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Sample records for form scar-like perivascular

  1. Olfactory ensheathing cell-neurite alignment enhances neurite outgrowth in scar-like cultures

    PubMed Central

    Khankan, Rana R.; Wanner, Ina B.; Phelps, Patricia E.

    2015-01-01

    The regenerative capacity of the adult CNS neurons after injury is strongly inhibited by the spinal cord lesion site environment that is composed primarily of the reactive astroglial scar and invading meningeal fibroblasts. Olfactory ensheathing cell (OEC) transplantation facilitates neuronal survival and functional recovery after a complete spinal cord transection, yet the mechanisms by which this recovery occurs remain unclear. We used a unique multicellular scar-like culture model to test if OECs promote neurite outgrowth in growth inhibitory areas. Astrocytes were mechanically injured and challenged by meningeal fibroblasts to produce key inhibitory elements of a spinal cord lesion. Neurite outgrowth of postnatal cerebral cortical neurons was assessed on three substrates: quiescent astrocyte control cultures, reactive astrocyte scar-like cultures, and scar-like cultures with OECs. Initial results showed that OECs enhanced total neurite outgrowth of cortical neurons in a scar-like environment by 60%. We then asked if the neurite growth-promoting properties of OECs depended on direct alignment between neuronal and OEC processes. Neurites that aligned with OECs were nearly three times longer when they grew on inhibitory meningeal fibroblast areas and twice as long on reactive astrocyte zones compared to neurites not associated with OECs. Our results show that OECs can independently enhance neurite elongation and that direct OEC-neurite cell contact can provide a permissive substrate that overcomes the inhibitory nature of the reactive astrocyte scar border and the fibroblast-rich spinal cord lesion core. PMID:25863021

  2. Perivascular-Like Cells Contribute to the Stability of the Vascular Network of Osteogenic Tissue Formed from Cell Sheet-Based Constructs

    PubMed Central

    Mendes, Luís F.; Pirraco, Rogério P.; Szymczyk, Wojciech; Frias, Ana M.; Santos, Tírcia C.; Reis, Rui L.; Marques, Alexandra P.

    2012-01-01

    In recent years several studies have been supporting the existence of a close relationship in terms of function and progeny between Mesenchymal Stem Cells (MSCs) and Pericytes. This concept has opened new perspectives for the application of MSCs in Tissue Engineering (TE), with special interest for the pre-vascularization of cell dense constructs. In this work, cell sheet technology was used to create a scaffold-free construct composed of osteogenic, endothelial and perivascular-like (CD146+) cells for improved in vivo vessel formation, maturation and stability. The CD146 pericyte-associated phenotype was induced from human bone marrow mesenchymal stem cells (hBMSCs) by the supplementation of standard culture medium with TGF-β1. Co-cultured cell sheets were obtained by culturing perivascular-like (CD146+) cells and human umbilical vein endothelial cells (HUVECs) on an hBMSCs monolayer maintained in osteogenic medium for 7 days. The perivascular-like (CD146+) cells and the HUVECs migrated and organized over the collagen-rich osteogenic cell sheet, suggesting the existence of cross-talk involving the co-cultured cell types. Furthermore the presence of that particular ECM produced by the osteoblastic cells was shown to be the key regulator for the singular observed organization. The osteogenic and angiogenic character of the proposed constructs was assessed in vivo. Immunohistochemistry analysis of the explants revealed the integration of HUVECs with the host vasculature as well as the osteogenic potential of the created construct, by the expression of osteocalcin. Additionally, the analysis of the diameter of human CD146 positive blood vessels showed a higher mean vessel diameter for the co-cultured cell sheet condition, reinforcing the advantage of the proposed model regarding blood vessels maturation and stability and for the in vitro pre-vascularization of TE constructs. PMID:22829909

  3. Perivascular Adipose Tissue

    PubMed Central

    Maille, Nicole; Clas, Darren; Osol, George

    2015-01-01

    Perivascular adipose tissue (PVAT) contributes to vasoregulation. The role of this adipose tissue bed in pregnancy has not been examined. Here, we tested the hypothesis that PVAT in pregnant rats decreases resistance artery tone. Mesenteric arteries from nonpregnant (NP) and late pregnant (LP) rats were exposed to phenylephrine (PHE) or KCl in the presence (+) versus absence (−) of PVAT. The LP PVAT(+) vessels showed a 44% decrease in sensitivity to PHE in the presence of PVAT. There was no attenuation of the contractile response to KCl when PVAT was present. The LP arteries perfused with LP or NP PVAT underwent vasodilation; unexpectedly, NP vessels in the presence of PVAT from LP rats sustained a 48% vasoconstriction. The PVAT attenuates vasoconstriction by a mechanism that involves hyperpolarization. The vasoconstriction observed when nonpregnant vessels were exposed to pregnant PVAT suggests pregnant vessels adapt to the vasoconstricting influence of pregnant PVAT. PMID:25527422

  4. EARLY SENESCENCE1 Encodes a SCAR-LIKE PROTEIN2 That Affects Water Loss in Rice1[OPEN

    PubMed Central

    Rao, Yuchun; Yang, Yaolong; Xu, Jie; Li, Xiaojing; Leng, Yujia; Dai, Liping; Huang, Lichao; Shao, Guosheng; Ren, Deyong; Hu, Jiang; Guo, Longbiao; Pan, Jianwei; Zeng, Dali

    2015-01-01

    The global problem of drought threatens agricultural production and constrains the development of sustainable agricultural practices. In plants, excessive water loss causes drought stress and induces early senescence. In this study, we isolated a rice (Oryza sativa) mutant, designated as early senescence1 (es1), which exhibits early leaf senescence. The es1-1 leaves undergo water loss at the seedling stage (as reflected by whitening of the leaf margin and wilting) and display early senescence at the three-leaf stage. We used map-based cloning to identify ES1, which encodes a SCAR-LIKE PROTEIN2, a component of the suppressor of cAMP receptor/Wiskott-Aldrich syndrome protein family verprolin-homologous complex involved in actin polymerization and function. The es1-1 mutants exhibited significantly higher stomatal density. This resulted in excessive water loss and accelerated water flow in es1-1, also enhancing the water absorption capacity of the roots and the water transport capacity of the stems as well as promoting the in vivo enrichment of metal ions cotransported with water. The expression of ES1 is higher in the leaves and leaf sheaths than in other tissues, consistent with its role in controlling water loss from leaves. GREEN FLUORESCENT PROTEIN-ES1 fusion proteins were ubiquitously distributed in the cytoplasm of plant cells. Collectively, our data suggest that ES1 is important for regulating water loss in rice. PMID:26243619

  5. Perivascular cells for regenerative medicine

    PubMed Central

    Crisan, Mihaela; Corselli, Mirko; Chen, William CW; Péault, Bruno; Moldovan, NI

    2012-01-01

    Mesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic cells for regenerative medicine related to osteoarticular, muscular, vascular and inflammatory diseases, although these cells remain heterogeneous and necessitate a better biological characterization. We and others recently described that MSC originate from two types of perivascular cells, namely pericytes and adventitial cells and contain the in situ counterpart of MSC in developing and adult human organs, which can be prospectively purified using well defined cell surface markers. Pericytes encircle endothelial cells of capillaries and microvessels and express the adhesion molecule CD146 and the PDGFRβ, but lack endothelial and haematopoietic markers such as CD34, CD31, vWF (von Willebrand factor), the ligand for Ulex europaeus 1 (UEA1) and CD45 respectively. The proteoglycan NG2 is a pericyte marker exclusively associated with the arterial system. Besides its expression in smooth muscle cells, smooth muscle actin (αSMA) is also detected in subsets of pericytes. Adventitial cells surround the largest vessels and, opposite to pericytes, are not closely associated to endothelial cells. Adventitial cells express CD34 and lack αSMA and all endothelial and haematopoietic cell markers, as for pericytes. Altogether, pericytes and adventitial perivascular cells express in situ and in culture markers of MSC and display capacities to differentiate towards osteogenic, adipogenic and chondrogenic cell lineages. Importantly, adventitial cells can differentiate into pericyte-like cells under inductive conditions in vitro. Altogether, using purified perivascular cells instead of MSC may bring higher benefits to regenerative medicine, including the possibility, for the first time, to use these cells uncultured. PMID:22882758

  6. The perivascular phenotype and behaviors of dedifferentiated cells derived from human mature adipocytes.

    PubMed

    Song, Ning; Kou, Liang; Lu, Xiao-Wen; Sugawara, Atsunori; Shimizu, Yutaka; Wu, Min-Ke; Du, Li; Wang, Hang; Sato, Soh; Shen, Jie-Fei

    2015-02-13

    Derived from mature adipocytes, dedifferentiated fat (DFAT) cells represent a special group of multipotent cells. However, their phenotype and cellular nature remain unclear. Our study found that human DFAT cells adopted perivascular characteristics and behaviors. Flow cytometry and immunofluorescent staining revealed that human DFAT cells positively expressed markers highly related to perivascular cell lineages, such as CD140b, NG2 and desmin, but were negative for common endothelial markers, including CD31, CD34, and CD309. Furthermore, DFAT cells displayed vascular network formation ability in Matrigel, and they noticeably promoted and stabilized the vessel structures formed by human umbilical vascular endothelial cells (HUVECs) in vitro. These results provide novel evidence on the pericyte nature of human DFAT cells, further supporting the recent model for the perivascular origin of adult stem cells, in which tissue-specific progenitor cells in mesenchymal tissues associate with blood vessels, exhibiting perivascular characteristics and functions. PMID:25603054

  7. Intracerebral hematoma extends via perivascular spaces and perineurium.

    PubMed

    Yin, Jia; Lü, Tian-Ming; Qiu, Guang; Huang, Rui-Yu; Fang, Min; Wang, Yuan-Yuan; Xiao, Duan; Liu, Xiao-Jia

    2013-01-01

    Intracerebral hemorrhage (ICH) is a devastating disorder associated with high morbidity and mortality. ICH results in the formation of hematoma that affects not only the primary site of injury but also the remote regions. In fact, hematoma can extend via perivascular spaces (also called Virchow-Robin spaces, VRS) and perineurium in an animal model of ICH. In the present study, we used magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) to investigate the characteristics of the perivascular and perineural extensions of hematomas in patients with ICH. A total of 20 ICH patients without secondary subarachnoid and secondary intraventricular hemorrhages were recruited. Brain MRI scans, including SWI, T1, and T2-weighted images, were performed between 17 h to 7 days after the onset of ICH. MRI with SWI revealed that paramagnetic substances spread along the VRS or the perineurium. Such distribution could cause the formation of cerebral microbleeds (CMBs). However, the distribution of remote hemorrhagic lesions varied, depending on the size and location of the original hematoma. The unenhanced CT scans of the 20 patients did not show any hyperdensity around the blood vessels and nerve tracts outside the hematoma. These results indicate the perivascular and perineural extensions of hematomas in patients with ICH, which is formed by the leakage of the original hematoma via the VRS or perineurium. We also provide a new explanation for the series of pathological processes involved in ICH, including the remote effects of hematoma and the formation of CMBs in patients with ICH. PMID:23812162

  8. Changes in the population of perivascular cells in the bone tissue remodeling zones under microgravity

    NASA Astrophysics Data System (ADS)

    Katkova, Olena; Rodionova, Natalia; Shevel, Ivan

    2016-07-01

    Microgravity and long-term hypokinesia induce reduction both in bone mass and mineral saturation, which can lead to the development of osteoporosis and osteopenia. (Oganov, 2003). Reorganizations and adaptive remodeling processes in the skeleton bones occur in the topographical interconnection with blood capillaries and perivascular cells. Radioautographic studies with 3H- thymidine (Kimmel, Fee, 1980; Rodionova, 1989, 2006) have shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic. Hence the study of populations of perivascular stromal cells in areas of destructive changes is actual. Perivascular cells from metaphysis of the rat femoral bones under conditions of modeling microgravity were studied using electron microscopy and cytochemistry (hindlimb unloading, 28 days duration) and biosatellite «Bion-M1» (duration of flight from April 19 till May 19, 2013 on C57, black mice). It was revealed that both control and test groups populations of the perivascular cells are not homogeneous in remodeling adaptive zones. These populations comprise of adjacent to endothelium poorly differentiated forms and isolated cells with signs of differentiation (specific increased volume of rough endoplasmic reticulum in cytoplasm). Majority of the perivascular cells in the control group (modeling microgravity) reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In poorly differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of experimental animals reaction to the alkaline phosphatase is registered not in all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. Under microgravity some poorly differentiated perivascular

  9. Pericyte Antigens in Perivascular Soft Tissue Tumors

    PubMed Central

    Shen, Jia; Shrestha, Swati; Yen, Yu-Hsin; Asatrian, Greg; Mravic, Marco; Soo, Chia; Ting, Kang; Dry, Sarah M.; Peault, Bruno; James, Aaron W.

    2015-01-01

    Introduction Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear line of differentiation, although most are presumed to originate from pericytes or modified perivascular cells. Among these, glomus tumor, myopericytoma, and angioleiomyoma share a spectrum of histologic findings and a perivascular growth pattern. In contrast, solitary fibrous tumor (previously termed hemangiopericytoma) was once hypothesized to have pericytic differentiation. Methods Here, we systematically examine pericyte immunohistochemical markers among glomus tumor (including malignant glomus tumor), myopericytoma, angioleiomyoma, and solitary fibrous tumor. Immunohistochemical staining and semiquantification was performed using well-defined pericyte antigens, including αSMA, CD146, and PDGFRβ. Results Glomus tumor and myopericytoma demonstrate diffuse staining for all pericyte markers, including immunohistochemical reactivity for αSMA, CD146, and PDGFRβ. Malignant glomus tumors all showed some degree of pericyte marker immunoreactivity, although it was significantly reduced. Angioleiomyoma shared a similar αSMA + CD146 + PDGFRβ+ immunophenotype; however, this was predominantly seen in the areas of perivascular tumor growth. Solitary fibrous tumors showed patchy PDGFRβ immunoreactivity only. Discussion In summary, pericyte marker expression is a ubiquitous finding in glomus tumor, myopericytoma, and angioleiomyoma. Malignant glomus tumor shows a comparative reduction in pericyte marker expression, which may represent partial loss of pericytic differentiation. Pericyte markers are essentially not seen in solitary fibrous tumor. The combination of αSMA, CD146, and PDGFRβ immunohistochemical stainings may be of utility for the evaluation of pericytic differentiation in soft tissue tumors. PMID:26085647

  10. Differentiation potentials of perivascular cells in the bone tissue remodeling zones under microgravity

    NASA Astrophysics Data System (ADS)

    Rodionova, Natalia; Katkova, Olena

    Adaptive remodeling processes in the skeleton bones occur in the close topographical interconnection with blood capillaries followed by perivascular cells. Radioautographic studies with 3Н- thymidine (Kimmel D.B., Fee W.S., 1980; Rodionova N.V., 1989, 2006) has shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic ones. Using electron microscopy and cytochemistry we studied perivsacular cells in metaphysis of the rats femoral bones under conditions of modeling microgravity (28 days duration) and in femoral bonеs metaphyses of rats flown on board of the space laboratory (Spacelab - 2) It was revealed that population of the perivascular cells is not homogeneous in adaptive zones of the remodeling in both control and test groups (lowering support loading). This population comprises adjacent to endothelium little differentiated forms and isolated cells with differentiation features (specific volume of rough endoplasmic reticulum in cytoplasm is increased). Majority of the perivascular cells in the control group reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In little differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of animals under microgravitaty reaction to the alkaline phosphatase is registered not for all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. There is also visible trend of individual alkaline phosphatase containing perivascular cells amounts decrease (i.e. osteogenic cells-precursors). Under microgravity some little differentiated perivascular cells reveal destruction signs. Found decrease trend of the alkaline phosphatase containing cells (i.e. osteogenic cells) number in

  11. Perivascular epithelioid cell tumors of the uterine cervix.

    PubMed

    Kudela, E; Biringer, K; Kasajova, P; Nachajova, M; Adamkov, M

    2016-08-01

    The World Health Organization (WHO) defines PEComas as mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular cells. Uterus is the most common site of a subgroup of PEComas not otherwise specified(NOS). PEComas of the uterine cervix are extremely rare, and only thirteen cases have been described in the English literature to date. In this review, we summarize the available data concerning diagnostics, immunohistochemical analysis, genetics and treatment of cervical PEComas. Radical hysterectomy with bilateral salpingooophorectomy is the best surgical approach available. Adjuvant therapy in its present form is not efficient. Therefore, further studies are needed to evaluate the newest treatment strategies. PMID:27083240

  12. CD163 Identifies Perivascular Macrophages in Normal and Viral Encephalitic Brains and Potential Precursors to Perivascular Macrophages in Blood

    PubMed Central

    Kim, Woong-Ki; Alvarez, Xavier; Fisher, Jeanne; Bronfin, Benjamin; Westmoreland, Susan; McLaurin, JoAnne; Williams, Kenneth

    2006-01-01

    Perivascular macrophages are uniquely situated at the intersection between the nervous and immune systems. Although combined myeloid marker detection differentiates perivascular from resident brain macrophages (parenchymal microglia), no single marker distinguishes perivascular macrophages in humans and mice. Here, we present the macrophage scavenger receptor CD163 as a marker for perivascular macrophages in humans, monkeys, and mice. CD163 was primarily confined to perivascular macrophages and populations of meningeal and choroid plexus macrophages in normal brains and in brains of humans and monkeys with human immunodeficiency virus or simian immunodeficiency virus (SIV) encephalitis. Scattered microglia in SIV encephalitis lesions and multinucleated giant cells were also CD163 positive. Consistent with prior findings that perivascular macrophages are primary targets of human immunodeficiency virus and SIV, all SIV-infected cells in the brain were CD163 positive. Using fluorescent dyes that definitively and selectively label perivascular macrophages in vivo, we confirmed that dye-labeled simian perivascular macrophages were CD163 positive and able to repopulate the central nervous system within 24 hours. Flow cytometric studies demonstrated a subset of monocytes (CD163+CD14+CD16+) that were immunophenotypically similar to brain perivascular macrophages. These findings recognize CD163+ blood monocytes/macrophages as a source of brain perivascular macrophages and underscore the utility of this molecule in studying the biology of perivascular macrophages and their precursors in humans, monkeys, and mice. PMID:16507898

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

    PubMed

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

    2012-01-01

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

  14. How do culture media influence in vitro perivascular cell behavior?

    PubMed

    Huber, Birgit; Volz, Ann-Cathrin; Kluger, Petra Juliane

    2015-12-01

    Perivascular cells are multilineage cells located around the vessel wall and important for wall stabilization. In this study, we evaluated a stem cell media and a perivascular cell-specific media for the culture of primary perivascular cells regarding their cell morphology, doubling time, stem cell properties, and expression of cell type-specific markers. When the two cell culture media were compared to each other, perivascular cells cultured in the stem cell medium had a more elongated morphology and a faster doubling rate and cells cultured in the pericyte medium had a more typical morphology, with several filopodia, and a slower doubling rate. To evaluate stem cell properties, perivascular cells, CD146(-) cells, and mesenchymal stem cells (MSCs) were differentiated into the adipogenic, osteogenic, and chondrogenic lineages. It was seen that perivascular cells, as well as CD146(-) cells and MSCs, cultured in stem cell medium showed greater differentiation than cells cultured in pericyte-specific medium. The expression of pericyte-specific markers CD146, neural/glial antigen 2 (NG2), platelet-derived growth factor receptor-β (PDGFR-β), myosin, and α-smooth muscle actin (α-SMA) could be found in both pericyte cultures, as well as to varying amounts in CD146(-) cells, MSCs, and endothelial cells. The here presented work shows that perivascular cells can adapt to their in vitro environment and cell culture conditions influence cell functionality, such as doubling rate or differentiation behavior. Pericyte-specific markers were shown to be expressed also from cells other than perivascular cells. We can further conclude that CD146(+) perivascular cells are inhomogeneous cell population probably containing stem cell subpopulations, which are located perivascular around capillaries. PMID:26179857

  15. Perivascular epithelioid cell tumour of the bladder

    PubMed Central

    Tarplin, Sarah; Osterberg, E Charles; Robinson, Brian D; Herman, Michael P; Rosoff, James S

    2014-01-01

    A 39-year-old woman presented with a long history of pelvic pain and urinary urgency. Prior workup by her primary care doctor had been negative. The patient's gynaecologist ultimately referred her to a urologist following an ultrasound that revealed a possible bladder mass. MRI of the abdomen and pelvis demonstrated a 4 cm soft tissue lesion arising from the bladder. Cystoscopy showed an atypical mass on the anterior bladder wall, and pathological examination of the TURBT (transurethral resection of the bladder tumour) specimen revealed a perivascular epithelioid cell tumour (PEComa) with involvement of the detrusor muscle. The patient underwent a robotically assisted laparoscopic partial cystectomy. Final pathology confirmed a PEComa with negative margins. The patient had an uncomplicated postoperative course and is doing well following surgery. A surveillance cystoscopy at 6 months showed no evidence of recurrence. This case underscores the variability of clinical presentation of PEComas while proposing an appropriate method of surgical management. PMID:25123573

  16. Human umbilical cord perivascular cells (HUCPVC)

    PubMed Central

    Zebardast, Nazlee; Lickorish, David

    2010-01-01

    Human bone marrow mesenchymal stem cells (hBM-MSC) have recently been employed in the clinical treatment of challenging skin defects. We have described an MSC population that can be easily harvested from human umbilical cord perivascular tissue, human umbilical cord perivascular cells (HUCPVC), which exhibit a higher proliferative rate and frequency than hBM-MSC. Our objective was to establish whether HUCPVC could promote healing of full thickness murine skin defects, and thus find utility as a cell source for dermal repair. To this end, bilateral full thickness defects were created on the dorsum of Balb/c nude mice. Fibrin was used as delivery vehicle for 1 × 106 PKH67-labeled HUCPVC with contralateral controls receiving fibrin only. Epifluorescent and brightfield microscopic evaluation of the wound site was carried out at 3 and 7 days while mechanical testing of wounds was carried out at 3, 7 and 10 days. Our results show that by 3 days, marked contraction of the wound was observed in the fibrin controls whilst the HUCPVC samples exhibited neither collapse nor contraction of the defect, and the dermal repair tissue was considerably thicker and more organized. By 7 days, complete re-epithelialization of the HUCPVC wounds was observed whilst in the controls re-epithelialization was limited to the wound margins. Wound strength was significantly increased in the HUCPVC treatment group by 3 and 7 days but no statistical difference was seen at 10 days. We conclude that HUCPVCs accelerate early wound healing in full thickness skin defects and thus represent a putative source of human MSCs for use in dermal tissue engineering. PMID:21220956

  17. Perivascular cells in blood vessel regeneration.

    PubMed

    Wanjare, Maureen; Kusuma, Sravanti; Gerecht, Sharon

    2013-04-01

    Vascular engineering seeks to design and construct functional blood vessels comprising endothelial cells (ECs) and perivascular cells (PCs), with the ultimate goal of clinical translation. While EC behavior has been extensively investigated, PCs play an equally significant role in the development of novel regenerative strategies, providing functionality and stability to vessels. The two major classes of PCs are vascular smooth muscle cells (vSMCs) and pericytes; vSMCs can be further sub-classified as either contractile or synthetic. The inclusion of these cell types is crucial for successful regeneration of blood vessels. Furthermore, understanding distinctions between vSMCs and pericytes will enable improved therapeutics in a tissue-specific manner. Here we focus on the approaches and challenges facing the use of PCs in vascular regeneration, including their characteristics, stem cell sources, and interactions with ECs. Finally, we discuss biochemical and microRNA (miR) regulators of PC behavior and engineering approaches that mimic various cues affecting PC function. PMID:23554249

  18. Cellular Kinetics of Perivascular MSC Precursors

    PubMed Central

    Chen, William C. W.; Murray, Iain R.; Lazzari, Lorenza; Huard, Johnny; Péault, Bruno

    2013-01-01

    Mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration. PMID:24023546

  19. Perivascular support of human hematopoietic stem/progenitor cells

    PubMed Central

    Corselli, Mirko; Chin, Chee Jia; Parekh, Chintan; Sahaghian, Arineh; Wang, Wenyuan; Ge, Shundi; Evseenko, Denis; Wang, Xiaoyan; Montelatici, Elisa; Lazzari, Lorenza; Crooks, Gay M.

    2013-01-01

    Hematopoietic stem and progenitor cells (HSPCs) emerge and develop adjacent to blood vessel walls in the yolk sac, aorta-gonad-mesonephros region, embryonic liver, and fetal bone marrow. In adult mouse bone marrow, perivascular cells shape a “niche” for HSPCs. Mesenchymal stem/stromal cells (MSCs), which support hematopoiesis in culture, are themselves derived in part from perivascular cells. In order to define their direct role in hematopoiesis, we tested the ability of purified human CD146+ perivascular cells, as compared with unfractionated MSCs and CD146− cells, to sustain human HSPCs in coculture. CD146+ perivascular cells support the long-term persistence, through cell-to-cell contact and at least partly via Notch activation, of human myelolymphoid HSPCs able to engraft primary and secondary immunodeficient mice. Conversely, unfractionated MSCs and CD146− cells induce differentiation and compromise ex vivo maintenance of HSPCs. Moreover, CD146+ perivascular cells express, natively and in culture, molecular markers of the vascular hematopoietic niche. Unexpectedly, this dramatic, previously undocumented ability to support hematopoietic stem cells is present in CD146+ perivascular cells extracted from the nonhematopoietic adipose tissue. PMID:23412095

  20. The pericyte antigen RGS5 in perivascular soft tissue tumors.

    PubMed

    Shen, Jia; Shrestha, Swati; Yen, Yu-Hsin; Scott, Michelle A; Soo, Chia; Ting, Kang; Peault, Bruno; Dry, Sarah M; James, Aaron W

    2016-01-01

    Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear lineage of differentiation, although most are presumed to originate from or differentiate to pericytes or a modified perivascular cell. Among these, glomus tumor, myopericytoma, and angioleiomyoma share a spectrum of histologic findings and a perivascular growth pattern. In contrast, solitary fibrous tumor was once hypothesized to have pericytic differentiation--although little bona fide evidence of pericytic differentiation exists. Likewise the perivascular epithelioid cell tumor (PEComa) family shares a perivascular growth pattern, but with distinctive dual myoid-melanocytic differentiation. RGS5, regulator of G-protein signaling 5, is a novel pericyte antigen with increasing use in animal models. Here, we describe the immunohistochemical expression patterns of RGS5 across perivascular soft tissue tumors, including glomus tumor (n = 6), malignant glomus tumor (n = 4), myopericytoma (n = 3), angioleiomyoma (n = 9), myofibroma (n = 4), solitary fibrous tumor (n = 10), and PEComa (n = 19). Immunohistochemical staining and semi-quantification was performed, and compared to αSMA (smooth muscle actin) expression. Results showed that glomus tumor (including malignant glomus tumor), myopericytoma, and angioleiomyoma shared a similar diffuse immunoreactivity for RGS5 and αSMA across all tumors examined. In contrast, myofibroma, solitary fibrous tumor and PEComa showed predominantly focal to absent RGS5 immunoreactivity. These findings further support a common pericytic lineage of differentiation in glomus tumors, myopericytoma and angioleiomyoma. The pericyte marker RGS5 may be of future clinical utility for the evaluation of pericytic differentiation in soft tissue tumors. PMID:26558691

  1. Perivascular adipose tissue contains functional catecholamines

    PubMed Central

    Ayala-Lopez, Nadia; Martini, Marisa; Jackson, William F; Darios, Emma; Burnett, Robert; Seitz, Bridget; Fink, Gregory D; Watts, Stephanie W

    2014-01-01

    The sympathetic nervous system and its neurotransmitter effectors are undeniably important to blood pressure control. We made the novel discovery that perivascular adipose tissue (PVAT) contains significant concentrations of catecholamines. We hypothesized that PVAT contains sufficient releasable catecholamines to affect vascular function. High-pressure liquid chromatography, isometric contractility, immunohistochemistry, whole animal approaches, and pharmacology were used to test this hypothesis. In normal rat thoracic aorta and superior mesenteric artery, the indirect sympathomimetic tyramine caused a concentration-dependent contraction that was dependent on the presence of PVAT. Tyramine stimulated release of norepinephrine (NA), dopamine (DA) and the tryptamine serotonin (5-hydroxytryptamine [5-HT]) from PVAT isolated from both arteries. In both arteries, tyramine-induced concentration-dependent contraction was rightward-shifted and reduced by the noradrenaline transporter inhibitor nisoxetine (1 μmol/L), the vesicular monoamine transporter inhibitor tetrabenazine (10 μmol/L), and abolished by the α adrenoreceptor antagonist prazosin (100 nmol/L). Inhibitors of the DA and 5-HT transporter did not alter tyramine-induced, PVAT-dependent contraction. Removal of the celiac ganglion as a neuronal source of catecholamines for superior mesenteric artery PVAT did not significantly reduce the maximum or shift the concentration-dependent contraction to tyramine. Electrical field stimulation of the isolated aorta was not affected by the presence of PVAT. These data suggest that PVAT components that are independent of sympathetic nerves can release NA in a tyramine-sensitive manner to result in arterial contraction. Because PVAT is intimately apposed to the artery, this raises the possibility of local control of arterial function by PVAT catecholamines. PMID:24904751

  2. Perivascular adipose tissue, vascular reactivity and hypertension.

    PubMed

    Oriowo, Mabayoje A

    2015-01-01

    Most blood vessels are surrounded by a variable amount of adventitial adipose tissue, perivascular adipose tissue (PVAT), which was originally thought to provide mechanical support for the vessel. It is now known that PVAT secretes a number of bioactive substances including vascular endothelial growth factor, tumor necrosis factor-alpha (TNF-α), leptin, adiponectin, insulin-like growth factor, interleukin-6, plasminogen activator substance, resistin and angiotensinogen. Several studies have shown that PVAT significantly modulated vascular smooth muscle contractions induced by a variety of agonists and electrical stimulation by releasing adipocyte-derived relaxing (ADRF) and contracting factors. The identity of ADRF is not yet known. However, several vasodilators have been suggested including adiponectin, angiotensin 1-7, hydrogen sulfide and methyl palmitate. The anticontractile effect of PVAT is mediated through the activation of potassium channels since it is abrogated by inhibiting potassium channels. Hypertension is characterized by a reduction in the size and amount of PVAT and this is associated with the attenuated anticontractile effect of PVAT in hypertension. However, since a reduction in size and amount of PVAT and the attenuated anticontractile effect of PVAT were already evident in prehypertensive rats with no evidence of impaired release of ADRF, there is the possibility that the anticontractile effect of PVAT was not directly related to an altered function of the adipocytes per se. Hypertension is characterized by low-grade inflammation and infiltration of macrophages. One of the adipokines secreted by macrophages is TNF-α. It has been shown that exogenously administered TNF-α enhanced agonist-induced contraction of a variety of vascular smooth muscle preparations and reduced endothelium-dependent relaxation. Other procontractile factors released by the PVAT include angiotensin II and superoxide. It is therefore possible that the loss could be due

  3. Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation

    PubMed Central

    Davalos, Dimitrios; Kyu Ryu, Jae; Merlini, Mario; Baeten, Kim M.; Le Moan, Natacha; Petersen, Mark A.; Deerinck, Thomas J.; Smirnoff, Dimitri S.; Bedard, Catherine; Hakozaki, Hiroyuki; Gonias Murray, Sara; Ling, Jennie B.; Lassmann, Hans; Degen, Jay L.; Ellisman, Mark H.; Akassoglou, Katerina

    2012-01-01

    Blood-brain barrier disruption, microglial activation and neurodegeneration are hallmarks of multiple sclerosis. However, the initial triggers that activate innate immune responses and their role in axonal damage remain unknown. Here we show that the blood protein fibrinogen induces rapid microglial responses toward the vasculature and is required for axonal damage in neuroinflammation. Using in vivo two-photon microscopy, we demonstrate that microglia form perivascular clusters before myelin loss or paralysis onset and that, of the plasma proteins, fibrinogen specifically induces rapid and sustained microglial responses in vivo. Fibrinogen leakage correlates with areas of axonal damage and induces reactive oxygen species release in microglia. Blocking fibrin formation with anticoagulant treatment or genetically eliminating the fibrinogen binding motif recognized by the microglial integrin receptor CD11b/CD18 inhibits perivascular microglial clustering and axonal damage. Thus, early and progressive perivascular microglial clustering triggered by fibrinogen leakage upon blood-brain barrier disruption contributes to axonal damage in neuroinflammatory disease. PMID:23187627

  4. The Perivascular Niche and Self-Renewal of Stem Cells

    PubMed Central

    Oh, Min; Nör, Jacques E.

    2015-01-01

    Postnatal stem cells are typically found in niches that provide signaling cues to maintain their self-renewal and multipotency. While stem cell populations may serve distinct purposes within their tissue of origin, understanding the conserved biology of stem cells and their respective niches provides insights to the behavior of these cells during homeostasis and tissue repair. Here, we discuss perivascular niches of two distinct stem cell populations (i.e., hematopoietic stem cells, mesenchymal stem cells) and explore mechanisms that sustain these stem cells postnatally. We highlight work that demonstrates the impact of cellular crosstalk to stem cell self-renewal and maintenance of functional perivascular niches. We also discuss the importance of the crosstalk within the perivascular niche to the biology of stem cells, and describe the regenerative potential of perivascular cells. We postulate that signaling events that establish and/or stabilize the perivascular niche, particularly through the modulation of self-renewing factors, are key to the long-term success of regenerated tissues. PMID:26696901

  5. Malignant perivascular epithelioid cell tumor of the gallbladder: a case report and review of literature.

    PubMed

    Zhao, Liena; Anders, Karl H

    2014-09-01

    Perivascular epithelioid cell tumors are rare mesenchymal neoplasms composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. The perivascular epithelioid cell tumor family includes angiomyolipoma, clear cell sugar tumor of the lung, lymphangioleiomyomatosis, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and rare clear cell tumors of other anatomic sites. Perivascular epithelioid cell tumors have been reported previously in various sites, but to our knowledge not in the gallbladder. We report here, for the first time, a malignant perivascular epithelioid cell tumor arising in the gallbladder. PMID:25171708

  6. Perivascular Arrest of CD8+ T Cells Is a Signature of Experimental Cerebral Malaria

    PubMed Central

    Strangward, Patrick; Dandamudi, Durga B.; Coles, Jonathan A.; Villegas-Mendez, Ana; Gallego-Delgado, Julio; van Rooijen, Nico; Zindy, Egor; Rodriguez, Ana; Brewer, James M.; Couper, Kevin N.; Dustin, Michael L.

    2015-01-01

    There is significant evidence that brain-infiltrating CD8+ T cells play a central role in the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the mechanisms through which they mediate their pathogenic activity during malaria infection remain poorly understood. Utilizing intravital two-photon microscopy combined with detailed ex vivo flow cytometric analysis, we show that brain-infiltrating T cells accumulate within the perivascular spaces of brains of mice infected with both ECM-inducing (P. berghei ANKA) and non-inducing (P. berghei NK65) infections. However, perivascular T cells displayed an arrested behavior specifically during P. berghei ANKA infection, despite the brain-accumulating CD8+ T cells exhibiting comparable activation phenotypes during both infections. We observed T cells forming long-term cognate interactions with CX3CR1-bearing antigen presenting cells within the brains during P. berghei ANKA infection, but abrogation of this interaction by targeted depletion of the APC cells failed to prevent ECM development. Pathogenic CD8+ T cells were found to colocalize with rare apoptotic cells expressing CD31, a marker of endothelial cells, within the brain during ECM. However, cellular apoptosis was a rare event and did not result in loss of cerebral vasculature or correspond with the extensive disruption to its integrity observed during ECM. In summary, our data show that the arrest of T cells in the perivascular compartments of the brain is a unique signature of ECM-inducing malaria infection and implies an important role for this event in the development of the ECM-syndrome. PMID:26562533

  7. Malignant perivascular epithelioid cell tumor of the uterus

    PubMed Central

    Bleeker, Jonathan S.; Quevedo, J. Fernando; Folpe, Andrew L.

    2012-01-01

    Perivascular epithelioid cell tumors (PEComas) are a rare collection of tumors arising in a wide array of anatomic locations and characterized by a myomelanocytic phenotype. PEComas which occur in non-classic anatomic distributions are known as perivascular epithelioid cell tumor-not otherwise specified (PEComa-NOS), and one of the most common primary sites for PEComa-NOS is the uterus. The risk of aggressive behavior of these tumors has been linked to a number of factors evaluable on pathologic review following initial surgical resection. We report a case of PEComa-NOS of the uterus with multiple high-risk features, including frank vascular invasion, with no evidence of recurrent disease 18 months following initial surgical resection. PMID:22532912

  8. Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

    PubMed Central

    Hughes, Russell; Qian, Bin-Zhi; Rowan, Charlotte; Muthana, Munitta; Keklikoglou, Ioanna; Olson, Oakley C.; Tazzyman, Simon; Danson, Sarah; Addison, Christina; Clemons, Mark; Gonzalez-Angulo, Ana Maria; Joyce, Johanna A.; De Palma, Michele; Pollard, Jeffrey W.; Lewis, Claire E.

    2016-01-01

    Tumor relapse after chemotherapy-induced regression is a major clinical problem, because it often involves inoperable metastatic disease. Tumor-associated macrophages (TAM) are known to limit the cytotoxic effects of chemotherapy in preclinical models of cancer. Here, we report that an alternatively activated (M2) subpopulation of TAMs (MRC1+TIE2HiCXCR4Hi) accumulate around blood vessels in tumors after chemotherapy, where they promote tumor revascularization and relapse, in part, via VEGF-A release. A similar perivascular, M2-related TAM subset was present in human breast carcinomas and bone metastases after chemotherapy. Although a small proportion of M2 TAMs were also present in hypoxic tumor areas, when we genetically ablated their ability to respond to hypoxia via hypoxia-inducible factors 1 and 2, tumor relapse was unaffected. TAMs were the predominant cells expressing immunoreactive CXCR4 in chemotherapy-treated mouse tumors, with the highest levels expressed by MRC1+ TAMs clustering around the tumor vasculature. Furthermore, the primary CXCR4 ligand, CXCL12, was upregulated in these perivascular sites after chemotherapy, where it was selectively chemotactic for MRC1+ TAMs. Interestingly, HMOX-1, a marker of oxidative stress, was also upregulated in perivascular areas after chemotherapy. This enzyme generates carbon monoxide from the breakdown of heme, a gas known to upregulate CXCL12. Finally, pharmacologic blockade of CXCR4 selectively reduced M2-related TAMs after chemotherapy, especially those in direct contact with blood vessels, thereby reducing tumor revascularization and regrowth. Our studies rationalize a strategy to leverage chemotherapeutic efficacy by selectively targeting this perivascular, relapse-promoting M2-related TAM cell population. PMID:26269531

  9. Perivascular mast cells regulate vein graft neointimal formation and remodeling

    PubMed Central

    Grassia, Gianluca; Cambrook, Helen; Ialenti, Armando; MacRitchie, Neil; Carberry, Jaclyn; Lawrence, Catherine

    2015-01-01

    Objective. Emerging evidence suggests an important role for mast cells in vein graft failure. This study addressed the hypothesis that perivascular mast cells regulate in situ vascular inflammatory and proliferative responses and subsequent vein graft neointimal lesion formation, using an optimized local mast cell reconstitution method. Methods and Results. Neointimal hyperplasia was induced by insertion of a vein graft into the right carotid artery in wild type and mast cell deficient KitW−sh/W−sh mice. In some experiments, mast cells were reconstituted systemically (tail vein injection of bone marrow-derived mast cells) or locally (directly into the right neck area) prior to vein grafting. Vein graft neointimal lesion formation was significantly (P < 0.05) reduced in KitW−sh/W−sh mice. Mast cell deficiency reduced the number of proliferating cells, and inhibited L-selectin, CCL2, M-CSF and MIP-3α expression in the vein grafts. Local but not systemic mast cell reconstitution restored a perivascular mast cell population that subsequently promoted neointimal formation in mast cell deficient mice. Conclusion. Our data demonstrate that perivascular mast cells play a key role in promoting neointima formation by inducing local acute inflammatory and proliferative responses. These results suggest that ex vivo intraoperative targeting of mast cells may have therapeutic potential for the prevention of pathological vein graft remodeling. PMID:26312183

  10. Cerebral amyloid angiopathy severity is linked to dilation of juxtacortical perivascular spaces.

    PubMed

    van Veluw, Susanne J; Biessels, Geert Jan; Bouvy, Willem H; Spliet, Wim Gm; Zwanenburg, Jaco Jm; Luijten, Peter R; Macklin, Eric A; Rozemuller, Annemieke Jm; Gurol, M Edip; Greenberg, Steven M; Viswanathan, Anand; Martinez-Ramirez, Sergi

    2016-03-01

    Perivascular spaces are an emerging marker of small vessel disease. Perivascular spaces in the centrum semiovale have been associated with cerebral amyloid angiopathy. However, a direct topographical relationship between dilated perivascular spaces and cerebral amyloid angiopathy severity has not been established. We examined this association using post-mortem magnetic resonance imaging in five cases with evidence of cerebral amyloid angiopathy pathology. Juxtacortical perivascular spaces dilation was evaluated on T2 images and related to cerebral amyloid angiopathy severity in overlying cortical areas on 34 tissue sections stained for Amyloid β. Degree of perivascular spaces dilation was significantly associated with cerebral amyloid angiopathy severity (odds ratio = 3.3, 95% confidence interval 1.3-7.9, p = 0.011). Thus, dilated juxtacortical perivascular spaces are a promising neuroimaging marker of cerebral amyloid angiopathy severity. PMID:26661250

  11. A systematic review: perivascular epithelioid cell tumor of gastrointestinal tract.

    PubMed

    Chen, Zehong; Han, Siqi; Wu, Jialin; Xiong, Minmin; Huang, Yanqiao; Chen, Jianhui; Yuan, Yujie; Peng, Jianjun; Song, Wu

    2016-07-01

    Perivascular epithelioid cell tumor (PEComa) is a rare entity with distinctive morphology and of expressing myomelanocytic markers. Gastrointestinal tract (GI) is one of the most common anatomic sites of origin and counts for 20% to 25% of all reported cases of perivascular epithelioid cell tumors not otherwise specified (PEComas-NOS). However, the biologic behavior of perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas-NOS) is still unclear. The aim of conducting this systematic review is to sum up what is known so far of the epidemiology, natural history, management and prognosis of GI PEComas-NOS.A systematic research was performed on PubMed and EMBASE using the following terms: ("perivascular epithelioid cell tumor" or "PEComa") and ("gastrointestinal tract" or "GI" or "oral " or "mouth" or "esophagus" or "gullet" or "gastric" or "stomach" or "duodenum" or "jejunum" or "ileum" or "cecum" or "colon" or "colorectal" or "sigmoid" or "rectum" or "anus" or "mesentery") up to December 1, 2015. Retrieved GI PEComas-NOS publications, which included these terms, contains case reports, case series to case characteristic researches.A total of 168 articles were reviewed, 41 GI PEComa-NOS English studies among which were retrieved for analysis. We reviewed epidemiology, natural history, management and prognosis of GI PEComa-NOS. Generally GI PEComa-NOS is believed to have women predomination. The most frequently involved location is colon with non-specific clinical signs. Pathologically, GI PEComas-NOS shows epithelioid predominance (70%), meanwhile coexpresses melanocytic and muscle markers characteristically, while immunohistochemistry is a useful tool for identify, which indicates that HMB-45 is regarded as the most sensitive reagent. Complete resection served as mainstay of treatment, while chemotherapy should be unanimously considered to apply in malignant cases. Eventually, it is necessary for closed and long-term follow-up with endoscope and

  12. A systematic review: perivascular epithelioid cell tumor of gastrointestinal tract

    PubMed Central

    Chen, Zehong; Han, Siqi; Wu, Jialin; Xiong, Minmin; Huang, Yanqiao; Chen, Jianhui; Yuan, Yujie; Peng, Jianjun; Song, Wu

    2016-01-01

    Abstract Perivascular epithelioid cell tumor (PEComa) is a rare entity with distinctive morphology and of expressing myomelanocytic markers. Gastrointestinal tract (GI) is one of the most common anatomic sites of origin and counts for 20% to 25% of all reported cases of perivascular epithelioid cell tumors not otherwise specified (PEComas-NOS). However, the biologic behavior of perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas-NOS) is still unclear. The aim of conducting this systematic review is to sum up what is known so far of the epidemiology, natural history, management and prognosis of GI PEComas-NOS. A systematic research was performed on PubMed and EMBASE using the following terms: (“perivascular epithelioid cell tumor” or “PEComa”) and (“gastrointestinal tract” or “GI” or “oral ” or “mouth” or “esophagus” or “gullet” or “gastric” or “stomach” or “duodenum” or “jejunum” or “ileum” or “cecum” or “colon” or “colorectal” or “sigmoid” or “rectum” or “anus” or “mesentery”) up to December 1, 2015. Retrieved GI PEComas-NOS publications, which included these terms, contains case reports, case series to case characteristic researches. A total of 168 articles were reviewed, 41 GI PEComa-NOS English studies among which were retrieved for analysis. We reviewed epidemiology, natural history, management and prognosis of GI PEComa-NOS. Generally GI PEComa-NOS is believed to have women predomination. The most frequently involved location is colon with non-specific clinical signs. Pathologically, GI PEComas-NOS shows epithelioid predominance (70%), meanwhile coexpresses melanocytic and muscle markers characteristically, while immunohistochemistry is a useful tool for identify, which indicates that HMB-45 is regarded as the most sensitive reagent. Complete resection served as mainstay of treatment, while chemotherapy should be unanimously considered to apply in malignant

  13. Follicular dendritic cells emerge from ubiquitous perivascular precursors.

    PubMed

    Krautler, Nike Julia; Kana, Veronika; Kranich, Jan; Tian, Yinghua; Perera, Dushan; Lemm, Doreen; Schwarz, Petra; Armulik, Annika; Browning, Jeffrey L; Tallquist, Michelle; Buch, Thorsten; Oliveira-Martins, José B; Zhu, Caihong; Hermann, Mario; Wagner, Ulrich; Brink, Robert; Heikenwalder, Mathias; Aguzzi, Adriano

    2012-07-01

    The differentiation of follicular dendritic cells (FDC) is essential to the remarkable microanatomic plasticity of lymphoid follicles. Here we show that FDC arise from ubiquitous perivascular precursors (preFDC) expressing platelet-derived growth factor receptor β (PDGFRβ). PDGFRβ-Cre-driven reporter gene recombination resulted in FDC labeling, whereas conditional ablation of PDGFRβ(+)-derived cells abolished FDC, indicating that FDC originate from PDGFRβ(+) cells. Lymphotoxin-α-overexpressing prion protein (PrP)(+) kidneys developed PrP(+) FDC after transplantation into PrP(-) mice, confirming that preFDC exist outside lymphoid organs. Adipose tissue-derived PDGFRβ(+) stromal-vascular cells responded to FDC maturation factors and, when transplanted into lymphotoxin β receptor (LTβR)(-) kidney capsules, differentiated into Mfge8(+)CD21/35(+)FcγRIIβ(+)PrP(+) FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte-deficient mice contained perivascular PDGFRβ(+) FDC precursors whose expansion required both lymphoid tissue inducer (LTi) cells and lymphotoxin. The ubiquity of preFDC and their strategic location at blood vessels may explain the de novo generation of organized lymphoid tissue at sites of lymphocytic inflammation. PMID:22770220

  14. Follicular Dendritic Cells Emerge from Ubiquitous Perivascular Precursors

    PubMed Central

    Krautler, Nike Julia; Kana, Veronika; Kranich, Jan; Tian, Yinghua; Perera, Dushan; Lemm, Doreen; Schwarz, Petra; Armulik, Annika; Browning, Jeffrey L.; Tallquist, Michelle; Buch, Thorsten; Oliveira-Martins, José B.; Zhu, Caihong; Hermann, Mario; Wagner, Ulrich; Brink, Robert; Heikenwalder, Mathias; Aguzzi, Adriano

    2013-01-01

    Summary The differentiation of follicular dendritic cells (FDC) is essential to the remarkable microanatomic plasticity of lymphoid follicles. Here we show that FDC arise from ubiquitous perivascular precursors (preFDC) expressing platelet-derived growth factor receptor β (PDGFRβ). PDGFRβ-Cre-driven reporter gene recombination resulted in FDC labeling, whereas conditional ablation of PDGFRβ+-derived cells abolished FDC, indicating that FDC originate from PDGFRβ+ cells. Lymphotoxin-α-overexpressing prion protein (PrP)+ kidneys developed PrP+ FDC after transplantation into PrP mice, confirming that preFDC exist outside lymphoid organs. Adipose tissue-derived PDGFRβ+ stromal-vascular cells responded to FDC maturation factors and, when transplanted into lymphotoxin β receptor (LTβR) kidney capsules, differentiated into Mfge8+CD21/35+ FcγRIIβ+PrP+ FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte-deficient mice contained perivascular PDGFRβ+ FDC precursors whose expansion required both lymphoid tissue inducer (LTi) cells and lymphotoxin. The ubiquity of preFDC and their strategic location at blood vessels may explain the de novo generation of organized lymphoid tissue at sites of lymphocytic inflammation. PMID:22770220

  15. Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche.

    PubMed

    Tamplin, Owen J; Durand, Ellen M; Carr, Logan A; Childs, Sarah J; Hagedorn, Elliott J; Li, Pulin; Yzaguirre, Amanda D; Speck, Nancy A; Zon, Leonard I

    2015-01-15

    Hematopoietic stem and progenitor cells (HSPCs) can reconstitute and sustain the entire blood system. We generated a highly specific transgenic reporter of HSPCs in zebrafish. This allowed us to perform high-resolution live imaging on endogenous HSPCs not currently possible in mammalian bone marrow. Using this system, we have uncovered distinct interactions between single HSPCs and their niche. When an HSPC arrives in the perivascular niche, a group of endothelial cells remodel to form a surrounding pocket. This structure appears conserved in mouse fetal liver. Correlative light and electron microscopy revealed that endothelial cells surround a single HSPC attached to a single mesenchymal stromal cell. Live imaging showed that mesenchymal stromal cells anchor HSPCs and orient their divisions. A chemical genetic screen found that the compound lycorine promotes HSPC-niche interactions during development and ultimately expands the stem cell pool into adulthood. Our studies provide evidence for dynamic niche interactions upon stem cell colonization. PAPERFLICK: PMID:25594182

  16. Mechanisms of perivascular adipose tissue dysfunction in obesity.

    PubMed

    Fernández-Alfonso, Maria S; Gil-Ortega, Marta; García-Prieto, Concha F; Aranguez, Isabel; Ruiz-Gayo, Mariano; Somoza, Beatriz

    2013-01-01

    Most blood vessels are surrounded by adipose tissue. Similarly to the adventitia, perivascular adipose tissue (PVAT) was considered only as a passive structural support for the vasculature, and it was routinely removed for isolated blood vessel studies. In 1991, Soltis and Cassis demonstrated for the first time that PVAT reduced contractions to noradrenaline in rat aorta. Since then, an important number of adipocyte-derived factors with physiological and pathophysiological paracrine vasoactive effects have been identified. PVAT undergoes structural and functional changes in obesity. During early diet-induced obesity, an adaptative overproduction of vasodilator factors occurs in PVAT, probably aimed at protecting vascular function. However, in established obesity, PVAT loses its anticontractile properties by an increase of contractile, oxidative, and inflammatory factors, leading to endothelial dysfunction and vascular disease. The aim of this review is to focus on PVAT dysfunction mechanisms in obesity. PMID:24307898

  17. Mechanisms of Perivascular Adipose Tissue Dysfunction in Obesity

    PubMed Central

    Fernández-Alfonso, Maria S.; García-Prieto, Concha F.; Aranguez, Isabel; Ruiz-Gayo, Mariano; Somoza, Beatriz

    2013-01-01

    Most blood vessels are surrounded by adipose tissue. Similarly to the adventitia, perivascular adipose tissue (PVAT) was considered only as a passive structural support for the vasculature, and it was routinely removed for isolated blood vessel studies. In 1991, Soltis and Cassis demonstrated for the first time that PVAT reduced contractions to noradrenaline in rat aorta. Since then, an important number of adipocyte-derived factors with physiological and pathophysiological paracrine vasoactive effects have been identified. PVAT undergoes structural and functional changes in obesity. During early diet-induced obesity, an adaptative overproduction of vasodilator factors occurs in PVAT, probably aimed at protecting vascular function. However, in established obesity, PVAT loses its anticontractile properties by an increase of contractile, oxidative, and inflammatory factors, leading to endothelial dysfunction and vascular disease. The aim of this review is to focus on PVAT dysfunction mechanisms in obesity. PMID:24307898

  18. PERIVASCULAR EPITHELIOID TUMOURS (PEComas) OF THE GYNAECOLOGICAL TRACT

    PubMed Central

    Conlon, Niamh; Soslow, Robert A.; Murali, Rajmohan

    2016-01-01

    Perivascular epithelioid tumour (PEComas) of the gynaecological tract are rare tumours which were first recognised and diagnosed within the last twenty years. They represent a unique diagnostic challenge with regard to their accurate and reproducible distinction from more common entities such as smooth muscle tumours of the uterine corpus. In this review article we trace the development of the concept of the PEComa tumour family, highlight what is known about extra-gynaecological tract PEComa at an immunohistochemical, molecular and therapeutic level and then present a summary of all reported cases of gynaecological tract PEComa to date. In the summary, we highlight rare subtypes of gynaecological tract PEComa, and compare the performances of extant prognostic classification systems for malignancy in these tumours. PMID:25750268

  19. Perivascular Spaces Are Associated with Atherosclerosis: An Insight from the Northern Manhattan Study

    PubMed Central

    Gutierrez, J.; Rundek, T.; Ekind, M.S.V.; Sacco, R.L.; Wright, C.B.

    2015-01-01

    Background and Purpose Perivascular spaces are potential spaces found between brain blood vessels and surrounding leptomeninges that have been associated with cardiovascular risk factors and dementia, but less is known about their relationship to atherosclerosis. We tested the hypothesis that perivascular spaces are associated with atherosclerosis. Materials and Methods Participants from the Northern Manhattan Study who remained stroke-free were invited to participate in an MR imaging substudy. Parenchymal hypointensities of <3 mm identified on brain axial T1-weighted MR imaging were scored as perivascular spaces. A semiquantitative score was created to express the degree of brain involvement. Generalized linear models were used to assess statistical associations with carotid plaque as a surrogate marker of atherosclerosis. Results The studied sample included 706 participants (mean age, 72.6 ±8.0 years; 60% women, 61% Hispanic, 68% with hypertension, 19% with diabetes, and 57% with high cholesterol). The perivascular spaces score ranged from 0 to 19 with 52% of the sample having a perivascular spaces score of ≤4. In unadjusted analysis, perivascular spaces were associated with age (β = 0.01 per year, P = <.001), non-Hispanic black race-ethnicity (β = 0.16, P = .02), hypertension (β = 0.24, P = <.001), and carotid plaque (β = 0.22, P < .001). In multivariable analysis, only age (β = 0.01, P = .02), hypertension (β = 0.17, P = .01), and carotid plaque (β = 0.22, P = < .001) remained independently associated with perivascular spaces. Conclusions Perivascular spaces were more frequently found in older participants, in those with hypertension, and in the presence of carotid plaque. These results suggest that mechanisms leading to atherosclerosis might also lead to an increased number of perivascular spaces. These results need confirmation in prospective studies. PMID:23557952

  20. Perivascular Stem Cells at the Tip of Mouse Incisors Regulate Tissue Regeneration.

    PubMed

    Pang, Yvonne Wy; Feng, Jifan; Daltoe, Felipe; Fatscher, Robert; Gentleman, Eileen; Gentleman, Molly M; Sharpe, Paul T

    2016-03-01

    Cells with in vitro properties similar to those of bone marrow stromal stem cells are present in tooth pulp as quiescent cells that are mobilized by damage. These dental pulp stem cells (DPSCs) respond to damage by stimulating proliferation and differentiation into odontoblast-like cells that form dentine to repair the damage. In continuously growing mouse incisors, tissue at the incisor tips is continuously being damaged by the shearing action between the upper and lower teeth acting to self-sharpen the tips. We investigated mouse incisor tips as a model for the role of DPSCs in a continuous natural repair/regeneration process. We show that the pulp at the incisor tip is composed of a disorganized mass of mineralized tissue produced by odontoblast-like cells. These cells become embedded into the mineralized tissue that is rapidly formed and then lost during feeding. Tetracycline labeling not only revealed the expected incorporation into newly synthesized dentine formation of the incisor but also a zone covering the pulp cavity at the tips of the incisors that is mineralized very rapidly. This tissue was dentine-like but had a significantly lower mineral content than dentine as determined by Raman spectroscopy. The mineral was more crystalline than dentine, indicative of small, defect-free mineral particles. To identify the origin of cells responsible for deposition of this mineralized tissue, we genetically labeled perivascular cells by crossing NG2(ERT2) Cre and Nestin Cre mice with reporter mice. A large number of pericyte-derived cells were visible in the pulp of incisor tips with some having elongated, odontoblast-like shapes. These results show that in mouse incisors, rapid, continuous mineralization occurs at the tip to seal off the pulp tissue from the external environment. The mineral is formed by perivascular-derived cells that differentiate into cells expressing dentin sialo-phosphoprotein (DSPP) and produce a dentine-like material in a process that

  1. Perivascular fat, AMP-activated protein kinase and vascular diseases

    PubMed Central

    Almabrouk, T A M; Ewart, M A; Salt, I P; Kennedy, S

    2014-01-01

    Perivascular adipose tissue (PVAT) is an active endocrine and paracrine organ that modulates vascular function, with implications for the pathophysiology of cardiovascular disease (CVD). Adipocytes and stromal cells contained within PVAT produce mediators (adipokines, cytokines, reactive oxygen species and gaseous compounds) with a range of paracrine effects modulating vascular smooth muscle cell contraction, proliferation and migration. However, the modulatory effect of PVAT on the vascular system in diseases, such as obesity, hypertension and atherosclerosis, remains poorly characterized. AMP-activated protein kinase (AMPK) regulates adipocyte metabolism, adipose biology and vascular function, and hence may be a potential therapeutic target for metabolic disorders such as type 2 diabetes mellitus (T2DM) and the vascular complications associated with obesity and T2DM. The role of AMPK in PVAT or the actions of PVAT have yet to be established, however. Activation of AMPK by pharmacological agents, such as metformin and thiazolidinediones, may modulate the activity of PVAT surrounding blood vessels and thereby contribute to their beneficial effect in cardiometabolic diseases. This review will provide a current perspective on how PVAT may influence vascular function via AMPK. We will also attempt to demonstrate how modulating AMPK activity using pharmacological agents could be exploited therapeutically to treat cardiometabolic diseases. PMID:24490856

  2. Microscopic endometrial perivascular epithelioid cell nodules: a case report with the earliest presentation of a uterine perivascular epithelioid cell tumor.

    PubMed

    Fang, Chia-Lang; Lin, Yun-Ho; Chen, Wei-Yu

    2012-01-01

    Perivascular epithelioid cell (PEC) tumors (PEComas) are a family of related mesenchymal tumors composed of PECs which co-express melanocytic and smooth muscle markers. Although their distinctive histologic, immunohistochemical, ultrastructural, and genetic features have been clearly demonstrated, their histogenesis and normal counterpart remain largely unknown. Precursor lesions of PEComas have rarely been reported. We herein describe a tuberous sclerosis patient with microscopic PEC nodules in the endometrium of adenomyosis, pelvic endometriosis, an ovarian endometriotic cyst, and the endometrium of the uterine cavity. The nodules showed a mixture of spindle-shaped and epithelioid cells concentrically arranged around small arteries. The cells exhibited uniform nuclei, light eosinophilic cytoplasm, and immunoreactivity with HMB-45 and CD10. Some nodules revealed continuity with a PEComa in the myometrium. These findings support microscopic endometrial PEC nodules possibly being precursor lesions of uterine PEComas. The wide distribution of the nodules in the pelvis may be related to the multicentricity of PEComas in tuberous sclerosis patients. Owing to the immunoreactivity with CD10, microscopic endometrial PEC nodules may be misinterpreted as endothelial stromal cells unless melanocytic markers are stained. To the best of our knowledge, this is a case with the earliest manifestation of PEC lesions occurring in the endometrium. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9658280017862643. PMID:22937790

  3. Insulin resistance in SHR/NDmc-cp rats correlates with enlarged perivascular adipocytes and endothelial cell dysfunction in skeletal muscle.

    PubMed

    Hariya, Natsuyo; Mochizuki, Kazuki; Inoue, Seiya; Morioka, Kosuke; Shimada, Masaya; Okuda, Tohru; Goda, Toshinao

    2014-01-01

    Ectopic adipose tissue in skeletal muscle is implicated in the development of insulin resistance, which is frequently induced by abnormal dietary habits such as excessive eating and a high-fat diet. However, the characteristics of ectopic adipocytes are unknown. In this study, we investigated the characteristics of ectopic adipocytes in the skeletal muscle of spontaneously hypertensive corpulent congenic (SHR/NDmc-cp) rats as a model of insulin resistance from excessive eating. SHR/NDmc-cp rats displayed overt insulin resistance with high plasma glucose, insulin, and triacylglycerol concentrations relative to control Wistar-Kyoto (WKY) rats. In contrast, streptozotocin (STZ)-treated WKY rats had high glucose but low insulin concentrations. Ectopic adipocytes were found around blood vessels in the gastrocnemius in SHR/NDmc-cp rats. Areas of perivascular adipocytes and protein expression of resistin were greater in SHR/NDmc-cp rats than in control and STZ-treated WKY rats. The level of the phosphorylated (active) form of endothelial nitric oxide synthase in the gastrocnemius was lower in SHR/NDmc-cp rats than in the other groups. Insulin-resistant SHR/NDmc-cp rats showed enlarged perivascular adipocytes and greater endothelial cell dysfunction in the gastrocnemius. PMID:24759260

  4. Glioblastoma stem cells are regulated by interleukin-8 signaling in a tumoral perivascular niche

    PubMed Central

    Infanger, David W.; Cho, YouJin; Lopez, Brina S.; Mohanan, Sunish; Liu, S. Chris; Gursel, Demirkan; Boockvar, John A.; Fischbach, Claudia

    2013-01-01

    Glioblastoma multiforme (GBM) contains a subpopulation of cancer stem-like cells (CSCs) believed to underlie tumorigenesis and therapeutic resistance. Recent studies have localized CSCs in this disease adjacent to endothelial cells (ECs) in what has been termed a perivascular niche, spurring investigation into the role of EC-CSC interactions in GBM pathobiology. However, these studies have been limited by a lack of in vitro models of three-dimensional disease that can recapitulate the relevant conditions of the niche. In this study, we engineered a scaffold-based culture system enabling brain ECs to form vascular networks. Using this system, we demonstrated that vascular assembly induces CSC maintenance and growth in vitro and accelerates tumor growth in vivo through paracrine IL-8 signaling. Relative to conventional monolayers, ECs cultured in this three dimensional system not only secreted enhanced levels of IL-8 but also induced CSCs to upregulate the IL-8 cognate receptors CXCR1 and CXCR2, which collectively enhanced CSC migration, growth and stemness properties. CXCR2 silencing in CSCs abolished the tumor-promoting effects of ECs in vivo, confirming a critical role for this signaling pathway in GMB pathogenesis. Together, our results reveal synergistic interactions between ECs and CSCs that promote the malignant properties of CSCs in an IL-8-dependent manner. Furthermore, our findings underscore the relevance of tissue-engineered cell culture platforms to fully analyze signaling mechanisms in the tumor microenvironment. PMID:24121485

  5. Coronary adventitial cells are linked to perivascular cardiac fibrosis via TGFβ1 signaling in the mdx mouse model of Duchenne Muscular Dystrophy

    PubMed Central

    Ieronimakis, Nicholas; Hays, Aislinn L.; Janebodin, Kajohnkiart; Mahoney, William M.; Duffield, Jeremy S.; Majesky, Mark W.; Reyes, Morayma

    2013-01-01

    In Duchenne Muscular Dystrophy (DMD), progressive accumulation of cardiac fibrosis promotes heart failure. While the cellular origins of fibrosis in DMD hearts remain enigmatic, fibrotic tissue conspicuously forms near the coronary adventitia. Therefore, we sought to characterize the role of coronary adventitial cells in the formation of perivascular fibrosis. Utilizing the mdx model of DMD, we have identified a population of Sca1+, PDGFRα+, CD31−, CD45− coronary adventitial cells responsible for perivascular fibrosis. Histopathology of dystrophic hearts revealed Sca1+ cells extend from the adventitia and occupy regions of perivascular fibrosis. The number of Sca1+ adventitial cells increased two-fold in fibrotic mdx hearts vs. age matched wild-type hearts. Moreover, relative to Sca1−, PDGFRα+, CD31−, CD45− cells and endothelial cells, Sca1+ adventitial cells FACS-sorted from mdx hearts expressed the highest level of Collagen1α1 and 3α1, Connective tissue growth factor, and Tgfβr1 transcripts. Surprisingly, mdx endothelial cells expressed the greatest level of the Tgfβ1 ligand. Utilizing Collagen1α1-GFP reporter mice, we confirmed that the majority of Sca1+ adventitial cells expressed type I collagen, an abundant component of cardiac fibrosis, in both wt (71% ±4.1) and mdx (77% ±3.5) hearts. In contrast, GFP+ interstitial fibroblasts were PDGFRα+ but negative for Sca1. Treatment of cultured Collagen1α1-GFP+ adventitial cells with TGFβ1 resulted in increased collagen synthesis, whereas pharmacological inhibition of TGFβR1 signaling reduced the fibrotic response. Therefore, perivascular cardiac fibrosis by coronary adventitial cells may be mediated by TGFβ1 signaling. Our results implicate coronary endothelial cells in mediating cardiac fibrosis via transmural TGFβ signaling, and suggest that the coronary adventitia is a promising target for developing novel anti-fibrotic therapies. PMID:23911435

  6. Decidualization induces a secretome switch in perivascular niche cells of the human endometrium.

    PubMed

    Murakami, Keisuke; Lee, Yie Hou; Lucas, Emma S; Chan, Yi-Wah; Durairaj, Ruban Peter; Takeda, Satoru; Moore, Jonathan D; Tan, Bee K; Quenby, Siobhan; Chan, Jerry K Y; Gargett, Caroline E; Brosens, Jan J

    2014-11-01

    The endometrial perivascular microenvironment is rich in mesenchymal stem-like cells that express type 1 integral membrane protein Sushi domain containing 2 (SUSD2) but the role of these cells in the decidual transformation of this tissue in pregnancy is unknown. We used an antibody directed against SUSD2 (W5C5) to isolate perivascular (W5C5(+)) and nonperivascular (W5C5(-)) fibroblasts from mid-luteal biopsies. We show that SUSD2 expression, and hence the ratio of W5C5(+):W5C5(-) cells, changes in culture depending on cell-cell contact and activation of the Notch signaling pathway. RNA sequencing revealed that cultures derived from W5C5(+) progenitor cells remain phenotypically distinct by the enrichment of novel and established endometrial perivascular signature genes. In an undifferentiated state, W5C5(+)-derived cells produced lower levels of various chemokines and inflammatory modulators when compared with their W5C5(-) counterparts. This divergence in secretomes was switched and became more pronounced upon decidualization, which transformed perivascular W5C5(+) cells into the dominant source of a range of chemokines and cytokines, including leukemia inhibitory factor and chemokine (C-C motif) ligand 7. Our findings suggest that the decidual response is spatially organized at the embryo-maternal interface with differentiating perivascular cells establishing distinct cytokine and chemokine profiles that could potentially direct trophoblast toward maternal vessels and govern local immune responses in pregnancy. PMID:25116707

  7. Isolation, characterisation and comparative analysis of human umbilical cord vein perivascular cells and cord blood mesenchymal stem cells.

    PubMed

    Gökçinar-Yagci, Beyza; Özyüncü, Özgür; Çelebi-Saltik, Betül

    2016-06-01

    Perivascular cells are known to be ancestors of mesenchymal stem cells (MSCs) and can be obtained from heart, skin, bone marrow, eye, placenta and umbilical cord (UC). However detailed characterization of perivascular cells around the human UC vein and comparative analysis of them with MSCs haven't been done yet. In this study, our aim is to isolate perivascular cells from human UC vein and characterize them versus UC blood MSCs (UCB-MSCs). For this purpose, perivascular cells around the UC vein were isolated enzymatically and then purified with magnetic activated cell sorting (MACS) method using CD146 Microbead Kit respectively. MSCs were isolated from UCB by Ficoll density gradient solution. Perivascular cells and UCB-MSCs were characterized by osteogenic and adipogenic differentiation procedures, flow cytometric analysis [CD146, CD105, CD31, CD34, CD45 and alpha-smooth muscle actin (α-SMA)], and immunofluorescent staining (MAP1B and Tenascin C). Alizarin red and Oil red O staining results showed that perivascular cells and MSCs had osteogenic and adipogenic differentiation capacity. However, osteogenic differentiation capacity of perivascular cells were found to be less than UCB-MSCs. According to flow cytometric analysis, CD146 expression of perivascular cells were appeared to be 4.8-fold higher than UCB-MSCs. Expression of α-SMA, MAP1B and Tenascin-C from perivascular cells was determined by flow cytometry analysis and immunfluorescent staining. The results appear to support the fact that perivascular cells are the ancestors of MSCs in vascular area. They may be used as alternative cells to MSCs in the field of vascular tissue engineering. PMID:26679930

  8. Malignant Perivascular Epithelioid Cell Neoplasm (PEComa) of the Pelvis: A Case Report

    PubMed Central

    D'Andrea, David; Hanspeter, Esther; D'Elia, Carolina; Martini, Thomas; Pycha, Armin

    2016-01-01

    Perivascular epithelioid cell neoplasms (PEComa) are rare mesenchymal tumors that can occur in any part of the body and have unpredictable pathological behavior. They are usually benign, but may be malignant. We present a case of malignant PEComa of the pelvic retroperitoneum treated with radical surgery. PMID:27169023

  9. Perivascular Spaces--MRI Marker of Inflammatory Activity in the Brain?

    ERIC Educational Resources Information Center

    Wuerfel, Jens; Haertle, Mareile; Waiczies, Helmar; Tysiak, Eva; Bechmann, Ingo; Wernecke, Klaus D.; Zipp, Frauke; Paul, Friedemann

    2008-01-01

    The Virchow-Robin spaces (VRS), perivascular compartments surrounding small blood vessels as they penetrate the brain parenchyma, are increasingly recognized for their role in leucocyte trafficking as well as for their potential to modulate immune responses. In the present study, we investigated VRS numbers and volumes in different brain regions…

  10. Perivascular adipose tissue: An unique fat compartment relevant for the cardiometabolic syndrome.

    PubMed

    Siegel-Axel, D I; Häring, H U

    2016-03-01

    Type 2 diabetes and its major risk factor, obesity, are an increasing worldwide health problem. The exact mechanisms that link obesity with insulin resistance, type 2 diabetes, hypertension, cardiovascular complications and renal diseases, are still not clarified sufficiently. Adipose tissue in general is an active endocrine and paracrine organ that may influence the development of these disorders. Excessive body fat in general obesity may also cause quantitative and functional alterations of specific adipose tissue compartments. Beside visceral and subcutaneous fat depots which exert systemic effects by the release of adipokines, cytokines and hormones, there are also locally acting fat depots such as peri- and epicardial fat, perivascular fat, and renal sinus fat. Perivascular adipose tissue is in close contact with the adventitia of large, medium and small diameter arteries, possesses unique features differing from other fat depots and may act also independently of general obesity. An increasing number of studies are dealing with the "good" or "bad" characteristics and functions of normally sized and dramatically increased perivascular fat mass in lean or heavily obese individuals. This review describes the origin of perivascular adipose tissue, its different locations, the dual role of a physiological and unphysiological fat mass and its impact on diabetes, cardiovascular and renal diseases. Clinical studies, new imaging methods, as well as basic research in cell culture experiments in the last decade helped to elucidate the various aspects of the unique fat compartment. PMID:26995737

  11. Perivascular epithelial cell tumor (PEComa) of the pancreas: a case report and review of previous literatures.

    PubMed

    Mizuuchi, Yusuke; Nishihara, Kazuyoshi; Hayashi, Akifumi; Tamiya, Sadafumi; Toyoshima, Satoshi; Oda, Yoshinao; Nakano, Toru

    2016-12-01

    Perivascular epithelial cell tumors (PEComas), firstly described by Bonetti in 1992, are a family of mesenchymal tumor composed of perivascular epithelioid cells having epithelioid or spindle morphology and exhibiting melanocytic and myogenic immunoreactivities. We herein described a 61-year-old woman who presented with epigastric pain. Preoperative imaging studies showed that 7-cm-sized mass was located in pancreatic head and body, and pancreaticoduodenectomy was performed. Histological findings showed that the tumor was composed of clear epithelioid cells with abundant glycogen granules, which grew in a nested and alveolar pattern around blood vessels. The tumor cells showed immunoreactivities for HMB-45 but did not express epithelial or endocrine markers. These histological features indicated those of PEComa. This report underlines that we should recognize PEComa as a preoperative differential diagnosis of pancreatic tumors. PMID:27307283

  12. Primary perivascular epithelioid cell tumor of the liver: new case report and literature review

    PubMed Central

    2014-01-01

    Perivascular epithelioid cell tumors (PEComas) encompass a group of rare mesenchymal neoplasms, which typically have a perivascular location with dual melanocytic and muscular differentiation. They are found in a variety of localizations, though lesions in the liver are exceedingly rare. Because of their rarity, the clinical, radiological and histological features of these tumors have yet to be established. This is why, it seems appropriate to report the observation of this rare hepatic tumor with a literary review including others published cases, assessing through it, clinicopathologic and radiologic features of all reported cases as well as their follow-up whenever possible. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1967094999126169 PMID:25034830

  13. Cutaneous perivascular epithelioid cell tumors: A review on an infrequent neoplasm

    PubMed Central

    Llamas-Velasco, Mar; Requena, Luis; Mentzel, Thomas

    2016-01-01

    Perivascular epithelioid cutaneous” cell tumors (PEComa) are a family of mesenchymal tumors with shared microscopic and immunohistochemical properties: They exhibit both smooth muscle cell and melanocytic differentiation. Non-neoplastic counterpart of PEComa’s cells are unknown, as well as the relationship between extracutaneous PEComa and primary cutaneous ones. We will review the clinical setting, histopathologic features, chromosomal abnormalities, differential diagnosis and treatment options for cutaneous PEComa. PMID:27019799

  14. Obesity-related hypertension: epidemiology, pathophysiology, treatments, and the contribution of perivascular adipose tissue.

    PubMed

    Aghamohammadzadeh, Reza; Heagerty, Anthony M

    2012-06-01

    The advent of the obesity epidemic has highlighted the need to re-assess more closely the pathophysiology of obesity-related hypertension with the aim of identifying new therapies. In this article, we review the role of the renin-angiotensin-aldosterone system, sympathetic nervous system, and inflammation in relation to the pathophysiology of this condition. We also discuss the potential role of the perivascular adipose tissue in the context of obesity-related hypertension. PMID:22713152

  15. Imaging the Perivascular Space as a Potential Biomarker of Neurovascular and Neurodegenerative Diseases.

    PubMed

    Ramirez, Joel; Berezuk, Courtney; McNeely, Alicia A; Gao, Fuqiang; McLaurin, JoAnne; Black, Sandra E

    2016-03-01

    Although the brain lacks conventional lymphatic vessels found in peripheral tissue, evidence suggests that the space surrounding the vasculature serves a similar role in the clearance of fluid and metabolic waste from the brain. With aging, neurodegeneration, and cerebrovascular disease, these microscopic perivascular spaces can become enlarged, allowing for visualization and quantification on structural MRI. The purpose of this review is to: (i) describe some of the recent pre-clinical findings from basic science that shed light on the potential neurophysiological mechanisms driving glymphatic and perivascular waste clearance, (ii) review some of the pathobiological etiologies that may lead to MRI-visible enlarged perivascular spaces (ePVS), (iii) describe the possible clinical implications of ePVS, (iv) evaluate existing qualitative and quantitative techniques used for measuring ePVS burden, and (v) propose future avenues of research that may improve our understanding of this potential clinical neuroimaging biomarker for fluid and metabolic waste clearance dysfunction in neurodegenerative and neurovascular diseases. PMID:26993511

  16. Macrophages migration through the brain parenchyma to the perivascular space following particle ingestion.

    PubMed Central

    McKeever, P. E.; Balentine, J. D.

    1978-01-01

    Forty-eight rats received intracerebral injections of sterile colloidal carbon. At intervals between 10 minutes and 31 days after carbon injection, the rats were perfused with glutaraldehyde, and autopsies were performed. Between 10 minutes and 3 hours after injection, carbon particles were extracellular and located strictly within the needle track. During the first few days the carbon was ingested by macrophages. Initially absent, carbon-laden macrophages spread to the neuropil immediately surrounding the injection site at 7 to 31 days following injection. These carbon-laden macrophages frequently were elongated within the neuropil and resembled microglia. Carbon-laden macrophages eventually accumulated around local vessels and in perivascular spaces. Many macrophages containing carbon remained in the injection site at the longest sampling interval of 31 days. Results indicate two macrophage responses to colloidal carbon in the central nervous system: a) an indolent population remains in the injection site for at least 1 month and b) a second population of macrophages emigrates through the neuropil. They eventually surround local vessels and enter the perivascular space. The migrating macrophages offer an explanation for the peculiar perivascular cells in Krabbe's disease and may provide a link between the CNS parenchyma and immunocompetent cells. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 1 Figure 2 PMID:696802

  17. Localization of NADPH Oxidase in Sympathetic and Sensory Ganglion Neurons and Perivascular Nerve Fibers

    PubMed Central

    Cao, Xian; Demel, Stacie L.; Quinn, Mark T.; Galligan, James J.; Kreulen, David L.

    2009-01-01

    Superoxide anion (O2−•) production was previously reported to be increased in celiac ganglia (CG) during DOCA-salt hypertension, possibly via activation of the reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase. This suggested a role for neuronal NADPH oxidase in autonomic neurovascular control. However, the expression and localization of NADPH oxidase in the peripheral neurons is not fully known. The purpose of this study was to examine the subcellular localization of NADPH oxidase in sympathetic and sensory ganglion neurons and perivascular nerve fibers. In rat CG, p22phox and neuropeptide Y (NPY) were colocalized in all neurons. P22phox was also localized to dorsal root ganglia (DRG) neurons that contain calcitonin gene related peptide (CGRP). In mesenteric arteries, p22phox and p47phox were colocalized with NPY or CGRP in perivascular nerve terminals. A similar pattern of nerve terminal staining of p22phox and p47phox was also found in cultured CG neurons and nerve growth factor (NGF)-differentiated PC12 cells. These data demonstrate a previously uncharacterized localization of NADPH oxidase in perivascular nerve fibers. The presence of a O2−• – generating enzyme in close vicinity to the sites of neurotransmitter handling in the nerve fibers suggests the possibility of novel redox-mediated mechanisms in peripheral neurovascular control. PMID:19716351

  18. Pulsed ultrasound expands the extracellular and perivascular spaces of the brain.

    PubMed

    Hersh, David S; Nguyen, Ben A; Dancy, Jimena G; Adapa, Arjun R; Winkles, Jeffrey A; Woodworth, Graeme F; Kim, Anthony J; Frenkel, Victor

    2016-09-01

    Diffusion within the extracellular and perivascular spaces of the brain plays an important role in biological processes, therapeutic delivery, and clearance mechanisms within the central nervous system. Recently, ultrasound has been used to enhance the dispersion of locally administered molecules and particles within the brain, but ultrasound-mediated effects on the brain parenchyma remain poorly understood. We combined an electron microscopy-based ultrastructural analysis with high-resolution tracking of non-adhesive nanoparticles in order to probe changes in the extracellular and perivascular spaces of the brain following a non-destructive pulsed ultrasound regimen known to alter diffusivity in other tissues. Freshly obtained rat brain neocortical slices underwent sham treatment or pulsed, low intensity ultrasound for 5min at 1MHz. Transmission electron microscopy revealed intact cells and blood vessels and evidence of enlarged spaces, particularly adjacent to blood vessels, in ultrasound-treated brain slices. Additionally, ultrasound significantly increased the diffusion rate of 100nm, 200nm, and 500nm nanoparticles that were injected into the brain slices, while 2000nm particles were unaffected. In ultrasound-treated slices, 91.6% of the 100nm particles, 20.7% of the 200nm particles, 13.8% of the 500nm particles, and 0% of the 2000nm particles exhibited diffusive motion. Thus, pulsed ultrasound can have meaningful structural effects on the brain extracellular and perivascular spaces without evidence of tissue disruption. PMID:27369449

  19. Vascular wound healing and neointima formation induced by perivascular electric injury in mice.

    PubMed Central

    Carmeliet, P.; Moons, L.; Stassen, J. M.; De Mol, M.; Bouché, A.; van den Oord, J. J.; Kockx, M.; Collen, D.

    1997-01-01

    Vascular interventions for atherothrombotic disease frequently induce neointima formation, which can contribute to restenosis of blood vessels. As the molecular mechanisms of this process remain largely unknown, quantitative models of arterial injury in transgenic animals may be useful to study this process at the genetic level. Here, an injury model is proposed in which surgically exposed femoral arteries in mice were injured perivascularly via a single delivery of an electric current. Transmission electron microscopy, light microscopy, and immunohistochemistry revealed that electric injury destroyed all medial smooth muscle cells, denuded the injured segment of intact endothelium, and transiently induced platelet-rich mural thrombosis. A vascular wound-healing response resulted that was characterized by degradation of the mural thrombus, transient infiltration of the vessel wall by inflammatory cells, and progressive removal of the necrotic debris. Topographic analysis revealed repopulation of the media and accumulation in the neointima of smooth muscle cells originating from the uninjured borders and progressing into the necrotic center. Within 3 weeks after injury, a neointima of 0.026 +/- 0.003 mm2 (n = 7 arteries) was formed that contained a maximum of 12 +/- 1 layers of smooth muscle alpha-actin-immunoreactive cells. Evans blue staining in five electrically injured arteries revealed a denuded distance of 2.8 +/- 0.2 mm immediately after injury, which became progressively re-endothelialized from the uninjured borders to 2.2 +/- 0.08 mm (P = 0.013 vs freshly injured by analysis of variance), 0.8 +/- 0.22 mm (P < 0.001), and 0.005 +/- 0.003 mm (P < 0.001) within 2, 7, and 14 days after injury, respectively. Analysis of 5'-bromo-2'-deoxyuridine incorporation revealed that a maximum of 35 +/- 10% endothelial cells proliferated within 2 days after injury and that in the media and neointima, a maximum of, respectively, 12 +/- 2% and 18 +/- 3% smooth muscle cells

  20. The role played by perivascular cells in kidney interstitial injury

    PubMed Central

    Rojas, Andres; Chang, Fan-Chi; Lin, Shuei-Liong; Duffield, Jeremy S.

    2012-01-01

    Fibrosis of the kidney is a disease affecting millions worldwide and is a harbinger of progressive loss of organ function resulting in organ failure. Recent findings suggest that understanding mechanisms of development and progression of fibrosis will lead to new therapies urgently required to counteract loss of organ function. Recently, little-known cells that line the kidney microvasculature, known as pericytes, were identified as the precursor cells which become the scar-forming myofibroblasts. Kidney pericytes are extensively branched cells located in the wall of capillaries, embedded within the microvascular basement membrane, and incompletely envelope endothelial cells with which they establish focal contacts. In response to kidney injuries, pericytes detach from endothelial cells and migrate into the interstitial space where they undergo a transition into myofibroblasts. Detachment leads to fibrosis but also leaves an unstable endothelium, prone to rarefaction. Endothelial-pericyte crosstalk at the vascular endothelial growth factor receptors and platelet derived growth factor receptors in response to injury have been identified as major new targets for therapeutic intervention. PMID:22551886

  1. Perivascular Lymphocytic Infiltration Is Not Limited to Metal-on-Metal Bearings

    PubMed Central

    Ng, Vincent Y.; Berend, Keith R.; Skeels, Michael D.; Adams, Joanne B.

    2010-01-01

    Background Perivascular lymphocytic infiltration (PVLI) suggests an adaptive immune response. Metal hypersensitivity after THA is presumed associated with idiopathic pain and aseptic loosening, but its incidence and relationship to metallic wear leading to revision are unclear as are its presence and relevance in non-metal-on-metal arthroplasty. Questions/purposes We compared (1) incidence and severity of PVLI in failed hip metal-on-metal (MoM) to non-MoM implants and TKA; (2) PVLI in MoM and non-MoM hip arthroplasty based on reason for revision; and (3) PVLI grade to diffuse lymphocytic infiltration (DLI) and tissue reaction to metal particles. Patients and Methods We retrospectively examined incidence and severity of PVLI, DLI, and tissue reaction in periprosthetic tissue from 215 THA and 242 TKA revisions including 32 MoM hips. Results Perivascular lymphocytic infiltration was present in more TKAs (40%) than overall hip arthroplasties (24%) without difference in severity. Compared to non-MoM hips, MoM bearings were more commonly associated with PVLI (59% versus 18%) and demonstrated increased severity (41% versus 3% greater than mild). Histologically, PVLI correlated (r = 0.51) with DLI, but not tissue reaction. In THA, PVLI was most commonly associated with idiopathic pain (70%) and aseptic loosening (54%) in MoM, and infection in all hip revisions (53%). Conclusions Perivascular lymphocytic infiltration is more extensive in revisions of MoM and in aseptic loosening, idiopathic pain, or infection but is also present in TKA, non-MoM, and different reasons for revision. It correlates with other signs of metal hypersensitivity, but not with histologic measures of metal particulate load. Level of Evidence Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:20878289

  2. Perivascular sustained release of atorvastatin from a hydrogel-microparticle delivery system decreases intimal hyperplasia.

    PubMed

    Mylonaki, Ioanna; Strano, Francesco; Deglise, Sebastien; Allémann, Eric; Alonso, Florian; Corpataux, Jean-Marc; Dubuis, Céline; Haefliger, Jacques-Antoine; Jordan, Olivier; Saucy, François; Delie, Florence

    2016-06-28

    Intimal hyperplasia (IH) is the major cause of grafted vessel occlusion and occurs frequently after bypass intervention. No pharmaceutical formulation is currently available to prevent this pathology. Local perivascular delivery of an appropriate active compound released in a time-dependent manner (from day one up to 4weeks) is necessary for an efficient single-administration preventive therapy. To this aim, we propose the combination of gel and microparticles delivery system containing atorvastatin (ATV). The incorporation of ATV in a cross-linked hyaluronic acid gel, provided in vitro a fast release over 3days, while ATV-loaded poly-lactic-co-glycolic acid (PLGA) microparticles dispersed in the gel gave a sustained release over 4weeks. In vivo, ATV formulations were applied perivascularly in mice undergoing carotid artery ligation. IH was significantly reduced (-68%) in presence of ATV incorporated in hyaluronic acid gel and encapsulated in microparticles compared to control. No significant IH alteration was observed when ATV was incorporated only in the gel (fast release) or only in the microparticles (slow release) demonstrating that a biphasic release of ATV is essential to interfere with the development of IH. ATV was detected in adjacent tissues 28days after the intervention, showing the sustained presence of the drug in vivo. After four weeks ATV was not detected in remote tissues, except at a very low concentration (0.044ng/mg) in the liver, suggesting a very low risk of systemic toxicity of locally delivered ATV. Additionally, the ex vivo data showed that ATV in solution permeates through isolated human saphenous veins and thus is a good candidate for perivascular delivery. Our data demonstrate that a local biphasic ATV release on the mice ligated carotid efficiently prevents the development of IH without apparent toxicity. PMID:27091698

  3. Protons modulate perivascular axo-axonal neurotransmission in the rat mesenteric artery

    PubMed Central

    Takatori, Shingo; Hirai, Kazuhiro; Ozaki, Shuichiro; Tangsucharit, Panot; Fukushima-Miyashita, Satoko; Goda, Mitsuhiro; Hashikawa-Hobara, Narumi; Ono, Nobufumi; Kawasaki, Hiromu

    2014-01-01

    Background and Purpose Previous studies have demonstrated that nicotine releases protons from adrenergic nerves via stimulation of nicotinic ACh receptors and activates transient receptor potential vanilloid-1 (TRPV1) receptors located on calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves, resulting in vasodilatation. The present study investigated whether perivascular nerves release protons, which modulate axon-axonal neurotransmission. Experiment Approach Perfusion pressure and pH levels of perfusate in rat-perfused mesenteric vascular beds without endothelium were measured with a pressure transducer and a pH meter respectively. Key Results Periarterial nerve stimulation (PNS) initially induced vasoconstriction, which was followed by long-lasting vasodilatation and decreased pH levels in the perfusate. Cold-storage denervation of the preparation abolished the decreased pH and vascular responses to PNS. The adrenergic neuron blocker guanethidine inhibited PNS-induced vasoconstriction and effects on pH, but not PNS-induced vasodilatation. Capsaicin (CGRP depletor), capsazepine and ruthenium red (TRPV1 inhibitors) attenuated the PNS-induced decrease in pH and vasodilatation. In denuded preparations, ACh caused long-lasting vasodilatation and lowered pH; these effects were inhibited by capsaicin pretreatment and atropine, but not by guanethidine or mecamylamine. Capsaicin injection induced vasodilatation and a reduction in pH, which were abolished by ruthenium red. The use of a fluorescent pH indicator demonstrated that application of nicotine, ACh and capsaicin outside small mesenteric arteries reduced perivascular pH levels and these effects were abolished in a Ca2+-free medium. Conclusion and Implication These results suggest that protons are released from perivascular adrenergic and CGRPergic nerves upon PNS and these protons modulate transmission in CGRPergic nerves. PMID:25117291

  4. Perivascular Cells Increase Expression of Ciliary Neurotrophic Factor Following Partial Denervation of the Rat Neurohypophysis

    PubMed Central

    Lo, David; SunRhodes, Neil; Watt, John A.

    2008-01-01

    The expression of ciliary neurotrophic factor (CNTF) was investigated immunocytochemically during the axonal degeneration and collateral axonal sprouting response that follows partial denervation of the rat neurohypophysis. A significant increase in the number of CNTF-immunoreactive (CNTF-ir) cells was observed in the neurohypophysis of partially denervated animals compared to age-matched sham-operated controls by 5 days post-denervation, remaining elevated throughout the 30 day post denervation period. Stereometric assessment of the numbers of CNTF-ir cells within the partially denervated neurohypophysis demonstrated a 36% increase by 3 days following denervation reaching 130% of control values by 10 days post-lesion. The cell numbers remained elevated throughout the 30 days post-lesion period suggesting that CNTF may play a role in the neurosecretory axonal sprouting process known to occur between 10 and 30 days post-denervation. Subsequent preparations pairing anti-CNTF with antibodies against ED1, CR3, p75 low affinity neurotrophin receptor (p75LNGFR), and S100β, demonstrated that CNTF was exclusively localized in a phenotypically-distinct population of perivascular cells. The association of perivascular cells with phagocytic activity was confirmed by dual label fluorescence microscopy showing the colocalization of P75LNGFR-ir and OX-42-ir in cells expressing the ED-1 antigen. No increase in CNTF-ir was observed in non-injured animals in which heightened levels of neurosecretory activity were induced physiologically. These results suggest that increased CNTF-ir occurs in response to conditions which induce high levels of phagocytic activity by perivascular cells in the axotomized neurohypophysis which is sustained throughout a period in which axonal sprouting is known to occur in the partially denervated neurohypophysis. PMID:18805412

  5. An extended chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids phenotype

    PubMed Central

    Lane, Chris; Phadke, Rahul; Howard, Robin

    2014-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described central nervous system inflammatory condition. In this case report we describe a patient initially with features consistent with this syndrome, who represented with seizures (not previously reported in this syndrome) and corresponding prominent cortical involvement on imaging (also not previously noted). Owing to diagnostic uncertainty, cerebral biopsy was performed revealing histology consistent with CLIPPERS, excluding other differentials. Following a further brainstem relapse, this patient was treated with high-dose steroids, subsequently switched to a tapering oral regime and now, azathioprine, a steroid-sparing agent. She remains well on this. PMID:24966263

  6. Perivascular Epithelioid Cell Tumor Arising from Ciliary Body Treated by Local Resection

    PubMed Central

    Goto, Hiroshi; Usui, Yoshihiko; Nagao, Toshitaka

    2015-01-01

    Aims Perivascular epithelioid cell tumor (PEComa) is a mesenchymal neoplasm originating from perivascular myoid cells. We report a case of PEComa arising from the ciliary body. Methods Case report. Results A 13-year-old girl was referred to our department with a clinical diagnosis of ciliary body melanoma in her right eye. Her visual acuity was 20/600 OD. Slit-lamp examination revealed a brown tumor behind the iris. The ocular fundus could not be observed due to a cataract. Ultrasonography depicted an oval mass approximately 10 mm in diameter at the ciliary body. The tumor was successfully treated by local resection, and the patient's visual acuity improved to 20/20. Histopathological and immunohistochemical findings of the excised tumor were compatible with the diagnosis of PEComa of the ciliary body. No local recurrence of the tumor was observed for over 4 years after surgery. Conclusion A very rare case of PEComa of the ciliary body was successfully treated by local resection, with favorable visual outcome and no recurrence for several years. PEComa can be differentiated from other ciliary body tumors by immunohistochemical study.

  7. EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells.

    PubMed

    Krusche, Benjamin; Ottone, Cristina; Clements, Melanie P; Johnstone, Ewan R; Goetsch, Katrin; Lieven, Huang; Mota, Silvia G; Singh, Poonam; Khadayate, Sanjay; Ashraf, Azhaar; Davies, Timothy; Pollard, Steven M; De Paola, Vincenzo; Roncaroli, Federico; Martinez-Torrecuadrada, Jorge; Bertone, Paul; Parrinello, Simona

    2016-01-01

    Glioblastomas (GBM) are aggressive and therapy-resistant brain tumours, which contain a subpopulation of tumour-propagating glioblastoma stem-like cells (GSC) thought to drive progression and recurrence. Diffuse invasion of the brain parenchyma, including along preexisting blood vessels, is a leading cause of therapeutic resistance, but the mechanisms remain unclear. Here, we show that ephrin-B2 mediates GSC perivascular invasion. Intravital imaging, coupled with mechanistic studies in murine GBM models and patient-derived GSC, revealed that endothelial ephrin-B2 compartmentalises non-tumourigenic cells. In contrast, upregulation of the same ephrin-B2 ligand in GSC enabled perivascular migration through homotypic forward signalling. Surprisingly, ephrin-B2 reverse signalling also promoted tumourigenesis cell-autonomously, by mediating anchorage-independent cytokinesis via RhoA. In human GSC-derived orthotopic xenografts, EFNB2 knock-down blocked tumour initiation and treatment of established tumours with ephrin-B2-blocking antibodies suppressed progression. Thus, our results indicate that targeting ephrin-B2 may be an effective strategy for the simultaneous inhibition of invasion and proliferation in GBM. PMID:27350048

  8. Pharmacological evidence for CGRP uptake into perivascular capsaicin sensitive nerve terminals

    PubMed Central

    Sams-Nielsen, Anette; Orskov, Cathrine; Jansen-Olesen, Inger

    2001-01-01

    Specific mechanisms, providing reuptake of cathecholamine and amino acid neurotransmitters (e.g. serotonin and glutamate) into cells of the central nervous system are well known, whereas neuronal uptake of neuropeptide transmitters have not previously been reported. In the present study we present evidence for uptake of the 37 amino acid neuropeptide, calcitonin gene-related peptide (CGRP) into perivascular terminals of capsaicin sensitive nerve fibres, innervating the guinea-pig basilar artery. Release of CGRP from perivascular nerve terminals was obtained by capsaicin-induced vanilloid receptor-stimulation and detected as CGRP receptor-mediated dilation of isolated segments of the guinea-pig basilar artery. Following three repeated capsaicin challenges, CGRP-depleted segments were incubated with CGRP. This caused significant reappearance of capsaicin-induced vasodilatory responses. These responses were dependent on duration and concentration of the preceding CGRP incubation and were inhibited by the CGRP receptor antagonist, CGRP8–37. The CGRP-re-depletion was significantly reduced when CGRP8–37 was present during the preceding CGRP incubation. Thus, presynaptic CGRP receptors are likely to be involved in neuronal CGRP uptake. Incubating the artery segments with 125I-CGRP allowed subsequent detection of capsaicin-induced 125I-release. Immunohistochemical experiments showed that only terminal CGRP is subject to capsaicin-induced depletion in vitro, whereas CGRP-immunoreactivity endures in the nerve fibres. PMID:11226146

  9. EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells

    PubMed Central

    Krusche, Benjamin; Ottone, Cristina; Clements, Melanie P; Johnstone, Ewan R; Goetsch, Katrin; Lieven, Huang; Mota, Silvia G; Singh, Poonam; Khadayate, Sanjay; Ashraf, Azhaar; Davies, Timothy; Pollard, Steven M; De Paola, Vincenzo; Roncaroli, Federico; Martinez-Torrecuadrada, Jorge; Bertone, Paul; Parrinello, Simona

    2016-01-01

    Glioblastomas (GBM) are aggressive and therapy-resistant brain tumours, which contain a subpopulation of tumour-propagating glioblastoma stem-like cells (GSC) thought to drive progression and recurrence. Diffuse invasion of the brain parenchyma, including along preexisting blood vessels, is a leading cause of therapeutic resistance, but the mechanisms remain unclear. Here, we show that ephrin-B2 mediates GSC perivascular invasion. Intravital imaging, coupled with mechanistic studies in murine GBM models and patient-derived GSC, revealed that endothelial ephrin-B2 compartmentalises non-tumourigenic cells. In contrast, upregulation of the same ephrin-B2 ligand in GSC enabled perivascular migration through homotypic forward signalling. Surprisingly, ephrin-B2 reverse signalling also promoted tumourigenesis cell-autonomously, by mediating anchorage-independent cytokinesis via RhoA. In human GSC-derived orthotopic xenografts, EFNB2 knock-down blocked tumour initiation and treatment of established tumours with ephrin-B2-blocking antibodies suppressed progression. Thus, our results indicate that targeting ephrin-B2 may be an effective strategy for the simultaneous inhibition of invasion and proliferation in GBM. DOI: http://dx.doi.org/10.7554/eLife.14845.001 PMID:27350048

  10. Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis

    PubMed Central

    Aronow, Bruce J.; Tong, Wilson S.; Manka, David; Tang, Yaoliang; Bogdanov, Vladimir Y.; Unruh, Dusten; Blomkalns, Andra L.; Piegore, Mark G.; Weintraub, Daniel S.; Rudich, Steven M.; Kuhel, David G.; Hui, David Y.; Weintraub, Neal L.

    2013-01-01

    Inflammatory cross talk between perivascular adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We previously reported that human perivascular (PV) adipocytes exhibit a proinflammatory phenotype and less adipogenic differentiation than do subcutaneous (SQ) adipocytes. To gain a global view of the genomic basis of biologic differences between PV and SQ adipocytes, we performed genome-wide expression analyses to identify differentially expressed genes between adipocytes derived from human SQ vs. PV adipose tissues. Although >90% of well-expressed genes were similarly regulated, we identified a signature of 307 differentially expressed genes that were highly enriched for functions associated with the regulation of angiogenesis, vascular morphology, inflammation, and blood clotting. Of the 156 PV upregulated genes, 59 associate with angiogenesis, vascular biology, or inflammation, noteworthy of which include TNFRSF11B (osteoprotegerin), PLAT, TGFB1, THBS2, HIF1A, GATA6, and SERPINE1. Of 166 PV downregulated genes, 21 associated with vascular biology and inflammation, including ANGPT1, ANGPTL1, and VEGFC. Consistent with the emergent hypothesis that PV adipocytes differentially regulate angiogenesis and inflammation, cell culture-derived adipocyte-conditioned media from PV adipocytes strongly enhanced endothelial cell tubulogenesis and monocyte migration compared with media from SQ adipocytes. These findings demonstrate that PV adipocytes have the potential to significantly modulate vascular inflammatory crosstalk in the setting of atherosclerosis by their ability to signal to both endothelial and inflammatory cells. PMID:23737535

  11. Cortical astrogliosis and increased perivascular aquaporin-4 in idiopathic intracranial hypertension.

    PubMed

    Eide, Per Kristian; Eidsvaag, Vigdis Andersen; Nagelhus, Erlend A; Hansson, Hans-Arne

    2016-08-01

    The syndrome idiopathic intracranial hypertension (IIH) includes symptoms and signs of raised intracranial pressure (ICP) and impaired vision, usually in overweight persons. The pathogenesis is unknown. In the present prospective observational study, we characterized the histopathological changes in biopsies from the frontal brain cortical parenchyma obtained from 18 IIH patients. Reference specimens were sampled from 13 patients who underwent brain surgery for epilepsy, tumors or acute vascular diseases. Overnight ICP monitoring revealed abnormal intracranial pressure wave amplitudes in 14/18 IIH patients, who underwent shunt surgery and all responded favorably. A remarkable histopathological observation in IIH patients was patchy astrogliosis defined as clusters of hypertrophic astrocytes enclosing a nest of nerve cells. Distinct astrocyte domains (i.e. no overlap between astrocyte processes) were lacking in most IIH biopsy specimens, in contrast to their prevalence in reference specimens. Evidence of astrogliosis in IIH was accompanied with significantly increased aquaporin-4 (AQP4) immunoreactivity over perivascular astrocytic endfeet, compared to the reference specimens, measured with densitometry. Scattered CD68 immunoreactive cells (activated microglia and macrophages) were recognized, indicative of some inflammation. No apoptotic cells were demonstrable. We conclude that the patchy astrogliosis is a major finding in patients with IIH. We propose that the astrogliosis impairs intracranial pressure-volume reserve capacity, i.e. intracranial compliance, and contributes to the IIH by restricting the outflow of fluid from the cranium. The increased perivascular AQP4 in IIH may represent a compensatory mechanism to enhance brain fluid drainage. PMID:27188961

  12. Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration.

    PubMed

    Lochhead, Jeffrey J; Wolak, Daniel J; Pizzo, Michelle E; Thorne, Robert G

    2015-03-01

    The intranasal administration route is increasingly being used as a noninvasive method to bypass the blood-brain barrier because evidence suggests small fractions of nasally applied macromolecules may reach the brain directly via olfactory and trigeminal nerve components present in the nasal mucosa. Upon reaching the olfactory bulb (olfactory pathway) or brainstem (trigeminal pathway), intranasally delivered macromolecules appear to rapidly distribute within the brains of rodents and primates. The mechanisms responsible for this distribution have yet to be fully characterized. Here, we have used ex vivo fluorescence imaging to show that bulk flow within the perivascular space (PVS) of cerebral blood vessels contributes to the rapid central distribution of fluorescently labeled 3 and 10 kDa dextran tracers after intranasal administration in anesthetized adult rats. Comparison of tracer plasma levels and fluorescent signal distribution associated with the PVS of surface arteries and internal cerebral vessels showed that the intranasal route results in unique central access to the PVS not observed after matched intravascular dosing in separate animals. Intranasal targeting to the PVS was tracer size dependent and could be regulated by modifying nasal epithelial permeability. These results suggest cerebral perivascular convection likely has a key role in intranasal drug delivery to the brain. PMID:25492117

  13. Perivascular Mast Cells Govern Shear Stress-Induced Arteriogenesis by Orchestrating Leukocyte Function.

    PubMed

    Chillo, Omary; Kleinert, Eike Christian; Lautz, Thomas; Lasch, Manuel; Pagel, Judith-Irina; Heun, Yvonn; Troidl, Kerstin; Fischer, Silvia; Caballero-Martinez, Amelia; Mauer, Annika; Kurz, Angela R M; Assmann, Gerald; Rehberg, Markus; Kanse, Sandip M; Nieswandt, Bernhard; Walzog, Barbara; Reichel, Christoph A; Mannell, Hanna; Preissner, Klaus T; Deindl, Elisabeth

    2016-08-23

    The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis) is unresolved. We show that extravasation of neutrophils mediated by the platelet receptor GPIbα and uPA results in Nox2-derived reactive oxygen radicals, which activate perivascular mast cells. These c-kit(+)/CXCR-4(+) cells stimulate arteriogenesis by recruiting additional neutrophils as well as growth-promoting monocytes and T cells. Additionally, mast cells may directly contribute to vascular remodeling and vascular cell proliferation through increased MMP activity and by supplying growth-promoting factors. Boosting mast cell recruitment and activation effectively promotes arteriogenesis, thereby protecting tissue from severe ischemic damage. We thus find that perivascular mast cells are central regulators of shear stress-induced arteriogenesis by orchestrating leukocyte function and growth factor/cytokine release, thus providing a therapeutic target for treatment of vascular occlusive diseases. PMID:27524614

  14. Local Control of Perivascular Malignant Liver Lesions Using Percutaneous Irreversible Electroporation: Initial Experiences

    SciTech Connect

    Eller, Achim Schmid, Axel; Schmidt, Joachim; May, Matthias Brand, Michael Saake, Marc Uder, Michael Lell, Michael

    2015-02-15

    PurposeThis study was designed to assess efficacy and safety in the treatment of perivascular malignant liver lesions using percutaneous, computed tomography (CT)-guided irreversible electroporation (IRE).MethodsFourteen patients (mean age 58 ± 11 years) with 18 malignant liver lesions were consecutively enrolled in this study. IRE was performed in patients not eligible for surgery and lesions abutting large vessels or bile ducts. Follow-up exams were performed using multislice-CT (MS-CT) or MRI.ResultsMedium lesion diameter was 20 ± 5 mm. Ten of 14 (71 %) were successfully treated with no local recurrence to date (mean follow-up 388 ± 160 days). One case left initial tumor control unclear and additional RFA was performed 4 weeks after IRE. Complications occurred in 4 of 14 (29 %) cases. In one case, intervention was terminated and abdominal bleeding required laparotomy. In two cases, a postinterventional hematothorax required intervention. In another case, abdominal bleeding could be managed conservatively. No complications related to the bile ducts occurred.ConclusionsPercutaneous IRE seems to be effective in perivascular lesions but is associated with a higher complication rate compared with thermoablative techniques.

  15. Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration

    PubMed Central

    Lochhead, Jeffrey J; Wolak, Daniel J; Pizzo, Michelle E; Thorne, Robert G

    2015-01-01

    The intranasal administration route is increasingly being used as a noninvasive method to bypass the blood–brain barrier because evidence suggests small fractions of nasally applied macromolecules may reach the brain directly via olfactory and trigeminal nerve components present in the nasal mucosa. Upon reaching the olfactory bulb (olfactory pathway) or brainstem (trigeminal pathway), intranasally delivered macromolecules appear to rapidly distribute within the brains of rodents and primates. The mechanisms responsible for this distribution have yet to be fully characterized. Here, we have used ex vivo fluorescence imaging to show that bulk flow within the perivascular space (PVS) of cerebral blood vessels contributes to the rapid central distribution of fluorescently labeled 3 and 10 kDa dextran tracers after intranasal administration in anesthetized adult rats. Comparison of tracer plasma levels and fluorescent signal distribution associated with the PVS of surface arteries and internal cerebral vessels showed that the intranasal route results in unique central access to the PVS not observed after matched intravascular dosing in separate animals. Intranasal targeting to the PVS was tracer size dependent and could be regulated by modifying nasal epithelial permeability. These results suggest cerebral perivascular convection likely has a key role in intranasal drug delivery to the brain. PMID:25492117

  16. Malignant Perivascular Epithelioid Cell Neoplasm of the Mediastinum and the Lung

    PubMed Central

    Liang, Wenjie; Xu, Shunliang; Chen, Feng

    2015-01-01

    Abstract A perivascular epithelioid cell neoplasm (PEComa) in the chest is rare, let alone in the mediastinum and lung. A 63-year-old man was admitted to our hospital with chest pain for more than 2 months and was found to have an opacity in his mediastinum and lung for 3 weeks. Enhanced chest computed tomography (CT) revealed a mass in both the left upper lobe and central anterior mediastinum. To identify the disease, a CT-guided percutaneous transthoracic needle biopsy of the upper left lung lesions was performed. The pathology result was consistent with epithelioid angiomyolipoma/PEComa. After a standard preparation for surgery, the neoplasms in the mediastinum and left lung were resected. The operative findings revealed extensive mediastinal tumor invasion in parts adjacent to the pericardium, including the mediastinal pleura, left pulmonary artery and vein, and phrenic nerve. The left lung tumor had invaded the lung membranes. The final pathologic diagnosis was malignant epithelioid angioleiomyoma in the left upper lung and mediastinum. Later, the mediastinal tumor recurred. The radiography of this case resembles left upper lobe lung cancer with mediastinal lymph node metastasis. Because this tumor lacks fat, the enhanced CT indicated that it was malignant but failed to identify it as a perivascular epithelioid cell neoplasm. This case reminds clinicians that, although most PEComa are benign, some can be malignant. As the radiology indicated, chest PEComas lack fat, which makes their preoperative diagnosis difficult. Therefore, needle biopsy is valuable for a definitive diagnosis. PMID:26039123

  17. Perivascular innervation: A multiplicity of roles in vasomotor control and myoendothelial signaling

    PubMed Central

    Westcott, Erika B.; Segal, Steven S.

    2013-01-01

    The control of vascular resistance and tissue perfusion reflect coordinated changes in the diameter of feed arteries and the arteriolar networks they supply. Against a background of myogenic tone and metabolic demand, vasoactive signals originating from perivascular sympathetic and sensory nerves are integrated with endothelium-derived signals to produce vasodilation or vasoconstriction. PVNs release adrenergic, cholinergic, peptidergic, purinergic, and nitrergic neurotransmitters that lead to SMC contraction or relaxation via their actions on SMCs, ECs, or other PVNs. ECs release autacoids that can have opposing actions on SMCs. Respective cell layers are connected directly to each other through GJs at discrete sites via MEJs projecting through holes in the IEL. Whereas studies of intercellular communication in the vascular wall have centered on endothelium-derived signals that govern SMC relaxation, attention has increasingly focused on signaling from SMCs to ECs. Thus, via MEJs, neurotransmission from PVNs can evoke distinct responses from ECs subsequent to acting on SMCs. To integrate this emerging area of investigation in light of vasomotor control, the present review synthesizes current understanding of signaling events that originate within SMCs in response to perivascular neurotransmission in light of EC feedback. Though often ignored in studies of the resistance vasculature, PVNs are integral to blood flow control and can provide a physiological stimulus for myoendothelial communication. Greater understanding of these underlying signaling events and how they may be affected by aging and disease will provide new approaches for selective therapeutic interventions. PMID:23289720

  18. Effects of fetal and neonatal exposure to nicotine on blood pressure and perivascular adipose tissue function in adult life.

    PubMed

    Gao, Yu-Jing; Holloway, Alison C; Su, Li-Ying; Takemori, Kumiko; Lu, Chao; Lee, Robert M K W

    2008-08-20

    In Wistar rats, maternal exposure to nicotine was shown to impair the inhibitory function of perivascular adipose tissue on vascular contractility in the aorta of the offspring. It is not known whether an impairment of perivascular adipose tissue function occurs in smaller arteries, and whether the control of blood pressure is affected. Here we studied the blood pressure effects and the alteration of perivascular adipose tissue function in mesenteric arteries of the offspring born to Wistar-Kyoto rat (WKY) dams exposed to nicotine. Nulliparous female WKY rats were given either nicotine bitartrate (1 mg/kg/day) or saline (vehicle) by subcutaneous injection 2 weeks prior to mating, during pregnancy and until weaning. Blood pressure of the offspring and functional studies with mesenteric arteries were conducted. Tissue samples (thoracic aorta, mesenteric arteries, and kidneys) were collected for morphological and immunohistochemical examinations. Blood pressure increased from 14 weeks of age onwards in the offspring born to nicotine-exposed dams. Nicotine-exposed offspring showed a significant increase in the number of brown adipocytes in aortic perivascular adipose tissue relative to control offspring. In mesenteric arteries from control offspring, contractile responses induced by phenylephrine, serotonin, and 9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F(2)alpha (U44619) were significantly attenuated in the presence of perivascular adipose tissue, an effect not observed in the nicotine-exposed tissues. Endothelium-dependent relaxation responses to carbachol, kidney weight, the total number of nephrons and glomerulus' size were comparable in nicotine and saline groups. We conclude that fetal and neonatal exposure to nicotine caused blood pressure elevation. Alterations in perivascular adipose tissue composition and modulatory function are some of the mechanisms associated with this blood pressure increase. PMID:18647709

  19. Isolated Anxa5{sup +}/Sca-1{sup +} perivascular cells from mouse meningeal vasculature retain their perivascular phenotype in vitro and in vivo

    SciTech Connect

    Brachvogel, Bent . E-mail: bent.brachvogel@uni-koeln.de; Pausch, Friederike; Farlie, Peter; Gaipl, Udo; Etich, Julia; Zhou, Zhigang; Cameron, Trevor; Mark, Klaus von der; Bateman, John F.; Poeschl, Ernst . E-mail: e.poschl@uea.ac.uk

    2007-07-15

    Pericytes are closely associated with endothelial cells, contribute to vascular stability and represent a potential source of mesenchymal progenitor cells. Using the specifically expressed annexin A5-LacZ fusion gene (Anxa5-LacZ), it became possible to isolate perivascular cells (PVC) from mouse tissues. These cells proliferate and can be cultured without undergoing senescence for multiple passages. PVC display phenotypic characteristics of pericytes, as they express pericyte-specific markers (NG2-proteoglycan, desmin, {alpha}SMA, PDGFR-{beta}). They also express stem cell marker Sca-1, whereas endothelial (PECAM), hematopoietic (CD45) or myeloid (F4/80, CD11b) lineage markers are not detectable. These characteristics are in common with the pericyte-like cell line 10T1/2. PVC also display a phagocytoic activity higher than 10T1/2 cells. During coculture with endothelial cells both cell types stimulate angiogenic processes indicated by an increased expression of PECAM in endothelial cells and specific deposition of basement membrane proteins. PVC show a significantly increased induction of endothelial specific PECAM expression compared to 10T1/2 cells. Accordingly, in vivo grafts of PVC aggregates onto chorioallantoic membranes of quail embryos recruit endothelial cells, get highly vascularized and deposit basement membrane components. These data demonstrate that isolated Anxa5-LacZ{sup +} PVC from mouse meninges retain their capacity for differentiation to pericyte-like cells and contribute to angiogenic processes.

  20. Cytogenesis in the adult monkey motor cortex: Perivascular NG2 cells are the major adult born cell type

    PubMed Central

    Stanton, Gregory B; Kohler, Shawn J; Boklweski, Jennifer; Cameron, Judy L; Greenough, William T

    2015-01-01

    We used confocal microscopy and immunohistochemistry (IHC) to look for new cells in the motor cortex of adult macaque monkeys that might form the cellular bases of improved brain function from exercise. Twenty-four female Macaca fascicularis monkeys divided into groups by age (10–12 years, 15–17 years), postexercise survival periods, and controls, received 10 weekly injections of the thymidine analog, bromodeoxyuridine (BrdU) to mark new cells. Sixteen monkeys survived 15 weeks (5 weeks postexercise) and 8 monkeys survived 27 weeks (12 weeks postexercise) after initial BrdU injections. Additionally, five Macaca mulatta female monkeys (∼5.5–7 years) received single injections of BrdU and survived 2 days, 2 weeks, and 6 weeks after BrdU injections. Neural and glial antibodies were used to identify new cell phenotypes and to look for changes in proportions of these cells with respect to time and experimental conditions. No BrdU+/DCx+ cells were found but about 7.5% of new cells were calretinin-positive (Cr+). BrdU+/GABA+ (gamma-aminobutyric acid) cells were also found but no new Cr+ or GABA+ cells colabeled with a mature neuron marker, NeuN or chondroitin sulfate antibody, NG2. The proportion of new cells that were NG2+ was about 85% for short and long survival monkeys of which two, newly described perivascular phenotypes (Pldv and Elu) and a small percentage of pericytes (2.5%) comprised 44% and 51% of the new NG2+ cells, respectively. Proportions of NG2+ phenotypes were affected by post-BrdU survival periods, monkey age, and possibly a postexercise sedentary period but no direct effect of exercise was found. PMID:25308320

  1. TFE3 Translocation Associated Perivascular Epithelioid Cell Neoplasm (PEComa) of the Gynecologic Tract: Morphology, Immunophenotype, Differential Diagnosis

    PubMed Central

    Schoolmeester, J. Kenneth; Dao, Linda N.; Sukov, William R.; Park, Kay J.; Murali, Rajmohan; Hameed, Meera R.; Soslow, Robert A.

    2016-01-01

    TFE3 translocation associated PEComa is a distinct form of perivascular epithelioid cell neoplasm, the features of which are poorly defined owing to their general infrequency and limited prior reports with confirmed rearrangement or fusion totaling nine cases. Recent investigation has found a lack of TSC gene mutation in these tumors compared to their nonrearranged counterparts which underscores the importance of recognizing the translocated variant due to hypothetical ineffectiveness of targeted mTOR inhibitor therapy. Six cases were identified and TFE3 rearrangement was confirmed by FISH. Patient age ranged 46 to 66 years (median 50) and none had a history of tuberous sclerosis complex. Three cases arose in the uterine corpus, one in the vagina, and one pelvic tumor and one pulmonary tumor were likely a recurrence/metastasis from a probable uterine primary. Five cases had purely clear cell epithelioid morphology that showed a spectrum of atypia while one case had a mixture of clear cell epithelioid and spindle cells. A mostly consistent immunophenotype was observed in the purely clear cell epithelioid cases: each demonstrated diffuse TFE3, HMB45, CathepsinK labeling, either focal or no melanA staining and variably weak reactivity to smooth muscle markers. The mixed clear cell epithelioid and spindle cell case had a similar pattern in its epithelioid component, but strong muscle marker positivity in its spindle cell component. Follow up ranged 1 to 57 months. Three cases demonstrated aggressive behavior and three cases had no evidence of recurrence. Both GYN-specific and traditional sets of criteria for malignancy were evaluated. The GYN model showed improved inclusion and specificity in comparison to the traditional model. PMID:25517951

  2. Perivascular infiltration in normal skin of patients with rheumatoid arthritis: association with rheumatoid factors and HLA-DR antigens.

    PubMed Central

    Bernelot Moens, H J; Ament, H J; Vroom, T M; Feltkamp, T E; van der Korst, J K

    1988-01-01

    The relation between immunohistological findings in biopsy specimens of apparently normal skin, HLA antigens, and rheumatoid factors (RF) was studied in 120 patients with rheumatoid arthritis (RA), selected for treatment with D-penicillamine. Perivascular infiltration (PVI) of more than three mononuclear cells was present in 77 (68%) of 114 patients, accompanied usually by the presence of IgM or C3, or both, in immunofluorescence studies. The number of perivascular cells was associated significantly with the titre of circulating RF. A weak relation of both perivascular cellular infiltration and RF with HLA-DR3 and DR4 did not reach statistical significance. It is concluded that the histological presence of perivascular inflammation is associated mainly with deposition of RF. It is suggested that the first is merely an epiphenomenon of the latter. PVI was not prognostic for the occurrence of the clinical syndrome of rheumatoid vasculitis. For practical purposes skin biopsies do not appear to be useful in the evaluation of individual patients with RA. PMID:3058055

  3. Posterior fossa giant tumefactive perivascular spaces: 8-year follow-up in an adolescent

    PubMed Central

    Branch, Byron C.; Tantiwongkosi, Bundhit; Altmeyer, Wilson; Bartanusz, Viktor

    2015-01-01

    Background: Cystic masses in the posterior fossa are ominous appearing lesions with broad differential diagnosis. Giant tumefactive perivascular spaces (GTPS) are rarely occurring pathological findings in the posterior fossa with unclear etiology and ill-defined long-term prognosis. Case Description: We present a case of a 15-year-old male diagnosed with posterior fossa GTPS. The patient remained asymptomatic during the 8-year follow-up after diagnosis with the serial magnetic resonance imaging (MRI) showing no change in the size and morphology of the lesion. Conclusion: This case supports prior literature on supratentorial GTPS suggesting that the natural history of GTPS is mostly benign. Identification of GTPS in the posterior fossa could prevent the patient from unnecessary surgery or other aggressive treatment modalities. PMID:25657855

  4. Pancreatic perivascular epithelioid cell tumor: A case report with clinicopathological features and a literature review

    PubMed Central

    Jiang, Hui; Ta, Na; Huang, Xiao-Yi; Zhang, Ming-Hua; Xu, Jing-Jing; Zheng, Kai-Lian; Jin, Gang; Zheng, Jian-Ming

    2016-01-01

    Perivascular epithelioid cell tumor (PEComa) of the pancreas is an unusual tumor deriving from mesenchyma. This paper described a case of pancreatic PEComa, which was initially suspected as neuroendocrine carcinoma by biopsy, and therefore surgical treatment was recommended due to undetermined diagnosis. Examination of the surgical specimen under a microscope showed that the tumor cell’s morphology was epithelioid or spindle-shaped, and ranged in a nested pattern. Additionally, these cells had a large extent of acidophilic cytoplasm, no mitotic figures, and expressed HMB-45, melan-p, and smooth muscle actin immunohistochemically. Pathological examination indicated that PEComa originated from the pancreas, but symptoms related to tuberous sclerosis were absent. Since PEComa is extremely rare in the pancreas, it is likely to be ignored in differential diagnosis. In conclusion, our article highlighted the clinicopathological features of PEComa, and we conducted a literature review focusing on PEComa so as to deepen the understanding of this tumor type. PMID:27053862

  5. Sclerosing Perivascular Epithelioid Cell Tumor of the Lung: A Case Report with Cytologic Findings

    PubMed Central

    Kim, Ha Yeon; Choi, Jin Hyuk; Lee, Hye Seung; Choi, Yoo Jin; Kim, Aeree; Kim, Han Kyeom

    2016-01-01

    Benign perivascular epithelioid cell tumor (PEComa) of the lung is a rare benign neoplasm, a sclerosing variant of which is even rarer. We present a case of 51-year-old man who was diagnosed with benign sclerosing PEComa by percutaneous fine needle aspiration cytology and biopsy. The aspirate revealed a few cell clusters composed of bland-looking polygonal or spindle cells with fine granular or clear cytoplasm. Occasional fine vessel-like structures with surrounding hyalinized materials were seen. The patient later underwent wedge resection of the lung. The histopathological study of the resected specimen revealed sheets of polygonal cells with clear vacuolated cytoplasm, variably sized thin blood vessels, and densely hyalinized stroma. In immunohistochemical studies, reactivity of tumor cells for human melanoma black 45 and Melan-A further supported the diagnosis of benign sclerosing PEComa. To the best of our knowledge, this is the first case of benign sclerosing PEComa described in lung. PMID:27068025

  6. A biodegradable perivascular wrap for controlled, local and directed drug delivery.

    PubMed

    Sanders, William G; Hogrebe, Paul C; Grainger, David W; Cheung, Alfred K; Terry, Christi M

    2012-07-10

    Perivascular delivery of anti-proliferative agents is an attractive approach to inhibit hyperplasia that causes stenosis of synthetic hemodialysis grafts and other vascular grafts. Perivascular drug delivery systems typically release drugs to both the vascular wall and non-target extravascular tissue. The objective of this study was to develop a biodegradable, perivascular delivery system for localized, sustained and unidirectional drug release in the context of synthetic arteriovenous (AV) grafts used for chronic hemodialysis. To this end, a dense non-porous polymer barrier layer was laminated to either i) a drug-loaded non-porous polymer layer or ii) a porous polymer layer. To provide tunability, the porous layer could be loaded with drug during casting or later infused with a drug-loaded hydrogel. The polymer bilayer wraps were prepared by a solvent casting, thermal-phase inversion technique using either polylactide-co-glycolide (PLGA) or polycaprolactone (PCL). Sunitinib, a multi-target receptor tyrosine kinase inhibitor, was used as a model drug. In a modified transwell chamber system, the barrier function of the non-porous PLGA backing was superior to the non-porous PCL backing although both markedly inhibited drug diffusion. As assessed by in vitro release assays, drug release duration from the drug-loaded non-porous PCL construct was almost 4-fold greater than release from the porous PCL construct infused with drug-laden hydrogel (22 days vs. 5 days); release duration from the drug-loaded non-porous PLGA construct was prolonged approximately 3-fold over release from the porous PLGA construct infused with drug-laden hydrogel (9 days vs. 3 days). Complete in vitro degradation of the PLGA porous and non-porous constructs occurred by approximately 35 days whereas the PCL constructs remained intact even after most of the drug was released (49 days). The PLGA non-porous bilayer wrap containing 143±5.5mg sunitinib in the inner layer was chosen for further

  7. Perivascular adipose tissue in vascular function and disease: a review of current research and animal models

    PubMed Central

    Brown, Nicholas K.; Zhou, Zhou; Zhang, Jifeng; Zeng, Rong; Wu, Jiarui; Eitzman, Daniel T.; Chen, Y. Eugene; Chang, Lin

    2014-01-01

    Perivascular adipose tissue (PVAT), long assumed to be nothing more than vessel-supporting connective tissue, is now understood to be an important, active component of the vasculature, with integral roles in vascular health and disease. PVAT is an adipose tissue with similarities to both brown and white adipose tissue, although recent evidence suggests that PVAT develops from its own precursors. Like other adipose tissue depots, PVAT secretes numerous biologically active substances that can act in both autocrine and paracrine fashion. PVAT has also proven to be involved in vascular inflammation. While PVAT can support inflammation during atherosclerosis via macrophage accumulation, emerging evidence suggests that PVAT also has anti-atherosclerotic properties related to its abilities to induce non-shivering thermogenesis and metabolize fatty acids. We here discuss the accumulated knowledge of PVAT biology, and related research on models of hypertension and atherosclerosis. PMID:24833795

  8. The FOXD1 lineage of kidney perivascular cells and myofibroblasts: functions and responses to injury

    PubMed Central

    Gomez, Ivan G; Duffield, Jeremy S

    2014-01-01

    Recent studies have identified a poorly appreciated yet extensive population of perivascular mesenchymal cells in the kidney, which are derived from metanephric mesenchyme progenitor cells during nephrogenesis at which time they express the transcription factor FOXD1. Some studies have called these resident fibroblasts, whereas others have called them pericytes. Regardless of nomenclature, many are partially integrated into the capillary basement membrane and contribute in important ways to the homeostasis of peritubular capillaries. Fate-mapping studies using conditional CreER recombinase-mediated tracing of discrete cell cohorts have identified these pericytes and resident fibroblasts as the major precursor population of interstitial myofibroblasts in animal models of kidney disease. Here, we will review the evidence that they are the major population of myofibroblast precursors, highlight some critical functions in homeostasis, and focus on the cell signaling pathways that are important to their differentiation into, and persistence as myofibroblasts. PMID:26312147

  9. A biodegradable perivascular wrap for controlled, local and directed drug delivery

    PubMed Central

    Sanders, William G.; Hogrebe, Paul C.; Grainger, David W.; Cheung, Alfred K.; Terry, Christi M.

    2012-01-01

    Perivascular delivery of anti-proliferative agents is an attractive approach to inhibit hyperplasia that causes stenosis of synthetic hemodialysis grafts and other vascular grafts. Perivascular drug delivery systems typically release drugs to both the vascular wall and non-target extravascular tissue. The objective of this study was to develop a biodegradable, perivascular delivery system for localized, sustained and unidirectional drug release in the context of synthetic arteriovenous (AV) grafts used for chronic hemodialysis. To this end, a dense non-porous polymer barrier layer was laminated to either i) a drug-loaded non-porous polymer layer, or ii) a porous polymer layer. To provide tuneability, the porous layer could be loaded with drug during casting or later infused with a drug-loaded hydrogel. The polymer bilayer wraps were prepared by a solvent casting, thermal-phase inversion technique using either polylactide-co-glycolide (PLGA) or polycaprolactone (PCL). Sunitinib, a multi-target receptor tyrosine kinase inhibitor, was used as a model drug. In a modified transwell chamber system, the barrier function of the non-porous PLGA backing was superior to the non-porous PCL backing although both markedly inhibited drug diffusion. As assessed by in vitro release assays, drug release duration from the drug-loaded non-porous PCL construct was almost 4-fold greater than release from the porous PCL construct infused with drug-laden hydrogel (22 days vs. 5 days); release duration from the drug-loaded non-porous PLGA construct was prolonged approximately 3-fold over release from the porous PLGA construct infused with drug-laden hydrogel (9 days vs. 3 days). Complete in vitro degradation of the PLGA porous and non-porous constructs occurred by approximately 35 days whereas the PCL constructs remained intact even after most drug was released (49 days). The PLGA non-porous bilayer wrap containing 143±5.5 mg sunitinib in the inner layer was chosen for further

  10. The role of epicardial and perivascular adipose tissue in the pathophysiology of cardiovascular disease

    PubMed Central

    Ouwens, D Margriet; Sell, Henrike; Greulich, Sabrina; Eckel, Juergen

    2010-01-01

    Abstract Obesity, insulin resistance and the metabolic syndrome, are characterized by expansion and inflammation of adipose tissue, including the depots surrounding the heart and the blood vessels. Epicardial adipose tissue (EAT) is a visceral thoracic fat depot located along the large coronary arteries and on the surface of the ventricles and the apex of the heart, whereas perivascular adipose tissue (PVAT) surrounds the arteries. Both fat depots are not separated by a fascia from the underlying tissue. Therefore, factors secreted from epicardial and PVAT, like free fatty acids and adipokines, can directly affect the function of the heart and blood vessels. In this review, we describe the alterations found in EAT and PVAT in pathological states like obesity, type 2 diabetes, the metabolic syndrome and coronary artery disease. Furthermore, we discuss how changes in adipokine expression and secretion associated with these pathological states could contribute to the pathogenesis of cardiac contractile and vascular dysfunction. PMID:20716126

  11. Visualization of perivascular spaces in the human brain at 7T: sequence optimization and morphology characterization.

    PubMed

    Zong, Xiaopeng; Park, Sang Hyun; Shen, Dinggang; Lin, Weili

    2016-01-15

    Noninvasive imaging of perivascular spaces (PVSs) may provide useful insights into their role in normal brain physiology and diseases. Fast MRI sequences with sub-millimeter spatial resolutions and high contrast-to-noise ratio (CNR) are required for accurate delineation of PVS in human. To achieve the optimal condition for PVS imaging at 7T, we carried out detailed simulation and experimental studies to characterize the dependence of CNR on imaging sequences (T1 versus T2-weighted) and sequence parameters. In addition, PVSs were segmented semi-automatically, which revealed much larger numbers of PVSs in young healthy subjects (age 21-37years) than previously reported. To the best of our knowledge, our study provides, for the first time, detailed length, volume, and diameter distributions of PVS in the white matter and subcortical nuclei, which can serve as a reference for future studies of PVS abnormalities under diseased conditions. PMID:26520772

  12. Age-dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice.

    PubMed

    Xu, Heping; Chen, Mei; Manivannan, Ayyakkannu; Lois, Noemi; Forrester, John V

    2008-01-01

    Fundus autofluorescence (AF) imaging by confocal scanning laser ophthalmoscopy has been widely used by ophthalmologists in the diagnosis/monitoring of various retinal disorders. It is believed that fundus AF is derived from lipofuscin in retinal pigment epithelial (RPE) cells; however, direct clinicopathological correlation has not been possible in humans. We examined fundus AF by confocal scanning laser ophthalmoscopy and confocal microscopy in normal C57BL/6 mice of different ages. Increasingly strong AF signals were observed with age in the neuroretina and subretinal/RPE layer by confocal scanning laser ophthalmoscopy. Unlike fundus AF detected in normal human subjects, mouse fundus AF appeared as discrete foci distributed throughout the retina. Most of the AF signals in the neuroretina were distributed around retinal vessels. Confocal microscopy of retinal and choroid/RPE flat mounts demonstrated that most of the AF signals were derived from Iba-1+ perivascular and subretinal microglia. An age-dependent accumulation of Iba-1+ microglia at the subretinal space was observed. Lipofuscin granules were detected in large numbers in subretinal microglia by electron microscopy. The number of AF+ microglia and the amount of AF granules/cell increased with age. AF granules/lipofuscin were also observed in RPE cells in mice older than 12 months, but the number of AF+ RPE cells was very low (1.48 mm(-2) and 5.02 mm(-2) for 12 and 24 months, respectively) compared to the number of AF+ microglial cells (20.63 mm(-2) and 76.36 mm(-2) for 6 and 24 months, respectively). The fluorescence emission fingerprints of AF granules in subretinal microglia were the same as those in RPE cells. Our observation suggests that perivascular and subretinal microglia are the main cells producing lipofuscin in normal aged mouse retina and are responsible for in vivo fundus AF. Microglia may play an important role in retinal aging and age-related retinal diseases. PMID:17988243

  13. The diagnostic value of perivascular infiltrates in muscle biopsy specimens for the assessment of rheumatoid vasculitis

    PubMed Central

    Voskuyl, A.; van Duinen, S. G; Zwinderman, A.; Breedveld, F.; Hazes, J.

    1998-01-01

    OBJECTIVE—To determine the diagnostic value of perivascular infiltrates (PVI) in randomly obtained muscle biopsy specimens for the assessment of rheumatoid vasculitis (RV).
METHODS—The number and size of PVIs, defined as the presence of mononuclear or polymorphonuclear cells around ⩾ 50% of the circumference of a vessel wall, as well as the presence of fibrinoid necrosis were determined in frozen sections of muscle samples of RV patients with histologically confirmed vasculitis in fixed muscle tissue (n=12). The findings were compared with those observed in frozen sections of muscle biopsy specimens of rheumatoid arthritis (RA) patients not suspected of vasculitis (n=14) and patients with osteoarthritis (OA) (n=11). The presence of PVIs and of fibrinoid necrosis were sought in four frozen sections of the muscle biopsy specimen.
RESULTS—PVIs were observed in 75% of the RV patients, which was significantly (p < 0.05) higher than the frequency found in RA (14%) or OA (18%) patients. PVIs with ⩾ three cell layers were found in 67% of the RV patients and in none of the RA and OA patients (p < 0.05). Fibrinoid necrosis was found in least one of four frozen section in 33% of the RV patients. There was a good intra-observer and inter-observer concordance on the presence of fibrinoid necrosis and of PVIs with ⩾ three cell layers.
CONCLUSIONS—The assessment of PVIs with ⩾ three cell layers in a muscle biopsy specimen is a specific and reliable test in discriminating RV from RA without vasculitis. The demonstration in muscle of PVIs with ⩾ three cell layers is more sensitive than that of fibrinoid necrosis in the diagnosis of RV.

 Keywords: rheumatoid arthritis; vasculitis; diagnosis; histology; perivascular infiltrates PMID:9613342

  14. Perivascular tissue mediated relaxation - a novel player in human vascular tone regulation.

    PubMed

    Deja, M A; Malinowski, M; Golba, K S; Piekarska, M; Wos, S

    2015-12-01

    Perivascular tissue (PVT) modulates vascular tone, releasing adventitia/adipocyte derived relaxing factor (ADRF). Its physiological role remains unclear. We studied isolated internal thoracic artery (ITA) segments obtained from 132 patients subjected to coronary artery bypass grafting. The vessels were skeletonized in vitro and the ITA rings and PVT were incubated in separate isolated organ baths. Skeletonized ITA segments were first precontracted with 10(-5.5)mol/L 5-hydroxytryptamine hydrochloride. The PVT was next transferred to the ITA tissue bath. This resulted in relaxation of ITA, presumably related to ADRF release from PVT which was floating freely in the tissue bath. The in-vitro relaxation responses were then correlated to patients' characteristics - including demographics, clinical and laboratory data, as well as therapy. Perivascular tissue transfer resulted in 49.7 ± 26.2% relaxation of precontracted ITA segments. In multiple linear regression modelling, the relaxation of ITAto PVT was negatively related to patient age (β = -0.67; 95% CI -1.17 - -0.17; P = 0.009), symptoms of CCS class 4 angina (β = -20.11; 95%CI -32.25 - -7.97; P = 0.001), and positively to body mass (β = 0.37; 95%CI 0.08 - 0.67; P = 0.01) and lack of heart failure symptoms (NYHA class 1) (β = 9.06; 95%CI 0.33 - 17.79; P = 0.04). The relaxation response to PVT was not related to patients' sex, diabetes, hypertension, lipid profile or therapy in both univariate and multivariate analysis. PVT might play an important role in regulating vascular tone in humans as exemplified by its changing physiological function with age and in atherosclerosis. PMID:26769833

  15. Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension

    PubMed Central

    Mikolajczyk, Tomasz P.; Nosalski, Ryszard; Szczepaniak, Piotr; Budzyn, Klaudia; Osmenda, Grzegorz; Skiba, Dominik; Sagan, Agnieszka; Wu, Jing; Vinh, Antony; Marvar, Paul J.; Guzik, Bartlomiej; Podolec, Jakub; Drummond, Grant; Lob, Heinrich E.; Harrison, David G.; Guzik, Tomasz J.

    2016-01-01

    Recent studies have emphasized the role of perivascular inflammation in cardiovascular disease. We studied mechanisms of perivascular leukocyte infiltration in angiotensin II (Ang II)-induced hypertension and their links to vascular dysfunction. Chronic Ang II infusion in mice increased immune cell content of T cells (255 ± 130 to 1664 ± 349 cells/mg; P < 0.01), M1 and M2 macrophages, and dendritic cells in perivascular adipose tissue. In particular, the content of T lymphocytes bearing CC chemokine receptor (CCR) 1, CCR3, and CCR5 receptors for RANTES chemokine was increased by Ang II (CCR1, 15.6 ± 1.5% vs. 31 ± 5%; P < 0.01). Hypertension was associated with an increase in perivascular adipose tissue expression of the chemokine RANTES (relative quantification, 1.2 ± 0.2 vs. 3.5 ± 1.1; P < 0.05), which induced T-cell chemotaxis and vascular accumulation of T cells expressing the chemokine receptors CCR1, CCR3, and CCR5. Mechanistically, RANTES−/− knockout protected against vascular leukocyte, and in particular T lymphocyte infiltration (26 ± 5% in wild type Ang II vs. 15 ± 4% in RANTES−/−), which was associated with protection from endothelial dysfunction induced by Ang II. This effect was linked with diminished infiltration of IFN-γ-producing CD8+ and double-negative CD3+CD4−CD8− T cells in perivascular space and reduced vascular oxidative stress while FoxP3+ T-regulatory cells were unaltered. IFN-γ ex vivo caused significant endothelial dysfunction, which was reduced by superoxide anion scavenging. In a human cohort, a significant inverse correlation was observed between circulating RANTES levels as a biomarker and vascular function measured as flow-mediated dilatation (R = −0.3, P < 0.01) or endothelial injury marker von Willebrand factor (R = +0.3; P < 0.01). Thus, chemokine RANTES is important in the regulation of vascular dysfunction through modulation of perivascular inflammation.—Mikolajczyk, T. P., Nosalski, R., Szczepaniak, P

  16. Perivascular Expression and Potent Vasoconstrictor Effect of Dynorphin A in Cerebral Arteries

    PubMed Central

    Ruisanchez, Éva; Cselenyák, Attila; Papp, Rege Sugárka; Németh, Tamás; Káldi, Krisztina; Sándor, Péter; Benyó, Zoltán

    2012-01-01

    Background Numerous literary data indicate that dynorphin A (DYN-A) has a significant impact on cerebral circulation, especially under pathophysiological conditions, but its potential direct influence on the tone of cerebral vessels is obscure. The aim of the present study was threefold: 1) to clarify if DYN-A is present in cerebral vessels, 2) to determine if it exerts any direct effect on cerebrovascular tone, and if so, 3) to analyze the role of κ-opiate receptors in mediating the effect. Methodology/Principal Findings Immunohistochemical analysis revealed the expression of DYN-A in perivascular nerves of rat pial arteries as well as in both rat and human intraparenchymal vessels of the cerebral cortex. In isolated rat basilar and middle cerebral arteries (BAs and MCAs) DYN-A (1–13) and DYN-A (1–17) but not DYN-A (1–8) or dynorphin B (DYN-B) induced strong vasoconstriction in micromolar concentrations. The maximal effects, compared to a reference contraction induced by 124 mM K+, were 115±6% and 104±10% in BAs and 113±3% and 125±9% in MCAs for 10 µM of DYN-A (1–13) and DYN-A (1–17), respectively. The vasoconstrictor effects of DYN-A (1–13) could be inhibited but not abolished by both the κ-opiate receptor antagonist nor-Binaltorphimine dihydrochloride (NORBI) and blockade of Gi/o-protein mediated signaling by pertussis toxin. Finally, des-Tyr1 DYN-A (2–13), which reportedly fails to activate κ-opiate receptors, induced vasoconstriction of 45±11% in BAs and 50±5% in MCAs at 10 µM, which effects were resistant to NORBI. Conclusion/Significance DYN-A is present in rat and human cerebral perivascular nerves and induces sustained contraction of rat cerebral arteries. This vasoconstrictor effect is only partly mediated by κ-opiate receptors and heterotrimeric Gi/o-proteins. To our knowledge our present findings are the first to indicate that DYN-A has a direct cerebral vasoconstrictor effect and that a dynorphin-induced vascular action may be

  17. CD146+ Human Umbilical Cord Perivascular Cells Maintain Stemness under Hypoxia and as a Cell Source for Skeletal Regeneration

    PubMed Central

    Tsang, Wing Pui; Shu, Yinglan; Kwok, Po Lam; Zhang, Fengjie; Lee, Kenneth Ka Ho; Tang, Mei Kuen; Li, Gang; Chan, Kai Ming; Chan, Wai-Yee; Wan, Chao

    2013-01-01

    The human umbilical cord perivascular cells (HUCPVCs) have been considered as an alternative source of mesenchymal progenitors for cell based regenerative medicine. However, the biological properties of these cells remain to be well characterized. In the present study, HUCPVCs were isolated and sorted by CD146+ pericyte marker. The purified CD146+ HUCPVCs were induced to differentiate efficiently into osteoblast, chondrocyte and adipocyte lineages in vitro. Six weeks following subcutaneous transplantation of CD146+ HUCPVCs-Gelfoam-alginate 3D complexes in severe combined immunodeficiency (SCID) mice, newly formed bone matrix with embedded osteocytes of donor origin was observed. The functional engraftment of CD146+ HUCPVCs in the new bone regenerates was further confirmed in a critical-sized bone defect model in SCID mice. Hypoxic conditions suppressed osteogenic differentiation while increased cell proliferation and colony-forming efficiency of CD146+ HUCPVCs as compared to that under normoxic conditions. Re-oxygenation restored the multi-differentiation potential of the CD146+ HUCPVCs. Western blot analysis revealed an upregulation of HIF-1α, HIF-2α, and OCT-4 protein expression in CD146+ HUCPVCs under hypoxia, while there was no remarkable change in SOX2 and NANOG expression. The gene expression profiles of stem cell transcription factors between cells treated by normoxia and hypoxic conditions were compared by PCR array analysis. Intriguingly, PPAR-γ was dramatically downregulated (20-fold) in mRNA expression under hypoxia, and was revealed to possess a putative binding site in the Hif-2α gene promoter region. Chromatin immunoprecipitation assays confirmed the binding of PPAR-γ protein to the Hif-2α promoter and the binding was suppressed by hypoxia treatment. Luciferase reporter assay showed that the Hif-2α promoter activity was suppressed by PPAR expression. Thus, PPAR-γ may involve in the regulation of HIF-2α for stemness maintenance and promoting

  18. The role of perivascular adipose tissue in vasoconstriction, arterial stiffness, and aneurysm

    PubMed Central

    Villacorta, Luis

    2015-01-01

    Since the “rediscovery” of brown adipose tissue in adult humans, significant scientific efforts are being pursued to identify the molecular mechanisms to promote a phenotypic change of white adipocytes into brown-like cells, a process called “browning”. It is well documented that white adipose tissue (WAT) mass and factors released from WAT influence the vascular function and positively correlate with cardiac arrest, stroke, and other cardiovascular complications. Similar to other fat depots, perivascular adipose tissue (PVAT) is an active endocrine organ and anatomically surrounds vessels. Both brown-like and white-like PVAT secrete various adipokines, cytokines, and growth factors that either prevent or promote the development of cardiovascular diseases (CVDs) depending on the relative abundance of each type and their bioactivity in the neighboring vasculature. Notably, pathophysiological conditions, such as obesity, hypertension, or diabetes, induce the imbalance of PVAT-derived vasoactive products that promote the infiltration of inflammatory cells. This then triggers derangements in vascular smooth muscle cells and endothelial cell dysfunction, resulting in the development of vascular diseases. In this review, we discuss the recent advances on the contribution of PVAT in CVDs. Specifically, we summarize the current proposed roles of PVAT in relationship with vascular contractility, endothelial dysfunction, neointimal formation, arterial stiffness, and aneurysm. PMID:25719334

  19. Gene transfer corrects acute GM2 gangliosidosis--potential therapeutic contribution of perivascular enzyme flow.

    PubMed

    Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2012-08-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity-as opposed to tremor-ataxia-were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue-long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system. PMID:22453766

  20. Neoadjuvant sirolimus for a large hepatic perivascular epithelioid cell tumor (PEComa)

    PubMed Central

    2014-01-01

    Perivascular epithelioid cell tumors (PEComas) are rare soft-tissue tumors with an extremely heterogeneous clinical behavior. They may arise in different organs and may behave indolently or sometimes metastasize with different grades of biological aggressiveness. We report the case of a young woman with a primary inoperable PEComa of the liver with malignant histological features. Since the mTOR pathway is often altered in PEComas and responses have been reported with mTOR-inhibitors such as sirolimus or temsirolimus, we decided to start a neoadjuvant treatment with sirolimus. The patient tolerated the treatment fairly well and after 8 months a favorable tumor shrinkage was obtained. The patient then stopped sirolimus and 2 weeks later underwent partial liver resection, with complete clinical recovery and normal liver function. The histological report confirmed a malignant PEComa with vascular invasion and negative margins. Then 6 additional months of post-operative sirolimus treatment were administered, followed by regular radiological follow-up. For patients with a large and histologically aggressive PEComa, we think that neoadjuvant treatment with mTOR-inhibitor sirolimus may be considered to facilitate surgery and allow early control of a potentially metastatic disease. For selected high-risk patients, the option of adjuvant treatment may be discussed. PMID:24575738

  1. alpha2-Adrenoceptors control the release of noradrenaline but not neuropeptide Y from perivascular nerve terminals.

    PubMed

    Donoso, M Veronica; Carvajal, Andrés; Paredes, Alfonso; Tomic, Alexander; Koenig, Cecilia S; Huidobro-Toro, J Pablo

    2002-09-01

    Neuropeptide Y (NPY) and noradrenaline (NA) are co-transmitters at many sympathetic synapses, but it is not yet clear if their release is independently regulated. To address this question, we quantified the electrically evoked release of these co-transmitters from perivascular nerve terminals to the mesenteric circulation in control and drug-treated rats. 6-Hydroxydopamine reduced the tissue content and the electrically evoked release of ir-NPY and NA as well as the rise in perfusion pressure. A 0.001 mg/kg reserpine reduced the content of ir-NPY and NA, but did not modify their release nor altered the rise in perfusion pressure elicited by the electrical stimuli. However, 0.1mg/kg reserpine reduced both the content and release of NA but decreased only the content but not the release of ir-NPY; the rise in perfusion pressure was halved. Clonidine did not affect the release of ir-NPY while it lowered the outflow of NA, not altering the rise in perfusion pressure elicited by the electrical stimuli. Yohimbine, did not modify the release of ir-NPY but increased the NA outflow, it antagonized the clonidine effect. Therefore, presynaptic alpha2-adrenoceptors modulate the release of NA but not NPY, implying separate regulatory mechanisms. PMID:12217427

  2. Perivascular Adipose Tissue Inhibits Endothelial Function of Rat Aortas via Caveolin-1

    PubMed Central

    Lee, Michelle Hui-Hsin; Chen, Shiu-Jen

    2014-01-01

    Perivascular adipose tissue (PVAT)-derived factors have been proposed to play an important role in the pathogenesis of atherosclerosis. Caveolin-1 (Cav-1), occupying the calcium/calmodulin binding site of endothelial NO synthase (eNOS) and then inhibiting nitric oxide (NO) production, is also involved in the development of atherosclerosis. Thus, we investigated whether PVAT regulated vascular tone via Cav-1 and/or endothelial NO pathways. Isometric tension studies were carried out in isolated thoracic aortas from Wistar rats in the presence and absence of PVAT. Concentration-response curves of phenylephrine, acetylcholine, and sodium nitroprusside were illustrated to examine the vascular reactivity and endothelial function. The protein expressions of eNOS and Cav-1 were also examined in aortic homogenates. Our results demonstrated that PVAT significantly enhanced vasoconstriction and inhibited vasodilatation via endothelium-dependent mechanism. The aortic NO production was diminished after PVAT treatment, whereas protein expression and activity of eNOS were not significantly affected. In addition, Cav-1 protein expression was significantly increased in aortas with PVAT transfer. Furthermore, a caveolae depleter methyl-β-cyclodextrin abolished the effect of PVAT on the enhancement of vasoconstriction, and reversed the impairment of aortic NO production. In conclusion, unknown factor(s) released from PVAT may inhibit endothelial NO production and induce vasocontraction via an increase of Cav-1 protein expression. PMID:24926683

  3. Differential role of CCR2 in the dynamics of microglia and perivascular macrophages during prion disease

    PubMed Central

    Gómez-Nicola, Diego; Schetters, Sjoerd TT; Hugh Perry, V

    2014-01-01

    The expansion of the microglial population is one of the hallmarks of numerous brain disorders. The addition of circulating progenitors to the pool of brain macrophages can contribute to the progression of brain disease and needs to be precisely defined to better understand the evolution of the glial and inflammatory reactions in the brain. We have analyzed the degree of infiltration/recruitment of circulating monocytes to the microglial pool, in a prion disease model of chronic neurodegeneration. Our results indicate a minimal/absent level of CCR2-dependent recruitment of circulating monocytes, local proliferation of microglia is the main driving force maintaining the amplification of the population. A deficiency in CCR2, and thus the absence of recruitment of circulating monocytes, does not impact microglial dynamics, the inflammatory profile or the temporal behavioral course of prion disease. However, the lack of CCR2 has unexpected effects including the failure to recruit perivascular macrophages in diseased but not healthy CNS and a small reduction in microglia proliferation. These data define the composition of the CNS-resident macrophage populations in prion disease and will help to understand the dynamics of the CNS innate immune response during chronic neurodegeneration. PMID:24648328

  4. Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche.

    PubMed

    Chen, James Y; Miyanishi, Masanori; Wang, Sean K; Yamazaki, Satoshi; Sinha, Rahul; Kao, Kevin S; Seita, Jun; Sahoo, Debashis; Nakauchi, Hiromitsu; Weissman, Irving L

    2016-02-11

    Haematopoietic stem cells (HSCs) are arguably the most extensively characterized tissue stem cells. Since the identification of HSCs by prospective isolation, complex multi-parameter flow cytometric isolation of phenotypic subsets has facilitated studies on many aspects of HSC biology, including self-renewal, differentiation, ageing, niche, and diversity. Here we demonstrate by unbiased multi-step screening, identification of a single gene, homeobox B5 (Hoxb5, also known as Hox-2.1), with expression in the bone marrow that is limited to long-term (LT)-HSCs in mice. Using a mouse single-colour tri-mCherry reporter driven by endogenous Hoxb5 regulation, we show that only the Hoxb5(+) HSCs exhibit long-term reconstitution capacity after transplantation in primary transplant recipients and, notably, in secondary recipients. Only 7-35% of various previously defined immunophenotypic HSCs are LT-HSCs. Finally, by in situ imaging of mouse bone marrow, we show that >94% of LT-HSCs (Hoxb5(+)) are directly attached to VE-cadherin(+) cells, implicating the perivascular space as a near-homogenous location of LT-HSCs. PMID:26863982

  5. sdf1 Expression Reveals a Source of Perivascular-Derived Mesenchymal Stem Cells in Zebrafish

    PubMed Central

    Lund, Troy C.; Patrinostro, Xiaobai; Kramer, Ashley C.; Stadem, Paul; Higgins, LeeAnn; Markowski, Todd W.; Wroblewski, Matt S.; Lidke, Diane S.; Tolar, Jakub; Blazar, Bruce R.

    2014-01-01

    There is accumulating evidence that mesenchymal stem cells (MSC) have their origin as perivascular cells (PVC) in vivo, but precisely identifying them has been a challenge, as they have no single definitive marker and are rare. We have developed a fluorescent transgenic vertebrate model in which PVC can be visualized in vivo based upon sdf1 expression in the zebrafish. Prospective isolation and culture of sdf1DsRed PVC demonstrated properties consistent with MSC including prototypical cell surface marker expression; mesodermal differentiation into adipogenic, osteogenic and chondrogenic lineages; and the ability to support hematopoietic cells. Global proteomic studies performed by 2-dimensional liquid chromatography and tandem mass spectrometry revealed a high degree of similarity to human MSC and discovery of novel markers (CD99, CD151 and MYOF) that were previously unknown to be expressed by hMSC. Dynamic in vivo imaging during fin regeneration showed that PVC may arise from undifferentiated mesenchyme providing evidence of a PVC – MSC relationship. This is the first model, established in zebrafish, in which MSC can be visualized in vivo and will allow us to better understand their function in a native environment. PMID:24905975

  6. Perivascular epithelioid cell tumour of the vagina in an 8 year old girl.

    PubMed

    Ong, Lin Yin; Hwang, Wei Sek; Wong, Adelina; Chan, Mei Yoke; Chui, Chan Hon

    2007-03-01

    Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor with an unpredictable natural history. We present the first reported case of PEComa of the vagina diagnosed in an 8-year-old girl. This was initially diagnosed on biopsy as an embryonal rhabdomyosarcoma, and the patient underwent 3 cycles of chemotherapy according to the Mesenchymal Malignant Tumour 1989 protocol. A repeat scan, however, revealed an increase in tumor size. Total resection was achieved via a transvaginal (vertical sleeve) partial vaginectomy. The resected tumor had the typical appearance of a PEComa. Immunostains showed positive staining of tumor cells for HMB45, neuron-specific enolase, and calponin but were negative for S100 protein, melaninA, chromogranin, smooth muscle actin, desmin, caldesmon, epithelial membrane antigen, AE1/3, and synaptophysin. Six months after surgery, she remains free of tumor and is on follow-up with regular local examinations under anesthesia and computed tomography scans. Our case highlights the importance of an accurate initial diagnosis, and we stress the importance of regular surveillance over a significant period. PMID:17336201

  7. Gene Transfer Corrects Acute GM2 Gangliosidosis—Potential Therapeutic Contribution of Perivascular Enzyme Flow

    PubMed Central

    Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2012-01-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay–Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity—as opposed to tremor-ataxia—were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue—long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system. PMID:22453766

  8. Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension

    PubMed Central

    Gálvez-Prieto, Beatriz; Somoza, Beatriz; Gil-Ortega, Marta; García-Prieto, Concha F.; de las Heras, Ana I.; González, M. Carmen; Arribas, Silvia; Aranguez, Isabel; Bolbrinker, Juliane; Kreutz, Reinhold; Ruiz-Gayo, Mariano; Fernández-Alfonso, Maria S.

    2012-01-01

    Leptin causes vasodilatation both by endothelium-dependent and -independent mechanisms. Leptin is synthesized by perivascular adipose tissue (PVAT). The hypothesis of this study is that a decrease of leptin production in PVAT of spontaneously hypertensive rats (SHR) might contribute to a diminished paracrine anticontractile effect of the hormone. We have determined in aorta from Wistar-Kyoto (WKY) and SHR (i) leptin mRNA and protein levels in PVAT, (ii) the effect of leptin and PVAT on contractile responses, and (iii) leptin-induced relaxation and nitric oxide (NO) production. Leptin mRNA and protein expression were significantly lower in PVAT from SHR. Concentration-response curves to angiotensin II were significantly blunted in presence of PVAT as well as by exogenous leptin (10−9 M) only in WKY. This anticontractile effect was endothelium-dependent. Vasodilatation induced by leptin was smaller in SHR than in WKY, and was also endothelium-dependent. Moreover, release of endothelial NO in response to acute leptin was higher in WKY compared to SHR, but completely abolished in the absence of endothelium. In conclusion, the reduced anticontractile effect of PVAT in SHR might be attributed to a reduced PVAT-derived leptin and to an abrogated effect of leptin on endothelial NO release probably due to an impaired activation of endothelial NO synthase. PMID:22679436

  9. Nicotine facilitates reinnervation of phenol-injured perivascular adrenergic nerves in the rat mesenteric resistance artery.

    PubMed

    Takatori, Shingo; Fujiwara, Hidetoshi; Hagimori, Kenta; Hashikawa-Hobara, Narumi; Yokomizo, Ayako; Takayama, Fusako; Tangsucharit, Panot; Ono, Nobufumi; Kawasaki, Hiromu

    2015-02-01

    Nicotine has been shown to have neuroprotective and neurotrophic actions in the central nervous system. To elucidate the peripheral neurotrophic effects of nicotine, we determined whether nicotine affected the reinnervation of mesenteric perivascular nerves following a topical phenol treatment. A topical phenol treatment was applied to the superior mesenteric artery proximal to the abdominal aorta in Wistar rats. We examined the immunohistochemistry of the distal small arteries 7 days after the treatment. The topical phenol treatment markedly reduced the density of tyrosine hydroxylase (TH)-LI and calcitonin gene-related peptide (CGRP)-LI fibers in these arteries. The administration of nicotine at a dose of 3 mg/kg/day (1.5 mg/kg/injection, twice a day), but not once a day or its continuous infusion using a mini-pump significantly increased the density of TH-LI nerves without affecting CGRP-LI nerves. A pretreatment with nicotinic acetylcholine receptor antagonists hexamethonium, mecamylamine, and methyllycaconitine, but not dextrometorphan, canceled the TH-LI nerve reinnervation induced by nicotine. Nicotine significantly increased NGF levels in the superior cervical ganglia (SCG) and mesenteric arteries, but not in the dorsal root ganglia, and also up-regulated the expression of NGF receptors (TrkA) in the SCG, which were canceled by hexamethonium. These results suggested that nicotine exhibited neurotrophic effects that facilitated the reinnervation of adrenergic TH-LI nerves by activating α7 nicotinic acetylcholine receptor and NGF in the SCG. PMID:25514605

  10. Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases.

    PubMed

    Bakker, Erik N T P; Bacskai, Brian J; Arbel-Ornath, Michal; Aldea, Roxana; Bedussi, Beatrice; Morris, Alan W J; Weller, Roy O; Carare, Roxana O

    2016-03-01

    The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (Aβ). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer's disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that Aβ is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of Aβ in the glia limitans in Alzheimer's disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of Aβ. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance. PMID:26993512

  11. Perivascular adipose tissue from human systemic and coronary vessels: the emergence of a new pharmacotherapeutic target

    PubMed Central

    Aghamohammadzadeh, Reza; Withers, Sarah; Lynch, Fiona; Greenstein, Adam; Malik, R; Heagerty, Anthony

    2012-01-01

    Fat cells or adipocytes are distributed ubiquitously throughout the body and are often regarded purely as energy stores. However, recently it has become clear that these adipocytes are engine rooms producing large numbers of metabolically active substances with both endocrine and paracrine actions. White adipocytes surround almost every blood vessel in the human body and are collectively termed perivascular adipose tissue (PVAT). It is now well recognized that PVAT not only provides mechanical support for any blood vessels it invests, but also secretes vasoactive and metabolically essential cytokines known as adipokines, which regulate vascular function. The emergence of obesity as a major challenge to our healthcare systems has contributed to the growing interest in adipocyte dysfunction with a view to discovering new pharmacotherapeutic agents to help rescue compromised PVAT function. Very few PVAT studies have been carried out on human tissue. This review will discuss these and the hypotheses generated from such research, as well as highlight the most significant and clinically relevant animal studies showing the most pharmacological promise. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21564083

  12. Hoxb5 marks long-term haematopoietic stem cells revealing a homogenous perivascular niche

    PubMed Central

    Chen, James Y.; Miyanishi, Masanori; Wang, Sean K.; Yamazaki, Satoshi; Sinha, Rahul; Kao, Kevin S.; Nakauchi, Hiromitsu; Weissman, Irving L.

    2016-01-01

    The hematopoietic stem cell (HSC) is arguably the most extensively characterized tissue stem cell. Since its identification by prospective isolation1, complex multi-parameter flow cytometric isolation of phenotypic subsets has facilitated studies on many aspects of HSC biology including, self-renewal2–4, differentiation, aging, niche5, and diversity6–8. Here we demonstrate by unbiased multi-step screening, identification of a single gene, Hoxb5 (homeobox B5 also known as Hox-2.1), whose expression in the bone marrow (BM) is limited to the long-term HSC (LT-HSC) in mice. Utilizing a single-color tri-mCherry reporter mouse driven by endogenous Hoxb5 regulation, only the Hoxb5-positive HSCs exhibit long-term reconstitution capacity after transplantation in primary transplant recipients, and critically, in secondary recipients. Only 7–35% of various previously defined immunophenotypic HSCs are LT-HSCs. Finally, by in situ imaging of mouse BM, we show that >94% of LT-HSC (Hoxb5+) are directly attached to VE-cadherin-positive cells, implicating a perivascular space as a near homogenous localization of the LT-HSC. PMID:26863982

  13. Perivascular Stem Cells Diminish Muscle Atrophy and Retain Viability in a Rotator Cuff Tear Model

    PubMed Central

    Eliasberg, Claire; Jensen, Andrew; Dar, Ayelet; Kowalski, Tomasz J.; Murray, Iain; Khan, Adam Z.; Natsuhara, Kyle; Garagozlo, Cameron; McAllister, David R.; Petrigliano, Frank A.

    2016-01-01

    Objectives: Rotator cuff tears (RCTs) are a common cause of shoulder pain and often necessitate surgical repair. Muscle changes including atrophy, fibrosis, and fatty degeneration can develop after RCTs, which may compromise surgical repair and clinical outcomes. Lipoaspirate-derived human perivascular stem cells (PSCs) have demonstrated myogenic and angiogenic potential in other small animal models of muscle injury. We hypothesized that the administration of PSCs following massive RCTs may help to diminish these muscle changes in a small animal model. Methods: A total of 90 immunodeficient mice were used (15 groups, N=6). Each was assigned to one of three surgical groups: i) sham, ii) supraspinatus and infraspinatus tendon transection (TT), or iii) TT and suprascapular nerve denervation (TT+DN). PSCs were harvested from human lipoaspirate and sorted using fluorescence-activated cell sorting into small blood vessel residing pericytes (CD146+ CD34- CD45- CD31-) and large blood perivascular adventitial cells (CD146- CD34+ CD45- CD31-). Mice received either a) no injection, b) saline injection, c) pericyte injection, or d) adventitial cell injection at the time of the index procedure or at two weeks following index surgery. The supraspinatus muscles were harvested six weeks after the index procedure. Muscle atrophy was assessed by measuring percent wet muscle weight change for each sample. Muscle fiber cross-sectional area (CSA), fibrosis, and fatty degeneration were analyzed using Image J™. Additionally, pericytes and adventitial cells were transduced with a luciferase-containing construct. Animals were given injections of luciferin and imaged using IVIS to track in vivo bioluminescence following injections to assess cell viability. Results: Treatment with PSC injection after TT resulted in less wet weight loss and greater muscle fiber CSA than control groups (P<0.05). The TT+DN groups treated with PSC injections two weeks post-op also had less muscle weight loss

  14. Diosgenin regulates adipokine expression in perivascular adipose tissue and ameliorates endothelial dysfunction via regulation of AMPK.

    PubMed

    Chen, Yan; Xu, Xiaoshan; Zhang, Yuanyuan; Liu, Kang; Huang, Fang; Liu, Baolin; Kou, Junping

    2016-01-01

    Perivascular adipose tissue (PVAT) has been recognized as an active contributor to vascular function due to its paracrine effects on cells contained within vascular wall. The present study was designed to investigate the effect of diosgenin on adipokine expression in PVAT with emphasis on the regulation of endothelial function. Palmitic acid (PA) stimulation induced inflammation and dysregulation of adipokine expression in PVAT. Diosgenin treatment inhibited IKKβ phosphorylation and downregulated mRNA expressions of proinflammatory cytokines/proteins including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein (MCP-1), and inducible nitric oxide synthase (iNOS), while reduced gene expressions for adiponectin, PPARγ, and arginase 1 (Arg-1) were reversed by diosgenin treatment. Diosgenin enhanced AMPK phosphorylation under basal and inflammatory conditions in PVAT, whereas knockdown of AMPK by SiRNA diminished its modulatory effect, indicating that diosgenin inhibited inflammation in an AMPK-dependent manner. We prepared conditioned medium from PA-stimulated PVAT to induce endothelial dysfunction and found that pre-treatment of PVAT with diosgenin effectively restored the loss of ACh-induced vasodilation and increased eNOS phosphorylation in rat aorta. High-fat diet feeding in rats induced inflammation in PVAT and the impairment of endothelium-dependent vasodilation, whereas these alterations were prevented by oral administration of diosgenin at doses of 20 and 40 mg/kg. In conclusion, the obtained data showed that diosgenin ameliorated inflammation-associated adipokine dysregulation, and thereby prevented endothelial dysfunction. Our findings would shed a novel insight into the potential mechanism by which diosgenin protected endothelial function against inflammatory insult. PMID:26277096

  15. Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity.

    PubMed

    Gil-Ortega, Marta; Stucchi, Paula; Guzmán-Ruiz, Rocío; Cano, Victoria; Arribas, Silvia; González, M Carmen; Ruiz-Gayo, Mariano; Fernández-Alfonso, Maria S; Somoza, Beatriz

    2010-07-01

    Perivascular adipose tissue (PVAT) plays a paracrine role in regulating vascular tone. We hypothesize that PVAT undergoes adaptative mechanisms during initial steps of diet-induced obesity (DIO) which contribute to preserve vascular function. Four-week-old male C57BL/6J mice were assigned either to a control [low-fat (LF); 10% kcal from fat] or to a high-fat diet (HF; 45% kcal from fat). After 8 wk of dietary treatment vascular function was analyzed in the whole perfused mesenteric bed (MB) and in isolated mesenteric arteries cleaned of PVAT. Relaxant responses to acetylcholine (10(-9)-10(-4) m) and sodium nitroprusside (10(-12)-10(-5) m) were significantly ameliorated in the whole MB from HF animals. However, there was no difference between HF and LF groups in isolated mesenteric arteries devoid of PVAT. The enhancement of relaxant responses detected in HF mice was not attributable to an increased release of nitric oxide (NO) from the endothelium nor to an increased sensitivity and/or activity of muscular guanilylcyclase. Mesenteric PVAT of HF animals showed an increased bioavailability of NO, detected by 4,5-diaminofluorescein diacetate (DAF2-DA) staining, which positively correlated with plasma leptin levels. DAF-2DA staining was absent in PVAT from ob/ob mice but was detected in these animals after 4-wk leptin replacement. The main finding in this study is that adaptative NO overproduction occurs in PVAT during early DIO which might be aimed at preserving vascular function. PMID:20410199

  16. Brain Atrophy Correlates with Severe Enlarged Perivascular Spaces in Basal Ganglia among Lacunar Stroke Patients

    PubMed Central

    Zhang, Xiaoyu; Ding, Lingling; Yang, Lei; Qin, Wei; Yuan, Junliang; Li, Shujuan; Hu, Wenli

    2016-01-01

    Background Enlarged perivascular spaces (EPVS) correlate with cognitive impairment and incident dementia. However, etiologies for severe basal ganglia EPVS (BG-EPVS) are still unclear. Our aim was to investigate the independent risk factors for severe BG-EPVS in patients with acute lacunar stroke. Methods We prospectively identified patients with lacunar stroke (diameter on DWI ≤ 20mm) from Jan 2011 to May 2015. Patients with severe BG-EPVS were identified on T2 weighted MRI. Age (± 1 year) and sex matched controls were also recruited in the same population (two controls for one case). Vascular risk factors, clinical data, EPVS in centrum semiovale (rated 0 to 4), white matter hyperintensities (WMH) (by Fazekas scale), brain atrophy (rated 0 to 6) were compared between two groups. Logistic regression was performed to determine independent risk factors for severe BG-EPVS. Results During study period, 89 patients with severe BG-EPVS and 178 matched controls were included. Vascular risk factors did not differ between two groups. Patients with severe BG-EPVS had lower level of HbA1c and diastolic BP at admission, but presented with larger infarct size, more severe WMH (including total WMH, periventricular WMH and deep WMH) and brain atrophy. In logistic regression, brain atrophy (OR = 1.40; 95%CI 1.13, 1.73) and deep WMH (OR = 1.88; 95%CI 1.24, 2.83) were independent risk factors for severe BG-EPVS. Conclusions Brain atrophy and deep WMH are independent risk factors for severe BG-EPVS, supporting the hypothesis that brain atrophy may be associated with the development of EPVS in basal ganglia. PMID:26900696

  17. Alterations in Perivascular Sympathetic and Nitrergic Innervation Function Induced by Late Pregnancy in Rat Mesenteric Arteries

    PubMed Central

    Caracuel, Laura; Callejo, María; Balfagón, Gloria

    2015-01-01

    Background and Purpose We investigated whether pregnancy was associated with changed function in components of perivascular mesenteric innervation and the mechanism/s involved. Experimental Approach We used superior mesenteric arteries from female Sprague-Dawley rats divided into two groups: control rats (in oestrous phase) and pregnant rats (20 days of pregnancy). Modifications in the vasoconstrictor response to electrical field stimulation (EFS) were analysed in the presence/absence of phentolamine (alpha-adrenoceptor antagonist) or L-NAME (nitric oxide synthase-NOS- non-specific inhibitor). Vasomotor responses to noradrenaline (NA), and to NO donor DEA-NO were studied, NA and NO release measured and neuronal NOS (nNOS) expression/activation analysed. Key Results EFS induced a lower frequency-dependent contraction in pregnant than in control rats. Phentolamine decreased EFS-induced vasoconstriction in segments from both experimental groups, but to a greater extent in control rats. EFS-induced vasoconstriction was increased by L-NAME in arteries from both experimental groups. This increase was greater in segments from pregnant rats. Pregnancy decreased NA release while increasing NO release. nNOS expression was not modified but nNOS activation was increased by pregnancy. Pregnancy decreased NA-induced vasoconstriction response and did not modify DEA-NO-induced vasodilation response. Conclusions and Implications Neural control of mesenteric vasomotor tone was altered by pregnancy. Diminished sympathetic and enhanced nitrergic components both contributed to the decreased vasoconstriction response to EFS during pregnancy. All these changes indicate the selective participation of sympathetic and nitrergic innervations in vascular adaptations produced during pregnancy. PMID:25951331

  18. Perivascular, but not Parenchymal, Cerebral Engraftment of Donor Cells after Non-Myeloablative Bone Marrow Transplantation

    PubMed Central

    Yang, Yue; Jorstad, Nikolas L.; Shiao, Christine; Cherne, Makenzie K.; Khademi, Shawn B.; Montine, Kathleen S.; Montine, Thomas J.; Keene, C. Dirk

    2013-01-01

    Myeloablative (MyA) bone marrow transplantation (BMT) results in robust engraftment of BMT-derived cells in the central nervous system (CNS) and is neuroprotective in diverse experimental models of neurodegenerative diseases of brain and retina. However, MyA irradiation is associated with significant morbidity and mortality and does not represent a viable therapeutic option for the elderly. Non-myeloablative (NMyA) BMT is less toxic, but it is not known if the therapeutic efficacy observed with MyA BMT is preserved. As a first step to address this important gap in knowledge, we evaluated and compared engraftment characteristics of BMT-derived monocytes/microglia using several clinically relevant NMyA pretransplant conditioning regimens in C57BL/6 mice. These included chemotherapy (fludarabine and cyclophosphamide) with or without 2 Gy irradiation, and 5.5 Gy irradiation alone. Each regimen was followed by transplantation of whole bone marrow from green fluorescent protein-expressing wild type (wt) mice. While stable hematopoietic engraftment occurred, to varying degrees, in all NMyA regimens, only 5.5 Gy irradiation resulted in significant engraftment of BMT-derived cells in brain, where these cells were exclusively localized to perivascular, leptomeningeal, and related anatomic regions. Engraftment in retina under 5.5 Gy NMyA conditions was significantly reduced compared to MyA, but robust engraftment was identified in optic nerve. Advancing the therapeutic applications of BMT to neurodegenerative diseases will require identification of the barrier mechanisms MyA, but not NMyA, is able to overcome. PMID:23567123

  19. Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats

    PubMed Central

    Zaborska, K E; Wareing, M; Edwards, G; Austin, C

    2016-01-01

    Rationale: Maternal obesity pre-programmes offspring to develop obesity and associated cardiovascular disease. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the vasculature, which is reduced in hypertension and obesity. Objective: The objective of this study was to determine whether maternal obesity pre-programmes offspring to develop PVAT dysfunction in later life. Methods: Female Sprague–Dawley rats were fed a diet containing 10% (control) or 45% fat (high fat diet, HFD) for 12 weeks prior to mating and during pregnancy and lactation. Male offspring were killed at 12 or 24 weeks of age and tension in PVAT-intact or -denuded mesenteric artery segments was measured isometrically. Concentration–response curves were constructed to U46619 and norepinephrine. Results: Only 24-week-old HFD offspring were hypertensive (P<0.0001), although the anti-contractile effect of PVAT was lost in vessels from HFD offspring of each age. Inhibition of nitric oxide (NO) synthase with 100 μM l-NMMA attenuated the anti-contractile effect of PVAT and increased contractility of PVAT-denuded arteries (P<0.05, P<0.0001). The increase in contraction was smaller in PVAT-intact than PVAT-denuded vessels from 12-week-old HFD offspring, suggesting decreased PVAT-derived NO and release of a contractile factor (P<0.07). An additional, NO-independent effect of PVAT was evident only in norepinephrine-contracted vessels. Activation of AMP-activated kinase (with 10 μM A769662) was anti-contractile in PVAT-denuded (P<0.0001) and -intact (P<0.01) vessels and was due solely to NO in controls; the AMPK effect was similar in HFD offspring vessels (P<0.001 and P<0.01, respectively) but was partially NO-independent. Conclusions: The diminished anti-contractile effects of PVAT in offspring of HFD dams are primarily due to release of a PVAT-derived contractile factor and reduced NO bioavailability. PMID:27102050

  20. Different Anti-Contractile Function and Nitric Oxide Production of Thoracic and Abdominal Perivascular Adipose Tissues

    PubMed Central

    Victorio, Jamaira A.; Fontes, Milene T.; Rossoni, Luciana V.; Davel, Ana P.

    2016-01-01

    Divergent phenotypes between the perivascular adipose tissue (PVAT) surrounding the abdominal and the thoracic aorta might be implicated in regional aortic differences, such as susceptibility to atherosclerosis. Although PVAT of the thoracic aorta exhibits anti-contractile function, the role of PVAT in the regulation of the vascular tone of the abdominal aorta is not well defined. In the present study, we compared the anti-contractile function, nitric oxide (NO) availability, and reactive oxygen species (ROS) formation in PVAT and vessel walls of abdominal and thoracic aorta. Abdominal and thoracic aortic tissue from male Wistar rats were used to perform functional and molecular experiments. PVAT reduced the contraction evoked by phenylephrine in the absence and presence of endothelium in the thoracic aorta, whereas this anti-contractile effect was not observed in the abdominal aorta. Abdominal PVAT exhibited a reduction in endothelial NO synthase (eNOS) expression compared with thoracic PVAT, without differences in eNOS expression in the vessel walls. In agreement with this result, NO production evaluated in situ using 4,5-diaminofluorescein was less pronounced in abdominal compared with thoracic aortic PVAT, whereas no significant difference was observed for endothelial NO production. Moreover, NOS inhibition with L-NAME enhanced the phenylephrine-induced contraction in endothelial-denuded rings with PVAT from thoracic but not abdominal aorta. ROS formation and lipid peroxidation products evaluated through the quantification of hydroethidine fluorescence and 4-hydroxynonenal adducts, respectively, were similar between PVAT and vessel walls from the abdominal and thoracic aorta. Extracellular superoxide dismutase (SOD) expression was similar between the vessel walls and PVAT of the abdominal and thoracic aorta. However, Mn-SOD levels were reduced, while CuZn-SOD levels were increased in abdominal PVAT compared with thoracic aortic PVAT. In conclusion, our results

  1. Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue.

    PubMed

    Ayala-Lopez, Nadia; Jackson, William F; Burnett, Robert; Wilson, James N; Thompson, Janice M; Watts, Stephanie W

    2015-12-01

    Perivascular adipose tissue (PVAT) reduces vasoconstriction to norepinephrine (NE). A mechanism by which PVAT could function to reduce vascular contraction is by decreasing the amount of NE to which the vessel is exposed. PVATs from male Sprague-Dawley rats were used to test the hypothesis that PVAT has a NE uptake mechanism. NE was detected by HPLC in mesenteric PVAT and isolated adipocytes. Uptake of NE (10 μM) in mesenteric PVAT was reduced by the NE transporter (NET) inhibitor nisoxetine (1 μM, 73.68 ± 7.62%, all values reported as percentages of vehicle), the 5-hydroxytryptamine transporter (SERT) inhibitor citalopram (100 nM) with the organic cation transporter 3 (OCT3) inhibitor corticosterone (100 μM, 56.18 ± 5.21%), and the NET inhibitor desipramine (10 μM) with corticosterone (100 μM, 61.18 ± 6.82%). Aortic PVAT NE uptake was reduced by corticosterone (100 μM, 53.01 ± 10.96%). Confocal imaging of mesenteric PVAT stained with 4-[4-(dimethylamino)-styrl]-N-methylpyridinium iodide (ASP(+)), a fluorescent substrate of cationic transporters, detected ASP(+) uptake into adipocytes. ASP(+) (2 μM) uptake was reduced by citalopram (100 nM, 66.68 ± 6.43%), corticosterone (100 μM, 43.49 ± 10.17%), nisoxetine (100 nM, 84.12 ± 4.24%), citalopram with corticosterone (100 nM and 100 μM, respectively, 35.75 ± 4.21%), and desipramine with corticosterone (10 and 100 μM, respectively, 50.47 ± 5.78%). NET protein was not detected in mesenteric PVAT adipocytes. Expression of Slc22a3 (OCT3 gene) mRNA and protein in PVAT adipocytes was detected by RT-PCR and immunocytochemistry, respectively. These end points support the presence of a transporter-mediated NE uptake system within PVAT with a potential mediator being OCT3. PMID:26432838

  2. Nerve growth factor facilitates redistribution of adrenergic and non-adrenergic non-cholinergic perivascular nerves injured by phenol in rat mesenteric resistance arteries.

    PubMed

    Yokomizo, Ayako; Takatori, Shingo; Hashikawa-Hobara, Narumi; Goda, Mitsuhiro; Kawasaki, Hiromu

    2016-01-01

    We previously reported that nerve growth factor (NGF) facilitated perivascular sympathetic neuropeptide Y (NPY)- and calcitonin gene-related peptide (CGRP)-containing nerves injured by the topical application of phenol in the rat mesenteric artery. We also demonstrated that mesenteric arterial nerves were distributed into tyrosine hydroxylase (TH)-, substance P (SP)-, and neuronal nitric oxide synthase (nNOS)-containing nerves, which had axo-axonal interactions. In the present study, we examined the effects of NGF on phenol-injured perivascular nerves, including TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves, in rat mesenteric arteries in more detail. Wistar rats underwent the in vivo topical application of 10% phenol to the superior mesenteric artery, proximal to the abdominal aorta, under pentobarbital-Na anesthesia. The distribution of perivascular nerves in the mesenteric arteries of the 2nd to 3rd-order branches isolated from 8-week-old Wistar rats was investigated immunohistochemically using antibodies against TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves. The topical phenol treatment markedly reduced the density of all nerves in these arteries. The administration of NGF at a dose of 20µg/kg/day with an osmotic pump for 7 days significantly increased the density of all perivascular nerves over that of sham control levels. These results suggest that NGF facilitates the reinnervation of all perivascular nerves injured by phenol in small resistance arteries. PMID:26671004

  3. Indirect evidence that purinergic modulation of perivascular adrenergic neurotransmission in the portal vein is a physiological process.

    PubMed Central

    Burnstock, G.; Crowe, R.; Kennedy, C.; Török, J.

    1984-01-01

    The effects of adenine nucleotides and nucleosides on the contractile response to perivascular nerve stimulation were compared in the isolated portal vein of rabbit, rat and guinea-pig. 2-Chloroadenosine was more potent than adenosine and ATP, which were equipotent in producing inhibition of neurogenic contractions in the rabbit and rat via prejunctional P1-purinoceptors. In contrast, neurogenic contractions of the guinea-pig portal vein were not inhibited by adenosine and were potentiated by 2-chloroadenosine and, to a lesser extent, by ATP. Fluorescence histochemical localization of quinacrine, which binds to high levels of ATP, revealed a dense perivascular nerve plexus in the portal vein of rabbit and rat but not of guinea-pig. After chemical sympathectomy, quinacrine-positive nerves persisted in the rabbit (supporting other evidence for the presence of purinergic nerves) but not in the rat (supporting other evidence for ATP as a cotransmitter in adrenergic nerves). It is concluded that a prejunctional purinergic modulatory mechanism operates in adrenergic neurotransmission in the portal vein of rabbit and rat but not guinea-pig, and it is suggested that this indicates a physiological mechanism. Images Figure 6 PMID:6329393

  4. Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival

    PubMed Central

    Corvigno, Sara; Wisman, G. Bea A.; Mezheyeuski, Artur; van der Zee, Ate G.J.; Nijman, Hans W.; Åvall-Lundqvist, Elisabeth; Östman, Arne; Dahlstrand, Hanna

    2016-01-01

    Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue microarray (TMA) with 186 tumors and 91 matched metastases was subjected to immunohistochemistry double staining with endothelial cell marker CD34 and fibroblast and pericyte markers α-SMA, PDGFβR and desmin. Images were digitally analyzed to yield “metrics” related to vasculature and stroma features. Intra-case analyses showed that PDGFβR in perivascular cells and fibroblasts were strongly correlated. Similar findings were observed concerning α-SMA. Most stroma characteristics showed large variations in intra-case comparisons of primary tumors and metastasis. Large PDGFβR-positive stroma fraction and high PDGFβFR positive perivascular intensity were both significantly associated with shorter survival in uni- and multi-variate analyses (HR 1.7, 95% CI 1.1-2.5; HR 1.7, 95% CI 1.1-2.8). In conclusion, we found PDGFβR- and α-SMA-expression to be largely independent of each other but concordantly activated in perivascular cells and in fibroblasts within the primary tumor. Stromal characteristics differed between primary tumors and metastases. PDGFβR in perivascular cells and in fibroblasts may be novel prognostic markers in serous ovarian cancer. PMID:26918345

  5. Ruptured pericardial perivascular epithelioid cell tumor (PEComa) leading to sudden death: an autopsy case report and review of the literature.

    PubMed

    Zhang, Lingxin; Carpenter, Danielle; Dehner, Louis P

    2016-01-01

    A 30-year-old man with past medical history of atrial fibrillation/flutter passed away after presenting with sudden-onset cardiac dysfunction. The postmortem examination revealed cardiac tamponade secondary to rupture of a 7.2-cm pericardial perivascular epithelioid cell tumor (PEComa). The tumor grossly appeared to arise from the transverse pericardial sinus and focally penetrated the epicardium of the right atrium. Microscopically, it was composed of predominately spindle cells with low nuclear grade, no pleomorphism, or readily apparent mitoses. Immunohistochemistry revealed cytoplasmic reactivity for HMB-45, desmin, and smooth muscle actin. Electron microscopic findings were characterized by melanosome-like structures intermixed with intermediate filaments and abundant stacked endoplasmic reticulum. The present case is unique among previously reported pericardial/myocardial PEComas as a first example resulting in unexpected cardiac tamponade and sudden cardiac death. PMID:26386746

  6. Celecoxib, but not indomethacin, ameliorates the hypertensive and perivascular fibrotic actions of cyclosporine in rats: Role of endothelin signaling

    SciTech Connect

    El-Mas, Mahmoud M.; Helmy, Maged W.; Ali, Rabab M.; El-Gowelli, Hanan M.

    2015-04-01

    The immunosuppressant drug cyclosporine (CSA) is used with nonsteroidal antiinflammatory drugs (NSAIDs) in arthritic conditions. In this study, we investigated whether NSAIDs modify the deleterious hypertensive action of CSA and the role of endothelin (ET) receptors in this interaction. Pharmacologic, protein expression, and histopathologic studies were performed in rats to investigate the roles of endothelin receptors (ET{sub A}/ET{sub B}) in the hemodynamic interaction between CSA and two NSAIDs, indomethacin and celecoxib. Tail-cuff plethysmography measurements showed that CSA (20 mg kg{sup −1} day{sup −1}, 10 days) increased systolic blood pressure (SBP) and heart rate (HR). CSA hypertension was associated with renal perivascular fibrosis and divergent changes in immunohistochemical signals of renal arteriolar ET{sub A} (increases) and ET{sub B} (decreases) receptors. While these effects of CSA were preserved in rats treated concomitantly with indomethacin (5 mg kg{sup −1} day{sup −1}), celecoxib (10 mg kg{sup −1} day{sup −1}) abolished the pressor, tachycardic, and fibrotic effects of CSA and normalized the altered renal ET{sub A}/ET{sub B} receptor expressions. Selective blockade of ET{sub A} receptors by atrasentan (5 mg kg{sup −1} day{sup −1}) abolished the pressor response elicited by CSA or CSA plus indomethacin. Alternatively, BQ788 (ET{sub B} receptor blocker, 0.1 mg kg{sup −1} day{sup −1}) caused celecoxib-sensitive elevations in SBP and potentiated the pressor response evoked by CSA. Together, the improved renovascular fibrotic and endothelin receptor profile (ET{sub A} downregulation and ET{sub B} upregulation) mediate, at least partly, the protective effect of celecoxib against the hypertensive effect of CSA. Clinically, the use of celecoxib along with CSA in the management of arthritic conditions might provide hypertension-free regimen. - Highlights: • Chronic CSA causes hypertension and renal perivascular fibrosis in rats.

  7. Aging Exacerbates Obesity-Induced Oxidative Stress and Inflammation in Perivascular Adipose Tissue in Mice: A Paracrine Mechanism Contributing to Vascular Redox Dysregulation and Inflammation

    PubMed Central

    Bailey-Downs, Lora C.; Tucsek, Zsuzsanna; Toth, Peter

    2013-01-01

    Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet–fed obese C57BL/6 mice. High-fat diet–induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet–induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals

  8. Perivascular Epithelioid Cell Tumor of the Uterus with Ovarian Involvement: A Case Report and Review of the Literature.

    PubMed

    Fitzpatrick, Megan; Pulver, Tanya; Klein, Molly; Murugan, Paari; Khalifa, Mahmoud; Amin, Khalid

    2016-01-01

    BACKGROUND Perivascular epithelioid cell tumors (PEComas) are a rare group of neoplasms composed of epithelioid cells that express both melanocytic and myoid markers. When considering PEComas of the female genital tract, the uterus is the most common location. Involvement of the ovary in the context of a primary uterine PEComa, in the absence of systemic disease associated with tuberous sclerosis, however, has only been reported in 1 previous case. CASE REPORT We report a case of a PEComa of the uterus with metastasis to the left ovary in a 61-year-old Caucasian woman. Gross examination of the uterus revealed a 10.7×10.5×10.2 cm tan-brown, mostly solid, partially cystic mass. Microscopic examination showed epithelioid cells with clear to eosinophilic cytoplasm, arranged in fascicles. Intranuclear pseudoinclusions were also noted. The tumor cells were smooth muscle actin, caldesmon, and desmin positive (diffuse); HMB-45 positive (focal); and Melan-A, AE1/AE3, CD10, and S100 negative by immunohistochemistry. CONCLUSIONS Distinguishing among mesenchymal neoplasms, including PEComas, endometrial stromal sarcomas, and leiomyosarcomas, can be difficult. Careful analysis of morphologic and immunohistochemical features is of the utmost importance. Differential diagnosis, including morphologic features and immunohistochemical patterns, is also discussed. PMID:27150246

  9. In Vitro Differentiation of First Trimester Human Umbilical Cord Perivascular Cells into Contracting Cardiomyocyte-Like Cells

    PubMed Central

    Szaraz, Peter; Librach, Matthew; Maghen, Leila; Iqbal, Farwah; Barretto, Tanya A.; Kenigsberg, Shlomit; Gauthier-Fisher, Andrée; Librach, Clifford L.

    2016-01-01

    Myocardial infarction (MI) causes an extensive loss of heart muscle cells and leads to congestive heart disease (CAD), the leading cause of mortality and morbidity worldwide. Mesenchymal stromal cell- (MSC-) based cell therapy is a promising option to replace invasive interventions. However the optimal cell type providing significant cardiac regeneration after MI is yet to be found. The aim of our study was to investigate the cardiomyogenic differentiation potential of first trimester human umbilical cord perivascular cells (FTM HUCPVCs), a novel, young source of immunoprivileged mesenchymal stromal cells. Based on the expression of cardiomyocyte markers (cTnT, MYH6, SIRPA, and CX43) FTM and term HUCPVCs achieved significantly increased cardiomyogenic differentiation compared to bone marrow MSCs, while their immunogenicity remained significantly lower as indicated by HLA-A and HLA-G expression and susceptibility to T cell mediated cytotoxicity. When applying aggregate-based differentiation, FTM HUCPVCs showed increased aggregate formation potential and generated contracting cells within 1 week of coculture, making them the first MSC type with this ability. Our results indicate that young FTM HUCPVCs have superior cardiomyogenic potential coupled with beneficial immunogenic properties when compared to MSCs of older tissue sources, suggesting that in vitro predifferentiation could be a potential strategy to increase their effectiveness in vivo. PMID:27123009

  10. Perivascular Epithelioid Cell Tumor of the Uterus with Ovarian Involvement: A Case Report and Review of the Literature

    PubMed Central

    Fitzpatrick, Megan; Pulver, Tanya; Klein, Molly; Murugan, Paari; Khalifa, Mahmoud; Amin, Khalid

    2016-01-01

    Patient: Female, 61 Final Diagnosis: Uterine PEComa with ovarian involvement Symptoms: Palpable abdominal mass Medication: — Clinical Procedure: Hysterectomy and bilateral salpingo-oophorectomy Specialty: Obstetrics and Gynecology Objective: Rare disease Background: Perivascular epithelioid cell tumors (PEComas) are a rare group of neoplasms composed of epithelioid cells that express both melanocytic and myoid markers. When considering PEComas of the female genital tract, the uterus is the most common location. Involvement of the ovary in the context of a primary uterine PEComa, in the absence of systemic disease associated with tuberous sclerosis, however, has only been reported in 1 previous case. Case Report: We report a case of a PEComa of the uterus with metastasis to the left ovary in a 61-year-old Caucasian woman. Gross examination of the uterus revealed a 10.7×10.5×10.2 cm tan-brown, mostly solid, partially cystic mass. Microscopic examination showed epithelioid cells with clear to eosinophilic cytoplasm, arranged in fascicles. Intranuclear pseudoinclusions were also noted. The tumor cells were smooth muscle actin, caldesmon, and desmin positive (diffuse); HMB-45 positive (focal); and Melan-A, AE1/AE3, CD10, and S100 negative by immunohistochemistry. Conclusions: Distinguishing among mesenchymal neoplasms, including PEComas, endometrial stromal sarcomas, and leiomyosarcomas, can be difficult. Careful analysis of morphologic and immunohistochemical features is of the utmost importance. Differential diagnosis, including morphologic features and immunohistochemical patterns, is also discussed. PMID:27150246

  11. Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids with a Significant Elevation of β-2 Microglobulin Levels

    PubMed Central

    Fujisawa, Naoaki; Mori, Harushi; Matsui, Toru

    2015-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relapsing-remitting disorder for which steroid administration is a key to control the progression. CLIPPERS can exhibit radiological features similar to malignant lymphoma, whose diagnosis is confounded by prior steroid administration. We report a case of CLIPPERS accompanied by abnormal elevation of β-2 microglobulin in the cerebrospinal fluid (CSF). A 62-year-old man started to experience numbness in all fingers of his left hand one year ago, which gradually extended to his body trunk and legs on both sides. Magnetic resonance imaging demonstrated numerous small enhancing spots scattered in his brain and spinal cord. CSF levels of β-2 microglobulin were elevated; although this often indicates central nervous system involvement in leukemia and lymphoma, the lesions were diagnosed as CLIPPERS based on the pathological findings from a biopsy specimen. We emphasize the importance of biopsy to differentiate between CLIPPERS and malignant lymphoma because the temporary radiological response to steroid might be the same in both diseases but the treatment strategies regarding the use of steroid are quite different. PMID:26713153

  12. Hypoxia-inducible factor-1 drives annexin A2 system-mediated perivascular fibrin clearance in oxygen-induced retinopathy in mice.

    PubMed

    Huang, Bihui; Deora, Arun B; He, Kai-Li; Chen, Kang; Sui, Guangzhi; Jacovina, Andrew T; Almeida, Dena; Hong, Peng; Burgman, Paul; Hajjar, Katherine A

    2011-09-01

    Oxygen-induced retinopathy (OIR) is a well-characterized model for retinopathy of prematurity, a disorder that results from rapid microvascular proliferation after exposure of the retina to high oxygen levels. Here, we report that the proliferative phase of OIR requires transcriptional induction of the annexin A2 (A2) gene through the direct action of the hypoxia-inducible factor-1 complex. We show, in addition, that A2 stabilizes its binding partner, p11, and promotes OIR-related angiogenesis by enabling clearance of perivascular fibrin. Adenoviral-mediated restoration of A2 expression restores neovascularization in the oxygen-primed Anxa2(-/-) retina and reinstates plasmin generation and directed migration in cultured Anxa2(-/-) endothelial cells. Systemic depletion of fibrin repairs the neovascular response to high oxygen treatment in the Anxa2(-/-) retina, whereas inhibition of plasminogen activation dampens angiogenesis under the same conditions. These findings show that the A2 system enables retinal neoangiogenesis in OIR by enhancing perivascular activation of plasmin and remodeling of fibrin. These data suggest new potential approaches to retinal angiogenic disorders on the basis of modulation of perivascular fibrinolysis. PMID:21788340

  13. Hypoxia-inducible factor-1 drives annexin A2 system-mediated perivascular fibrin clearance in oxygen-induced retinopathy in mice

    PubMed Central

    Huang, Bihui; Deora, Arun B.; He, Kai-Li; Chen, Kang; Sui, Guangzhi; Jacovina, Andrew T.; Almeida, Dena; Hong, Peng; Burgman, Paul

    2011-01-01

    Oxygen-induced retinopathy (OIR) is a well-characterized model for retinopathy of prematurity, a disorder that results from rapid microvascular proliferation after exposure of the retina to high oxygen levels. Here, we report that the proliferative phase of OIR requires transcriptional induction of the annexin A2 (A2) gene through the direct action of the hypoxia-inducible factor-1 complex. We show, in addition, that A2 stabilizes its binding partner, p11, and promotes OIR-related angiogenesis by enabling clearance of perivascular fibrin. Adenoviral-mediated restoration of A2 expression restores neovascularization in the oxygen-primed Anxa2−/− retina and reinstates plasmin generation and directed migration in cultured Anxa2−/− endothelial cells. Systemic depletion of fibrin repairs the neovascular response to high oxygen treatment in the Anxa2−/− retina, whereas inhibition of plasminogen activation dampens angiogenesis under the same conditions. These findings show that the A2 system enables retinal neoangiogenesis in OIR by enhancing perivascular activation of plasmin and remodeling of fibrin. These data suggest new potential approaches to retinal angiogenic disorders on the basis of modulation of perivascular fibrinolysis. PMID:21788340

  14. Effects of Maternal Exposure to Ultrafine Carbon Black on Brain Perivascular Macrophages and Surrounding Astrocytes in Offspring Mice

    PubMed Central

    Onoda, Atsuto; Umezawa, Masakazu; Takeda, Ken; Ihara, Tomomi; Sugamata, Masao

    2014-01-01

    Perivascular macrophages (PVMs) constitute a subpopulation of resident macrophages in the central nervous system (CNS). They are located at the blood-brain barrier and can contribute to maintenance of brain functions in both health and disease conditions. PVMs have been shown to respond to particle substances administered during the prenatal period, which may alter their phenotype over a long period. We aimed to investigate the effects of maternal exposure to ultrafine carbon black (UfCB) on PVMs and astrocytes close to the blood vessels in offspring mice. Pregnant mice were exposed to UfCB suspension by intranasal instillation on gestational days 5 and 9. Brains were collected from their offspring at 6 and 12 weeks after birth. PVM and astrocyte phenotypes were examined by Periodic Acid Schiff (PAS) staining, transmission electron microscopy and PAS-glial fibrillary acidic protein (GFAP) double staining. PVM granules were found to be enlarged and the number of PAS-positive PVMs was decreased in UfCB-exposed offspring. These results suggested that in offspring, “normal” PVMs decreased in a wide area of the CNS through maternal UfCB exposure. The increase in astrocytic GFAP expression level was closely related to the enlargement of granules in the attached PVMs in offspring. Honeycomb-like structures in some PVM granules and swelling of astrocytic end-foot were observed under electron microscopy in the UfCB group. The phenotypic changes in PVMs and astrocytes indicate that maternal UfCB exposure may result in changes to brain blood vessels and be associated with increased risk of dysfunction and disorder in the offspring brain. PMID:24722459

  15. Pharmacological activation of AMPK ameliorates perivascular adipose/endothelial dysfunction in a manner interdependent on AMPK and SIRT1.

    PubMed

    Sun, Yan; Li, Jia; Xiao, Na; Wang, Meng; Kou, Junping; Qi, Lianwen; Huang, Fang; Liu, Baolin; Liu, Kang

    2014-11-01

    Adipose and endothelial dysfunction is tightly associated with cardiovascular diseases in obesity and insulin resistance. Because perivascular adipose tissue (PVAT) surrounds vessels directly and influences vessel functions through paracrine effect, and AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) show similarities in modulation of metabolic pathway, we hypothesized that activation of AMPK and SIRT1 in PVAT might regulate the endothelial function in pathological settings. Thus, in this study, we focused on the regulation of AMPK and SIRT1 activities implicated in adipocytokine expression and endothelial homeostasis under inflammatory conditions by using salicylate, metformin, AICA riboside (AICAR) and resveratrol as AMPK activating agents. We prepared conditioned medium (CM) by stimulating PVAT with palmitic acid (PA) and observed the effects of AMPK activating agents on adipocytokine expression and vessel vasodilation in rats. Moreover, we explored the effects of resveratrol and metformin in fructose-fed rats. We observed that PA stimulation induced inflammation and dysregulation of adipocytokine expression accompanied with reduced AMPK activity and SIRT1 abundance in PVAT. AMPK activating agents inhibited NF-κB p65 phosphorylation and suppressed gene expression of pro-inflammatory adipocytokines, and upregulated adiponectin and PPARγ expression in PVAT in an AMPK/SIRT1-interdependent manner. Meanwhile, CM stimulation impaired endothelium-dependent vasodilation in response to acetylcholine (ACh). Pretreatment of CM with AMPK-activating agents enhanced eNOS phosphorylation in the aorta and restored the loss of endothelium-dependent vasodilation, whereas this action was abolished by co-treatment with AMPK inhibitor compound C or SIRT1 inhibitor nicotinamide. Long-term fructose-feeding in rats induced dysregulation of adipocytokine expression in PVAT and the loss of endothelium-dependent vasodilation, whereas these alterations were reversed by oral

  16. Quantifying Perivascular Sympathetic Innervation: Regional Differences in Male C57BL/6 Mice at 3 and 20 Months

    PubMed Central

    Long, Jennifer B.; Segal, Steven S.

    2009-01-01

    Perivascular sympathetic innervation density (PSID) is a key determinant of vasomotor responses to sympathetic nerve activity. However, total axonal length (for en passant neurotransmission) per vessel surface area has not been well defined, particularly while preserving 3-dimensional vascular structure. We developed a novel method for quantifying PSID using 3-dimensional anatomical reconstruction and compare a variety of blood vessels in Young (3 months) and Old (20 months) male C57BL/6 mice. Individual vessels were dissected and immunolabeled for tyrosine hydroxylase. The total length of fluorescent axons in defined vessel surface areas was quantified by mapping Z-stack images (magnification = 760×). For young mice, innervation densities (μm axon length/μm2 vessel surface area) in mesenteric (0.075 ± 0.002) and femoral (0.080 ± 0.003) arteries were greater (P<0.05) than mesenteric veins (0.052 ± 0.002) and gracilis muscle feed arteries (0.040 ± 0.002). Carotid arteries and gracilis muscle veins were not immunoreactive nor were there significant differences in PSID between Young and Old animals. We demonstrate a novel approach to quantify sympathetic innervation of the vasculature while preserving its 3-dimensional structure and document regional variation in PSID that persists with aging in mice. This analytical approach may used for quantifying PSID in other tissues that have superficial vessels which can be studied in situ or from which embedded vessels can be excised. With appropriate visualization of neuronal projections, it may also be applied to tissues that have other sources of superficial innervation. PMID:19651158

  17. Segmentation of perivascular spaces in 7T MR image using auto-context model with orientation-normalized features.

    PubMed

    Park, Sang Hyun; Zong, Xiaopeng; Gao, Yaozong; Lin, Weili; Shen, Dinggang

    2016-07-01

    Quantitative study of perivascular spaces (PVSs) in brain magnetic resonance (MR) images is important for understanding the brain lymphatic system and its relationship with neurological diseases. One of the major challenges is the accurate extraction of PVSs that have very thin tubular structures with various directions in three-dimensional (3D) MR images. In this paper, we propose a learning-based PVS segmentation method to address this challenge. Specifically, we first determine a region of interest (ROI) by using the anatomical brain structure and the vesselness information derived from eigenvalues of image derivatives. Then, in the ROI, we extract a number of randomized Haar features which are normalized with respect to the principal directions of the underlying image derivatives. The classifier is trained by the random forest model that can effectively learn both discriminative features and classifier parameters to maximize the information gain. Finally, a sequential learning strategy is used to further enforce various contextual patterns around the thin tubular structures into the classifier. For evaluation, we apply our proposed method to the 7T brain MR images scanned from 17 healthy subjects aged from 25 to 37. The performance is measured by voxel-wise segmentation accuracy, cluster-wise classification accuracy, and similarity of geometric properties, such as volume, length, and diameter distributions between the predicted and the true PVSs. Moreover, the accuracies are also evaluated on the simulation images with motion artifacts and lacunes to demonstrate the potential of our method in segmenting PVSs from elderly and patient populations. The experimental results show that our proposed method outperforms all existing PVS segmentation methods. PMID:27046107

  18. Human umbilical cord perivascular cells exhibit enhanced cardiomyocyte reprogramming and cardiac function after experimental acute myocardial infarction.

    PubMed

    Yannarelli, Gustavo; Dayan, Victor; Pacienza, Natalia; Lee, Chyan-Jang; Medin, Jeffrey; Keating, Armand

    2013-01-01

    We were interested in evaluating the ability of the mesenchymal stromal cell (MSC) population, human umbilical cord perivascular cells (HUCPVCs), to undergo cardiomyocyte reprogramming in an established coculture system with rat embryonic cardiomyocytes. Results were compared with human bone marrow-derived (BM) MSCs. The transcription factors GATA4 and Mef 2c were expressed in HUCPVCs but not BM-MSCs at baseline and, at 7 days, increased 7.6- and 3.5-fold, respectively, compared with BM-MSCs. Although cardiac-specific gene expression increased in both cell types in coculture, upregulation was more significant in HUCPVCs, consistent with Mef 2c-GATA4 synergism. Using a lentivector with eGFP transcribed from the α-myosin heavy chain (α-MHC) promoter, we found that cardiac gene expression was greater in HUCPVCs than BM-MSCs after 14 days coculture (52±17% vs. 29±6%, respectively). A higher frequency of HUCPVCs expressed α-MHC protein compared with BM-MSCs (11.6±0.9% vs. 5.3±0.3%); however, both cell types retained MSC-associated determinants. We also assessed the ability of the MSC types to mediate cardiac regeneration in a NOD/SCID γ mouse model of acute myocardial infarction (AMI). Fourteen days after AMI, cardiac function was significantly better in cell-treated mice compared with control animals and HUCPVCs exhibited greater improvement. Although human cells persisted in the infarct area, the frequency of α-MHC expression was low. Our results indicate that HUCPVCs exhibit a greater degree of cardiomyocyte reprogramming but that differentiation for both cell types is partial. We conclude that HUCPVCs may be preferable to BM-MSCs in the cell therapy of AMI. PMID:23043977

  19. Stimulated release of a hyperpolarizing factor (ADHF) from mesenteric artery perivascular adipose tissue: involvement of myocyte BKCa channels and adiponectin

    PubMed Central

    Weston, A H; Egner, I; Dong, Y; Porter, E L; Heagerty, A M; Edwards, G

    2013-01-01

    Background and Purpose Perivascular adipose tissue (PVAT) releases adipocyte-derived hyperpolarizing factors (ADHFs) that may partly act by opening myocyte K+ channels. The present study in rat and mouse mesenteric arteries aimed to identify the myocyte K+ channel activated by PVAT and to determine whether adiponectin contributed to the hyperpolarizing effects of PVAT. Experimental Approach Myocyte membrane potential was recorded from de-endothelialized, non-contracted rat and mouse mesenteric arteries in the presence and absence of PVAT. Key Results The β3-adrenoceptor agonist, CL-316,243 (10 μM), generated PVAT-dependent, iberiotoxin-sensitive myocyte hyperpolarizations resulting from BKCa channel opening and which were partially blocked by L-NMMA (100 μM). Adiponectin (5 μg·mL−1) also produced iberiotoxin-sensitive hyperpolarizations in PVAT-denuded arterioles. Activation of myocyte AMP-activated protein kinase (AMPK) using 5 μM A-769662 also induced BKCa-mediated hyperpolarizations. Dorsomorphin abolished hyperpolarizations to CL-316,243, adiponectin and A-769662. In vessels from Adipo−/− mice, hyperpolarizations to CL-316,243 were absent whereas those to A-769662 and adiponectin were normal. In rat vessels, adipocyte-dependent hyperpolarizations were blocked by glibenclamide and clotrimazole but those to NS1619 (33 μM) were unaltered. Conclusions and Implications Under basal, non-contracted conditions, β3-adrenoceptor stimulation of PVAT releases an ADHF, which is probably adiponectin. This activates AMPK to open myocyte BKCa channels indirectly and additionally liberates NO, which also contributes to the observed PVAT-dependent myocyte hyperpolarizations. Clotrimazole and glibenclamide each reversed hyperpolarizations to adiponectin and A-769662, suggesting the involvement of myocyte TRPM4 channels in the ADHF-induced myocyte electrical changes mediated via the opening of BKCa channels. PMID:23488724

  20. Design, fabrication and perivascular implantation of bioactive scaffolds engineered with human adventitial progenitor cells for stimulation of arteriogenesis in peripheral ischemia.

    PubMed

    Carrabba, M; De Maria, C; Oikawa, A; Reni, C; Rodriguez-Arabaolaza, I; Spencer, H; Slater, S; Avolio, E; Dang, Z; Spinetti, G; Madeddu, P; Vozzi, G

    2016-03-01

    Cell therapy represents a promising option for revascularization of ischemic tissues. However, injection of dispersed cells is not optimal to ensure precise homing into the recipient's vasculature. Implantation of cell-engineered scaffolds around the occluded artery may obviate these limitations. Here, we employed the synthetic polymer polycaprolactone for fabrication of 3D woodpile- or channel-shaped scaffolds by a computer-assisted writing system (pressure assisted micro-syringe square), followed by deposition of gelatin (GL) nanofibers by electro-spinning. Scaffolds were then cross-linked with natural (genipin, GP) or synthetic (3-glycidyloxy-propyl-trimethoxy-silane, GPTMS) agents to improve mechanical properties and durability in vivo. The composite scaffolds were next fixed by crown inserts in each well of a multi-well plate and seeded with adventitial progenitor cells (APCs, 3 cell lines in duplicate), which were isolated/expanded from human saphenous vein surgical leftovers. Cell density, alignment, proliferation and viability were assessed 1 week later. Data from in vitro assays showed channel-shaped/GPTMS-crosslinked scaffolds confer APCs with best alignment and survival/growth characteristics. Based on these results, channel-shaped/GPTMS-crosslinked scaffolds with or without APCs were implanted around the femoral artery of mice with unilateral limb ischemia. Perivascular implantation of scaffolds accelerated limb blood flow recovery, as assessed by laser Doppler or fluorescent microspheres, and increased arterial collaterals around the femoral artery and in limb muscles compared with non-implanted controls. Blood flow recovery and perivascular arteriogenesis were additionally incremented by APC-engineered scaffolds. In conclusion, perivascular application of human APC-engineered scaffolds may represent a novel option for targeted delivery of therapeutic cells in patients with critical limb ischemia. PMID:27011300

  1. Effects of Obesity on Perivascular Adipose Tissue Vasorelaxant Function: Nitric Oxide, Inflammation and Elevated Systemic Blood Pressure

    PubMed Central

    Aghamohammadzadeh, Reza; Unwin, Richard D.; Greenstein, Adam S.; Heagerty, Anthony M.

    2016-01-01

    Introduction Perivascular adipose tissue (PVAT) surrounds most vessels in the human body. Healthy PVAT has a vasorelaxant effect which is not observed in obesity. We assessed the contribution of nitric oxide (NO), inflammation and endothelium to obesity-induced PVAT damage. Methods Rats were fed a high-fat diet or normal chow. PVAT function was assessed using wire myography. Skeletonised and PVAT-intact mesenteric vessels were prepared with and without endothelium. Vessels were incubated with L-NNA or superoxide dismutase (SOD) and catalase. Gluteal fat biopsies were performed on 10 obese and 10 control individuals, and adipose tissue was assessed using proteomic analysis. Results In the animals, there were significant correlations between weight and blood pressure (BP; r = 0.5, p = 0.02), weight and PVAT function (r = 0.51, p = 0.02), and PVAT function and BP (r = 0.53, p = 0.01). PVAT-intact vessel segments from healthy animals constricted significantly less than segments from obese animals (p < 0.05). In a healthy state, there was preservation of the PVAT vasorelaxant function after endothelium removal (p < 0.05). In endothelium-denuded vessels, L-NNA attenuated the PVAT vasorelaxant function in control vessels (p < 0.0001). In obesity, incubation with SOD and catalase attenuated PVAT-intact vessel contractility in the presence and absence of endothelium (p < 0.001). In obese humans, SOD [Cu-Zn] (SOD1; fold change −2.4), peroxiredoxin-1 (fold change −2.15) and adiponectin (fold change −2.1) were present in lower abundances than in healthy controls. Conclusions Incubation with SOD and catalase restores PVAT vasorelaxant function in animal obesity. In the rodent model, obesity-induced PVAT damage is independent of endothelium and is in part due to reduced NO bioavailability within PVAT. Loss of PVAT function correlates with rising BP in our animal obesity model. In keeping with our hypothesis of inflammation-induced damage to PVAT function in obesity, there

  2. Comparison between perivascular and perineural ultrasound-guided axillary brachial plexus block using levobupivacaine: A prospective, randomised clinical study

    PubMed Central

    Ambi, Uday; Bhanupriya, PVV; Hulkund, Shivanand Y; Prakashappa, DS

    2015-01-01

    Background and Aims: Ultrasound (US)-guided regional blocks are becoming increasingly popular as its use increases success rate, shortens block onset time and reduces complications. Currently, there exist two methods to perform US-guided axillary brachial plexus block (US-ABPB), the perivascular (PV) and the perineural (PN) techniques. We compared the two techniques to study the block characteristics and other variables using levobupivacaine. Methods: In this prospective, randomised trial, 60 patients were randomly allocated to receive a PV (n = 30) or PN (n = 30) US-ABPB. The local anaesthetic agent, 0.5% levobupivacaine and total volume of 36 ml of solution were identical in all the subjects. For both the groups, the musculocutaneous nerve was first located and then anaesthetised with 6 ml. Subsequently in the PV group, 30 ml was deposited dorsal to the axillary artery (6 o’clock position). In PN group, the median, ulnar and radial nerves were individually anaesthetised with volumes of 10 ml each. The onset and duration of sensory block, the onset and duration of motor block, number of failed blocks and complications were noted. Results: No difference was observed between the two groups in terms of success rate (PV - 93.33%, PN - 96.66%), sensory onset (PN: 8.07 (standard deviation [SD] ± 0.651) min and PV: 8.14 [SD ± 1.079] min; P = 0.754), motor onset (PN: 14.62 [SD ± 2.077] min and PV: 14.93 [SD ± 1.844] min; P = 0.557) and total duration of anaesthesia. No complications were observed in both groups. Conclusion: The PV technique provides a simple alternative for PN US-ABPB. In the light of emerging needling positions for PV and PN techniques, this study calls for large scale trials and much research in this area before one defines best or safe approach. PV technique may be considered as an alternative method for US-ABPB in patients with anatomical variation or difficulties in identifying the individual nerves. PMID:26644614

  3. Development and initial evaluation of a semi-automatic approach to assess perivascular spaces on conventional magnetic resonance images

    PubMed Central

    Wang, Xin; Valdés Hernández, Maria del C.; Doubal, Fergus; Chappell, Francesca M.; Piper, Rory J.; Deary, Ian J.; Wardlaw, Joanna M.

    2016-01-01

    Purpose Perivascular spaces (PVS) are associated with ageing, cerebral small vessel disease, inflammation and increased blood brain barrier permeability. Most studies to date use visual rating scales to assess PVS, but these are prone to observer variation. Methods We developed a semi-automatic computational method that extracts PVS on bilateral ovoid basal ganglia (BG) regions on intensity-normalised T2-weighted magnetic resonance images. It uses Analyze™10.0 and was applied to 100 mild stroke patients’ datasets. We used linear regression to test association between BGPVS count, volume and visual rating scores; and between BGPVS count & volume, white matter hyperintensity (WMH) rating scores (periventricular: PVH; deep: DWMH) & volume, atrophy rating scores and brain volume. Results In the 100 patients WMH ranged from 0.4 to 119 ml, and total brain tissue volume from 0.65 to 1.45 l. BGPVS volume increased with BGPVS count (67.27, 95%CI [57.93 to 76.60], p < 0.001). BGPVS count was positively associated with WMH visual rating (PVH: 2.20, 95%CI [1.22 to 3.18], p < 0.001; DWMH: 1.92, 95%CI [0.99 to 2.85], p < 0.001), WMH volume (0.065, 95%CI [0.034 to 0.096], p < 0.001), and whole brain atrophy visual rating (1.01, 95%CI [0.49 to 1.53], p < 0.001). BGPVS count increased as brain volume (as % of ICV) decreased (−0.33, 95%CI [−0.53 to −0.13], p = 0.002). Comparison with existing method BGPVS count and volume increased with the overall increase of BGPVS visual scores (2.11, 95%CI [1.36 to 2.86] for count and 0.022, 95%CI [0.012 to 0.031] for volume, p < 0.001). Distributions for PVS count and visual scores were also similar. Conclusions This semi-automatic method is applicable to clinical protocols and offers quantitative surrogates for PVS load. It shows good agreement with a visual rating scale and confirmed that BGPVS are associated with WMH and atrophy measurements. PMID:26416614

  4. Proliferating cells in psoriatic dermis are comprised primarily of T cells, endothelial cells, and factor XIIIa+ perivascular dendritic cells

    SciTech Connect

    Morganroth, G.S.; Chan, L.S.; Weinstein, G.D.; Voorhees, J.J.; Cooper, K.D. )

    1991-03-01

    Determination of the cell types proliferating in the dermis of patients with psoriasis should identify those cells experiencing activation or responding to growth factors in the psoriatic dermal milieu. Toward that end, sections of formalin-fixed biopsies obtained from 3H-deoxyuridine (3H-dU)-injected skin of eight psoriatic patients were immunostained, followed by autoradiography. Proliferating dermal cells exhibit silver grains from tritium emissions. The identity of the proliferating cells could then be determined by simultaneous visualization with antibodies specific for various cell types. UCHL1+ (CD45RO+) T cells (recall antigen-reactive helper T-cell subset) constituted 36.6 +/- 3.1% (mean +/- SEM, n = 6) of the proliferating dermal cells in involved skin, whereas Leu 18+ (CD45RA+) T cells (recall antigen naive T-cell subsets) comprised only 8.7 +/- 1.5% (n = 6). The Factor XIIIa+ dermal perivascular dendritic cell subset (24.9 +/- 1.5% of proliferating dermal cells, n = 6) and Factor VIII+ endothelial cells represented the two other major proliferating populations in lesional psoriatic dermis. Differentiated tissue macrophages, identified by phase microscopy as melanophages or by immunostaining with antibodies to Leu M1 (CD15) or myeloid histiocyte antigen, comprised less than 5% of the proliferating population in either skin type. In addition to calculating the relative proportions of these cells to each other as percent, we also determined the density of cells, in cells/mm2 of tissue. The density of proliferating cells within these populations was increased in involved versus uninvolved skin: UCHL1+, 9.0 +/- 1.7 cells/mm2 versus 1.8 +/- 0.6 cells/mm2, p less than 0.01; Factor XIIIa+, 6.0 +/- 0.7 cells/mm2 versus 1.5 +/- 0.5 cells/mm2, p less than 0.01; Factor VIII+, 5.5 +/- 1.4 cells/mm2 versus 0.0 cells/mm2, p less than 0.05.

  5. Proliferation of Perivascular Macrophages Contributes to the Development of Encephalitic Lesions in HIV-Infected Humans and in SIV-Infected Macaques.

    PubMed

    Filipowicz, Adam R; McGary, Christopher M; Holder, Gerard E; Lindgren, Allison A; Johnson, Edward M; Sugimoto, Chie; Kuroda, Marcelo J; Kim, Woong-Ki

    2016-01-01

    The aim of the present study was to investigate if macrophage proliferation occurs in the brain during simian immunodeficiency virus (SIV) infection of adult macaques. We examined the expression of the Ki-67 proliferation marker in the brains of uninfected and SIV-infected macaques with or without encephalitis. Double-label immunohistochemistry using antibodies against the pan-macrophage marker CD68 and Ki-67 showed that there was a significant increase in CD68+Ki-67+ cells in macaques with SIV encephalitis (SIVE) compared to uninfected and SIV-infected animals without encephalitis, a trend that was also confirmed in brain samples from patients with HIV encephalitis. Multi-label immunofluorescence for CD163 and Ki-67 confirmed that the vast majority of Ki-67+ nuclei were localized to CD163+ macrophages in perivascular cuffs and lesions. The proliferative capacity of Ki-67+ perivascular macrophages (PVM) was confirmed by their nuclear incorporation of bromodeoxyuridine. Examining SIVE lesions, using double-label immunofluorescence with antibodies against SIV-Gag-p28 and Ki-67, showed that the population of Ki-67+ cells were productively infected and expanded proportionally with lesions. Altogether, this study shows that there are subpopulations of resident PVM that express Ki-67 and are SIV-infected, suggesting a mechanism of macrophage accumulation in the brain via PVM proliferation. PMID:27610547

  6. Cordocytes-stem cells cooperation in the human brain with emphasis on pivotal role of cordocytes in perivascular areas of broken and thrombosed vessels.

    PubMed

    Pais, Viorel; Danaila, Leon; Pais, Emil

    2013-12-01

    This study is based on data analysis by light and transmission electron microscopy of the surgical cases in cerebral tumors, cerebrovascular malformations, thromboses in the carotid system, and other injuries such as perivascular hemorrhage. We examined cortical arteries and veins, perivascular areas with old hematic masses, vasculogenic foci, and broken large vessels. We identified, characterized, and compared both undifferentiated cells and well-differentiated cordocytes within periadventitial areas where these cells cooperate very well with precursor/stem cells to perform vital functions for cerebral vasculature with immediate effect on brain parenchyma. This useful cellular cooperation was observed by serial sections pointing out the main role of cordocytes during the entire process of collateral vessel formation after thrombosis and, respectively, in vascular wall repair after ruptures. This is the first cytohistopathological study which illustrates and explains some facets of cordocytes-stem cells cooperation around the vessels of human brain with emphasis on the fundamental role of cordocytes in response to vascular injuries. Our pioneering study will be completed for both basic science and modern medical care by further studies. PMID:24205927

  7. Proliferation of Perivascular Macrophages Contributes to the Development of Encephalitic Lesions in HIV-Infected Humans and in SIV-Infected Macaques

    PubMed Central

    Filipowicz, Adam R.; McGary, Christopher M.; Holder, Gerard E.; Lindgren, Allison A.; Johnson, Edward M.; Sugimoto, Chie; Kuroda, Marcelo J.; Kim, Woong-Ki

    2016-01-01

    The aim of the present study was to investigate if macrophage proliferation occurs in the brain during simian immunodeficiency virus (SIV) infection of adult macaques. We examined the expression of the Ki-67 proliferation marker in the brains of uninfected and SIV-infected macaques with or without encephalitis. Double-label immunohistochemistry using antibodies against the pan-macrophage marker CD68 and Ki-67 showed that there was a significant increase in CD68+Ki-67+ cells in macaques with SIV encephalitis (SIVE) compared to uninfected and SIV-infected animals without encephalitis, a trend that was also confirmed in brain samples from patients with HIV encephalitis. Multi-label immunofluorescence for CD163 and Ki-67 confirmed that the vast majority of Ki-67+ nuclei were localized to CD163+ macrophages in perivascular cuffs and lesions. The proliferative capacity of Ki-67+ perivascular macrophages (PVM) was confirmed by their nuclear incorporation of bromodeoxyuridine. Examining SIVE lesions, using double-label immunofluorescence with antibodies against SIV-Gag-p28 and Ki-67, showed that the population of Ki-67+ cells were productively infected and expanded proportionally with lesions. Altogether, this study shows that there are subpopulations of resident PVM that express Ki-67 and are SIV-infected, suggesting a mechanism of macrophage accumulation in the brain via PVM proliferation. PMID:27610547

  8. Spironolactone Prevents Endothelial Nitric Oxide Synthase Uncoupling and Vascular Dysfunction Induced by β-Adrenergic Overstimulation: Role of Perivascular Adipose Tissue.

    PubMed

    Victorio, Jamaira A; Clerici, Stefano P; Palacios, Roberto; Alonso, María J; Vassallo, Dalton V; Jaffe, Iris Z; Rossoni, Luciana V; Davel, Ana P

    2016-09-01

    Sustained stimulation of β-adrenoceptors (β-ARs) and activation of renin-angiotensin-aldosterone system are common features of cardiovascular diseases with rising sympathetic activation, including essential hypertension, myocardial infarction, and heart failure. In this study, we investigated the role of AT1 receptor and mineralocorticoid receptor (MR) in the vascular alterations caused by β-AR overstimulation. β-AR overstimulation with associated cardiac hypertrophy and increased vasoconstrictor response to phenylephrine in aorta were modeled in rats by 7-day isoproterenol treatment. The increased vasoconstrictor response to phenylephrine in this model was blunted by the MR antagonist spironolactone, but not by the AT1 receptor antagonist losartan, despite the blunting of cardiac hypertrophy with both drugs. Spironolactone, but not losartan, restored NO bioavailability in association with lower endothelial nitric oxide synthase-derived superoxide production, increased endothelial nitric oxide synthase dimerization, and aortic HSP90 upregulation. MR genomic and nongenomic functions were activated in aortas from isoproterenol-treated rats. Isoproterenol did not modify plasma levels of MR ligands aldosterone and corticosterone but rather increased perivascular adipose tissue-derived corticosterone in association with increased expression of 11β-hydroxysteroid dehydrogenase type 1. The anticontractile effect of aortic perivascular adipose tissue was impaired by β-AR overstimulation and restored by MR blockade. These results suggest that activation of vascular MR signaling contributes to the vascular dysfunction induced by β-AR overstimulation associated with endothelial nitric oxide synthase uncoupling. These findings reveal an additional explanation for the protective effects of MR antagonists in cardiovascular disorders with sympathetic activation. PMID:27432866

  9. H2O2 generated from mitochondrial electron transport chain in thoracic perivascular adipose tissue is crucial for modulation of vascular smooth muscle contraction.

    PubMed

    Costa, Rafael M; Filgueira, Fernando P; Tostes, Rita C; Carvalho, Maria Helena C; Akamine, Eliana H; Lobato, Nubia S

    2016-09-01

    The perivascular adipose tissue (PVAT) releases a variety of factors that affect vascular function. PVAT in the thoracic aorta shares characteristics with the brown adipose tissue, including a large amount of mitochondria. PVAT-derived factors influence both endothelial and smooth muscle function via several signaling mechanisms including the release/generation of reactive nitrogen and oxygen species. Considering the importance of reactive oxygen species (ROS) on vascular function and that mitochondria are an important source of ROS, we hypothesized that mitochondria-derived ROS in the PVAT modulates vascular reactivity. Vascular reactivity to norephinephrine (NE) was evaluated in thoracic aortic rings, with or without endothelium and/or PVAT, from male Wistar rats. Mitochondrial uncoupling, as well as hydrogen peroxide (H2O2) removal, increased the contraction in vessels surrounded by PVAT. PVAT stimulated with NE exhibited increased protein expression, determined by Western blot analysis, of manganese superoxide dismutase (Mn-SOD) and decreased protein expression of catalase. Ultimately, NE increased superoxide anion (O2(-)) generation in PVAT via increases in intracellular calcium. These results clearly demonstrate that mitochondrial electron transport chain (mETC) in PVAT contributes to modulation of aortic muscle contraction by generating higher amounts of O2(-) that is, in turn, dismutated to hydrogen peroxide, which then acts as a pivotal signaling molecule regulating vascular smooth muscle contraction. PMID:27252154

  10. Time lapse in vivo microscopy reveals distinct dynamics of microglia-tumor environment interactions-a new role for the tumor perivascular space as highway for trafficking microglia.

    PubMed

    Bayerl, Simon Heinrich; Niesner, Raluca; Cseresnyes, Zoltan; Radbruch, Helena; Pohlan, Julian; Brandenburg, Susan; Czabanka, Marcus Alexander; Vajkoczy, Peter

    2016-07-01

    Microglial cells are critical for glioma growth and progression. However, only little is known about intratumoral microglial behavior and the dynamic interaction with the tumor. Currently the scarce understanding of microglial appearance in malignant gliomas merely originates from histological studies and in vitro investigations. In order to understand the pattern of microglia activity, motility and migration we designed an intravital study in an orthotopic murine glioma model using CX3CR1-eGFP(GFP/wt) mice. We analysed the dynamics of intratumoral microglia accumulation and activity, as well as microglia/tumor blood vessel interaction by epi-illumination and 2-photon laser scanning microscopy. We further investigated cellular and tissue function, including the enzyme activity of intratumoral and microglial NADPH oxidase measured by in vivo fluorescence lifetime imaging. We identified three morphological phenotypes of tumor-associated microglia cells with entirely different motility patterns. We found that NADPH oxidase activation is highly divergent in these microglia subtypes leading to different production levels of reactive oxygen species (ROS). We observed that microglia motility is highest within the perivascular niche, suggesting relevance of microglia/tumor blood vessel interactions. In line, reduction of tumor blood vessels by antivascular therapy confirmed the relevance of the tumor vessel compartment on microglia biology in brain tumors. In summary, we provide new insights into in vivo microglial behavior, regarding both morphology and function, in malignant gliomas. GLIA 2016;64:1210-1226. PMID:27143298

  11. Overexpression of CD44 in Neural Precursor Cells Improves Trans- Endothelial Migration and Facilitates Their Invasion of Perivascular Tissues In Vivo

    PubMed Central

    Deboux, Cyrille; Ladraa, Sophia; Cazaubon, Sylvie; Ghribi-Mallah, Siham; Weiss, Nicolas; Chaverot, Nathalie; Couraud, Pierre Olivier; Evercooren, Anne Baron-Van

    2013-01-01

    Neural precursor (NPC) based therapies are used to restore neurons or oligodendrocytes and/or provide neuroprotection in a large variety of neurological diseases. In multiple sclerosis models, intravenously (i.v) -delivered NPCs reduced clinical signs via immunomodulation. We demonstrated recently that NPCs were able to cross cerebral endothelial cells in vitro and that the multifunctional signalling molecule, CD44 involved in trans-endothelial migration of lymphocytes to sites of inflammation, plays a crucial role in extravasation of syngeneic NPCs. In view of the role of CD44 in NPCs trans-endothelial migration in vitro, we questioned presently the benefit of CD44 overexpression by NPCs in vitro and in vivo, in EAE mice. We show that overexpression of CD44 by NPCs enhanced over 2 folds their trans-endothelial migration in vitro, without impinging on the proliferation or differentiation potential of the transduced cells. Moreover, CD44 overexpression by NPCs improved significantly their elongation, spreading and number of filopodia over the extracellular matrix protein laminin in vitro. We then tested the effect of CD44 overexpression after i.v. delivery in the tail vein of EAE mice. CD44 overexpression was functional in vivo as it accelerated trans-endothelial migration and facilitated invasion of HA expressing perivascular sites. These in vitro and in vivo data suggest that CD44 may be crucial not only for NPC crossing the endothelial layer but also for facilitating invasion of extravascular tissues. PMID:23468987

  12. Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy☆

    PubMed Central

    Keable, Abby; Fenna, Kate; Yuen, Ho Ming; Johnston, David A.; Smyth, Neil R.; Smith, Colin; Salman, Rustam Al-Shahi; Samarasekera, Neshika; Nicoll, James A.R.; Attems, Johannes; Kalaria, Rajesh N.; Weller, Roy O.; Carare, Roxana O.

    2016-01-01

    Deposition of amyloid β (Aβ) in the walls of cerebral arteries as cerebral amyloid angiopathy (CAA) suggests an age-related failure of perivascular drainage of soluble Aβ from the brain. As CAA is associated with Alzheimer's disease and with intracerebral haemorrhage, the present study determines the unique sequence of changes that occur as Aβ accumulates in artery walls. Paraffin sections of post-mortem human occipital cortex were immunostained for collagen IV, fibronectin, nidogen 2, Aβ and smooth muscle actin and the immunostaining was analysed using Image J and confocal microscopy. Results showed that nidogen 2 (entactin) increases with age and decreases in CAA. Confocal microscopy revealed stages in the progression of CAA: Aβ initially deposits in basement membranes in the tunica media, replaces first the smooth muscle cells and then the connective tissue elements to leave artery walls completely or focally replaced by Aβ. The pattern of development of CAA in the human brain suggests expansion of Aβ from the basement membranes to progressively replace all tissue elements in the artery wall. Establishing this full picture of the development of CAA is pivotal in understanding the clinical presentation of CAA and for developing therapies to prevent accumulation of Aβ in artery walls. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26327684

  13. Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy.

    PubMed

    Keable, Abby; Fenna, Kate; Yuen, Ho Ming; Johnston, David A; Smyth, Neil R; Smith, Colin; Al-Shahi Salman, Rustam; Samarasekera, Neshika; Nicoll, James A R; Attems, Johannes; Kalaria, Rajesh N; Weller, Roy O; Carare, Roxana O

    2016-05-01

    Deposition of amyloid β (Aβ) in the walls of cerebral arteries as cerebral amyloid angiopathy (CAA) suggests an age-related failure of perivascular drainage of soluble Aβ from the brain. As CAA is associated with Alzheimer's disease and with intracerebral haemorrhage, the present study determines the unique sequence of changes that occur as Aβ accumulates in artery walls. Paraffin sections of post-mortem human occipital cortex were immunostained for collagen IV, fibronectin, nidogen 2, Aβ and smooth muscle actin and the immunostaining was analysed using Image J and confocal microscopy. Results showed that nidogen 2 (entactin) increases with age and decreases in CAA. Confocal microscopy revealed stages in the progression of CAA: Aβ initially deposits in basement membranes in the tunica media, replaces first the smooth muscle cells and then the connective tissue elements to leave artery walls completely or focally replaced by Aβ. The pattern of development of CAA in the human brain suggests expansion of Aβ from the basement membranes to progressively replace all tissue elements in the artery wall. Establishing this full picture of the development of CAA is pivotal in understanding the clinical presentation of CAA and for developing therapies to prevent accumulation of Aβ in artery walls. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26327684

  14. Human Umbilical Cord Perivascular Cells Exhibited Enhanced Migration Capacity towards Hepatocellular Carcinoma in Comparison with Bone Marrow Mesenchymal Stromal Cells: A Role for Autocrine Motility Factor Receptor

    PubMed Central

    Aquino, Jorge B.; Malvicini, Mariana; Bolontrade, Marcela; Podhajcer, Osvaldo; Garcia, Mariana G.; Mazzolini, Guillermo

    2014-01-01

    Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs) and human umbilical cord perivascular cells (HUCPVCs) towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC. PMID:25147818

  15. Human umbilical cord perivascular cells exhibited enhanced migration capacity towards hepatocellular carcinoma in comparison with bone marrow mesenchymal stromal cells: a role for autocrine motility factor receptor.

    PubMed

    Bayo, Juan; Fiore, Esteban; Aquino, Jorge B; Malvicini, Mariana; Rizzo, Manglio; Peixoto, Estanislao; Alaniz, Laura; Piccioni, Flavia; Bolontrade, Marcela; Podhajcer, Osvaldo; Garcia, Mariana G; Mazzolini, Guillermo

    2014-01-01

    Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs) and human umbilical cord perivascular cells (HUCPVCs) towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC. PMID:25147818

  16. Unveiling the Differences of Secretome of Human Bone Marrow Mesenchymal Stem Cells, Adipose Tissue-Derived Stem Cells, and Human Umbilical Cord Perivascular Cells: A Proteomic Analysis.

    PubMed

    Pires, Ana O; Mendes-Pinheiro, Barbara; Teixeira, Fábio G; Anjo, Sandra I; Ribeiro-Samy, Silvina; Gomes, Eduardo D; Serra, Sofia C; Silva, Nuno A; Manadas, Bruno; Sousa, Nuno; Salgado, Antonio J

    2016-07-15

    The use of human mesenchymal stem cells (hMSCs) has emerged as a possible therapeutic strategy for CNS-related conditions. Research in the last decade strongly suggests that MSC-mediated benefits are closely related with their secretome. Studies published in recent years have shown that the secretome of hMSCs isolated from different tissue sources may present significant variation. With this in mind, the present work performed a comparative proteomic-based analysis through mass spectrometry on the secretome of hMSCs derived from bone marrow (BMSCs), adipose tissue (ASCs), and human umbilical cord perivascular cells (HUCPVCs). The results revealed that BMSCs, ASCs, and HUCPVCs differed in their secretion of neurotrophic, neurogenic, axon guidance, axon growth, and neurodifferentiative proteins, as well as proteins with neuroprotective actions against oxidative stress, apoptosis, and excitotoxicity, which have been shown to be involved in several CNS disorder/injury processes. Although important changes were observed within the secretome of the cell populations that were analyzed, all cell populations shared the capability of secreting important neuroregulatory molecules. The difference in their secretion pattern may indicate that their secretome is specific to a condition of the CNS. Nevertheless, the confirmation that the secretome of MSCs isolated from different tissue sources is rich in neuroregulatory molecules represents an important asset not only for the development of future neuroregenerative strategies but also for their use as a therapeutic option for human clinical trials. PMID:27226274

  17. Dahl SS rats demonstrate enhanced aortic perivascular adipose tissue-mediated buffering of vasoconstriction through activation of NOS in the endothelium.

    PubMed

    Spradley, Frank T; Ho, Dao H; Pollock, Jennifer S

    2016-02-01

    Perivascular adipose tissue (PVAT) mediates buffering of vasoconstriction through activation of endothelium-derived factors. We hypothesized that the PVAT of Dahl salt-sensitive (Dahl SS) rats has reduced ability to buffer vasoconstriction. Vascular reactivity experiments were performed on aortic rings with PVAT intact (+PVAT) or removed (-PVAT), and endothelium intact (+ENDO) or removed (-ENDO) from Dahl SS rats and control SS.13(BN) rats (Dahl SS rats that have had chromosome 13 completely replaced with that of the Brown Norway rat, rendering this strain insensitive to high-salt or high-fat diet-induced hypertension). Endothelial dysfunction, assessed by ACh-mediated vasorelaxation, was confirmed in aortic rings of Dahl SS rats. The +PVAT+ENDO aortic rings had indistinguishable phenylephrine-induced vasoconstriction between genotypes. In both strains, removal of PVAT significantly enhanced vasoconstriction. Dahl SS rat -PVAT+ENDO aortic rings displayed exaggerated vasoconstriction to phenylephrine vs. SS.13(BN) rats, indicating that PVAT-mediated buffering of vasoconstriction was greater in Dahl SS rats. Removal of both the ENDO and PVAT restored vasoconstriction in both strains. The nitric oxide synthase (NOS) inhibitor, N(ω)-nitro-L-arginine methyl ester (L-NAME), produced a similar effect as that seen with -ENDO. These data indicate that the function of the PVAT to activate endothelium-derived NOS is enhanced in Dahl SS compared with SS.13(BN) rats and, most likely, occurs through a pathway that is distinct from ACh-mediated activation of NOS. PVAT weight and total PVAT leptin levels were greater in Dahl SS rats. Leptin induced a significantly decreased vasoconstriction in -PVAT+ENDO aortic rings from Dahl SS rats, but not SS.13(BN) rats. In contrast to our initial hypothesis, PVAT in Dahl SS rats buffers vasoconstriction by activating endothelial NOS via mechanisms that may include the involvement of leptin. Thus, the PVAT serves a vasoprotective role in

  18. Developmental aspects of the intracerebral microvasculature and perivascular spaces: insights into brain response to late-life diseases.

    PubMed

    Marín-Padilla, Miguel; Knopman, David S

    2011-12-01

    The development of the microvasculature of the human cerebral cortex offers insight into the response of the cerebral cortex to later-life brain injury. We describe the 3 basic and distinct components of the developmental anatomy of the cerebral cortical microvascular system. The first compartment is meningeal and, therefore, extracerebral. In addition to the major venous sinuses, arachnoidal arteries, and veins, the pial anastomotic capillary plexus that covers the surface of the developing and adult cerebral cortex represents the source of thepenetrating vessels that become the second component, the intracerebral extrinsic microvascular compartment. During embryogenesis, sprouting vascular elements from pial capillaries pierce the brain's external glial limiting membrane and penetrate the cortex. These vessels, which eventually differentiate into arterioles and venules, are separated from the cortical tissue by the extravascular Virchow-Robin compartment (V-RC) formed between the internal vascular and the external glial basal laminae. The V-RC remains open to the meningeal interstitial spaces and outside the blood-brain barrier (BBB) and acts asa prelymphatic drainage system for removal of substances that cannot be transported into the blood or catabolized intracellularly. The third element is the dense intracerebralintrinsic microvascular compartment. Intracerebral capillary vessels sprout from the perforating vessels, penetrate through the Virchow-Robin glial membrane, and enter the neuropil. Intracerebral capillaries lack smooth muscle and a V-RC and consist only of endothelial cells separated from the intracerebral space by a basal lamina. Their role as the physiological BBB is the exchange of oxygen, glucose, and small molecules. This developmental perspective highlights 3 principles: (a) the V-RC is intimately related to the cortical penetrating arterioles and venules and represents an inefficient protolymphatic system that lacks the anatomic and

  19. The Role of DPO-1 and XE991-Sensitive Potassium Channels in Perivascular Adipose Tissue-Mediated Regulation of Vascular Tone

    PubMed Central

    Tsvetkov, Dmitry; Tano, Jean-Yves; Kassmann, Mario; Wang, Ning; Schubert, Rudolf; Gollasch, Maik

    2016-01-01

    The anti-contractile effect of perivascular adipose tissue (PVAT) is an important mechanism in the modulation of vascular tone in peripheral arteries. Recent evidence has implicated the XE991-sensitive voltage-gated KV (KCNQ) channels in the regulation of arterial tone by PVAT. However, until now the in vivo pharmacology of the involved vascular KV channels with regard to XE991 remains undetermined, since XE991 effects may involve Ca2+ activated BKCa channels and/or voltage-dependent KV1.5 channels sensitive to diphenyl phosphine oxide-1 (DPO-1). In this study, we tested whether KV1.5 channels are involved in the control of mesenteric arterial tone and its regulation by PVAT. Our study was also aimed at extending our current knowledge on the in situ vascular pharmacology of DPO-1 and XE991 regarding KV1.5 and BKCa channels, in helping to identify the nature of K+ channels that could contribute to PVAT-mediated relaxation. XE991 at 30 μM reduced the anti-contractile response of PVAT, but had no effects on vasocontraction induced by phenylephrine (PE) in the absence of PVAT. Similar effects were observed for XE991 at 0.3 μM, which is known to almost completely inhibit mesenteric artery VSMC KV currents. 30 μM XE991 did not affect BKCa currents in VSMCs. Kcna5−/− arteries and wild-type arteries incubated with 1 μM DPO-1 showed normal vasocontractions in response to PE in the presence and absence of PVAT. KV current density and inhibition by 30 μM XE991 were normal in mesenteric artery VSMCs isolated from Kcna5−/− mice. We conclude that KV channels are involved in the control of arterial vascular tone by PVAT. These channels are present in VSMCs and very potently inhibited by the KCNQ channel blocker XE991. BKCa channels and/or DPO-1 sensitive KV1.5 channels in VSMCs are not the downstream mediators of the XE991 effects on PVAT-dependent arterial vasorelaxation. Further studies will need to be undertaken to examine the role of other KV channels in the

  20. Form classification

    NASA Astrophysics Data System (ADS)

    Reddy, K. V. Umamaheswara; Govindaraju, Venu

    2008-01-01

    The problem of form classification is to assign a single-page form image to one of a set of predefined form types or classes. We classify the form images using low level pixel density information from the binary images of the documents. In this paper, we solve the form classification problem with a classifier based on the k-means algorithm, supported by adaptive boosting. Our classification method is tested on the NIST scanned tax forms data bases (special forms databases 2 and 6) which include machine-typed and handwritten documents. Our method improves the performance over published results on the same databases, while still using a simple set of image features.

  1. Permission Forms

    ERIC Educational Resources Information Center

    Zirkel, Perry A.

    2005-01-01

    The prevailing practice in public schools is to routinely require permission or release forms for field trips and other activities that pose potential for liability. The legal status of such forms varies, but they are generally considered to be neither rock-solid protection nor legally valueless in terms of immunity. The following case and the…

  2. Tidal Forms

    NASA Astrophysics Data System (ADS)

    Bolla Pittaluga, M.; Seminara, G.; Tambroni, N.

    2003-04-01

    We give an overview of some recent investigations on the mechanics of the processes whereby forms develop in tidal environments. The viewpoint taken here is mechanistic. Some of the questions which deserve an answer may be summarised as follows: i) do tidal channels tend to some altimetric long term equilibrium? ii) why are they typically convergent and weakly meandering? iii) how is such equilibrium affected by the hydrodynamics and morphodynamics of tidal inlets? iv) what is the hydrodynamic and morphodynamic role played by tidal flats adjacent to the channels? Some of the above questions have received a considerable attention in the last few years. Schuttelaars and de Swart (1996), Lanzoni and Seminara (2002) and, more recently, Bolla Pittaluga (2003) have investigated the first problem. In particular, the latter two contributions have shown that a straight tidal channel connected to a tidal sea at one end and closed at the other end tends to reach a long term equilibrium profile, which is slightly concave seaward and convex landward where a beach forms. The equilibrium profile is strongly sensitive to the harmonic content of the tidal forcing as well as to the value of sediment concentration established by the coastal hydrodynamics in the far field of the inlet region. Less important are the effect of channel convergence and the role of settling lag in the transport of suspended load. Insufficient attention has been devoted to the understanding of what mechanisms control channel convergence and meandering, though some similarities and differences between tidal and fluvial channels have emerged from some recent works. In particular, free bars form in tidal channels due to an instability mechanism essentially similar to that occurring under steady conditions though the oscillatory character of the flow field makes the bar pattern non migrating (Seminara and Tubino, 2001). Similarly, forced bars in curved tidal channels are driven by the development of

  3. Epsilon toxin: a fascinating pore-forming toxin.

    PubMed

    Popoff, Michel R

    2011-12-01

    Epsilon toxin (ETX) is produced by strains of Clostridium perfringens classified as type B or type D. ETX belongs to the heptameric β-pore-forming toxins including aerolysin and Clostridium septicum alpha toxin, which are characterized by the formation of a pore through the plasma membrane of eukaryotic cells consisting in a β-barrel of 14 amphipatic β strands. By contrast to aerolysin and C. septicum alpha toxin, ETX is a much more potent toxin and is responsible for enterotoxemia in animals, mainly sheep. ETX induces perivascular edema in various tissues and accumulates in particular in the kidneys and brain, where it causes edema and necrotic lesions. ETX is able to pass through the blood-brain barrier and stimulate the release of glutamate, which accounts for the symptoms of nervous excitation observed in animal enterotoxemia. At the cellular level, ETX causes rapid swelling followed by cell death involving necrosis. The precise mode of action of ETX remains to be determined. ETX is a powerful toxin, however, it also represents a unique tool with which to vehicle drugs into the central nervous system or target glutamatergic neurons. PMID:21535407

  4. Densified waste form and method for forming

    DOEpatents

    Garino, Terry J.; Nenoff, Tina M.; Sava Gallis, Dorina Florentina

    2016-05-17

    Materials and methods of making densified waste forms for temperature sensitive waste material, such as nuclear waste, formed with low temperature processing using metallic powder that forms the matrix that encapsulates the temperature sensitive waste material. The densified waste form includes a temperature sensitive waste material in a physically densified matrix, the matrix is a compacted metallic powder. The method for forming the densified waste form includes mixing a metallic powder and a temperature sensitive waste material to form a waste form precursor. The waste form precursor is compacted with sufficient pressure to densify the waste precursor and encapsulate the temperature sensitive waste material in a physically densified matrix.

  5. Densified waste form and method for forming

    SciTech Connect

    Garino, Terry J.; Nenoff, Tina M.; Sava Gallis, Dorina Florentina

    2015-08-25

    Materials and methods of making densified waste forms for temperature sensitive waste material, such as nuclear waste, formed with low temperature processing using metallic powder that forms the matrix that encapsulates the temperature sensitive waste material. The densified waste form includes a temperature sensitive waste material in a physically densified matrix, the matrix is a compacted metallic powder. The method for forming the densified waste form includes mixing a metallic powder and a temperature sensitive waste material to form a waste form precursor. The waste form precursor is compacted with sufficient pressure to densify the waste precursor and encapsulate the temperature sensitive waste material in a physically densified matrix.

  6. PSF/SFPQ is a very common gene fusion partner in TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas) and melanotic Xp11 translocation renal cancers: clinicopathologic, immunohistochemical, and molecular characteristics suggesting classification as a distinct entity.

    PubMed

    Rao, Qiu; Shen, Qin; Xia, Qiu-yuan; Wang, Zi-yu; Liu, Biao; Shi, Shan-shan; Shi, Qun-li; Yin, Hong-lin; Wu, Bo; Ye, Sheng-bing; Li, Li; Chen, Jie-Yu; Pan, Min-hong; Li, Qing; Li, Rui; Wang, Xuan; Zhang, Ru-song; Yu, Bo; Ma, Heng-hui; Lu, Zhen-feng; Zhou, Xiao-jun

    2015-09-01

    An increasing number of TFE3 rearrangement-associated tumors, such as TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas), melanotic Xp11 translocation renal cancers, and melanotic Xp11 neoplasms, have recently been reported. We examined 12 such cases, including 5 TFE3 rearrangement-associated PEComas located in the pancreas, cervix, or pelvis and 7 melanotic Xp11 translocation renal cancers, using clinicopathologic, immunohistochemical, and molecular analyses. All the tumors shared a similar morphology, including a purely nested or sheet-like architecture separated by a delicate vascular network, purely epithelioid cells displaying a clear or granular eosinophilic cytoplasm, a lack of papillary structures and spindle cell or fat components, uniform round or oval nuclei containing small visible nucleoli, and, in most cases (11/12), melanin pigmentation. The levels of mitotic activity and necrosis varied. All 12 cases displayed moderately (2+) or strongly (3+) positive immunoreactivity for TFE3 and cathepsin K. One case labeled focally for HMB45 and Melan-A, whereas the others typically labeled moderately (2+) or strongly (3+) for 1 of these markers. None of the cases were immunoreactive for smooth muscle actin, desmin, CKpan, S100, or PAX8. PSF-TFE3 fusion genes were confirmed by reverse transcription polymerase chain reaction in cases (7/7) in which a novel PSF-TFE3 fusion point was identified. All of the cases displayed TFE3 rearrangement associated with Xp11 translocation. Furthermore, we developed a PSF-TFE3 fusion fluorescence in situ hybridization assay for the detection of the PSF-TFE3 fusion gene and detected it in all 12 cases. Clinical follow-up data were available for 7 patients. Three patients died, and 2 patients (cases 1 and 3) remained alive with no evidence of disease after initial resection. Case 2 experienced recurrence and remained alive with disease. Case 5, a recent case, remained alive with extensive abdominal cavity

  7. Involvement of IGF-1 and MEOX2 in PI3K/Akt1/2 and ERK1/2 pathways mediated proliferation and differentiation of perivascular adipocytes

    SciTech Connect

    Liu, Ping; Kong, Feng; Wang, Jue; Lu, Qinghua; Xu, Haijia; Qi, Tonggang; Meng, Juan

    2015-02-01

    Perivascular adipocyte (PVAC) proliferation and differentiation were closely involved in cardiovascular disease. We aimed to investigate whether phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways enhance PVAC functions activated by insulin-like growth factor 1(IGF-1) and suppressed by mesenchyme homeobox 2 (MEOX2). In this study, PVACs from primary culture were cultured and induced to differentiate. Cell viability assays demonstrated that IGF-1 promoted PVAC proliferation and differentiation. However MEOX2 counteracted these IGF-1-mediated actions. Flow Cytometry revealed that IGF-1 increased S phase cells and decreased apoptosis; however, MEOX2 decreased S phase cells, increased G0–G1 phase cells, and promoted apoptosis. During PVAC proliferation and differentiation, IGF-1 activated PI3K/Akt1/2 and ERK1/2 signaling pathways, upregulated the expression of these signaling proteins and FAS, and increased PVAC lipid content. In contrast, MEOX2 constrained the phosphorylation of ERK1/2 and Akt1/2 protein, down-regulated these signaling molecules and FAS, and decreased PVAC lipid content. Instead, MEOX2 knockdown enhanced the ERK1/2 and Akt1/2 phosphorylation, augmented the expression of these signaling molecules and FAS, and increased PVAC lipid content. Our findings suggested that PI3K/Akt1/2 and ERK1/2 activation mediated by IGF-1 is essential for PVAC proliferation and differentiation, and MEOX2 is a promising therapeutic gene to intervene in the signaling pathways and inhibit PVAC functions. - Highlights: • IGF-1 activated PI3K/Akt2 and ERK1/2 pathways to mediate PVAC proliferation and differentiation. • The expression of ERK1, ERK 2, PI3K, Akt1 and Akt2 showed different change trends between PVAC proliferation and differentiation. • MEOX2 effectively expressed in PVAC, increased early and late cellular apoptosis, and inhibited its proliferation. • MEOX2 depressed PVAC differentiation and FAS expression

  8. The perivascular niche regulates breast tumour dormancy.

    PubMed

    Ghajar, Cyrus M; Peinado, Héctor; Mori, Hidetoshi; Matei, Irina R; Evason, Kimberley J; Brazier, Hélène; Almeida, Dena; Koller, Antonius; Hajjar, Katherine A; Stainier, Didier Y R; Chen, Emily I; Lyden, David; Bissell, Mina J

    2013-07-01

    In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumour cells (DTCs) are kept dormant, and what wakes them up, are fundamental problems in tumour biology. To address these questions, we used metastasis assays in mice and showed that dormant DTCs reside on microvasculature of lung, bone marrow and brain. We then engineered organotypic microvascular niches to determine whether endothelial cells directly influence breast cancer cell (BCC) growth. These models demonstrated that endothelial-derived thrombospondin-1 induces sustained BCC quiescence. This suppressive cue was lost in sprouting neovasculature; time-lapse analysis showed that sprouting vessels not only permit, but accelerate BCC outgrowth. We confirmed this surprising result in dormancy models and in zebrafish, and identified active TGF-β1 and periostin as tumour-promoting factors derived from endothelial tip cells. Our work reveals that stable microvasculature constitutes a dormant niche, whereas sprouting neovasculature sparks micrometastatic outgrowth. PMID:23728425

  9. The perivascular niche regulates breast tumor dormancy

    PubMed Central

    Peinado, Héctor; Mori, Hidetoshi; Matei, Irina R.; Evason, Kimberley J.; Brazier, Hélène; Almeida, Dena; Koller, Antonius; Hajjar, Katherine A.; Stainier, Didier Y.R.; Chen, Emily I.; Lyden, David

    2013-01-01

    In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumor cells (DTCs) are kept dormant, and what ‘wakes them up’, are fundamental problems in tumor biology. To address these questions, we utilized metastasis assays in mice to show that dormant DTCs reside upon microvasculature of lung, bone marrow and brain. We then engineered organotypic microvascular niches to determine whether endothelial cells directly influence breast cancer cell (BCC) growth. These models demonstrated that endothelial-derived thrombospondin-1 induces sustained BCC quiescence. This suppressive cue was lost in sprouting neovasculature; time-lapse analysis showed that sprouting vessels not only permit, but accelerate BCC outgrowth. We confirmed this surprising result in dormancy models and in zebrafish, and identified active TGF-β1 and periostin as tumor-promoting, endothelial tip cell-derived factors. Our work reveals that stable microvasculature constitutes a ‘dormant niche,’ whereas sprouting neovasculature sparks micrometastatic outgrowth. PMID:23728425

  10. Careers (A Course of Study). Unit V: Forms, Forms, Forms.

    ERIC Educational Resources Information Center

    Turley, Kay

    Designed to enable special needs students to understand and complete various job-related forms, this set of activities devoted to forms encountered before and after one obtains a job is the fifth in a nine-unit secondary level careers course intended to provide handicapped students with the knowledge and tools necessary to succeed in the world of…

  11. The "FORM" Approach to Reading Forms.

    ERIC Educational Resources Information Center

    Sandel, Lenore

    The FORM approach is designed to help persons in the senior population with the task of filling out the forms or applications required for a myriad of societal and human needs. The acronym represents a four-part approach consisting of: Facing the issue; applying Overview; Rewriting headings as questions; and Matching information as appropriate…

  12. Form 5-Mining venture agreement model form

    SciTech Connect

    Not Available

    1984-01-01

    This text acts as a reference of the basic terms and conditions for a negotiated mining venture agreement. Alternative clauses and provisions, along with extensive commentary, are supplied. The model form contains many articles which define and detail the process.

  13. Handbook of Poetic Forms.

    ERIC Educational Resources Information Center

    Padgett, Ron, Ed.

    Intended for secondary teachers and student writers but useful for anyone interested in poetic forms, this book defines 74 basic poetic forms, summarizes their histories, quotes examples from noted poets, and offers professional tricks of the trade on how to use each form. The book covers the following poetic forms: abstract poem, acrostic,…

  14. Bacteria form tellurium nanocrystals

    USGS Publications Warehouse

    Oremland, R.S.

    2007-01-01

    A team of researchers have found two bacterial species that produce tellurium oxyanions as respiratory electron acceptors for growth, leaving elemental tellurium in the form of nanoparticles. The crystals from the two organisms exhibit distinctively different structures. Bacillus selenitireducens initially forms nanorods that cluster together to form rosettes. Sulfurospirillum barnesii forms irregularly-shaped nanospheres that coalesce into larger composite aggregates.

  15. Molecular Profiling of a Rare Rosette-Forming Glioneuronal Tumor Arising in the Spinal Cord

    PubMed Central

    Bidinotto, Lucas Tadeu; Scapulatempo-Neto, Cristovam; Mackay, Alan; de Almeida, Gisele Caravina; Berardinelli, Gustavo Noriz; Torrieri, Raul; Clara, Carlos Afonso; Feltrin, Leonir Terezinha; Viana-Pereira, Marta; Varella-Garcia, Marileila; Jones, Chris; Reis, Rui Manuel

    2015-01-01

    Rosette-forming glioneuronal tumor (RGNT) of the IV ventricle is a rare and recently recognized brain tumor entity. It is histologically composed by two distinct features: a glial component, resembling pilocytic astrocytoma, and a component forming neurocytic rosettes and/or perivascular rosettes. Herein, we describe a 33-year-old man with RGNT arising in the spinal cord. Following an immunohistochemistry validation, we further performed an extensive genomic analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology. We observed the loss of 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16. Local amplifications in 9q34.2 and 19p13.3 (encompassing the gene SBNO2) were identified. Moreover, we observed focal gains/losses in several chromosomes. Additionally, on chromosome 7, we identified the presence of the KIAA1549:BRAF gene fusion, which was further validated by RT-PCR and FISH. Across all mutational analyses, we detected and validated the somatic mutations of the genes MLL2, CNNM3, PCDHGC4 and SCN1A. Our comprehensive molecular profiling of this RGNT suggests that MAPK pathway and methylome changes, driven by KIAA1549:BRAF fusion and MLL2 mutation, respectively, could be associated with the development of this rare tumor entity. PMID:26371886

  16. Forms of Arthritis

    MedlinePlus

    ... this page please turn Javascript on. Forms of Arthritis Past Issues / Fall 2006 Table of Contents Today, ... of Linda Saisselin Osteoarthritis (OA) — the form of arthritis typically occurring during middle or old age, this ...

  17. Forms of Arthritis

    MedlinePlus

    ... stiffness, inflammation, swelling and, sometimes, destruction of joints. Gout — a form of arthritis that occurs when uric ... the joints. Some 2.1 million Americans have gout. Lupus — a form of arthritis, like rheumatoid arthritis, ...

  18. Forms in Space.

    ERIC Educational Resources Information Center

    Moore, Paula

    1998-01-01

    Uses the work of M. C. Escher to instruct upper elementary students in the transformation of flat shape into three-dimensional form. Outlines the lesson as a series of sections: (1) reviewing form drawing; (2) creating three-dimensional effects; (3) imagining the forms in an inhabited world; and (4) using color and shading. (DSK)

  19. Mesonic Form Factors

    SciTech Connect

    Frederic D. R. Bonnet; Robert G. Edwards; George T. Fleming; Randal Lewis; David Richards

    2003-07-22

    We have started a program to compute the electromagnetic form factors of mesons. We discuss the techniques used to compute the pion form factor and present preliminary results computed with domain wall valence fermions on MILC asqtad lattices, as well as Wilson fermions on quenched lattices. These methods can easily be extended to rho-to-gamma-pi transition form factors.

  20. Method for forming ammonia

    DOEpatents

    Kong, Peter C.; Pink, Robert J.; Zuck, Larry D.

    2008-08-19

    A method for forming ammonia is disclosed and which includes the steps of forming a plasma; providing a source of metal particles, and supplying the metal particles to the plasma to form metal nitride particles; and providing a substance, and reacting the metal nitride particles with the substance to produce ammonia, and an oxide byproduct.

  1. Methods of forming steel

    DOEpatents

    Branagan, Daniel J.; Burch, Joseph V.

    2001-01-01

    In one aspect, the invention encompasses a method of forming a steel. A metallic glass is formed and at least a portion of the glass is converted to a crystalline steel material having a nanocrystalline scale grain size. In another aspect, the invention encompasses another method of forming a steel. A molten alloy is formed and cooled the alloy at a rate which forms a metallic glass. The metallic glass is devitrified to convert the glass to a crystalline steel material having a nanocrystalline scale grain size. In yet another aspect, the invention encompasses another method of forming a steel. A first metallic glass steel substrate is provided, and a molten alloy is formed over the first metallic glass steel substrate to heat and devitrify at least some of the underlying metallic glass of the substrate.

  2. Enhanced expression of constitutive and inducible forms of nitric oxide synthase in autoimmune encephalomyelitis.

    PubMed

    Kim, S; Moon, C; Wie, M B; Kim, H; Tanuma, N; Matsumoto, Y; Shin, T

    2000-06-01

    To elucidate the role of nitric oxide synthase (NOS) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), we analyzed the expression of constitutive neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) in the spinal cords of rats with EAE. We further examined the structural interaction between apoptotic cells and spinal cord cells including neurons and astrocytes, which are potent cell types of nitric oxide (NO) production in the brain. Western blot analysis showed that three forms of NOS significantly increased in the spinal cords of rats at the peak stage of EAE, while small amounts of these enzymes were identified in the spinal cords of rats without EAE. Immunohistochemical study showed that the expression of either nNOS or eNOS increased in the brain cells including neurons and astrocytes during the peak and recovery stages of EAE, while the expression of iNOS was found mainly in the inflammatory macrophages in the perivascular EAE lesions. Double labeling showed that apoptotic cells had intimate contacts with either neurons or astrocytes, which are major cell types to express nNOS and eNOS constitutively. Our results suggest that the three NOS may play an important role in the recovery of EAE. PMID:14612615

  3. Accounting Forms. Instructor's Handbook.

    ERIC Educational Resources Information Center

    Itter, Pat

    Supporting performance objective of the 16 V-TECS (Vocational-Technical Education Consortium of States) Bookkeeper Catalog, this instructor's manual contains copies of accounting forms which can be used to make spirit masters or transparencies. (This module is the first in a set of ten on bookkeeping [CE 019 480-489].) Twenty forms grouped under…

  4. Method of forming nanodielectrics

    DOEpatents

    Tuncer, Enis [Knoxville, TN; Polyzos, Georgios [Oak Ridge, TN

    2014-01-07

    A method of making a nanoparticle filled dielectric material. The method includes mixing nanoparticle precursors with a polymer material and reacting the nanoparticle mixed with the polymer material to form nanoparticles dispersed within the polymer material to form a dielectric composite.

  5. Method for forming materials

    DOEpatents

    Tolle, Charles R.; Clark, Denis E.; Smartt, Herschel B.; Miller, Karen S.

    2009-10-06

    A material-forming tool and a method for forming a material are described including a shank portion; a shoulder portion that releasably engages the shank portion; a pin that releasably engages the shoulder portion, wherein the pin defines a passageway; and a source of a material coupled in material flowing relation relative to the pin and wherein the material-forming tool is utilized in methodology that includes providing a first material; providing a second material, and placing the second material into contact with the first material; and locally plastically deforming the first material with the material-forming tool so as mix the first material and second material together to form a resulting material having characteristics different from the respective first and second materials.

  6. Spin forming development

    SciTech Connect

    Gates, W.G.

    1982-05-01

    Bendix product applications require the capability of fabricating heavy gage, high strength materials. Five commercial sources have been identified that have the capability of spin forming metal thicknesses greater than 9.5 mm and four equiment manufacturers produce machines with this capability. Twelve assemblies selected as candidates for spin forming applications require spin forming of titanium, 250 maraging steel, 17-4 pH stainless steel, Nitronic 40 steel, 304 L stainless steel, and 6061 aluminum. Twelve parts have been cold spin formed from a 250 maraging steel 8.1 mm wall thickness machine preform, and six have been hot spin formed directly from 31.8-mm-thick flat plate. Thirty-three Ti-6Al-4V titanium alloy parts and 26 17-4 pH stainless steel parts have been hot spin formed directly from 31.8-mm-thick plate. Hot spin forming directly from plate has demonstrated the feasibility and favorable economics of this fabrication technique for Bendix applications.

  7. Electromagnetic nucleon form factors

    SciTech Connect

    Bender, A.; Roberts, C.D.; Frank, M.R.

    1995-08-01

    The Dyson-Schwinger equation framework is employed to obtain expressions for the electromagnetic nucleon form factor. In generalized impulse approximation the form factor depends on the dressed quark propagator, the dressed quark-photon vertex, which is crucial to ensuring current conservation, and the nucleon Faddeev amplitude. The approach manifestly incorporates the large space-like-q{sup 2} renormalization group properties of QCD and allows a realistic extrapolation to small space-like-q{sup 2}. This extrapolation allows one to relate experimental data to the form of the quark-quark interaction at small space-like-q{sup 2}, which is presently unknown. The approach provides a means of unifying, within a single framework, the treatment of the perturbative and nonperturbative regimes of QCD. The wealth of experimental nucleon form factor data, over a large range of q{sup 2}, ensures that this application will provide an excellent environment to test, improve and extend our approach.

  8. Image forming apparatus

    DOEpatents

    Satoh, Hisao; Haneda, Satoshi; Ikeda, Tadayoshi; Morita, Shizuo; Fukuchi, Masakazu

    1996-01-01

    In an image forming apparatus having a detachable process cartridge in which an image carrier on which an electrostatic latent image is formed, and a developing unit which develops the electrostatic latent image so that a toner image can be formed, both integrally formed into one unit. There is provided a developer container including a discharge section which can be inserted into a supply opening of the developing unit, and a container in which a predetermined amount of developer is contained, wherein the developer container is provided to the toner supply opening of the developing unit and the developer is supplied into the developing unit housing when a toner stirring screw of the developing unit is rotated.

  9. Handprinted Forms and Characters

    National Institute of Standards and Technology Data Gateway

    NIST Handprinted Forms and Characters (PC database for purchase)   NIST Special Database 19 contains NIST's entire corpus of training materials for handprinted document and character recognition. It supersedes NIST Special Databases 3 and 7.

  10. Shell forming system

    NASA Technical Reports Server (NTRS)

    Kendall, Jr., James M. (Inventor); Wang, Taylor G. (Inventor); Elleman, Daniel D. (Inventor)

    1990-01-01

    Hollow shells of high uniformity are formed by emitting liquid through an outer nozzle and gas through an inner nozzle, to form a hollow extrusion, by flowing the gas at a velocity between about 1.3 and 10 times the liquid velocity. The natural breakup rate of the extrusion can be increased to decrease shell size by applying periodic perturbations to one of the materials prior to exiting the nozzles, to a nozzle, or to the extrusion.

  11. Composite hot drape forming

    NASA Technical Reports Server (NTRS)

    Ott, Thomas

    1994-01-01

    This program was initiated to replace labor-intensive ply-by-ply layup of composite I-beam posts and angle stiffeners used in the Space Station Freedom (SSF) rack structure. Hot drape forming (HDF) has been successfully implemented by BCAG for 777 composite I-stringers and by Bell Helicopter/Textron for the V-22 I-stingers. The two companies utilize two vastly different approaches to the I-beam fabrication process. A drape down process is used by Bell Helicopter where the compacted ply charge is placed on top of a forming mandrel and heated. When the heated ply charge reached a set temperature, vacuum pressure is applied and the plies are formed over the mandrel. The BCAG 777 process utilizes an inverted forming process where the ply stack is placed on a forming table and the mandrel is inverted and placed upon the ply stack. A heating and vacuum bladder underneath the ply stack form the play stack up onto the mandrels after reaching the temperature setpoint. Both methods have their advantages, but the drape down process was selected for SSF because it was more versatile and could be fabricated from readily available components.

  12. Composite hot drape forming

    NASA Astrophysics Data System (ADS)

    Ott, Thomas

    1994-02-01

    This program was initiated to replace labor-intensive ply-by-ply layup of composite I-beam posts and angle stiffeners used in the Space Station Freedom (SSF) rack structure. Hot drape forming (HDF) has been successfully implemented by BCAG for 777 composite I-stringers and by Bell Helicopter/Textron for the V-22 I-stingers. The two companies utilize two vastly different approaches to the I-beam fabrication process. A drape down process is used by Bell Helicopter where the compacted ply charge is placed on top of a forming mandrel and heated. When the heated ply charge reached a set temperature, vacuum pressure is applied and the plies are formed over the mandrel. The BCAG 777 process utilizes an inverted forming process where the ply stack is placed on a forming table and the mandrel is inverted and placed upon the ply stack. A heating and vacuum bladder underneath the ply stack form the play stack up onto the mandrels after reaching the temperature setpoint. Both methods have their advantages, but the drape down process was selected for SSF because it was more versatile and could be fabricated from readily available components.

  13. Major trends in stem anatomy and growth forms in the perianth-bearing Piperales, with special focus on Aristolochia

    PubMed Central

    Wagner, Sarah T.; Hesse, Linnea; Isnard, Sandrine; Samain, Marie-Stéphanie; Bolin, Jay; Maass, Erika; Neinhuis, Christoph; Rowe, Nick P.; Wanke, Stefan

    2014-01-01

    Background and Aims The order Piperales has the highest diversity of growth forms among the earliest angiosperm lineages, including trees, shrubs, climbers and herbs. However, within the perianth-bearing Piperales (Asarum, Saruma, Lactoris, Hydnora, Prosopanche, Thottea and Aristolochia), climbing species only occur in the most species-rich genus Aristolochia. This study traces anatomical and morphological traits among these lineages, to detect trends in growth form evolution and developmental processes. Methods Transverse stem sections of different developmental stages of representatives of Asarum, Saruma, Lactoris, Hydnora, Thottea and Aristolochia were compared and anatomical traits were linked to growth form evolution. Biomechanical properties of representative climbers were determined in three-point bending tests and are discussed based on the anatomical observations. Growth form evolution of the perianth-bearing Piperales was reconstructed by ancestral character state reconstruction using Mesquite. Key Results While species of Asarum and Saruma are exclusively herbaceous, species of the remaining genera show a higher diversity of growth habit and anatomy. This growth form diversity is accompanied by a more complex stem anatomy and appropriate biomechanical properties. The ancestral growth form of the perianth-bearing Piperales is reconstructed with either a shrub-like or herbaceous character state, while the following three backbone nodes in the reconstruction show a shrub-like character state. Accordingly, the climbing habit most probably evolved in the ancestor of Aristolochia. Conclusions Since the ancestor of the perianth-bearing Piperales has been reconstructed with a herb- or shrub-like habit, it is proposed that the climbing habit is a derived growth form, which evolved with the diversification of Aristolochia, and might have been a key feature for its diversification. Observed anatomical synapomorphies, such as the perivascular fibres in Lactoris

  14. Laser forming process development

    SciTech Connect

    Blake, R.J.

    1996-12-31

    This paper is a summary of the activities performed for the process development of laser thermal forming sheet metal parts in support of rapid prototyping. A 400 watt pulsed Nd:YAG laser and 50 watt desktop CO{sub 2} laser were used during initial process development. Several tool-assisted laser forming approaches were conceived during the development of the process, and simple fixtures for process development/understanding were used throughout all testing. Much of the actual forming was performed with the base material in an unfixtured state. CRES (304) was used for baseline development, but the effort was directed toward forming titanium (e.g., 6Al-4V, 15V-3Cr-3Sn-3Al). Several DOE (i.e., Design of Experiment) techniques were employed during development and a Neural Net Computer Model was conceived for process control. This program was a joint effort in cooperation with the American Welding Society under contract with the Defense Advanced Research Projects Agency (DARPA). A synopsis of the laser forming process development, future opportunities, and applications are presented.

  15. Methods for forming particles

    DOEpatents

    Fox, Robert V.; Zhang, Fengyan; Rodriguez, Rene G.; Pak, Joshua J.; Sun, Chivin

    2016-06-21

    Single source precursors or pre-copolymers of single source precursors are subjected to microwave radiation to form particles of a I-III-VI.sub.2 material. Such particles may be formed in a wurtzite phase and may be converted to a chalcopyrite phase by, for example, exposure to heat. The particles in the wurtzite phase may have a substantially hexagonal shape that enables stacking into ordered layers. The particles in the wurtzite phase may be mixed with particles in the chalcopyrite phase (i.e., chalcopyrite nanoparticles) that may fill voids within the ordered layers of the particles in the wurtzite phase thus produce films with good coverage. In some embodiments, the methods are used to form layers of semiconductor materials comprising a I-III-VI.sub.2 material. Devices such as, for example, thin-film solar cells may be fabricated using such methods.

  16. Changing Organizational Forms.

    ERIC Educational Resources Information Center

    1997

    This document contains three papers from a symposium on changing organizational forms. "Goal Integration in a Multi-divisional Organization" (Richard J. Torraco, Mary Finnegan), reports on a study that examined how goals are integrated into organizational activities once they have been identified, proposes a model of goal integration, and develops…

  17. Literature: External Forms.

    ERIC Educational Resources Information Center

    Regional Curriculum Project, Atlanta, GA.

    This curriculum guide, developed as part of a total English curriculum for pre-kindergarten through grade 10, suggests that students can best understand literature by understanding its recurring external forms or genres, and includes (1) an overview describing the four literary genres of drama, narrative poetry, narrative fiction, and lyric poetry…

  18. Literature: Internal Forms.

    ERIC Educational Resources Information Center

    Regional Curriculum Project, Atlanta, GA.

    This curriculum guide in literature, developed as part of a total English curriculum for pre-kindergarten through grade 10, suggests that students can best understand literature by recognizing its internal forms (i.e., characteristics that recur in settings, characters, and narrative patterns). Materials cover (1) an overview for teachers on the…

  19. Apparatus for forming targets

    DOEpatents

    Woerner, Robert L.

    1980-01-01

    Apparatus and method for cryoinduced uniform deposition of cryogenic materials, such as deuterium-tritium (DT) mixtures, on the inner surface of hollow spherical members, such as inertially imploded targets. By vaporizing and quickly refreezing cryogenic materials contained within a hollow spherical member, a uniform layer of the materials is formed on the inner surface of the spherical member. Heating of the cryogenic material, located within a non-isothermal compact freezing cell, is accomplished by an electrical heat pulse, whereafter the material is quickly frozen forming a uniform layer on the inner surface of the spherical member. The method is not restricted to producing a frozen layer on only the inner surface of the innermost hollow member, but where multiple concentric hollow spheres are involved, such as in multiple shell targets for lasers, electron beams, etc., layers of cryogenic material may also be formed on the inner surface of intermediate or outer spherical members, thus providing the capability of forming targets having multiple concentric layers or shells of frozen DT.

  20. Method for forming targets

    DOEpatents

    Woerner, Robert L.

    1979-01-01

    Method for cryoinduced uniform deposition of cryogenic materials, such as deuterium-tritium (DT) mixtures, on the inner surface of hollow spherical members, such as inertially imploded targets. By vaporizing and quickly refreezing cryogenic materials contained within a hollow spherical member, a uniform layer of the materials is formed on the inner surface of the spherical member. Heating of the cryogenic material, located within a non-isothermal compact freezing cell, is accomplished by an electrical heat pulse, whereafter the material is quickly frozen forming a uniform layer on the inner surface of the spherical member. The method is not restricted to producing a frozen layer on only the inner surface of the innermost hollow member, but where multiple concentric hollow spheres are involved, such as in multiple shell targets for lasers, electron beams, etc., layers of cryogenic material may also be formed on the inner surface of intermediate or outer spherical members, thus providing the capability of forming targets having multiple concentric layers or shells of frozen DT.

  1. Inelastic Scattering Form Factors

    Energy Science and Technology Software Center (ESTSC)

    1992-01-01

    ATHENA-IV computes form factors for inelastic scattering calculations, using single-particle wave functions that are eigenstates of motion in either a Woods-Saxon potential well or a harmonic oscillator well. Two-body forces of Gauss, Coulomb, Yukawa, and a sum of cut-off Yukawa radial dependences are available.

  2. Forms of Soft Sculpture

    ERIC Educational Resources Information Center

    Tucker, Dorothy

    1978-01-01

    For the past several years, students at Madison Senior High School in San Diego have responded to the tactile texture and draping quality of soft materials. They experimented enthusiastically with three-dimensional forms made out of foam rubber. Here is the result of their efforts and experimentation. (Author/RK)

  3. High energy forming facility

    NASA Technical Reports Server (NTRS)

    Ciurlionis, B.

    1967-01-01

    Watertight, high-explosive forming facility, 25 feet in diameter and 15 feet deep, withstands repeated explosions of 10 pounds of TNT equivalent. The shell is fabricated of high strength steel and allows various structural elements to deform or move elastically and independently while retaining structural integrity.

  4. Many Forms of Culture

    ERIC Educational Resources Information Center

    Cohen, Adam B.

    2009-01-01

    Psychologists interested in culture have focused primarily on East-West differences in individualism-collectivism, or independent-interdependent self-construal. As important as this dimension is, there are many other forms of culture with many dimensions of cultural variability. Selecting from among the many understudied cultures in psychology,…

  5. Formed photovoltaic module busbars

    DOEpatents

    Rose, Douglas; Daroczi, Shan; Phu, Thomas

    2015-11-10

    A cell connection piece for a photovoltaic module is disclosed herein. The cell connection piece includes an interconnect bus, a plurality of bus tabs unitarily formed with the interconnect bus, and a terminal bus coupled with the interconnect bus. The plurality of bus tabs extend from the interconnect bus. The terminal bus includes a non-linear portion.

  6. Geodiversity and land form

    NASA Astrophysics Data System (ADS)

    Gray, Murray

    2014-05-01

    The Earth's surface has a dynamic and topographically varied natural landscape. In some cases the resulting landforms are given generic names reflecting their form and/or origin, (e.g. sand dunes, eskers, ox-bow lakes) but in many cases the land surface has a more amorphous form and is less easily categorized other than at a landscape scale (e.g. dissected plateau, Chalk downland). Across much of Europe, while the natural vegetation has been removed or radically modified, the natural land form/topography remains in tact. In this context and in terms of geoconservation we ought to be: • allowing the dynamic natural processes that create, carve and modify landscapes to continue to operate; and • retaining natural topographic character and geomorphological authenticity in the face of human actions seeking to remodel the land surface. In this presentation examples of this approach to geoconservation of land form will be given from the UK and other parts of the world. This will include examples of both appropriate and inappropriate topographic modifications.

  7. Waste-form development

    SciTech Connect

    Neilson, R.M. Jr.; Colombo, P.

    1982-01-01

    Contemporary solidification agents are being investigated relative to their applications to major fuel cycle and non-fuel cycle low-level waste (LLW) streams. Work is being conducted to determine the range of conditions under which these solidification agents can be applied to specific LLW streams. These studies are directed primarily towards defining operating parameters for both improved solidification of problem wastes and solidification of new LLW streams generated from advanced volume reduction technologies. Work is being conducted to measure relevant waste form properties. These data will be compiled and evaluated to demonstrate compliance with waste form performance and shallow land burial acceptance criteria and transportation requirements (both as they exist and as they are modified with time).

  8. Formed HIP Can Processing

    SciTech Connect

    Clarke, Kester Diederik

    2015-07-27

    The intent of this report is to document a procedure used at LANL for HIP bonding aluminum cladding to U-10Mo fuel foils using a formed HIP can for the Domestic Reactor Conversion program in the NNSA Office of Material, Management and Minimization, and provide some details that may not have been published elsewhere. The HIP process is based on the procedures that have been used to develop the formed HIP can process, including the baseline process developed at Idaho National Laboratory (INL). The HIP bonding cladding process development is summarized in the listed references. Further iterations with Babcock & Wilcox (B&W) to refine the process to meet production and facility requirements is expected.

  9. Nucleon Electromagnetic Form Factors

    SciTech Connect

    Kees de Jager

    2004-08-01

    Although nucleons account for nearly all the visible mass in the universe, they have a complicated structure that is still incompletely understood. The first indication that nucleons have an internal structure, was the measurement of the proton magnetic moment by Frisch and Stern (1933) which revealed a large deviation from the value expected for a point-like Dirac particle. The investigation of the spatial structure of the nucleon, resulting in the first quantitative measurement of the proton charge radius, was initiated by the HEPL (Stanford) experiments in the 1950s, for which Hofstadter was awarded the 1961 Nobel prize. The first indication of a non-zero neutron charge distribution was obtained by scattering thermal neutrons off atomic electrons. The recent revival of its experimental study through the operational implementation of novel instrumentation has instigated a strong theoretical interest. Nucleon electro-magnetic form factors (EMFFs) are optimally studied through the exchange of a virtual photon, in elastic electron-nucleon scattering. The momentum transferred to the nucleon by the virtual photon can be selected to probe different scales of the nucleon, from integral properties such as the charge radius to scaling properties of its internal constituents. Polarization instrumentation, polarized beams and targets, and the measurement of the polarization of the recoiling nucleon have been essential in the accurate separation of the charge and magnetic form factors and in studies of the elusive neutron charge form factor.

  10. Electromagnetic pion form factor

    SciTech Connect

    Roberts, C.D.

    1995-08-01

    A phenomenological Dyson-Schwinger/Bethe-Salpeter equation approach to QCD, formalized in terms of a QCD-based model field theory, the Global Color-symmetry Model (GCM), was used to calculate the generalized impulse approximation contribution to the electromagnetic pion form factor at space-like q{sup 2} on the domain [0,10] GeV{sup 2}. In effective field theories this form factor is sometimes understood as simply being due to Vector Meson Dominance (VMD) but this does not allow for a simple connection with QCD where the VMD contribution is of higher order than that of the quark core. In the GCM the pion is treated as a composite bound state of a confined quark and antiquark interacting via the exchange of colored vector-bosons. A direct study of the quark core contribution is made, using a quark propagator that manifests the large space-like-q{sup 2} properties of QCD, parameterizes the infrared behavior and incorporates confinement. It is shown that the few parameters which characterize the infrared form of the quark propagator may be chosen so as to yield excellent agreement with the available data. In doing this one directly relates experimental observables to properties of QCD at small space-like-q{sup 2}. The incorporation of confinement eliminates endpoint and pinch singularities in the calculation of F{sub {pi}}(q{sup 2}). With asymptotic freedom manifest in the dressed quark propagator the calculation yields q{sup 4}F{sub {pi}}(q{sup 2}) = constant, up to [q{sup 2}]- corrections, for space-like-q{sup 2} {approx_gt} 35 GeV{sup 2}, which indicates that soft, nonperturbative contributions dominate the form factor at presently accessible q{sup 2}. This means that the often-used factorization Ansatz fails in this exclusive process. A paper describing this work was submitted for publication. In addition, these results formed the basis for an invited presentation at a workshop on chiral dynamics and will be published in the proceedings.

  11. Space form of motionsickness

    NASA Technical Reports Server (NTRS)

    Komendantov, G. L.; Kopanev, V. I.

    1975-01-01

    Spacesickness under weightlessness conditions is explained mainly by disruption of the activity of the functional system perceiving space and participating in carrying out the balancing function, consisting, in particular, of the vestibular, proprioceptive, interoceptive, visual and cutaneomechanical analyzers. It can be assumed that, under specific conditions, Coriolis acceleration also is a cause of spacesickness. Adaptation is possible by formation of a new functional system which is adequate to the new mechanical conditions of weightlessness. Selection, training, creation of optimum conditions in the spacecraft cabin, medicinal, and technical improvement of spacecraft play an important role in prophylaxis of the space form of seasickness.

  12. Nucleon elastic form factors

    SciTech Connect

    D. Day

    2007-03-01

    The nucleon form factors are still the subject of active investigation even after an experimental effort spanning 50 years. This is because they are of critical importance to our understanding of the electromagnetic properties of nuclei and provide a unique testing ground for QCD motivated models of nucleon structure. Progress in polarized beams, polarized targets and recoil polarimetry have allowed an important and precise set of data to be collected over the last decade. I will review the experimental status of elastic electron scattering from the nucleon along with an outlook for future progress.

  13. GlassForm

    Energy Science and Technology Software Center (ESTSC)

    2011-09-16

    GlassForm is a software tool for generating preliminary waste glass formulas for a given waste stream. The software is useful because it reduces the number of verification melts required to develop a suitable additive composition. The software includes property models that calculate glass properties of interest from the chemical composition of the waste glass. The software includes property models for glass viscosity, electrical conductivity, glass transition temperature, and leach resistance as measured by the 7-daymore » product consistency test (PCT).« less

  14. Spun Almost Normal Form

    NASA Astrophysics Data System (ADS)

    Paullin, Katherine L.

    Many of a 3-manifold's properties are determined by the surfaces they contain, and this knowledge leads to the foundation of decision algorithms for 3- manifolds. Popular work influencing the work of 3-manifold algorithms has it's roots in normal surface theory. In a triangulated 3-manifold, Haken and Kneser showed that we could put any incompressible surface into normal form. Expanding on those techniques, Rubinstein and Stocking later showed we could put any strongly irreducible surface into almost normal form. Walsh has more recently shown that in an ideal triangulation of a hyperbolic manifold many surfaces can be spun normalized. One unsolved problem in 3-manifold algorithms is studying the complexity of Lens Space Recognition. Spun almost normalization appears to be a part of solving this larger problem. In this dissertation, I will first discuss a nontraditional technique using graphs of equivalence classes of compressing disks that allows us to take a combinatorial approach to generalize the result of Walsh's to nonhyperbolic manifolds. Using that method, I'll also explore the conditions needed to show that a surface can be spun almost normalized.

  15. MLKL forms cation channels

    PubMed Central

    Xia, Bingqing; Fang, Sui; Chen, Xueqin; Hu, Hong; Chen, Peiyuan; Wang, Huayi; Gao, Zhaobing

    2016-01-01

    The mixed lineage kinase domain-like (MLKL) protein is a key factor in tumor necrosis factor-induced necroptosis. Recent studies on necroptosis execution revealed a commitment role of MLKL in membrane disruption. However, our knowledge of how MLKL functions on membrane remains very limited. Here we demonstrate that MLKL forms cation channels that are permeable preferentially to Mg2+ rather than Ca2+ in the presence of Na+ and K+. Moreover, the N-terminal domain containing six helices (H1-H6) is sufficient to form channels. Using the substituted cysteine accessibility method, we further determine that helix H1, H2, H3, H5 and H6 are transmembrane segments, while H4 is located in the cytoplasm. Finally, MLKL-induced membrane depolarization and cell death exhibit a positive correlation to its channel activity. The Mg2+-preferred permeability and five transmembrane segment topology distinguish MLKL from previously identified Mg2+-permeable channels and thus establish MLKL as a novel class of cation channels. PMID:27033670

  16. Bipolar pulse forming line

    DOEpatents

    Rhodes, Mark A.

    2008-10-21

    A bipolar pulse forming transmission line module for linear induction accelerators having first, second, third, fourth, and fifth planar conductors which form an interleaved stack with dielectric layers between the conductors. Each conductor has a first end, and a second end adjacent an acceleration axis. The first and second planar conductors are connected to each other at the second ends, the fourth and fifth planar conductors are connected to each other at the second ends, and the first and fifth planar conductors are connected to each other at the first ends via a shorting plate adjacent the first ends. The third planar conductor is electrically connectable to a high voltage source, and an internal switch functions to short a high voltage from the first end of the third planar conductor to the first end of the fourth planar conductor to produce a bipolar pulse at the acceleration axis with a zero net time integral. Improved access to the switch is enabled by an aperture through the shorting plate and the proximity of the aperture to the switch.

  17. 78 FR 58605 - Proposed Collection; Comment Request for Form 8453-EMP, Form 8453-F, Form 8453-FE, Form 8879-F...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-24

    ... 8879-F, IRS e-file Signature Authorization for Form 1041. DATES: Written comments should be received on... (Form 1041). Title: U.S. Estate or Trust Declaration and Signature for an IRS e- File Return. OMB Number... Electronic Filing. This form will only be used as a signature letter to Form 1041. This new form...

  18. Pion form factor

    SciTech Connect

    Ryong Ji, C.; Pang, A.; Szczepaniak, A.

    1994-04-01

    It is pointed out that the correct criterion to define the legal PQCD contribution to the exclusive processes in the lightcone perturbative expansion should be based on the large off-shellness of the lightcone energy in the intermediate states. In the lightcone perturbative QCD calculation of the pion form factor, the authors find that the legal PQCD contribution defined by the lightcone energy cut saturates in the smaller Q{sup 2} region compared to that defined by the gluon four-momentum square cut. This is due to the contribution by the highly off-energy-shell gluons in the end point regions of the phase space, indicating that the gluon four-momentum-square cut may have cut too much to define the legal PQCD.

  19. Shell forming system

    NASA Technical Reports Server (NTRS)

    Kendall, Jr., James M. (Inventor); Wang, Taylor G. (Inventor); Elleman, Daniel D. (Inventor)

    1987-01-01

    An apparatus is provided for forming gas-filled spheres of metal, glass or other material, which produces spheres (12) of uniform size and wall thickness in a relatively simple system. The system includes concentric nozzles, including an inner nozzle (18) through which gas flows and and an outer nozzle (20), which jointly define an annular passageway (50) through which a liquid flows. The flow rates are adjusted so that the gas flows at greater velocity than does the liquid, out of their respective nozzles, e.g. three times as great, in order to produce an extrusion (30) which undergoes axisymmetric oscillations resulting in the pinch off into hollow spheres with very uniform spacing. The system is useful not only where gas-filled spheres are required, but also is useful to accurately control the dispensing of solid, liquid, or gaseous materials.

  20. Shell forming apparatus

    NASA Technical Reports Server (NTRS)

    Wang, Taylor G. (Inventor); Granett, Dan (Inventor); Akutagawa, Wesley M. (Inventor)

    1987-01-01

    A nozzle assembly is described for use in a system that forms small gas-filled shells, which avoids the need for holding a miniature inner nozzle precisely concentric with a miniature outer nozzle. The outer nozzle has a diameter which is less than about 0.7 millimeter, which results in fluid passing through the nozzle having a progressively greater velocity at locations progressively further from the walls of the outer nozzle across most of the nozzle. This highly variable velocity profile automatically forces gas to the center of the outer nozzle. The end of the inner nozzle, which emits gas, is spaced upstream from the tip of the outer nozzle, to provide a distance along which to center the gas. This self-centering characteristic permits the inner nozzle to be positioned so its axis is not concentric with the axis of the outer nozzle.

  1. Nucleon Electromagnetic Form Factors

    SciTech Connect

    Marc Vanderhaeghen; Charles Perdrisat; Vina Punjabi

    2007-10-01

    There has been much activity in the measurement of the elastic electromagnetic proton and neutron form factors in the last decade, and the quality of the data has greatly improved by performing double polarization experiments, in comparison with previous unpolarized data. Here we review the experimental data base in view of the new results for the proton, and neutron, obtained at JLab, MAMI, and MIT-Bates. The rapid evolution of phenomenological models triggered by these high-precision experiments will be discussed, including the recent progress in the determination of the valence quark generalized parton distributions of the nucleon, as well as the steady rate of improvements made in the lattice QCD calculations.

  2. Spray-formed tooling

    SciTech Connect

    McHugh, K.M.; Key, J.F.

    1994-12-31

    The United States Council for Automotive Research (USCAR) has formed a partnership with the Idaho National Engineering Laboratory (INEL) to develop a process for the rapid production of low-cost tooling based on spray forming technology developed at the INEL. Phase 1 of the program will involve bench-scale system development, materials characterization, and process optimization. In Phase 2, prototype systems will be de signed, constructed, evaluated, and optimized. Process control and other issues that influence commercialization will be addressed during this phase of the project. Technology transfer to USCAR, or a tooling vendor selected by USCAR, will be accomplished during Phase 3. The approach INEL is using to produce tooling, such as plastic injection molds and stamping dies, combines rapid solidification processing and net-shape materials processing into a single step. A bulk liquid metal is pressure-fed into a de Laval spray nozzle transporting a high velocity, high temperature inert gas. The gas jet disintegrates the metal into fine droplets and deposits them onto a tool pattern made from materials such as plastic, wax, clay, ceramics, and metals. The approach is compatible with solid freeform fabrication techniques such as stereolithography, selective laser sintering, and laminated object manufacturing. Heat is extracted rapidly, in-flight, by convection as the spray jet entrains cool inert gas to produce undercooled and semi-solid droplets. At the pattern, the droplets weld together while replicating the shape and surface features of the pattern. Tool formation is rapid; deposition rates in excess of 1 ton/h have been demonstrated for bench-scale nozzles.

  3. Spray-formed tooling

    NASA Astrophysics Data System (ADS)

    McHugh, K. M.; Key, J. F.

    The United States Council for Automotive Research (USCAR) has formed a partnership with the Idaho National Engineering Laboratory (INEL) to develop a process for the rapid production of low-cost tooling based on spray forming technology developed at the INEL. Phase 1 of the program will involve bench-scale system development, materials characterization, and process optimization. In Phase 2, prototype systems will be designed, constructed, evaluated, and optimized. Process control and other issues that influence commercialization will be addressed during this phase of the project. Technology transfer to USCAR, or a tooling vendor selected by USCAR, will be accomplished during Phase 3. The approach INEL is using to produce tooling, such as plastic injection molds and stamping dies, combines rapid solidification processing and net-shape materials processing into a single step. A bulk liquid metal is pressure-fed into a de Laval spray nozzle transporting a high velocity, high temperature inert gas. The gas jet disintegrates the metal into fine droplets and deposits them onto a tool pattern made from materials such as plastic, wax, clay, ceramics, and metals. The approach is compatible with solid freeform fabrication techniques such as stereolithography, selective laser sintering, and laminated object manufacturing. Heat is extracted rapidly, in-flight, by convection as the spray jet entrains cool inert gas to produce undercooled and semi-solid droplets. At the pattern, the droplets weld together while replicating the shape and surface features of the pattern. Tool formation is rapid; deposition rates in excess of 1 ton/h have been demonstrated for bench-scale nozzles.

  4. Forming Spirals From Shadows

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-07-01

    What causes the large-scale spiral structures found in some protoplanetary disks? Most models assume theyre created by newly-forming planets, but a new study suggests that planets might have nothing to do with it.Perturbations from Planets?In some transition disks protoplanetary disks with gaps in their inner regions weve directly imaged large-scale spiral arms. Many theories currently attribute the formation of these structures to young planets: either the direct perturbations of a planet embedded in the disk cause the spirals, or theyre indirectly caused by the orbit of a planetary body outside of the arms.Another example of spiral arms detected in a protoplanetary disk, MWC 758. [NASA/ESA/ESO/M. Benisty et al.]But what if you could get spirals without any planets? A team of scientists led by Matas Montesinos (University of Chile) have recently published a study in which they examine what happens to a shadowed protoplanetary disk.Casting Shadows with WarpsIn the teams setup, they envision a protoplanetary disk that is warped: the inner region is slightly tilted relative to the outer region. As the central star casts light out over its protoplanetary disk, this disk warping would cause some regions of the disk to be shaded in a way that isnt axially symmetric with potentially interesting implications.Montesinos and collaborators ran 2D hydrodynamics simulations to determine what happens to the motion of particles within the disk when they pass in and out of the shadowed regions. Since the shadowed regions are significantly colder than the illuminated disk, the pressure in these regions is much lower. Particles are therefore accelerated and decelerated as they pass through these regions, and the lack of axial symmetry causes spiral density waves to form in the disk as a result.Initial profile for the stellar heating rate per unit area for one of the authors simulations. The regions shadowed as a result of the disk warp subtend 0.5 radians each (shown on the left

  5. Moon (Form-Origin)

    NASA Astrophysics Data System (ADS)

    Tsiapas, Elias

    2014-05-01

    When the Earth was formed, it was in a state of burning heat. As time went by, temperature on the planet's surface was falling due to radiation and heat transfer, and various components (crusts) began taking solid form at the Earth's poles. The formation of crusts took place at the Earth's poles, because the stirring of burning and fluid masses on the surface of the Earth was significantly slighter there than it was on the equator. Due to centrifugal force and Coriolis Effect, these solid masses headed towards the equator; those originating from the North Pole followed a south-western course, while those originating from the South Pole followed a north-western course and there they rotated from west to east at a lower speed than the underlying burning and liquid earth, because of their lower initial linear velocity, their solid state and inertia. Because inertia is proportional to mass, the initially larger solid body swept all new solid ones, incorporating them to its western side. The density of the new solid masses was higher, because the components on the surface would freeze and solidify first, before the underlying thicker components. As a result, the western side of the initial islet of solid rocks submerged, while the east side elevated. . As a result of the above, this initial islet began to spin in reverse, and after taking on the shape of a sphere, it formed the "heart" of the Moon. The Moon-sphere, rolling on the equator, would sink the solid rocks that continued to descend from the Earth's poles. The sinking rocks partially melted because of higher temperatures in the greater depths that the Moon descended to, while part of the rocks' mass bonded with the Moon and also served as a heat-insulating material, preventing the descended side of the sphere from melting. Combined with the Earth's liquid mass that covered its emerging eastern surface, new sphere-shaped shells were created, with increased density and very powerful structural cohesion. During the

  6. Moon (Form-Origin)

    NASA Astrophysics Data System (ADS)

    Tsiapas, Elias

    2015-04-01

    When the Earth was formed, it was in a state of burning heat. As time went by, temperature on the planet's surface was falling due to radiation and heat transfer, and various components (crusts) began taking solid form at the Earth's poles. The formation of crusts took place at the Earth's poles, because the stirring of burning and fluid masses on the surface of the Earth was significantly slighter there than it was on the equator. Due to centrifugal force and Coriolis Effect, these solid masses headed towards the equator; those originating from the North Pole followed a south-western course, while those originating from the South Pole followed a north-western course and there they rotated from west to east at a lower speed than the underlying burning and liquid earth, because of their lower initial linear velocity, their solid state and inertia. Because inertia is proportional to mass, the initially larger solid body swept all new solid ones, incorporating them to its western side. The density of the new solid masses was higher, because the components on the surface would freeze and solidify first, before the underlying thicker components. As a result, the western side of the initial islet of solid rocks submerged, while the east side elevated. . As a result of the above, this initial islet began to spin in reverse, and after taking on the shape of a sphere, it formed the "heart" of the Moon. The Moon-sphere, rolling on the equator, would sink the solid rocks that continued to descend from the Earth's poles. The sinking rocks partially melted because of higher temperatures in the greater depths that the Moon descended to, while part of the rocks' mass bonded with the Moon and also served as a heat-insulating material, preventing the descended side of the sphere from melting. Combined with the Earth's liquid mass that covered its emerging eastern surface, new sphere-shaped shells were created, with increased density and very powerful structural cohesion. During the

  7. Moon (Form-Origin)

    NASA Astrophysics Data System (ADS)

    Tsiapas, Elias

    2016-04-01

    When the Earth was formed, it was in a state of burning heat. As time went by, temperature on the planet's surface was falling due to radiation and heat transfer, and various components (crusts) began taking solid form at the Earth's poles. The formation of crusts took place at the Earth's poles, because the stirring of burning and fluid masses on the surface of the Earth was significantly slighter there than it was on the equator. Due to centrifugal force and Coriolis Effect, these solid masses headed towards the equator; those originating from the North Pole followed a south-western course, while those originating from the South Pole followed a north-western course and there they rotated from west to east at a lower speed than the underlying burning and liquid earth, because of their lower initial linear velocity, their solid state and inertia. Because inertia is proportional to mass, the initially larger solid body swept all new solid ones, incorporating them to its western side. The density of the new solid masses was higher, because the components on the surface would freeze and solidify first, before the underlying thicker components. As a result, the western side of the initial islet of solid rocks submerged, while the east side elevated. . As a result of the above, this initial islet began to spin in reverse, and after taking on the shape of a sphere, it formed the "heart" of the Moon. The Moon-sphere, rolling on the equator, would sink the solid rocks that continued to descend from the Earth's poles. The sinking rocks partially melted because of higher temperatures in the greater depths that the Moon descended to, while part of the rocks' mass bonded with the Moon and also served as a heat-insulating material, preventing the descended side of the sphere from melting. Combined with the Earth's liquid mass that covered its emerging eastern surface, new sphere-shaped shells were created, with increased density and very powerful structural cohesion. During the

  8. New education coalition formed

    NASA Astrophysics Data System (ADS)

    Watt Ireto, M. Frank

    The Coalition for Earth Science Education (CESE) was recently formed to promote Earth science education at all levels. Earth science is a diverse group of sciences and as a result, professional and academic organizations from the various areas, though united in their goal to stimulate student enthusiasm for the Earth sciences, have not had an effective way of reaching students or their precollege teachers. Over the past year, meetings sponsored by the National Academy of Science's Board on Earth Sciences and Resources and the National Science Foundation have paved the way for this coalition. Victor Mayer, Director of the Program for Leadership in Earth Systems Science (PLESE) project at the University of Ohio, has been the leader in initiating and promoting this effort for the last several years.The purpose of CESE is to promote communication among the member organizations and to coordinate projects in Earth science education. Individual organizations will continue to develop and run projects, but will be able to find out what types of projects others are working on or have completed through a coalition clearinghouse. The clearinghouse should aid organizations as they design projects and should afford opportunities for collaborative efforts. This will directly benefit teachers, who will be able to contact one source for information on the multitude of projects in the Earth and space sciences. The new coalition's steering committee is working on goals and guidelines, and will give a report at the next coalition meeting at the National Science Teachers Association annual convention in Boston.

  9. How delusion is formed?

    PubMed

    Park, Jong Suk; Kang, Ung Gu

    2016-02-01

    Traditionally, delusions have been considered to be the products of misinterpretation and irrationality. However, some theorists have argued that delusions are normal or rational cognitive responses to abnormal experiences. That is, when a recently experienced peculiar event is more plausibly explained by an extraordinary hypothesis, confidence in the veracity of this extraordinary explanation is reinforced. As the number of such experiences, driven by the primary disease process in the perceptual domain, increases, this confidence builds and solidifies, forming a delusion. We tried to understand the formation of delusions using a simulation based on Bayesian inference. We found that (1) even if a delusional explanation is only marginally more plausible than a non-delusional one, the repetition of the same experience results in a firm belief in the delusion. (2) The same process explains the systematization of delusions. (3) If the perceived plausibility of the explanation is not consistent but varies over time, the development of a delusion is delayed. Additionally, this model may explain why delusions are not corrected by persuasion or rational explanation. This Bayesian inference perspective can be considered a way to understand delusions in terms of rational human heuristics. However, such experiences of "rationality" can lead to irrational conclusions, depending on the characteristics of the subject. PMID:26826642

  10. How desert varnish forms?

    NASA Astrophysics Data System (ADS)

    Perry, Randall S.; Kolb, Vera M.; Lynne, Bridget Y.; Sephton, Mark A.; Mcloughlin, Nicola; Engel, Michael H.; Olendzenski, Lorraine; Brasier, Martin; Staley, James T., Jr.

    2005-09-01

    Desert varnish is a black, manganese-rich rock coating that is widespread on Earth. The mechanism underlying its formation, however, has remained unresolved. We present here new data and an associated model for how desert varnish forms, which substantively challenges previously accepted models. We tested both inorganic processes (e.g. clays and oxides cementing coatings) and microbial methods of formation. Techniques used in this preliminary study include SEM-EDAX with backscatter, HRTEM of focused ion beam prepared (FIB) wafers and several other methods including XRPD, Raman spectroscopy, XPS and Tof-SIMS. The only hypothesis capable of explaining a high water content, the presence of organic compounds, an amorphous silica phase (opal-A) and lesser quantities of clays than previously reported, is a mechanism involving the mobilization and redistribution of silica. The discovery of silica in desert varnish suggests labile organics are preserved by interaction with condensing silicic acid. Organisms are not needed for desert varnish formation but Bacteria, Archaea, Eukarya, and other organic compounds are passively incorporated and preserved as organominerals. The rock coatings thus provide useful records of past environments on Earth and possibly other planets. Additionally this model also helps to explain the origin of key varnish and rock glaze features, including their hardness, the nature of the "glue" that binds heterogeneous components together, its layered botryoidal morphology, and its slow rate of formation.

  11. Watching How Planets Form

    NASA Astrophysics Data System (ADS)

    2006-09-01

    Anatomy of a Planet-Forming Disc around a Star More Massive than the Sun With the VISIR instrument on ESO's Very Large Telescope, astronomers have mapped the disc around a star more massive than the Sun. The very extended and flared disc most likely contains enough gas and dust to spawn planets. It appears as a precursor of debris discs such as the one around Vega-like stars and thus provides the rare opportunity to witness the conditions prevailing prior to or during planet formation. "Planets form in massive, gaseous and dusty proto-planetary discs that surround nascent stars. This process must be rather ubiquitous as more than 200 planets have now been found around stars other than the Sun," said Pierre-Olivier Lagage, from CEA Saclay (France) and leader of the team that carried out the observations. "However, very little is known about these discs, especially those around stars more massive than the Sun. Such stars are much more luminous and could have a large influence on their disc, possibly quickly destroying the inner part." The astronomers used the VISIR instrument [1] on ESO's Very Large Telescope to map in the infrared the disc surrounding the young star HD 97048. With an age of a few million years [2], HD 97048 belongs to the Chameleon I dark cloud, a stellar nursery 600 light-years away. The star is 40 times more luminous than our Sun and is 2.5 times as massive. The astronomers could only have achieved such a detailed view due to the high angular resolution offered by an 8-metre size telescope in the infrared, reaching a resolution of 0.33 arcsecond. They discovered a very large disc, at least 12 times more extended than the orbit of the farthest planet in the Solar System, Neptune. The observations suggest the disc to be flared. "This is the first time such a structure, predicted by some theoretical models, is imaged around a massive star," said Lagage. ESO PR Photo 36/06 ESO PR Photo 36/06 A Flared Proto-Planetary Disc Such a geometry can only be

  12. Waste form product characteristics

    SciTech Connect

    Taylor, L.L.; Shikashio, R.

    1995-01-01

    The Department of Energy has operated nuclear facilities at the Idaho National Engineering Laboratory (INEL) to support national interests for several decades. Since 1953, it has supported the development of technologies for the storage and reprocessing of spent nuclear fuels (SNF) and the resultant wastes. However, the 1992 decision to discontinue reprocessing of SNF has left nearly 768 MT of SNF in storage at the INEL with unspecified plans for future dispositioning. Past reprocessing of these fuels for uranium and other resource recovery has resulted in the production of 3800 M{sup 3} calcine and a total inventory of 7600 M{sup 3} of radioactive liquids (1900 M{sup 3} destined for immediate calcination and the remaining sodium-bearing waste requiring further treatment before calcination). These issues, along with increased environmental compliance within DOE and its contractors, mandate operation of current and future facilities in an environmentally responsible manner. This will require satisfactory resolution of spent fuel and waste disposal issues resulting from the past activities. A national policy which identifies requirements for the disposal of SNF and high level wastes (HLW) has been established by the Nuclear Waste Policy Act (NWPA) Sec.8,(b) para(3)) [1982]. The materials have to be conditioned or treated, then packaged for disposal while meeting US Environmental Protection Agency (EPA) and Nuclear Regulatory Commission (NRC) regulations. The spent fuel and HLW located at the INEL will have to be put into a form and package that meets these regulatory criteria. The emphasis of Idaho Chemical Processing Plant (ICPP) future operations has shifted toward investigating, testing, and selecting technologies to prepare current and future spent fuels and waste for final disposal. This preparation for disposal may include mechanical, physical and/or chemical processes, and may differ for each of the various fuels and wastes.

  13. Doing Focus-on-Form.

    ERIC Educational Resources Information Center

    Ellis, Rod; Basturkmen, Helen; Loewen, Shawn

    2002-01-01

    Considers the rationale for using a focus on form approach to teaching form as opposed to the more traditional focus on forms approach where linguistic features are treated sequentially. Describes methodological options for attending to form in communication. (Author/VWL)

  14. Science Grade 7, Long Form.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Bureau of Curriculum Development.

    The Grade 7 Science course of study was prepared in two parallel forms. A short form designed for students who had achieved a high measure of success in previous science courses; the long form for those who have not been able to maintain the pace. Both forms contain similar content. The Grade 7 guide is the first in a three-year sequence for…

  15. Heated die facilitates tungsten forming

    NASA Technical Reports Server (NTRS)

    Chattin, J. H.; Haystrick, J. E.; Laughlin, J. C.; Leidy, R. A.

    1966-01-01

    Tungsten forming in a press brake employs a bottom die assembly with a heating manifold between two water-cooled die sections. The manifold has hydrogen-oxygen burners spaced along its length for even heat during forming.

  16. Investigating Form-Focused Instruction.

    ERIC Educational Resources Information Center

    Ellis, Rod

    2001-01-01

    Provides an historical sketch of form-focused instruction research, defines what is meant by form-focused instruction, and discusses the main research methods that have been used to investigate form-focused instruction in terms of a broad distinction between confirmatory and interpretive research. (Author/VWL)

  17. Warm Forming of Mg Sheets: From Incremental to Electromagnetic Forming

    NASA Astrophysics Data System (ADS)

    Ulacia, Ibai; Galdos, Lander; Esnaola, Jon Ander; Larrañaga, Jon; Arruebarrena, Gurutze; de Argandoña, Eneko Saenz; Hurtado, Iñaki

    2014-07-01

    Magnesium alloys are generating interest in the automotive and aeronautic industries due to their low density and potential to reduce gross vehicular weight. However, the formability of these alloys is poor and they are very difficult to be formed at room temperature due to their strong basal texture in rolled form. In this paper, the potential of magnesium alloy sheets to be processed at warm conditions is studied for four different forming technologies: incremental forming (IF), deep drawing (DD), hydroforming (HF), and electromagnetic forming (EMF). Forming mechanisms and process window are experimentally characterized by monitoring different process parameters. Special focus is made on the influence of the forming temperature and the strain rate. Thus, experiments at temperatures from room to 523 K (250 °C) and a wide range of strain rates, between 10-3 up to 103 s-1 according to each process nature and scope, are conducted. It is observed that, even the inherent forming rate range of each process vary considerably, increasing forming temperature increases formability for all of these forming processes. In the other hand, an opposing effect of the strain rate is observed between the quasi-static processes (IF, DD, and HF) and the high speed process (EMF). Thus, a detrimental effect on formability is observed when increasing strain rate for quasi-static processes, while a mild increase is observed for EMF.

  18. Perivascular Inflammatory Reaction After Percutaneous Placement of Covered Stents

    SciTech Connect

    Link, Johann; Mueller-Huelsbeck, Stefan; Brossmann, Joachim; Steffens, Johann C.; Heller, Martin

    1996-09-15

    A 52-year-old woman with an extensive superficial femoral artery occlusion was treated with percutaneous transluminal angioplasty. Because of extensive dissections, two covered stents were placed percutaneously. The intervention was successful with respect to vessel patency, but local pain and fever developed 5 hr after the intervention. Swelling of the thigh occurred, but deep venous thrombosis was excluded. MRI revealed pronounced soft-tissue edema in the adductor canal that persisted for 4 weeks. The fever responded to antiinflammatory medication, but the pain remained for 4 weeks. The vessel was patent at the last follow-up, 8 weeks after graft placement. Soft-tissue edema after percutaneous placement of covered stents has been reported previously. The cause of the inflammatory reaction is unclear.

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

    PubMed

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

    2012-12-10

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

  20. Laminin isoforms in endothelial and perivascular basement membranes

    PubMed Central

    Yousif, Lema F.; Di Russo, Jacopo; Sorokin, Lydia

    2013-01-01

    Laminins, one of the major functional components of basement membranes, are found underlying endothelium, and encasing pericytes and smooth muscle cells in the vessel wall. Depending on the type of blood vessel (capillary, venule, postcapillary venule, vein or artery) and their maturation state, both the endothelial and mural cell phenotype vary, with associated changes in laminin isoform expression. Laminins containing the α4 and α5 chains are the major isoforms found in the vessel wall, with the added contribution of laminin α2 in larger vessels. We here summarize current data on the precise localization of these laminin isoforms and their receptors in the different layers of the vessel wall, and their potential contribution to vascular homeostasis. PMID:23263631

  1. Index of NASA prefixed forms

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This Handbook sets forth information for the guidance of all users of the NASA Forms Management Program System. It is issued in accordance with the Federal Information Resources Management Regulation (FIRMR), Subpart 201-9.1. This Handbook sets forth an alpha-functional index of NASA-prefixed forms by title, identifying number, and unit of issue. The automated processing two-letter code (NF) has been substituted for the spelling out of the NASA form-prefix preceding the form number. To indicate a description in lieu of a distinct title, the entire reference under the Form Title/Description column has been enclosed in parentheses. A list of current forms, shown by number and page, is included for cross-reference and to preclude the ordering of those forms which have been deleted from the system. This Handbook will be updated, as appropriate. NHB 1420.2H dated July 1986, is cancelled.

  2. The semantics of biological forms.

    PubMed

    Albertazzi, Liliana; Canal, Luisa; Dadam, James; Micciolo, Rocco

    2014-01-01

    This study analyses how certain qualitative perceptual appearances of biological forms are correlated with expressions of natural language. Making use of the Osgood semantic differential, we presented the subjects with 32 drawings of biological forms and a list of 10 pairs of connotative adjectives to be put in correlations with them merely by subjective judgments. The principal components analysis made it possible to group the semantics of forms according to two distinct axes of variability: harmony and dynamicity. Specifically, the nonspiculed, nonholed, and flat forms were perceived as harmonic and static; the rounded ones were harmonic and dynamic. The elongated forms were somewhat disharmonious and somewhat static. The results suggest the existence in the general population of a correspondence between perceptual and semantic processes, and of a nonsymbolic relation between visual forms and their adjectival expressions in natural language. PMID:25669053

  3. Undercuts by Laser Shock Forming

    SciTech Connect

    Wielage, Hanna; Vollertsen, Frank

    2011-05-04

    In laser shock forming TEA-CO{sub 2}-laser induced shock waves are used to form metal foils, such as aluminum or copper. The process utilizes an initiated plasma shock wave on the target surface, which leads to a forming of the foil. A challenge in forming technologies is the manufacturing of undercuts. By conventional forming methods these special forms are not feasible. In this article, it is presented that undercuts in the micro range can be produced by laser shock deep drawing. Different drawing die diameters, drawing die depths and the material aluminum in the thicknesses 20 and 50 {mu}m were investigated. It will be presented that smaller die diameters facilitate undercuts compared to bigger die diameters. The phenomena can be explained by Barlow's formula. Furthermore, it is shown which maximum undercut depth at different die diameters can be reached. To this end, cross-sections of the different parameter combinations are displayed.

  4. Seal for fluid forming tools

    DOEpatents

    Golovashchenko, Sergey Fedorovich; Bonnen, John Joseph Francis

    2012-03-20

    An electro-hydraulic forming tool for forming a sheet metal blank in a one-sided die has first and second rigid rings that engage opposite sides of a sheet metal blank. The rigid rings are contained within slots on a die portion and a hydraulic force applicator portion of the forming tool. The seals are either resiliently biased by an elastomeric member or inherently resiliently biased into contact with the blank.

  5. System for forming janus particles

    DOEpatents

    Hong, Liang; Jiang, Shan; Granick, Steve

    2011-01-25

    The invention is a method of forming Janus particles, that includes forming an emulsion that contains initial particles, a first liquid, and a second liquid; solidifying the first liquid to form a solid that contains at least a portion of the initial particles on a surface of the solid; and treating the exposed particle sides with a first surface modifying agent, to form the Janus particles. Each of the initial particles on the surface has an exposed particle side and a blocked particle side.

  6. L Form of Neisseria gonorrhoeae

    PubMed Central

    Roberts, Richard B.

    1966-01-01

    Roberts, Richard B. (Walter Reed Army Institute of Research, Washington, D.C.). L form of Neisseria gonorrhoeae. J. Bacteriol. 92:1609–1614. 1966.—L forms were produced by the penicillin gradient plate technique from a recently isolated strain of Neisseria gonorrhoeae. To date, these L forms have had 30 serial passages on medium containing penicillin. Stabilized L forms developed on penicillin-free medium after 10 or more passages in the presence of penicillin. Morphological characteristics of these organisms were identical to L forms of meningococci. Medium and environmental conditions necessary for optimal growth included: Brain Heart Infusion of pH 7.2 to 7.4, 1.1 to 1.3% agar, 10 to 20% sucrose, 10 to 20% horse serum, temperature at 35 to 36 C, and increased CO2 tension (candle jar). L forms were more resistant than the parent gonococcus to penicillin, ampicillin, methicillin, cycloserine, and cephalothin, whereas both organisms had similar sensitivities to bacitracin, vancomycin, ristocetin, novobiocin, tetracycline, and erythromycin. Revertant gonococci were produced on penicillin-free medium from L forms which had had 1, 5, and 10 serial passages. Morphology and fermentative reactions of revertant strains were identical to those of the parent gonococcus. Revertant strains produced L forms more readily than the parent organism; in fact, L forms from certain revertants did not require penicillin, but only serum and sucrose for their production and propagation on artificial medium. Images PMID:4959715

  7. Improving the forming capability of laser dynamic forming by using rubber as a forming medium

    NASA Astrophysics Data System (ADS)

    Shen, Zongbao; Liu, Huixia; Wang, Xiao; Wang, Cuntang

    2016-04-01

    Laser dynamic forming (LDF) is a novel high velocity forming technique, which employs laser-generated shock wave to load the sample. The forming velocity induced by the high energy laser pulse may exceed the critical forming velocity, resulting in the occurrence of premature fracture. To avoid the above premature fracture, rubber is introduced in LDF as a forming medium to prolong the loading duration in this paper. Laser induced shock wave energy is transferred to the sample in different forming stages, so the forming velocity can be kept below the critical forming velocity when the initial laser energy is high for fracture. Bulge forming experiments with and without rubber were performed to study the effect of rubber on loading duration. The experimental results show that, the shock wave energy attenuates during the propagation through the rubber layer, the rubber can avoid the premature fracture. So the plastic deformation can continue, the forming capability of LDF is improved. Due to the severe plastic deformation under rubber compression, adiabatic shear bands (ASB) occur in LDF with rubber. The material softening in ASB leads to the irregular fracture, which is different from the premature fracture pattern (regular fracture) in LDF without rubber. To better understand this deformation behavior, Johnson-Cook model is used to simulate the dynamic response and the evolution of ASB of copper sample. The simulation results also indicate the rubber can prolong the loading duration.

  8. Legal forms and reproductive norms.

    PubMed

    Fletcher, Ruth

    2003-06-01

    This article draws on Pashukanis's concept of legal form and on O'Brien's concept of synthetic value to argue that legal form plays a role in reproductive relations by constructing legal subjects as the bearers of reproductive responsibilities. Pashukanis conceived of legal form as playing a particular role in capitalist exchange relations by interpellating subjects as the bearers of property rights. O'Brien argued that reproduction's specific value is synthetic value, which represents the value of integrating nature and reason in species continuity. Synthetic value is distinct from exchange value or emotional value which may also attach to reproductive process. By working through Pashukanis's method of extracting legal form from specific social relations and by adapting it to reproductive relations, an example is provided of how legal form analysis can be extended beyond the particular context of capitalist exchange relations. Just as legal form constitutes owners and non-owners as legal subjects, so it constitutes reproducers and non-reproducers. By tracing the way in which law attributes reproductive responsibility, legal form analysis shows us how law draws a line between wanting to attribute responsibility and not to attribute it, and this contradiction is a hook which social forces such as sexuality, gender, race, class and disability can latch on to in pushing legal form to shape reproductive responsibilities in a particular way. Each legal form is also externally contradicted by other legal forms. When law negotiates a balance between the reproductive norms of responsibilities and rights, it demonstrates how particular legal forms manage the interaction of different sets of social relations, such as reproduction and exchange. PMID:15871155

  9. When Permission Forms Work Best

    ERIC Educational Resources Information Center

    Zirkel, Perry A.

    2005-01-01

    Public schools routinely require permission or release forms for field trips and other activities of potential liability. The legal status of such forms varies, but they are generally considered neither rock-solid protection nor legally valueless in terms of immunity. This article presents a case involving a student who sustained bicycle injuries…

  10. Method of forming ceramic bricks

    DOEpatents

    Poeppel, Roger B.; Claar, Terry D.; Silkowski, Peter

    1988-01-01

    A method for forming free standing ceramic bricks for use as tritium breeder material is disclosed. Aqueous solutions of sodium carbonate and potassium carbonate are mixed with an organic hydrocolloid dispersion and powdered lithium carbonate, spray dried, and ceramic bricks formed by molding in a die and firing.