol/L (euglycemia) or 2.5 mmol/L (hypoglycemia). Executive functions were assessed with a validated test suite (Delis-Kaplan Executive Function). A general linear model (repeated-measures ANOVA) was used. Glycemic condition (euglycemia or hypoglycemia) was the within-participant factor. Between-participant factors were order of session (euglycemia-hypoglycemia or hypoglycemia-euglycemia), test battery used, and diabetes status (with or without diabetes). RESULTS Compared with euglycemia, executive functions (with one exception) were significantly impaired during hypoglycemia; lower test scores were recorded with more time required for completion. Large Cohen d values (>0.8) suggest that hypoglycemia induces decrements in aspects of executive function with large effect sizes. In some tests, the performance of participants with diabetes was more impaired than those without diabetes. CONCLUSIONS Executive cognitive function, which is necessary to carry out many everyday activities, is impaired during hypoglycemia in adults with and without type 1 diabetes. This important aspect of cognition has not received previous systematic study with respect to hypoglycemia. The effect size is large in terms of both accuracy and speed. PMID:23780950

  8. Annual Psychological Screening in Youth and Young Adults with Type 1 Diabetes

    PubMed Central

    KLEMENČIČ, Simona; de WIT, Maartje; RUTAR, Miha; BATTELINO, Tadej; BRATINA, Nataša

    2015-01-01

    Aim Youth and young adults with type 1 diabetes are at a great risk for developing depression and diabetes specific distress, therefore, systematic psychological screening is recommended. Routine psychological screening was implemented in Slovene diabetes clinic for children, adolescents and young adults in 2012. One-year results are presented. Methods Adolescents and young adults (N = 159, aged 11 – 25 years), attending the obligatory yearly educational outpatient visit at University Children’s Hospital, Ljubljana, Slovenia, were examined using questionnaires measuring depression (depression scale from Slovene version of Trauma Symptom Checklist for Children) and diabetes distress (Diabetes Distress Screening Scale). Six additional items were included to assess the fear of hypoglycemia and family support. Socio-demographic and diabetes-related data were collected. Questionnaires were analyzed by a psychologist, and the patients that scored above cut-off point were invited to an individual psychological assessment. Results Of the sample, 1.3 % reached the threshold for elevated depressive symptoms, and 32.7 % reported significant diabetes distress. The need for psychological support from a specialist was expressed by 5.0 %. There were statistically significant associations between all psychological variables; moreover, better glycemic control was associated with lower diabetes distress and better family support. Nine patients (5.7 %) started with psychological treatment according to the referrals after screening. Conclusions The results after one year of psychological screening in Slovene type 1 diabetes population displayed small rates of depression and a large proportion of diabetes distress. Only a small percentage of patients attended the offered individual psychological assessment.

  9. Provider Types Utilized and Recency of Mental Health Service Use among African American Emerging Adults

    PubMed Central

    Williams, Sha-Lai

    2014-01-01

    Objective This study examined factors associated with mental health service utilization among African American emerging adults, specifically, when services were used (recency) and the types of providers utilized (mental health/non-mental health). Methods Guided by the Behavioral Model for Vulnerable Populations, secondary analysis of the National Survey of American Life (2001-2003) was conducted. A nationally representative sample of African American emerging adults, ages 18-29 (n=806), were assessed using the Composite International Diagnostic Interview. “Evaluated need” was determined by endorsement for one of four DSM-IV diagnosis types (mood, anxiety, substance use, impulse control). Respondents who reported a need for services for emotional/substance use problems were considered to have a “perceived need”. Those who reported voluntary use of mental health/health services to address these problems were considered to have utilized services. Results 25%of the sample utilized services in their lifetime, while 9% utilized services in the past 12 months. Females were more likely than males to utilize services in three of the four service use categories (lifetime, mental health sector, and non-mental health sector).Respondents with an evaluated need for services were 2-12 times more likely to have utilized services compared to those without a need. Conclusions Little is known about why African American emerging adults underutilize mental health services. These findings indicate that being female and having an evaluated need for services were associated with greater odds of service use among this sample. This suggests the need for additional examination of gender differences in service utilization and greater mental health outreach/education among African American males. PMID:24981778

  10. Stem cells: a promising source of pancreatic islets for transplantation in type 1 diabetes.

    PubMed

    Street, Cale N; Rajotte, Ray V; Korbutt, Gregory S

    2003-01-01

    Diabetes is a disease that affects millions and causes a major burden on the health care system. Type 1 diabetes has traditionally been managed with exogenous insulin therapy, however factors such as cost, lifestyle restriction, and life threatening complications necessitate the development of a more efficient treatment alternative. Pancreas transplantation, and more recently transplant of purified pancreatic islets, has offered the potential for independence from insulin injections. Islet transplantation is gaining acceptance as it has been shown to be effective for certain patients with type 1 diabetes. One obstacle, however, is the fact that there is an inadequate supply of cadaveric human islets to implement this procedure on a widespread clinical basis. A promising source of transplantable islets in the future will come through the use of adult or embryonic stem cells. This chapter presents an overview of the advancements made in the development of a stem cell based application to islet transplantation. Advantages and limitations are discussed regarding the use of embryonic stem cells, adult pancreatic stem/progenitor cells, and the use of nonpancreatic tissues based on current experimental models in the literature. It is concluded that stem cells offer the greatest potential for the development of an abundant source of pancreatic islets, although specific obstacles must be overcome before this can become a reality. PMID:14711014

  11. Development of skeletal system for mesh-type ICRP reference adult phantoms

    NASA Astrophysics Data System (ADS)

    Yeom, Yeon Soo; Wang, Zhao Jun; Tat Nguyen, Thang; Kim, Han Sung; Choi, Chansoo; Han, Min Cheol; Kim, Chan Hyeong; Lee, Jai Ki; Chung, Beom Sun; Zankl, Maria; Petoussi-Henss, Nina; Bolch, Wesley E.; Lee, Choonsik

    2016-10-01

    The reference adult computational phantoms of the international commission on radiological protection (ICRP) described in Publication 110 are voxel-type computational phantoms based on whole-body computed tomography (CT) images of adult male and female patients. The voxel resolutions of these phantoms are in the order of a few millimeters and smaller tissues such as the eye lens, the skin, and the walls of some organs cannot be properly defined in the phantoms, resulting in limitations in dose coefficient calculations for weakly penetrating radiations. In order to address the limitations of the ICRP-110 phantoms, an ICRP Task Group has been recently formulated and the voxel phantoms are now being converted to a high-quality mesh format. As a part of the conversion project, in the present study, the skeleton models, one of the most important and complex organs of the body, were constructed. The constructed skeleton models were then tested by calculating red bone marrow (RBM) and endosteum dose coefficients (DCs) for broad parallel beams of photons and electrons and comparing the calculated values with those of the original ICRP-110 phantoms. The results show that for the photon exposures, there is a generally good agreement in the DCs between the mesh-type phantoms and the original voxel-type ICRP-110 phantoms; that is, the dose discrepancies were less than 7% in all cases except for the 0.03 MeV cases, for which the maximum difference was 14%. On the other hand, for the electron exposures (⩽4 MeV), the DCs of the mesh-type phantoms deviate from those of the ICRP-110 phantoms by up to ~1600 times at 0.03 MeV, which is indeed due to the improvement of the skeletal anatomy of the developed skeleton mesh models.