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Sample records for lymphatic vasculature formation

  1. Imaging vasculature and lymphatic flow in mice using quantum dots

    DEFF Research Database (Denmark)

    Ballou, Byron; Ernst, Lauren A.; Andreko, Susan

    2009-01-01

    Quantum dots are ideal probes for fluorescent imaging of vascular and lymphatic tissues. On injection into appropriate sites, red- and near-infrared-emitting quantum dots provide excellent definition of vasculature, lymphoid organs, and lymph nodes draining both normal tissues and tumors. We detail...

  2. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice.

    Science.gov (United States)

    Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M; Gautier, Emmanuel L; Westerterp, Marit; Bittman, Robert; Tall, Alan R; Chen, Shu-Hsia; Thomas, Michael J; Kreisel, Daniel; Swartz, Melody A; Sorci-Thomas, Mary G; Randolph, Gwendalyn J

    2013-04-01

    Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin--1 surgical and the other genetic--to quantitatively track RCT following injection of [3H]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.

  3. The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity.

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    Escobedo, Noelia; Oliver, Guillermo

    2017-10-03

    Obesity is a key risk factor for metabolic and cardiovascular diseases, and although we understand the mechanisms regulating weight and energy balance, the causes of some forms of obesity remain enigmatic. Despite the well-established connections between lymphatics and lipids, and the fact that intestinal lacteals play key roles in dietary fat absorption, the function of the lymphatic vasculature in adipose metabolism has only recently been recognized. It is well established that angiogenesis is tightly associated with the outgrowth of adipose tissue, as expanding adipose tissue requires increased nutrient supply from blood vessels. Results supporting a crosstalk between lymphatic vessels and adipose tissue, and linking lymphatic function with metabolic diseases, obesity, and adipose tissue, also started to accumulate in the last years. Here we review our current knowledge of the mechanisms by which defective lymphatics contribute to obesity and fat accumulation in mouse models, as well as our understanding of the lymphatic-adipose tissue relationship. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice

    NARCIS (Netherlands)

    Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M.; Gautier, Emmanuel L.; Westerterp, Marit; Bittman, Robert; Tall, Alan R.; Chen, Shu-Hsia; Thomas, Michael J.; Kreisel, Daniel; Swartz, Melody A.; Sorci-Thomas, Mary G.; Randolph, Gwendalyn J.

    2013-01-01

    Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic

  5. Semaphorin3A, Neuropilin-1, and PlexinA1 are required for lymphatic valve formation.

    Science.gov (United States)

    Bouvrée, Karine; Brunet, Isabelle; Del Toro, Raquel; Gordon, Emma; Prahst, Claudia; Cristofaro, Brunella; Mathivet, Thomas; Xu, Yunling; Soueid, Jihane; Fortuna, Vitor; Miura, Nayoki; Aigrot, Marie-Stéphane; Maden, Charlotte H; Ruhrberg, Christiana; Thomas, Jean Léon; Eichmann, Anne

    2012-08-03

    The lymphatic vasculature plays a major role in fluid homeostasis, absorption of dietary lipids, and immune surveillance. Fluid transport depends on the presence of intraluminal valves within lymphatic collectors. Defective formation of lymphatic valves leads to lymphedema, a progressive and debilitating condition for which curative treatments are currently unavailable. How lymphatic valve formation is regulated remains largely unknown. We investigated if the repulsive axon guidance molecule Semaphorin3A (Sema3A) plays a role in lymphatic valve formation. We show that Sema3A mRNA is expressed in lymphatic vessels and that Sema3A protein binds to lymphatic valves expressing the Neuropilin-1 (Nrp1) and PlexinA1 receptors. Using mouse knockout models, we show that Sema3A is selectively required for lymphatic valve formation, via interaction with Nrp1 and PlexinA1. Sema3a(-/-) mice exhibit defects in lymphatic valve formation, which are not due to abnormal lymphatic patterning or sprouting, and mice carrying a mutation in the Sema3A binding site of Nrp1, or deficient for Plxna1, develop lymphatic valve defects similar to those seen in Sema3a(-/-) mice. Our data demonstrate an essential direct function of Sema3A-Nrp1-PlexinA1 signaling in lymphatic valve formation.

  6. Immmunohistochemical study of the blood and lymphatic vasculature and the innervation of mouse gut and gut-associated lymphoid tissue.

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    Ma, B; von Wasielewski, R; Lindenmaier, W; Dittmar, K E J

    2007-02-01

    The blood and lymphatic vascular system of the gut plays an important role in tissue fluid homeostasis, nutrient absorption and immune surveillance. To obtain a better understanding of the anatomic basis of these functions, the blood and lymphatic vasculature of the lower segment of mouse gut and several constituents of gut-associated lymphoid tissue (GALT) including Peyer's patch, specialized lymphoid nodules in the caecum, small lymphoid aggregates and lymphoid nodules in the colon were studied by using confocal microscopy. Additionally, the innervation and nerve/immune cell interactions in the gut and Peyer's patch were investigated by using cell surface marker PGP9.5 and Glial fibrillary acidic protein (GFAP). In the gut and Peyer's patch, the nerves have contact with B cell, T cell and B220CD3 double-positive cells. Dendritic cells, the most important antigen-presenting cells, were closely apposed to some nerves. Some dendritic cells formed membrane-membrane contact with nerve terminals and neuron cell body. Many fine nerve fibres, which are indirectly detected by GFAP, have contact with dendritic cells and other immune cells in the Peyer's patch. Furthermore, the expression of Muscarinic Acetylcholine receptor (subtype M2) was characterized on dendritic cells and other cell population. These findings are expected to provide a route to understand the anatomic basis of neuron-immune regulation/cross-talk and probably neuroinvasion of prion pathogens in the gut and GALT.

  7. IL-20 activates human lymphatic endothelial cells causing cell signalling and tube formation

    DEFF Research Database (Denmark)

    Hammer, Troels; Tritsaris, Katerina; Hübschmann, Martin V

    2009-01-01

    IL-20 is an arteriogenic cytokine that remodels collateral networks in vivo, and plays a role in cellular organization. Here, we investigate its role in lymphangiogenesis using a lymphatic endothelial cell line, hTERT-HDLEC, which expresses the lymphatic markers LYVE-1 and podoplanin. Upon stimul...

  8. Mechanisms of edema formation in myxedema--increased protein extravasation and relatively slow lymphatic drainage

    DEFF Research Database (Denmark)

    Parving, H H; Hansen, J M; Nielsen, S L

    1979-01-01

    of generalized edema (P less than 0.05). All variables returned to normal during l-thyroxine treatment. The extravascular accumulation of albumin, and presumably of all other plasma proteins, is important in the generalized edema typically found in myxedema. Inadequate lymphatic drainage may also explain...

  9. Modulation of VEGF-induced migration and network formation by lymphatic endothelial cells: Roles of platelets and podoplanin.

    Science.gov (United States)

    Langan, Stacey A; Navarro-Núñez, Leyre; Watson, Steve P; Nash, Gerard B

    2017-07-20

    Lymphatic endothelial cells (LEC) express the transmembrane receptor podoplanin whose only known endogenous ligand CLEC-2 is found on platelets. Both podoplanin and CLEC-2 are required for normal lymphangiogenesis as mice lacking either protein develop a blood-lymphatic mixing phenotype. We investigated the roles of podoplanin and its interaction with platelets in migration and tube formation by LEC. Addition of platelets or antibody-mediated crosslinking of podoplanin inhibited LEC migration induced by vascular endothelial growth factors (VEGF-A or VEGF-C), but did not modify basal migration or the response to basic fibroblast growth factor or epidermal growth factor. In addition, platelets and podoplanin crosslinking disrupted networks of LEC formed in co-culture with fibroblasts. Depletion of podoplanin in LEC using siRNA negated the pro-migratory effect of VEGF-A and VEGF-C. Inhibition of RhoA or Rho-kinase reduced LEC migration induced by VEGF-C, but had no further effect after crosslinking of podoplanin, suggesting that podoplanin is required for signaling downstream of VEGF-receptors but upstream of RhoA. Together, these data reveal for the first time that podoplanin is an intrinsic specific regulator of VEGF-mediated migration and network formation in LEC and identify crosslinking of podoplanin by platelets or antibodies as mechanisms to modulate this pathway.

  10. Lymphatic imaging in unsedated infants and children

    Science.gov (United States)

    Rasmussen, John C.; Balaguru, Duraisamy; Douglas, William I.; Breinholt, John P.; Greives, Matthew R.; Aldrich, Melissa B.; Sevick-Muraca, Eva M.

    2017-02-01

    Primary lymphedema and lymphatic malformations in the pediatric population remains poorly diagnosed and misunderstood due to a lack of information on the underlying anatomy and function of the lymphatic system. Diagnostics for the lymphatic vasculature are limited, consisting of lymphoscintigraphy or invasive lymphangiography, both of which require sedation that can restrict use in infants and children. As a result, therapeutic protocols for pediatric patients with lymphatic disorders remain sparse and with little evidence to support them. Because near-infrared fluorescence (NIRF) imaging enables image acquisition on the order of tenths of seconds with trace administration of fluorescent dye, sedation is not necessary. The lack of harmful radiation and radioactive contrast agents further facilitates imaging. Herein we summarize our experiences in imaging infants and children who are suspected to have disorders of the lymphatic vascular system using indocyanine green (ICG) and who have developed chylothorax following surgery for congenital heart defects. The results show both anatomical as well as functional lymphatic deficits in children with congenital disease. In the future, NIRF lymphatic imaging could provide new opportunities to tailor effective therapies and monitor responses. The opportunity to use expand NIRF imaging for pediatric diagnostics beyond the lymphatic vasculature is also afforded by the rapid acquisition following trace administration of NIRF contrast agent.

  11. Podoplanin-expressing Cells Derived from Bone Marrow Play a Crucial Role in Postnatal Lymphatic Neovascularization

    Science.gov (United States)

    Lee, Ji Yoon; Park, Changwon; Cho, Yong Pil; Lee, Eugine; Kim, Hyongbum; Kim, Pilhan; Yun, Seok H.; Yoon, Young-sup

    2010-01-01

    Background Emerging evidence has suggested a contribution of bone marrow (BM) cells to lymphatic vessel formation; however, the exact phenotype of the cells with lymphatic endothelial progenitor cell (LEPC) function has yet to be identified. Here we investigate the identity of BM-derived LEPCs and their role in lymphatic neovascularization. Methods and Results Culture of BM-mononuclear cells (MNCs) in the presence of VEGFA, VEGFC and EGF resulted in expression of lymphatic endothelial cell (LEC) markers. Among these cells, podoplanin+ cells were isolated by magnetic-labeled cell separation system (MACS) and characterized by FACS and immunocytochemistry. These podoplanin+ cells highly express markers for LECs, hematopoietic lineages, and stem/progenitor cells, and upon further cultivation, generate LECs. We further confirmed that podoplanin+ cells exist in small numbers in BM and peripheral blood (PB) of normal mice, but are significantly (15 fold) augmented upon lymphangiogenic stimuli such as tumor implantation. Next, to evaluate the potential of podoplanin+ cells for the formation of new lymphatic vessels in vivo, we injected culture-isolated or freshly isolated BM-derived podoplanin+ cells into wound and tumor models. Immunohistochemistry demonstrated that the injected cells were incorporated into the lymphatic vasculature, displayed LEC phenotypes, and increased lymphatic vascular density in tissues, suggesting lymphvasculogenesis. Podoplanin+ cells also expressed high levels of lymphangiogenic cytokines and increased proliferation of LECs during co-culture, suggesting a lymphangiogenic or paracrine role. Conclusions Our results provide compelling evidence that BM-derived podoplanin+ cells, a previously unrecognized cell type, function as LEPCs and participate in postnatal lymphatic neovascularization through both lymphvasculogenesis and lymphangiogenesis. PMID:20855662

  12. Lymphatics and lymphatic-like structures in melanoma : a pathobiological study

    NARCIS (Netherlands)

    Clarijs, Johannes Antonius Godefridus Marinus

    2003-01-01

    Solid malignant tumors can be regarded as a functional tissue in which architecture and function are maintained by a dynamic interplay between tumor cells and a microenvironment consisting of extracellular matrix (ECM) containing fibroblasts, blood and lymphatic vasculature and infiltrating and

  13. Pleural function and lymphatics.

    Science.gov (United States)

    Negrini, D; Moriondo, A

    2013-02-01

    The pleural space plays an important role in respiratory function as the negative intrapleural pressure regimen ensures lung expansion and in the mean time maintains the tight mechanical coupling between the lung and the chest wall. The efficiency of the lung-chest wall coupling depends upon pleural liquid volume, which in turn reflects the balance between the filtration of fluid into and its egress out of the cavity. While filtration occurs through a single mechanism passively driving fluid from the interstitium of the parietal pleura into the cavity, several mechanisms may co-operate to remove pleural fluid. Among these, the pleural lymphatic system emerges as the most important one in quantitative terms and the only one able to cope with variable pleural fluid volume and drainage requirements. In this review, we present a detailed account of the actual knowledge on: (a) the complex morphology of the pleural lymphatic system, (b) the mechanism supporting pleural lymph formation and propulsion, (c) the dependence of pleural lymphatic function upon local tissue mechanics and (d) the effect of lymphatic inefficiency in the development of clinically severe pleural and, more in general, respiratory pathologies. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

  14. Lymphatic Education & Research Network

    Science.gov (United States)

    Lymphatic Education & Research Network Donate Now Become a Supporting Member X Living with LYMPHEDEMA AND Lymphatic Disease FAQs About ... December 8, 2017 11.08.2017 The Lymphatic Education & Research Network… Read More > ASRM LE&RN Combined ...

  15. Effect of VEGF-C siRNA and endostatin on ring formation and proliferation of esophageal squamous cell carcinoma lymphatic endothelial cells

    Directory of Open Access Journals (Sweden)

    Zheng YP

    2016-10-01

    Full Text Available Yuping Zheng,1–3,* Miaomiao Sun,4,* Jinyan Chen,1,2 Lulu He,1,2 Na Zhao,1,2 Kuisheng Chen1,2 1Pathology Department, The First Affiliated Hospital of Zhengzhou University, 2Henan Key Laboratory of Tumor Pathology, 3Pathology Department, The Second Hospital of Shandong University, Jinan, 4Pathology Department, Henan Tumor Hospital, Zhengzhou, People’s Republic of China *These authors contributed equally to this work Objective: To study the effects of vascular endothelial growth factor C small interfering RNA and endostatin on esophageal squamous cell carcinoma-related ring formation in vitro and proliferation of lymphatic endothelial cells.Materials and methods: KYSE150 cells were subjected to analysis of cell transfection and endostatin operation. The groups were as follows: negative group, blank group, negative plus endostatin group, endostatin group, SG1 group, SG2 group, SG1 plus endostatin group, and SG2 plus endostatin group. The esophageal cancer-related microlymphatic endothelial cells were three-dimensionally cultured. Cell Counting Kit-8 (CCK-8 assay was employed to detect cell proliferation.Results: The negative group’s three-dimensional culture result was the highest, followed by the blank group, negative plus endostatin group, endostatin group, SG2 group, SG1 group, SG1 plus endostatin group, and SG2 plus endostatin group. The quantity of living cells in the blank group was the highest, followed by the negative control, endostatin, SG2, SG1, negative plus endostatin, SG1 plus endostatin, and SG2 plus endostatin groups. Conclusion: Both vascular endothelial growth factor C small interfering RNA and endostatin could inhibit ring formation in esophageal squamous cell carcinoma and proliferation of lymphatic endothelial cells. Keywords: esophageal squamous carcinoma cells, esophageal cancer-associated lymphatic endothelial cells, VEGF-C, ring formation, proliferation

  16. Ligand-directed targeting of lymphatic vessels uncovers mechanistic insights in melanoma metastasis.

    Science.gov (United States)

    Christianson, Dawn R; Dobroff, Andrey S; Proneth, Bettina; Zurita, Amado J; Salameh, Ahmad; Dondossola, Eleonora; Makino, Jun; Bologa, Cristian G; Smith, Tracey L; Yao, Virginia J; Calderone, Tiffany L; O'Connell, David J; Oprea, Tudor I; Kataoka, Kazunori; Cahill, Dolores J; Gershenwald, Jeffrey E; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2015-02-24

    Metastasis is the most lethal step of cancer progression in patients with invasive melanoma. In most human cancers, including melanoma, tumor dissemination through the lymphatic vasculature provides a major route for tumor metastasis. Unfortunately, molecular mechanisms that facilitate interactions between melanoma cells and lymphatic vessels are unknown. Here, we developed an unbiased approach based on molecular mimicry to identify specific receptors that mediate lymphatic endothelial-melanoma cell interactions and metastasis. By screening combinatorial peptide libraries directly on afferent lymphatic vessels resected from melanoma patients during sentinel lymphatic mapping and lymph node biopsies, we identified a significant cohort of melanoma and lymphatic surface binding peptide sequences. The screening approach was designed so that lymphatic endothelium binding peptides mimic cell surface proteins on tumor cells. Therefore, relevant metastasis and lymphatic markers were biochemically identified, and a comprehensive molecular profile of the lymphatic endothelium during melanoma metastasis was generated. Our results identified expression of the phosphatase 2 regulatory subunit A, α-isoform (PPP2R1A) on the cell surfaces of both melanoma cells and lymphatic endothelial cells. Validation experiments showed that PPP2R1A is expressed on the cell surfaces of both melanoma and lymphatic endothelial cells in vitro as well as independent melanoma patient samples. More importantly, PPP2R1A-PPP2R1A homodimers occur at the cellular level to mediate cell-cell interactions at the lymphatic-tumor interface. Our results revealed that PPP2R1A is a new biomarker for melanoma metastasis and show, for the first time to our knowledge, an active interaction between the lymphatic vasculature and melanoma cells during tumor progression.

  17. Role of Hyperplasia of Gingival Lymphatics in Periodontal Inflammation.

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    Papadakou, P; Bletsa, A; Yassin, M A; Karlsen, T V; Wiig, H; Berggreen, E

    2017-04-01

    Lymphatic vessels are important for maintenance of tissue fluid homeostasis and afferent antigen transport. In chronic inflammation, lymphangiogenesis takes place and is characterized by lymphatic endothelial cell proliferation and lymphatic hyperplasia. Vascular endothelial growth factor C (VEGFC) is the main known lymphangiogenic growth factor, and its expression is increased in periodontitis, a common chronic infectious disease that results in tissue destruction and alveolar bone loss. The role of lymphangiogenesis during development of periodontitis is unknown. Here, we test if transgenic overexpression of epithelial VEGFC in a murine model is followed by hyperplasia of lymphatic vessels in oral mucosa and if the lymphatic drainage capacity is altered. We also test if lymphatic hyperplasia protects against periodontal disease development. Transgenic keratin 14 (K14)-VEGFC mice had significant hyperplasia of lymphatics in oral mucosa, including gingiva, without changes in blood vessel vasculature. The basal lymph flow was normal but slightly lower than in wild-type mice when oral mucosa was challenged with lipopolysaccharide from Porphyromonas gingivalis. Under normal conditions, K14-VEGFC mice exhibited an increased number of neutrophils in gingiva, demonstrated enhanced phagocyte recruitment in the cervical lymph nodes, and had more alveolar bone when compared with their wild-type littermates. After induction of periodontitis, no strain differences were observed in the periodontal tissues with respect to granulocyte recruitment, bone resorption, angiogenesis, cytokines, and bone-related protein expressions or in draining lymph node immune cell proportions and vascularization. We conclude that overexpression of VEGFC results in hyperplastic lymphatics, which do not enhance lymphatic drainage capacity but facilitate phagocyte transport to draining lymph nodes. Hyperplasia of lymphatics does not protect against development of ligature-induced periodontitis.

  18. The effect of lymphatic valve morphology on fluid transport

    Science.gov (United States)

    Alexeev, Alexander; Ballard, Matthew; Nepiyushchikh, Zhanna; Dixon, Brandon

    2016-11-01

    The lymphatic vasculature is present in nearly all invertebrate tissue, and is essential in the transport of fluid and particles such as immune cells, antigens, proteins and lipids from the tissue to lymph nodes and to the venous circulation. Lymphatic vessels are made of up a series of contractile units that work together in harmony as "micro hearts" to pump fluid against a pressure gradient. Lymphatic valves are critical to this functionality, as they open and close with the oscillating pressure gradients from contractions, thus allowing flow in only one direction and leading to a net pumping effect. We use a hybrid lattice-Boltzmann lattice spring model which captures fluid-solid interactions through two-way coupling between a viscous fluid and lymphatic valves in a section of a lymphatic vessel to study the dynamics of lymphatic valves and their effect on fluid transport. Further, we investigate the effect of variations in valve geometry and material properties on fluid pumping. This work helps to increase our understanding of the mechanisms of lymphatic fluid transport, which has implications in a variety of pathologies, including cancer metastasis, autoimmunity, atherosclerosis and obesity. Support from NSF CMMI 1635133 is gratefully acknowledged.

  19. Structural and functional features of central nervous system lymphatic vessels.

    Science.gov (United States)

    Louveau, Antoine; Smirnov, Igor; Keyes, Timothy J; Eccles, Jacob D; Rouhani, Sherin J; Peske, J David; Derecki, Noel C; Castle, David; Mandell, James W; Lee, Kevin S; Harris, Tajie H; Kipnis, Jonathan

    2015-07-16

    One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.

  20. Phenotypically heterogeneous podoplanin-expressing cell populations are associated with the lymphatic vessel growth and fibrogenic responses in the acutely and chronically infarcted myocardium.

    Science.gov (United States)

    Cimini, Maria; Cannatá, Antonio; Pasquinelli, Gianandrea; Rota, Marcello; Goichberg, Polina

    2017-01-01

    Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts. Podoplanin immunoreactivity detected LYVE-1-positive lymphatic vessels, as well as masses of LYVE-1-negative cells dispersed between myocytes, predominantly in the vicinity of the infarcted region. Podoplanin-carrying populations displayed a mesenchymal progenitor marker PDGFRα, and intermittently expressed Prox-1, a master regulator of the lymphatic endothelial fate. At the stages of scar formation and maturation, concomitantly with the enlargement of lymphatic network in the injured myocardium, the podoplanin-rich LYVE-1-negative multicellular assemblies were apparent in the fibrotic area, aligned with extracellular matrix deposits, or located in immediate proximity to activated blood vessels with high VEGFR-2 content. Of note, these podoplanin-containing cells acquired the expression of PDGFRβ or a hematoendothelial epitope CD34. Although Prox-1 labeling was abundant in the area affected by MI, the podoplanin-presenting cells were not consistently Prox-1-positive. The concordance of podoplanin with VEGFR-3 similarly varied. Thus, our data reveal previously unknown phenotypic and structural heterogeneity within the podoplanin-positive cell compartment in the infarcted heart, and suggest an alternate ability of podoplanin-presenting cardiac cells to generate lymphatic endothelium and pro

  1. Phenotypically heterogeneous podoplanin-expressing cell populations are associated with the lymphatic vessel growth and fibrogenic responses in the acutely and chronically infarcted myocardium.

    Directory of Open Access Journals (Sweden)

    Maria Cimini

    Full Text Available Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI. However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts. Podoplanin immunoreactivity detected LYVE-1-positive lymphatic vessels, as well as masses of LYVE-1-negative cells dispersed between myocytes, predominantly in the vicinity of the infarcted region. Podoplanin-carrying populations displayed a mesenchymal progenitor marker PDGFRα, and intermittently expressed Prox-1, a master regulator of the lymphatic endothelial fate. At the stages of scar formation and maturation, concomitantly with the enlargement of lymphatic network in the injured myocardium, the podoplanin-rich LYVE-1-negative multicellular assemblies were apparent in the fibrotic area, aligned with extracellular matrix deposits, or located in immediate proximity to activated blood vessels with high VEGFR-2 content. Of note, these podoplanin-containing cells acquired the expression of PDGFRβ or a hematoendothelial epitope CD34. Although Prox-1 labeling was abundant in the area affected by MI, the podoplanin-presenting cells were not consistently Prox-1-positive. The concordance of podoplanin with VEGFR-3 similarly varied. Thus, our data reveal previously unknown phenotypic and structural heterogeneity within the podoplanin-positive cell compartment in the infarcted heart, and suggest an alternate ability of podoplanin-presenting cardiac cells to generate lymphatic endothelium

  2. Lymphatic System Flows

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    Moore, James E., Jr.; Bertram, Christopher D.

    2018-01-01

    The supply of oxygen and nutrients to tissues is performed by the blood system and involves a net leakage of fluid outward at the capillary level. One of the principal functions of the lymphatic system is to gather this fluid and return it to the blood system to maintain overall fluid balance. Fluid in the interstitial spaces is often at subatmospheric pressure, and the return points into the venous system are at pressures of approximately 20 cmH2O. This adverse pressure difference is overcome by the active pumping of collecting lymphatic vessels, which feature closely spaced one-way valves and contractile muscle cells in their walls. Passive vessel squeezing causes further pumping. The dynamics of lymphatic pumping have been investigated experimentally and mathematically, revealing complex behaviors that indicate that the system performance is robust against minor perturbations in pressure and flow. More serious disruptions can lead to incurable swelling of tissues called lymphedema.

  3. Lymphatic involvement in the histopathogenesis of mucous retention cyst.

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    Kundu, Sukalyan; Cheng, Jun; Maruyama, Satoshi; Suzuki, Makoto; Kawashima, Hiroyuki; Saku, Takashi

    2007-01-01

    Mucous retention cyst results from extravasation of saliva. Our intent was to study the role of lymphatics in its pathogenesis. Twenty-three surgical specimens of mucous retention cyst of the lip were examined for involvement of lymphatic vessels by a comparative immunohistochemical demonstration of lymphatic and blood vascular endothelial cells, as well as lymphatic and salivary contents. Mucous retention cysts were histopathologically classified into three stages: early, intermediate, and advanced. In the early stage, there was diffuse extravasation of mucous material in the interstitium of the lamina propria or the submucosal layer of the oral mucosa. In the intermediate stage, lymphatics, which were clearly revealed and immunohistochemically distinguished from blood vessels by monoclonal antibody D2-40, were dilated and finally ruptured, leaving fragments of lymphatic walls in the periphery of mucous pools. In the advanced stage, thick cyst walls of granulation tissue were formed around mucous retention. Lymphatics were no longer involved in the granulation tissue wall, which was actively driven by blood vessel formation. The results suggest that the lymphatic rupture seems to contribute to the enlargement in the pathogenesis of mucous retention cyst.

  4. Spleen and Lymphatic System

    Science.gov (United States)

    ... Wrong Print en español El bazo y el sistema linfático The lymphatic system is an extensive drainage ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

  5. [Pleural lymphatics and effusions].

    Science.gov (United States)

    Mordant, P; Arame, A; Legras, A; Le Pimpec Barthes, F; Riquet, M

    2013-06-01

    The pleural lymphatic system has a great absorption capacity. Its most known function is fluid resorption. The pleura which cover the lungs (visceral pleura), the mediastinum, diaphragm and thoracic wall (parietal pleura) are formed by a mesothelial cell layer (mesothelium). This permeable layer is in direct contact with the vascular endothelium. The mesothelium is based over a connective tissue (interstitium) containing the blood and lymphatic vessels. The primary lymphatic vessels drain interstitium but are also in direct contact with pleural space by the stoma or openings, situated in the lower parts of parietal pleura, i.e: diaphragm, over lower ribs and mediastinum but not existing in the adjacent visceral pleura. In addition, a part of interstitial pulmonary fluid entered in the pleural cavity by passing the visceral pleura would be absorbed by these openings. The resorption process is active and directly related to the function of smooth muscles of lymphatic vessels. Besides resorption, we must emphasize that this "pumping" activity is permanent and the origin of negative pressure (the pleural void) in pleural cavity, a unique property. The other resorbed elements are molecules, bacterial and cellular debris, cells, red blood and cancer cells. Copyright © 2013. Published by Elsevier Masson SAS.

  6. Chapter 20. Lymphatic system

    International Nuclear Information System (INIS)

    Meyniel, G.; Plagne, R.; Veyre, A.

    1975-01-01

    It is recalled than in isotopic lymphography the tracer may be introduced into the lymphatic system by two methods: direct lymphography when the product is injected directly into a lymphatic vessel or lymph node, indirect lymphography when the product is injected into interstitial tissues, taken up by the lymph flow and fixed by the glands. The disadvantages of the direct method at present restrict the radioisotopic exploration of the lymphatic system to indirect lymphography. This technique, whereby the lymphatic draining of the tracer injection zone may be followed, is described. The use of metallic colloids (Au-198, In-111, Tc-99m) fixed by the glands gives a sharp and lasting contrast, but also possesses disadvantages. The conditions required of a selective tracer are examined and the possibilities of various types of molecules for this study estimated. In spite of undeniable disadvantages the colloids of technetium-99m are being used more and more because of the quality of the images obtained. The results are interpreted and the chief indications of the method defined. The therapeutic possibilities of isotopic lymphography are also shown [fr

  7. Importance Rat Liver Morphology and Vasculature in Surgical Research.

    Science.gov (United States)

    Vdoviaková, Katarína; Vdoviaková, Katarína; Petrovová, Eva; Krešáková, Lenka; Maloveská, Marcela; Teleky, Jana; Jenčová, Janka; Živčák, Jozef; Jenča, Andrej

    2016-12-02

    BACKGROUND The laboratory rat is one of the most popular experimental models for the experimental surgery of the liver. The objective of this study was to investigate the morphometric parameters, physiological data, differences in configuration of liver lobes, biliary system, and vasculature (arteries, veins, and lymphatic vessels) of the liver in laboratory rats. In addition, this study supports the anatomic literature and identified similarities and differences with human and other mammals. MATERIAL AND METHODS Forty laboratory rats were dissected to prepare corrosion casts of vascular system specimens (n=20), determine the lymph vessels and lymph nodes (n=10), and for macroscopic anatomical dissection (n=10) of the rat liver. The results are listed in percentages. The anatomical nomenclature of the liver morphology, its arteries, veins, lymph nodes, and lymphatic vessels are in accordance with Nomina Anatomica Veterinaria. RESULTS We found many variations in origin, direction, and division of the arterial, venous, and lymphatic systems in rat livers, and found differences in morphometric parameters compared to results reported by other authors. The portal vein was formed by 4 tributaries in 23%, by 3 branches in 64%, and by 2 tributaries in 13%. The liver lymph was drained to the 2 different lymph nodes. The nomenclature and morphological characteristics of the rat liver vary among authors. CONCLUSIONS Our results may be useful for the planing of experimental surgery and for cooperation with other investigation methods to help fight liver diseases in human populations.

  8. Pulmonary lymphatics and radiation

    International Nuclear Information System (INIS)

    Leeds, S.E.

    1976-01-01

    Knowledge of the anatomy and physiology of the respiratory system has been more difficult to acquire than that of other organ systems owing to the complexity of the respiratory function of the lungs and to the technical difficulties involved. This is especially true of the lymphatics of the lung and is illustrated by the fact that the first measurement of pulmonary lymph flow was in 1942 by Warren and Drinker. A review of the literature reveals that few experiments have been designed to study the pulmonary lymphatics per se in relation to the effects of external radiation or after the inhalation of radioactive particles. However, the documented involvement of hilar lymph nodes implies that the lung lymphatics have a role in transporting particles from the alveoli or malignant cells from the parenchyma. Information from clinical and experimental sources, though scattered, is fairly abundant and of value in assessing the role of the pulmonary lymphatics. Our method for collecting pulmonary lymph is presented. Studies on the pulmonary lymph flow in normal dogs and in dogs with experimental congestive heart failure are described. We irradiated (4000 to 5000 R) the medial one-third of both lungs of a series of dogs. The lymph flow of the lungs was measured immediately after the course of irradiation and after a period of about 5 months. Although lung biopsies showed characteristic radiation pneumonitis in many areas, alterations in the lung parenchyma were not quantitatively reflected in the pulmonary lymph flow either in the acute stage or after fibrosis had time to develop

  9. Brain drains: new insights into brain clearance pathways from lymphatic biology.

    Science.gov (United States)

    Bower, Neil I; Hogan, Benjamin M

    2018-05-01

    The lymphatic vasculature act as the drainage system for most of our tissues and organs, clearing interstitial fluid and waste and returning them to the blood circulation. This is not the case for the central nervous system (CNS), which is devoid of parenchymal lymphatic vessels. Nevertheless, the brain is responsible for 25% of the body's metabolism and only compromises 2% of the body's mass. This high metabolic load requires an efficient system to remove waste products and maintain homeostasis. Well-described mechanisms of waste clearance include phagocytic immune cell functions as well as perivascular fluid flow; however, the need for active drainage of waste from the brain is becoming increasingly appreciated. Recent developments in lymphatic vascular biology challenge the proposition that the brain lacks lymphatic drainage or an equivalent. In this review, we describe the roles of the glymphatic system (a key drainage mechanism in the absence of lymphatics), the recently characterized meningeal lymphatic vessels, and explore an enigmatic cell population found in zebrafish called mural lymphatic endothelial cells. These systems may play important individual and collective roles in draining and clearing wastes from the brain.

  10. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules.

    Science.gov (United States)

    Aspelund, Aleksanteri; Antila, Salli; Proulx, Steven T; Karlsen, Tine Veronica; Karaman, Sinem; Detmar, Michael; Wiig, Helge; Alitalo, Kari

    2015-06-29

    The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease. © 2015 Aspelund et al.

  11. Expression and lymphatic microvessel density in primary tumors of node-neagtive colorectal cancer patients predict disease recurrence

    NARCIS (Netherlands)

    Doekhie, F.S.; Morreau, H.; de Bock, G.H.; Speetjens, F.M.; Dekker-Ensink, N.G.; Putter, H.; vand e Velde, C.J.H.; Tollenaar, R.A.E.M.; Kuppen, P.J.K.; Sialyl lewis, X.

    2008-01-01

    Up to 30% of curatively resected colorectal cancer patients with tumor-negative lymph nodes, show disease recurrence. We assessed whether these high-risk patients can be identified by examining primary tumors for the following blood and lymphatic vasculature markers: A) sialyl Lewis X (sLeX),

  12. Photoacoustic imaging of lymphatic pumping

    Science.gov (United States)

    Forbrich, Alex; Heinmiller, Andrew; Zemp, Roger J.

    2017-10-01

    The lymphatic system is responsible for fluid homeostasis and immune cell trafficking and has been implicated in several diseases, including obesity, diabetes, and cancer metastasis. Despite its importance, the lack of suitable in vivo imaging techniques has hampered our understanding of the lymphatic system. This is, in part, due to the limited contrast of lymphatic fluids and structures. Photoacoustic imaging, in combination with optically absorbing dyes or nanoparticles, has great potential for noninvasively visualizing the lymphatic vessels deep in tissues. Multispectral photoacoustic imaging is capable of separating the components; however, the slow wavelength switching speed of most laser systems is inadequate for imaging lymphatic pumping without motion artifacts being introduced into the processed images. We investigate two approaches for visualizing lymphatic processes in vivo. First, single-wavelength differential photoacoustic imaging is used to visualize lymphatic pumping in the hindlimb of a mouse in real time. Second, a fast-switching multiwavelength photoacoustic imaging system was used to assess the propulsion profile of dyes through the lymphatics in real time. These approaches may have profound impacts in noninvasively characterizing and investigating the lymphatic system.

  13. Lymphatic vessel density and function in experimental bladder cancer

    International Nuclear Information System (INIS)

    Saban, Marcia R; Wu, Xue-Ru; Saban, Ricardo; Towner, Rheal; Smith, Nataliya; Abbott, Andrew; Neeman, Michal; Davis, Carole A; Simpson, Cindy; Maier, Julie; Mémet, Sylvie

    2007-01-01

    The lymphatics form a second circulatory system that drains the extracellular fluid and proteins from the tumor microenvironment, and provides an exclusive environment in which immune cells interact and respond to foreign antigen. Both cancer and inflammation are known to induce lymphangiogenesis. However, little is known about bladder lymphatic vessels and their involvement in cancer formation and progression. A double transgenic mouse model was generated by crossing a bladder cancer-induced transgenic, in which SV40 large T antigen was under the control of uroplakin II promoter, with another transgenic mouse harboring a lacZ reporter gene under the control of an NF-κB-responsive promoter (κB-lacZ) exhibiting constitutive activity of β-galactosidase in lymphatic endothelial cells. In this new mouse model (SV40-lacZ), we examined the lymphatic vessel density (LVD) and function (LVF) during bladder cancer progression. LVD was performed in bladder whole mounts and cross-sections by fluorescent immunohistochemistry (IHC) using LYVE-1 antibody. LVF was assessed by real-time in vivo imaging techniques using a contrast agent (biotin-BSA-Gd-DTPA-Cy5.5; Gd-Cy5.5) suitable for both magnetic resonance imaging (MRI) and near infrared fluorescence (NIRF). In addition, IHC of Cy5.5 was used for time-course analysis of co-localization of Gd-Cy5.5 with LYVE-1-positive lymphatics and CD31-positive blood vessels. SV40-lacZ mice develop bladder cancer and permitted visualization of lymphatics. A significant increase in LVD was found concomitantly with bladder cancer progression. Double labeling of the bladder cross-sections with LYVE-1 and Ki-67 antibodies indicated cancer-induced lymphangiogenesis. MRI detected mouse bladder cancer, as early as 4 months, and permitted to follow tumor sizes during cancer progression. Using Gd-Cy5.5 as a contrast agent for MRI-guided lymphangiography, we determined a possible reduction of lymphatic flow within the tumoral area. In addition, NIRF

  14. A novel podoplanin-GFPCre mouse strain for gene deletion in lymphatic endothelial cells.

    Science.gov (United States)

    Gil, Hyea Jin; Ma, Wanshu; Oliver, Guillermo

    2018-04-01

    The lymphatic vascular system is a one-direction network of thin-walled capillaries and larger vessels covered by a continuous layer of endothelial cells responsible for maintaining fluid homeostasis. Some of the main functions of the lymphatic vasculature are to drain fluid from the extracellular spaces and return it back to the blood circulation, lipid absorption from the intestinal tract, and transport of immune cells to lymphoid organs. A number of genes controlling the development of the mammalian lymphatic vasculature have been identified in the last few years, and their functional roles started to be characterized using gene inactivation approaches in mice. Unfortunately, only few mouse Cre strains relatively specific for lymphatic endothelial cells (LECs) are currently available. In this article, we report the generation of a novel Podoplanin (Pdpn) GFPCre transgenic mouse strain using its 5' regulatory region. Pdpn encodes a transmembrane mucin-type O-glycoprotein that is expressed on the surface of embryonic and postnatal LECs, in addition to few other cell types. Our detailed characterization of this novel strain indicates that it will be a valuable additional genetic tool for the analysis of gene function in LECs. © 2018 Wiley Periodicals, Inc.

  15. Diaphragmatic lymphatic vessel behavior during local skeletal muscle contraction.

    Science.gov (United States)

    Moriondo, Andrea; Solari, Eleonora; Marcozzi, Cristiana; Negrini, Daniela

    2015-02-01

    The mechanism through which the stresses developed in the diaphragmatic tissue during skeletal muscle contraction sustain local lymphatic function was studied in 10 deeply anesthetized, tracheotomized adult Wistar rats whose diaphragm was exposed after thoracotomy. To evaluate the direct effect of skeletal muscle contraction on the hydraulic intraluminal lymphatic pressures (Plymph) and lymphatic vessel geometry, the maximal contraction of diaphragmatic fibers adjacent to a lymphatic vessel was elicited by injection of 9.2 nl of 1 M KCl solution among diaphragmatic fibers while Plymph was recorded through micropuncture and vessel geometry via stereomicroscopy video recording. In lymphatics oriented perpendicularly to the longitudinal axis of muscle fibers and located at skeletal muscle contraction (Dmc) decreased to 61.3 ± 1.4% of the precontraction value [resting diameter (Drest)]; however, if injection was at >900 μm from the vessel, Dmc enlarged to 131.1 ± 2.3% of Drest. In vessels parallel to muscle fibers, Dmc increased to 122.8 ± 2.9% of Drest. During contraction, Plymph decreased as much as 22.5 ± 2.6 cmH2O in all submesothelial superficial vessels, whereas it increased by 10.7 ± 5.1 cmH2O in deeper vessels running perpendicular to contracting muscle fibers. Hence, the three-dimensional arrangement of the diaphragmatic lymphatic network seems to be finalized to efficiently exploit the stresses exerted by muscle fibers during the contracting inspiratory phase to promote lymph formation in superficial submesothelial lymphatics and its further propulsion in deeper intramuscular vessels. Copyright © 2015 the American Physiological Society.

  16. The effect of cisterna chyli ablation combined with thoracic duct ligation on abdominal lymphatic drainage.

    Science.gov (United States)

    Sicard, Gretchen K; Waller, Ken R; McAnulty, Jonathan F

    2005-01-01

    To evaluate the effect of cisterna chyli ablation (CCA) and thoracic duct ligation (TDL) on abdominal lymphatic drainage in normal dogs. Experimental study. Nine female beagle dogs. TDL was performed in 3 dogs and was combined with CCA (CCA-TDL) and local omentalization in 6 dogs. Contrast lymphangiography was attempted in all dogs immediately before and after TDL. Dogs were reanesthetized at 31-37 days for lymphatic studies by new methylene blue (NMB) injection into a mesenteric lymph node and by contrast lymphangiography. In 6 CCA-TDL dogs, 2 had direct shunting of contrast from the lymphatic system into major abdominal veins, 3 had contrast material that dissipated into abdominal vessels within the mesenteric root, and 1 had shunting into the azygous vein. NMB was not observed within the omental pedicle after CCA-TDL. Chylous drainage was by the azygous vein in all 3 TDL dogs. CCA-TDL disrupted chylous drainage to the thoracic duct and resulted in direct intraabdominal lymphaticovenous anastomoses identified by shunting of lymphatic flow directly into the abdominal vasculature in 5 of 6 CCA-TDL dogs. Omentalization of the cisternal ablation site was not beneficial in augmenting extrathoracic lymphatic drainage and is not recommended with CCA-TDL. CCA-TDL represents a novel approach to surgical redirection of chylous drainage to the venous circulation outside of the thorax and may be useful in the treatment of spontaneous chylothorax in the dog.

  17. Mechanisms of lymphatic regeneration after tissue transfer.

    Directory of Open Access Journals (Sweden)

    Alan Yan

    2011-02-01

    Full Text Available Lymphedema is the chronic swelling of an extremity that occurs commonly after lymph node resection for cancer treatment. Recent studies have demonstrated that transfer of healthy tissues can be used as a means of bypassing damaged lymphatics and ameliorating lymphedema. The purpose of these studies was to investigate the mechanisms that regulate lymphatic regeneration after tissue transfer.Nude mice (recipients underwent 2-mm tail skin excisions that were either left open or repaired with full-thickness skin grafts harvested from donor transgenic mice that expressed green fluorescent protein in all tissues or from LYVE-1 knockout mice. Lymphatic regeneration, expression of VEGF-C, macrophage infiltration, and potential for skin grafting to bypass damaged lymphatics were assessed.Skin grafts healed rapidly and restored lymphatic flow. Lymphatic regeneration occurred beginning at the peripheral edges of the graft, primarily from ingrowth of new lymphatic vessels originating from the recipient mouse. In addition, donor lymphatic vessels appeared to spontaneously re-anastomose with recipient vessels. Patterns of VEGF-C expression and macrophage infiltration were temporally and spatially associated with lymphatic regeneration. When compared to mice treated with excision only, there was a 4-fold decrease in tail volumes, 2.5-fold increase in lymphatic transport by lymphoscintigraphy, 40% decrease in dermal thickness, and 54% decrease in scar index in skin-grafted animals, indicating that tissue transfer could bypass damaged lymphatics and promote rapid lymphatic regeneration.Our studies suggest that lymphatic regeneration after tissue transfer occurs by ingrowth of lymphatic vessels and spontaneous re-connection of existing lymphatics. This process is temporally and spatially associated with VEGF-C expression and macrophage infiltration. Finally, tissue transfer can be used to bypass damaged lymphatics and promote rapid lymphatic regeneration.

  18. Investigation of intratumoural and peritumoural lymphatics expressed by podoplanin and LYVE-1 in the hybridoma-induced tumours

    Science.gov (United States)

    Ji, RC; Eshita, Y; Kato, S

    2007-01-01

    Tumour-associated lymphatics contribute to a key component of metastatic spread, however, the biological interaction of tumour cells with intratumoural and peritumoural lymphatics (ITLs and PTLs) has remained unclear. To address this important issue, we have focused on the morphological and molecular aspects of newly formed lymphatics (lymphangiogenesis) and pre-existing lymphatics in the intratumoural and peritumoural tissues by using a hybridoma-induced tumour model. In the present study, ITLs with very high vessel density within the tumour mass showed small and flattened contours that varied from non-solid-to-solid tumours, whereas PTLs were relatively disorganized and tortuous, and packed with a cluster of tumour cells at the tumour periphery. Lymphatic endothelial cells (LECs) both in ITLs and PTLs were expressed with LYVE-1 and podoplanin in various tumour tissues, in which initial lymphatics were extremely extended and dilated. The tumour cells were frequently detected adhering to or penetrating lymphatic walls, especially near the open junctions. In the metastatic tissues, lymphangiogenic vasculatures occurred within the tumour matrix, and collecting PTLs represented abnormal twisty valve leaflets. The Western blot and RT-PCR analysis showed local variations of LEC proliferating potentials and lymphatic involvement in metastasis by a distinct profile of the protein and mRNA expression by LYVE-1, podoplanin, Prox-1 and vascular endothelial growth factor-3 (VEGFR-3). These findings indicated that both ITLs and PTLs, including enlarged pre-existing and newly formed lymphatics, may play a crucial role in metastasis with an active tumour cell adhesion, invasion, migration and implantation. PMID:17696907

  19. Macrophage-Mediated Lymphangiogenesis: The Emerging Role of Macrophages as Lymphatic Endothelial Progenitors

    International Nuclear Information System (INIS)

    Ran, Sophia; Montgomery, Kyle E.

    2012-01-01

    It is widely accepted that macrophages and other inflammatory cells support tumor progression and metastasis. During early stages of neoplastic development, tumor-infiltrating macrophages (TAMs) mount an immune response against transformed cells. Frequently, however, cancer cells escape the immune surveillance, an event that is accompanied by macrophage transition from an anti-tumor to a pro-tumorigenic type. The latter is characterized by high expression of factors that activate endothelial cells, suppress immune response, degrade extracellular matrix, and promote tumor growth. Cumulatively, these products of TAMs promote tumor expansion and growth of both blood and lymphatic vessels that facilitate metastatic spread. Breast cancers and other epithelial malignancies induce the formation of new lymphatic vessels (i.e., lymphangiogenesis) that leads to lymphatic and subsequently, to distant metastasis. Both experimental and clinical studies have shown that TAMs significantly promote tumor lymphangiogenesis through paracrine and cell autonomous modes. The paracrine effect consists of the expression of a variety of pro-lymphangiogenic factors that activate the preexisting lymphatic vessels. The evidence for cell-autonomous contribution is based on the observed tumor mobilization of macrophage-derived lymphatic endothelial cell progenitors (M-LECP) that integrate into lymphatic vessels prior to sprouting. This review will summarize the current knowledge of macrophage-dependent growth of new lymphatic vessels with specific emphasis on an emerging role of macrophages as lymphatic endothelial cell progenitors (M-LECP)

  20. Lymphatic filariasis control in Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Derua, Yahya A.; Kisinza, William N.

    2013-01-01

    Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA...

  1. Lymphatic Filariasis control in Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Pedersen, Erling Møller; Rwegoshora, Rwehumbiza T.

    2010-01-01

    In most countries of sub-Saharan Africa the control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. Here we present the first detailed study on the effect of 3 repeated MDAs...

  2. The Pleiotropic Role of L1CAM in Tumor Vasculature

    Directory of Open Access Journals (Sweden)

    Francesca Angiolini

    2017-01-01

    Full Text Available Angiogenesis, the formation of new vessels, is a key step in the development, invasion, and dissemination of solid tumors and, therefore, represents a viable target in the context of antitumor therapy. Indeed, antiangiogenic approaches have given promising results in preclinical models and entered the clinical practice. However, in patients, the results obtained so far with antiangiogenic drugs have not completely fulfilled expectations, especially because their effect has been transient with tumors developing resistance and evasion mechanisms. A better understanding of the mechanisms that underlie tumor vascularization and the functional regulation of cancer vessels is a prerequisite for the development of novel and alternative antiangiogenic treatments. The L1 cell adhesion molecule (L1CAM, a cell surface glycoprotein previously implicated in the development and plasticity of the nervous system, is aberrantly expressed in the vasculature of various cancer types. L1CAM plays multiple pro-angiogenic roles in the endothelial cells of tumor-associated vessels, thus emerging as a potential therapeutic target. In addition, L1CAM prevents the maturation of cancer vasculature and its inhibition promotes vessel normalization, a process that is thought to improve the therapeutic response of tumors to cytotoxic drugs. We here provide an overview on tumor angiogenesis and antiangiogenic therapies and summarize the current knowledge on the biological role of L1CAM in cancer vasculature. Finally, we highlight the clinical implications of targeting L1CAM as a novel antiangiogenic and vessel-normalizing approach.

  3. Lymphatics and Lymphangiogenesis in the Eye

    Directory of Open Access Journals (Sweden)

    Shintaro Nakao

    2012-01-01

    Full Text Available Lymphatic is a prerequisite for the maintenance of tissue fluid balance and immunity in the body. A body of evidence also shows that lymphangiogenesis plays important roles in the pathogenesis of diseases such as tumor metastasis and inflammation. The eye was thought to lack lymphatic vessels except for the conjunctiva; however, advances in the field, including the identification of lymphatic endothelial markers (e.g., LYVE-1 or podoplanin and lymphangiogenic factors (e.g., VEGF-C, have revealed the exsitence and possible roles of lymphatics and lymphangiogenesis in the eye. Recent studies have shown that corneal limbus, ciliary body, lacrimal gland, orbital meninges, and extraocular muscles contain lymphatic vessels and that the choroid might have a lymphatic-like system. There is no known lymphatic outflow from the eye. However, several lymphatic channels including uveolymphatic pathway might serve the ocular fluid homeostasis. Furthermore, lymphangiogenesis plays important roles in pathological conditions in the eye including corneal transplant rejection and ocular tumor progression. Yet, the role of lymphangiogenesis in most eye diseases, especially inflammatory disease or edema, remains unknown. A better understanding of lymphatic and lymphangiogenesis in the eye will open new therapeutic opportunities to prevent vision loss in ocular diseases.

  4. Lymphatics and cancer : VEGF-C and nitric oxide in lymphatic function, lymphangiogenesis, and metastasis

    NARCIS (Netherlands)

    Hagendoorn, Jeroen

    2006-01-01

    The lymphatics are a primary route for cancer metastasis and lymph node metastasis is an important clinical prognostic factor. The process of lymphatic metastasis is, however, not well understood. This thesis examines the function of lymphatic vessels in relation to cancer progression and

  5. Scaling of the surface vasculature on the human placenta

    Science.gov (United States)

    Leonard, A. S.; Lee, J.; Schubert, D.; Croen, L. A.; Fallin, M. D.; Newschaffer, C. J.; Walker, C. K.; Salafia, C. M.; Morgan, S. P.; Vvedensky, D. D.

    2017-10-01

    The networks of veins and arteries on the chorionic plate of the human placenta are analyzed in terms of Voronoi cells derived from these networks. Two groups of placentas from the United States are studied: a population cohort with no prescreening, and a cohort from newborns with an elevated risk of developing autistic spectrum disorder. Scaled distributions of the Voronoi cell areas in the two cohorts collapse onto a single distribution, indicating common mechanisms for the formation of the complete vasculatures, but which have different levels of activity in the two cohorts.

  6. Low lymphatic vessel density associates with chronic rhinosinusitis with nasal polyps.

    Science.gov (United States)

    Luukkainen, A; Seppälä, M; Renkonen, J; Renkonen, R; Hagstrő M, J; Huhtala, H; Rautiainen, M; Myller, J; Paavonen, T; Ranta, A; Torkkeli, T; Toppila-Salmi, S

    2017-06-01

    Chronic rhinosinusitis with and without nasal polyps (CRSwNP and CRSsNP) and antrochoanal polyps (ACP) are different upper airway inflammation phenotypes with different pathomechanisms. In order to understand the development of tissue edema, the present study aimed to evaluate lymphatic vessel density in CRSsNP, CRSwNP and ACP. 120 retrospective nasal and maxillary sinus specimens were stained immunohistochemically with a von Willebrand factor polyclonal antibody recognizing vascular and lymphatic endothelium, and with a podoplanin monoclonal antibody recognizing lymphatic endothelium. Vessels were studied by microscopy in a blinded fashion, and the vessel density and the relative density of lymphatic vessels were calculated. Patient characteristic factors and follow-up data of in average 9 years were collected from patient records. In the nasal cavity, the low absolute and relative density of vessels and of lymphatic vessels was associated with CRSwNP and ACP tissues compared to control inferior turbinate. This was observed also in the inflammatory hotspot area. In the maxillary sinus, lower absolute and relative density of lymphatic vessels associated with the CRSwNP phenotype. High lymphatic vessel density in polyp tissue associated with the need for revision CRS-surgery. As a conclusion, low density of lymphatic vessels distinguished patients with CRSwNP not only in the hotspot area of polyp tissue, but also in maxillary sinus mucosa. Yet, higher lymphatic vessel density seems to associate with polyp recurrence. Further studies are still needed to explore if formation of nasal polyps could be diminished by intranasal therapeutics affecting lymphangiogenesis.

  7. Analysis of homeobox gene action may reveal novel angiogenic pathways in normal placental vasculature and in clinical pregnancy disorders associated with abnormal placental angiogenesis.

    Directory of Open Access Journals (Sweden)

    Padma eMurthi

    2014-06-01

    Full Text Available Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. Homeobox genes comprise an important family of transcription factors, which are characterised by a well conserved DNA binding motif; the homeodomain. The specificity of the homeodomain allows the transcription factor to bind to the promoter regions of batteries of target genes and thereby regulates their expression. Target genes identified for homeodomain proteins have been shown to control fundamental cell processes such as proliferation, differentiation and apoptosis. We and others have reported that homeobox genes are expressed in the placental vasculature, but our knowledge of their downstream target genes is limited. This review highlights the importance of studying the cellular and molecular mechanisms by which homeobox genes and their downstream targets may regulate important vascular cellular processes such as proliferation, migration, and endothelial tube formation, which are essential for placental vasculogenesis and angiogenesis. A better understanding of the molecular targets of homeobox genes may lead to new therapies for aberrant angiogenesis associated with clinically important pregnancy pathologies, including fetal growth restriction and preeclampsia.

  8. VIPAR, a quantitative approach to 3D histopathology applied to lymphatic malformations.

    Science.gov (United States)

    Hägerling, René; Drees, Dominik; Scherzinger, Aaron; Dierkes, Cathrin; Martin-Almedina, Silvia; Butz, Stefan; Gordon, Kristiana; Schäfers, Michael; Hinrichs, Klaus; Ostergaard, Pia; Vestweber, Dietmar; Goerge, Tobias; Mansour, Sahar; Jiang, Xiaoyi; Mortimer, Peter S; Kiefer, Friedemann

    2017-08-17

    Lack of investigatory and diagnostic tools has been a major contributing factor to the failure to mechanistically understand lymphedema and other lymphatic disorders in order to develop effective drug and surgical therapies. One difficulty has been understanding the true changes in lymph vessel pathology from standard 2D tissue sections. VIPAR (volume information-based histopathological analysis by 3D reconstruction and data extraction), a light-sheet microscopy-based approach for the analysis of tissue biopsies, is based on digital reconstruction and visualization of microscopic image stacks. VIPAR allows semiautomated segmentation of the vasculature and subsequent nonbiased extraction of characteristic vessel shape and connectivity parameters. We applied VIPAR to analyze biopsies from healthy lymphedematous and lymphangiomatous skin. Digital 3D reconstruction provided a directly visually interpretable, comprehensive representation of the lymphatic and blood vessels in the analyzed tissue volumes. The most conspicuous features were disrupted lymphatic vessels in lymphedematous skin and a hyperplasia (4.36-fold lymphatic vessel volume increase) in the lymphangiomatous skin. Both abnormalities were detected by the connectivity analysis based on extracted vessel shape and structure data. The quantitative evaluation of extracted data revealed a significant reduction of lymphatic segment length (51.3% and 54.2%) and straightness (89.2% and 83.7%) for lymphedematous and lymphangiomatous skin, respectively. Blood vessel length was significantly increased in the lymphangiomatous sample (239.3%). VIPAR is a volume-based tissue reconstruction data extraction and analysis approach that successfully distinguished healthy from lymphedematous and lymphangiomatous skin. Its application is not limited to the vascular systems or skin. Max Planck Society, DFG (SFB 656), and Cells-in-Motion Cluster of Excellence EXC 1003.

  9. Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Souheil El-Chemaly

    2012-09-01

    Full Text Available The primary function of the lymphatic system is absorbing and transporting macromolecules and immune cells to the general circulation, thereby regulating fluid, nutrient absorption and immune cell trafficking. Lymphangiogenesis plays an important role in tissue inflammation and tumour cell dissemination. Lymphatic involvement is seen in lymphangioleiomyomatosis (LAM and idiopathic pulmonary fibrosis (IPF. LAM, a disease primarily affecting females, involves the lung (cystic destruction, kidney (angiomyolipoma and axial lymphatics (adenopathy and lymphangioleiomyoma. LAM occurs sporadically or in association with tuberous sclerosis complex (TSC. Cystic lung destruction results from proliferation of LAM cells, which are abnormal smooth muscle-like cells with mutations in the TSC1 or TSC2 gene. Lymphatic abnormalities arise from infiltration of LAM cells into the lymphatic wall, leading to damage or obstruction of lymphatic vessels. Benign appearing LAM cells possess metastatic properties and are found in the blood and other body fluids. IPF is a progressive lung disease resulting from fibroblast proliferation and collagen deposition. Lymphangiogenesis is associated with pulmonary destruction and disease severity. A macrophage subset isolated from IPF bronchoalveolar lavage fluid (BALF express lymphatic endothelial cell markers in vitro, in contrast to the same macrophage subset from normal BALF. Herein, we review lymphatic involvement in LAM and IPF.

  10. Endothelial ERK signaling controls lymphatic fate specification

    Science.gov (United States)

    Deng, Yong; Atri, Deepak; Eichmann, Anne; Simons, Michael

    2013-01-01

    Lymphatic vessels are thought to arise from PROX1-positive endothelial cells (ECs) in the cardinal vein in response to induction of SOX18 expression; however, the molecular event responsible for increased SOX18 expression has not been established. We generated mice with endothelial-specific, inducible expression of an RAF1 gene with a gain-of-function mutation (RAF1S259A) that is associated with Noonan syndrome. Expression of mutant RAF1S259A in ECs activated ERK and induced SOX18 and PROX1 expression, leading to increased commitment of venous ECs to the lymphatic fate. Excessive production of lymphatic ECs resulted in lymphangiectasia that was highly reminiscent of abnormal lymphatics seen in Noonan syndrome and similar “RASopathies.” Inhibition of ERK signaling during development abrogated the lymphatic differentiation program and rescued the lymphatic phenotypes induced by expression of RAF1S259A. These data suggest that ERK activation plays a key role in lymphatic EC fate specification and that excessive ERK activation is the basis of lymphatic abnormalities seen in Noonan syndrome and related diseases. PMID:23391722

  11. A review of mathematical models for the formation of vascular networks

    KAUST Repository

    Scianna, M.

    2013-09-01

    Two major mechanisms are involved in the formation of blood vasculature: vasculogenesis and angiogenesis. The former term describes the formation of a capillary-like network from either a dispersed or a monolayered population of endothelial cells, reproducible also in vitro by specific experimental assays. The latter term describes the sprouting of new vessels from an existing capillary or post-capillary venule. Similar mechanisms are also involved in the formation of the lymphatic system through a process generally called lymphangiogenesis. A number of mathematical approaches have been used to analyze these phenomena. In this paper, we review the different types of models, with special emphasis on their ability to reproduce different biological systems and to predict measurable quantities which describe the overall processes. Finally, we highlight the advantages specific to each of the different modelling approaches. © 2013 Elsevier Ltd.

  12. Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish

    DEFF Research Database (Denmark)

    Dahl Ejby Jensen, Lasse; Cao, Renhai; Hedlund, Eva-Maria

    2009-01-01

    and lymphatic perfusion. Here we show in the adult zebrafish and glass catfish (Kryptopterus bicirrhis) that blood-lymphatic conduits directly connect arterial vessels to the lymphatic system. Under hypoxic conditions, arterial-lymphatic conduits (ALCs) became highly dilated and linearized by NO...

  13. Prototyping of cerebral vasculature physical models.

    Science.gov (United States)

    Khan, Imad S; Kelly, Patrick D; Singer, Robert J

    2014-01-01

    Prototyping of cerebral vasculature models through stereolithographic methods have the ability to accurately depict the 3D structures of complicated aneurysms with high accuracy. We describe the method to manufacture such a model and review some of its uses in the context of treatment planning, research, and surgical training. We prospectively used the data from the rotational angiography of a 40-year-old female who presented with an unruptured right paraclinoid aneurysm. The 3D virtual model was then converted to a physical life-sized model. The model constructed was shown to be a very accurate depiction of the aneurysm and its associated vasculature. It was found to be useful, among other things, for surgical training and as a patient education tool. With improving and more widespread printing options, these models have the potential to become an important part of research and training modalities.

  14. Coxsackie- and adenovirus receptor (CAR) is expressed in lymphatic vessels in human skin and affects lymphatic endothelial cell function in vitro

    International Nuclear Information System (INIS)

    Vigl, Benjamin; Zgraggen, Claudia; Rehman, Nadia; Banziger-Tobler, Nadia E.; Detmar, Michael; Halin, Cornelia

    2009-01-01

    Lymphatic vessels play an important role in tissue fluid homeostasis, intestinal fat absorption and immunosurveillance. Furthermore, they are involved in pathologic conditions, such as tumor cell metastasis and chronic inflammation. In comparison to blood vessels, the molecular phenotype of lymphatic vessels is less well characterized. Performing comparative gene expression analysis we have recently found that coxsackie- and adenovirus receptor (CAR) is significantly more highly expressed in cultured human, skin-derived lymphatic endothelial cells (LECs), as compared to blood vascular endothelial cells. Here, we have confirmed these results at the protein level, using Western blot and FACS analysis. Immunofluorescence performed on human skin confirmed that CAR is expressed at detectable levels in lymphatic vessels, but not in blood vessels. To address the functional significance of CAR expression, we modulated CAR expression levels in cultured LECs in vitro by siRNA- and vector-based transfection approaches. Functional assays performed with the transfected cells revealed that CAR is involved in distinct cellular processes in LECs, such as cell adhesion, migration, tube formation and the control of vascular permeability. In contrast, no effect of CAR on LEC proliferation was observed. Overall, our data suggest that CAR stabilizes LEC-LEC interactions in the skin and may contribute to lymphatic vessel integrity

  15. Pneumocystis carinii Pneumonia in Acute Lymphatic Leukaemia ...

    African Journals Online (AJOL)

    A case report of a patient who developed fatal pneumocystis pneumonia while in remission from acute lymphatic leukaemia is presented. Clinical and aetiological aspects of this rare infection are discussed. Attention is drawn to diagnostic pitfalls encountered in leukaemia.

  16. Lymphatic vessels assessment in feline mammary tumours

    International Nuclear Information System (INIS)

    Sarli, Giuseppe; Sassi, Francesco; Brunetti, Barbara; Rizzo, Antonio; Diracca, Laura; Benazzi, Cinzia

    2007-01-01

    The lymphatic vessels play a crucial role in a variety of human cancers since tumour cell lymphatic invasion significantly influences prognosis. It is not known if pre-existing lymphatics are enough for tumour dissemination or de novo development is necessary. VEGFR-3 is an angiogenetic mediator for both lymphatic and blood vessels during embryonic development, and only for lymphatics after birth. VEGF is a mediator of both vasculogenesis and angiogenesis, regulates the growth of lymphatics in various experimental models, and is produced in many solid tumours. CD44 mediates hyaluronic acid (HA)-dependent cell adhesion: besides promoting invasion, this interaction also supports neoangiogenesis that indirectly stimulates tumour cell proliferation. The expression of VEGF-C (Vascular Endothelial Growth Factor – C), its receptor VEGFR-3 and CD44, were studied on feline mammary samples to assess the importance of lymphangiogenesis and lymphangiotrophism in neoplasia. Samples were taken from six normal mammary glands (NMG), ten benign (BT) and 32 malignant (MT) tumours. Immunohistochemical laminin/VEGFR-3 double stain, VEGF-C and CD44 stains were applied to 4 μm-thick sections, and their expression evaluated in intratumoral/extratumoral and intramammary/extramammary fields. All groups revealed a higher number of lymphatics in the extratumoral/extramammary areas. VEGF-C expression in the epithelium paralleled the number of positive vessels in the NMG, BT and MT, whereas VEGF-C higher expression was noted in the intratumoral fields only in infiltrating MT. CD44 score was lower in extratumoral than intratumoral fields in tumours and showed a significant increase in extramammary/extratumoral fields from NMG to MT. Pearson test showed a significant and inversely proportional correlation between CD44 expression and the number of lymphatic vessels with VEGFR-3 in malignant infiltrating tumours. The number of both VEGFR-3 positive and negative lymphatics in the extratumoral

  17. Comparative and Developmental Anatomy of Cardiac Lymphatics

    Directory of Open Access Journals (Sweden)

    A. Ratajska

    2014-01-01

    Full Text Available The role of the cardiac lymphatic system has been recently appreciated since lymphatic disturbances take part in various heart pathologies. This review presents the current knowledge about normal anatomy and structure of lymphatics and their prenatal development for a better understanding of the proper functioning of this system in relation to coronary circulation. Lymphatics of the heart consist of terminal capillaries of various diameters, capillary plexuses that drain continuously subendocardial, myocardial, and subepicardial areas, and draining (collecting vessels that lead the lymph out of the heart. There are interspecies differences in the distribution of lymphatic capillaries, especially near the valves, as well as differences in the routes and number of draining vessels. In some species, subendocardial areas contain fewer lymphatic capillaries as compared to subepicardial parts of the heart. In all species there is at least one collector vessel draining lymph from the subepicardial plexuses and running along the anterior interventricular septum under the left auricle and further along the pulmonary trunk outside the heart and terminating in the right venous angle. The second collector assumes a different route in various species. In most mammalian species the collectors run along major branches of coronary arteries, have valves and a discontinuous layer of smooth muscle cells.

  18. The lymphatics of the esophagus

    International Nuclear Information System (INIS)

    Okanobu, Koji

    1990-01-01

    For the studies of the esophageal lymphatics, endoscopic RI-lymphoscintigraphy was performed in 23 cases of esophageal cancer, 3 cases of lung cancer and 5 cases of gastric cancer. 99m Tc-Rhenium colloid was endoscopically injected into the submucosal layer of the esophagus near the tumor and the images of th lymph flow were obtained after about 3 hours. Single photon emission computerized tomography (SPECT) was used to acquire the three-dimensional images of the esophageal lymph flow on 19 patients. RI-uptake of all dissected lymph nodes was also counted after the operation. The results were shown as follows. Whole neck, thoracic and abdominal lymph nodes could be imaged in any case injected at any part of the thoracic esophagus. But the lymph flow in the upper third of the esophagus tended to move mainly upward, and the lymph flow in the lower third tended to move mainly downward. The block of intra-mural lymph vessels by the tumor had very important roles upon the esophageal lymph flow. The removal of upper mediastinal lymph nodes and intraabdominal lumph nodes as well as paraesophageal lymph nodes seemed to be very important for curative resection of carcinoma of the esophagus. (author)

  19. Giant pediatric cervicofacial lymphatic malformations.

    Science.gov (United States)

    Benazzou, Salma; Boulaadas, Malik; Essakalli, Leila

    2013-07-01

    Lymphatic malformations (LMs) are benign lesions. Most of them are found in head and neck regions as asymptomatic mass, but giant lymphangiomas may affect breathing or swallowing and constitute a major therapeutic challenge. A retrospective analysis of giant head and neck LMs with impairment of respiration or swallow for the past 11 years was performed in the Department of Maxillofacial Surgery and ENT of the Avicenne Medical University Center. Seven patients with large and extensive LMs of the head and neck were identified. There were 3 males and 4 females with a mean age of 6 years. The predominant reason for referral was airway compromise necessitating tracheostomy (57%) and dysphagia (43%). Three patients had macrocystic lesions; others were considered mixed or microcystic. All the patients underwent surgical excision as a primary treatment modality. Complete surgical resection was realized in 4 patients, and subtotal resection in 3 patients. Of 7 patients, 4 patients had complications including nerve damage and recurrence of the disease. The majority of the patients underwent only a single surgical procedure. Cervicofacial LMs in children should be managed in multidisciplinary setting. Surgery remains the first treatment for managing giant, life-threatening lesions.

  20. Cranial vasculature in zebrafish forms by angioblast cluster-derived angiogenesis.

    Science.gov (United States)

    Proulx, Kira; Lu, Annie; Sumanas, Saulius

    2010-12-01

    Formation of embryonic vasculature involves vasculogenesis as endothelial cells differentiate and aggregate into vascular cords and angiogenesis which includes branching from the existing vessels. In the zebrafish which has emerged as an advantageous model to study vasculogenesis, cranial vasculature is thought to originate by a combination of vasculogenesis and angiogenesis, but how these processes are coordinated is not well understood. To determine how angioblasts assemble into cranial vasculature, we generated an etsrp:GFP transgenic line in which GFP reporter is expressed under the promoter control of an early regulator of vascular and myeloid development, etsrp/etv2. By utilizing time-lapse imaging we show that cranial vessels originate by angiogenesis from angioblast clusters, which themselves form by the mechanism of vasculogenesis. The two major pairs of bilateral clusters include the rostral organizing center (ROC) which gives rise to the most rostral cranial vessels and the midbrain organizing center (MOC) which gives rise to the posterior cranial vessels and to the myeloid and endocardial lineages. In Etsrp knockdown embryos initial cranial vasculogenesis proceeds normally but endothelial and myeloid progenitors fail to initiate differentiation, migration and angiogenesis. Such angioblast cluster-derived angiogenesis is likely to be involved during vasculature formation in other vertebrate systems as well. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Vascular endothelial growth factor-D over-expressing tumor cells induce differential effects on uterine vasculature in a mouse model of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Stacker Steven A

    2010-07-01

    Full Text Available Abstract Background It has been hypothesised that increased VEGF-D expression may be an independent prognostic factor for endometrial cancer progression and lymph node metastasis; however, the mechanism by which VEGF-D may promote disease progression in women with endometrial cancer has not been investigated. Our aim was to describe the distribution of lymphatic vessels in mouse uterus and to examine the effect of VEGF-D over-expression on these vessels in a model of endometrial cancer. We hypothesised that VEGF-D over-expression would stimulate growth of new lymphatic vessels into the endometrium, thereby contributing to cancer progression. Methods We initially described the distribution of lymphatic vessels (Lyve-1, podoplanin, VEGFR-3 and VEGF-D expression in the mouse uterus during the estrous cycle, early pregnancy and in response to estradiol-17beta and progesterone using immunohistochemistry. We also examined the effects of VEGF-D over-expression on uterine vasculature by inoculating uterine horns in NOD SCID mice with control or VEGF-D-expressing 293EBNA tumor cells. Results Lymphatic vessels positive for the lymphatic endothelial cell markers Lyve-1, podoplanin and VEGFR-3 profiles were largely restricted to the connective tissue between the myometrial circular and longitudinal muscle layers; very few lymphatic vessel profiles were observed in the endometrium. VEGF-D immunostaining was present in all uterine compartments (epithelium, stroma, myometrium, although expression was generally low. VEGF-D immunoexpression was slightly but significantly higher in estrus relative to diestrus; and in estradiol-17beta treated mice relative to vehicle or progesterone treated mice. The presence of VEGF-D over-expressing tumor cells did not induce endometrial lymphangiogenesis, although changes were observed in existing vessel profiles. For myometrial lymphatic and endometrial blood vessels, the percentage of profiles containing proliferating

  2. Cholinergic innervation of human mesenteric lymphatic vessels.

    Science.gov (United States)

    D'Andrea, V; Bianchi, E; Taurone, S; Mignini, F; Cavallotti, C; Artico, M

    2013-11-01

    The cholinergic neurotransmission within the human mesenteric lymphatic vessels has been poorly studied. Therefore, our aim is to analyse the cholinergic nerve fibres of lymphatic vessels using the traditional enzymatic techniques of staining, plus the biochemical modifications of acetylcholinesterase (AChE) activity. Specimens obtained from human mesenteric lymphatic vessels were subjected to the following experimental procedures: 1) drawing, cutting and staining of tissues; 2) staining of total nerve fibres; 3) enzymatic staining of cholinergic nerve fibres; 4) homogenisation of tissues; 5) biochemical amount of proteins; 6) biochemical amount of AChE activity; 6) quantitative analysis of images; 7) statistical analysis of data. The mesenteric lymphatic vessels show many AChE positive nerve fibres around their wall with an almost plexiform distribution. The incubation time was performed at 1 h (partial activity) and 6 h (total activity). Moreover, biochemical dosage of the same enzymatic activity confirms the results obtained with morphological methods. The homogenates of the studied tissues contain strong AChE activity. In our study, the lymphatic vessels appeared to contain few cholinergic nerve fibres. Therefore, it is expected that perivascular nerve stimulation stimulates cholinergic nerves innervating the mesenteric arteries to release the neurotransmitter AChE, which activates muscarinic or nicotinic receptors to modulate adrenergic neurotransmission. These results strongly suggest, that perivascular cholinergic nerves have little or no effect on the adrenergic nerve function in mesenteric arteries. The cholinergic nerves innervating mesenteric arteries do not mediate direct vascular responses.

  3. Lamb congenital lymphatic malformation - a case report

    Directory of Open Access Journals (Sweden)

    Neria Santos

    2014-01-01

    Full Text Available Lymphatic malformations have been rarely reported in literature either in humans or in animals. However, in recent years, concern about these malformations in humans has increased. A five-month-old Rasa Aragonesa male lamb was received at the Ovine Clinical Service of the Veterinary Faculty of Zaragoza, Spain, with a history of cervical protuberances coming from birth. The lamb showed three round swollen lumps (5–12 cm in diameter parallel to the trachea on the left side of the neck. Clinical examination, haematology, ultrasonography, fluid examination and histopathology were performed. No abnormalities were found in blood samples and ultrasound confirmed a multicystic lesion with internal separations. Histological evaluation of the tissue revealed dilated lymphatic vessels and channels in the dermis and hypodermis; some lymphatic vessels were filled with amorphous proteinaceous material and occasional lymphocytes and macrophages. These protuberances were diagnosed as congenital lymphatic malformations. Most of the gross and microscopical lesions were very similar to those described in humans. To the authors’ knowledge, this is the first time that a congenital lymphatic malformation is described in sheep.

  4. Exercise training improves obesity-related lymphatic dysfunction.

    Science.gov (United States)

    Hespe, Geoffrey E; Kataru, Raghu P; Savetsky, Ira L; García Nores, Gabriela D; Torrisi, Jeremy S; Nitti, Matthew D; Gardenier, Jason C; Zhou, Jie; Yu, Jessie Z; Jones, Lee W; Mehrara, Babak J

    2016-08-01

    Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti-inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic

  5. Exercise training improves obesity‐related lymphatic dysfunction

    Science.gov (United States)

    Hespe, Geoffrey E.; Kataru, Raghu P.; Savetsky, Ira L.; García Nores, Gabriela D.; Torrisi, Jeremy S.; Nitti, Matthew D.; Gardenier, Jason C.; Zhou, Jie; Yu, Jessie Z.; Jones, Lee W.

    2016-01-01

    Key points Obesity results in perilymphatic inflammation and lymphatic dysfunction.Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells.Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Abstract Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti‐inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene

  6. Lymphatic Vascular Regeneration : The Next Step in Tissue Engineering

    NARCIS (Netherlands)

    Huethorst, Eline; Krebber, Merle M; Fledderus, Joost O; Gremmels, Hendrik; Xu, Yan Juan; Pei, Jiayi; Verhaar, Marianne C; Cheng, Caroline

    2016-01-01

    The lymphatic system plays a crucial role in interstitial fluid drainage, lipid absorption, and immunological defense. Lymphatic dysfunction results in lymphedema, fluid accumulation, and swelling of soft tissues, as well as a potentially impaired immune response. Lymphedema significantly reduces

  7. Evaluation of lymphatic regeneration in rat incisional wound healing ...

    African Journals Online (AJOL)

    Nevine M.F. El Deeb

    2014-06-20

    Jun 20, 2014 ... migration of connective tissue cells, and re-epithelialization of the wound ... lymphatic vessels sprouting in experimental rabbit ear wounds.9The ..... of lymphatic flow within 14 days, regaining the ability to drain fluid and ...

  8. Angiomodulin is a specific marker of vasculature and regulates VEGF-A dependent neo-angiogenesis

    Science.gov (United States)

    Hooper, Andrea T.; Shmelkov, Sergey V.; Gupta, Sunny; Milde, Till; Bambino, Kathryn; Gillen, Kelly; Goetz, Mollie; Chavala, Sai; Baljevic, Muhamed; Murphy, Andrew J.; Valenzuela, David M.; Gale, Nicholas W.; Thurston, Gavin; Yancopoulos, George D.; Vahdat, Linda; Evans, Todd; Rafii, Shahin

    2010-01-01

    Blood vessel formation is controlled by the balance between pro- and anti-angiogenic pathways. Although much is known about the factors that drive sprouting of neovessels, the factors that stabilize and pattern neovessels are undefined. The expression of angiomodulin (AGM), a VEGF-A binding protein, was increased in the vasculature of several human tumors as compared to normal tissue, raising the hypothesis that AGM may modulate VEGF-A-dependent vascular patterning. To elucidate the expression pattern of AGM, we developed an AGM knockin reporter mouse (AGMlacZ/+) wherein we demonstrate that AGM is predominantly expressed in the vasculature of developing embryos and adult organs. During physiological and pathological angiogenesis, AGM is upregulated in the angiogenic vasculature. Using the zebrafish model, we found that AGM is restricted to developing vasculature by 17-22 hpf. Blockade of AGM activity with morpholino oligomers (MO) results in prominent angiogenesis defects in vascular sprouting and remodeling. Concurrent knockdown of both AGM and VEGF-A results in synergistic angiogenesis defects. When VEGF-A is overexpressed, the compensatory induction of the VEGF-A receptor, VEGFR-2/flk-1, is blocked by the simultaneous injection of AGM MO. These results demonstrate that the vascular-specific marker AGM modulates vascular remodeling in part by temporizing the pro-angiogenic effects of VEGF-A. PMID:19542015

  9. Factor VIII-associated antigen in human lymphatic endothelium.

    Science.gov (United States)

    Nagle, R B; Witte, M H; Martinez, A P; Witte, C L; Hendrix, M J; Way, D; Reed, K

    1987-03-01

    Lymphatic vascular endothelium both on tissue section and in culture exhibits positivity for Factor VIII-associated antigen although staining is generally less intense and more spotty than in comparable blood vascular endothelium. Lymphatic endothelium also exhibits Weibel-Palade bodies. Neither marker, therefore, reliably distinguishes blood vascular endothelium from lymphatic endothelium.

  10. Genetic determinants of hyaloid and retinal vasculature in zebrafish

    Directory of Open Access Journals (Sweden)

    Hyde David R

    2007-10-01

    Full Text Available Abstract Background The retinal vasculature is a capillary network of blood vessels that nourishes the inner retina of most mammals. Developmental abnormalities or microvascular complications in the retinal vasculature result in severe human eye diseases that lead to blindness. To exploit the advantages of zebrafish for genetic, developmental and pharmacological studies of retinal vasculature, we characterised the intraocular vasculature in zebrafish. Results We show a detailed morphological and developmental analysis of the retinal blood supply in zebrafish. Similar to the transient hyaloid vasculature in mammalian embryos, vessels are first found attached to the zebrafish lens at 2.5 days post fertilisation. These vessels progressively lose contact with the lens and by 30 days post fertilisation adhere to the inner limiting membrane of the juvenile retina. Ultrastructure analysis shows these vessels to exhibit distinctive hallmarks of mammalian retinal vasculature. For example, smooth muscle actin-expressing pericytes are ensheathed by the basal lamina of the blood vessel, and vesicle vacuolar organelles (VVO, subcellular mediators of vessel-retinal nourishment, are present. Finally, we identify 9 genes with cell membrane, extracellular matrix and unknown identity that are necessary for zebrafish hyaloid and retinal vasculature development. Conclusion Zebrafish have a retinal blood supply with a characteristic developmental and adult morphology. Abnormalities of these intraocular vessels are easily observed, enabling application of genetic and chemical approaches in zebrafish to identify molecular regulators of hyaloid and retinal vasculature in development and disease.

  11. Lymphatic malformations: a proposed management algorithm.

    LENUS (Irish Health Repository)

    Oosthuizen, J C

    2012-02-01

    OBJECTIVE: The aim of this study was to develop a management algorithm for cervicofacial lymphatic malformations, based on the authors\\' experience in managing these lesions as well as current literature on the subject. STUDY DESIGN AND METHODS: A retrospective medical record review of all the patients treated for lymphatic malformations at our institution during a 10-year period (1998-2008) was performed. DATA COLLECTED: age at diagnosis, location and type of lesion, radiologic investigation performed, presenting symptoms, treatment modality used, complications and results achieved. RESULTS: 14 patients were identified. Eight (57%) male and six (43%) female. There was an equal distribution between the left and right sides. The majority (71%) of cases were diagnosed within the first year of life. The majority of lesions were located in the suprahyoid region. The predominant reason for referral was an asymptomatic mass in 7 cases (50%) followed by airway compromise (36%) and dysphagia (14%). Management options employed included: observation, OK-432 injection, surgical excision and laser therapy. In 5 cases (36%) a combination of these were used. CONCLUSION: Historically surgical excision has been the management option of choice for lymphatic malformations. However due to the morbidity and high complication rate associated this is increasingly being questioned. Recent advances in sclerotherapy e.g. OK-432 injection have also shown significant promise. Based on experience in managing these lesions as well as current literature the authors of this paper have developed an algorithm for the management of cervicofacial lymphatic malformations.

  12. Spleen and Lymphatic System (For Parents)

    Science.gov (United States)

    ... System Print en español El bazo y el sistema linfático The lymphatic system is an extensive drainage ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

  13. Modelling Lymphatic Filariasis: Transmission and Control

    NARCIS (Netherlands)

    S. Swaminathan

    2004-01-01

    textabstractLymphatic filariasis (LF) is a mosquito borne parasitic disease of the tropics. Of the three species of parasites causing the disease, W. bancrofti transmitted by Culex quinquefasciatus is the most widely prevalent. Infection can lead to disabling chronic manifestations: lymphoedema,

  14. Lymphatic Filariasis: Transmission, Treatment and Elimination

    NARCIS (Netherlands)

    W.A. Stolk (Wilma)

    2005-01-01

    textabstractLymphatic filariasis (LF) is a mosquito-borne, tropical disease caused by filarial worms. Infection can lead to disabling chronic disease, characterized by swelling of extremities or external genitalia (lymphoedema, elephantiasis and hydrocele). Mass treatment with antifilarial drugs is

  15. The deep lymphatic anatomy of the hand.

    Science.gov (United States)

    Ma, Chuan-Xiang; Pan, Wei-Ren; Liu, Zhi-An; Zeng, Fan-Qiang; Qiu, Zhi-Qiang

    2018-04-03

    The deep lymphatic anatomy of the hand still remains the least described in medical literature. Eight hands were harvested from four nonembalmed human cadavers amputated above the wrist. A small amount of 6% hydrogen peroxide was employed to detect the lymphatic vessels around the superficial and deep palmar vascular arches, in webs from the index to little fingers, the thenar and hypothenar areas. A 30-gauge needle was inserted into the vessels and injected with a barium sulphate compound. Each specimen was dissected, photographed and radiographed to demonstrate deep lymphatic distribution of the hand. Five groups of deep collecting lymph vessels were found in the hand: superficial palmar arch lymph vessel (SPALV); deep palmar arch lymph vessel (DPALV); thenar lymph vessel (TLV); hypothenar lymph vessel (HTLV); deep finger web lymph vessel (DFWLV). Each group of vessels drained in different directions first, then all turned and ran towards the wrist in different layers. The deep lymphatic drainage of the hand has been presented. The results will provide an anatomical basis for clinical management, educational reference and scientific research. Copyright © 2018 Elsevier GmbH. All rights reserved.

  16. Laryngeal spaces and lymphatics: current anatomic concepts

    International Nuclear Information System (INIS)

    Welsh, L.W.; Welsh, J.J.; Rizzo, T.A. Jr.

    1983-01-01

    This investigation evaluates the anatomic concepts of individual spaces or compartments within the larynx by isotope and dye diffusion. The authors identified continuity of spaces particularly within the submucosal planes and a relative isolation within the fixed structures resulting from the longitudinal pattern of fibroelastic tissues, muscle bands, and perichondrium. The historical data of anatomic resistance are refuted by the radioisotope patterns of dispersion and the histologic evidence of tissue permeability to the carbon particles. There is little clinical application of the compartment concept to the perimeter of growth and the configuration of extensive endolaryngeal cancers. The internal and extralaryngeal lymphatic network is presented and the regional associations are identified. The normal ipsilateral relationship is distorted by dispersion within the endolarynx supervening the anatomic midline. The effects of lymphatic obstruction caused by regional lymphadenectomy, tumor fixation, and irradiation-infection sequelae are illustrated; these result in widespread bilateral lymphatic nodal terminals. Finally, the evidence suggests that the internal network is modified by external interruption to accommodate an outflow system in continuity with the residual patent lymphatic channels

  17. Lymphatic filariasis control in Tanga Region, Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Derua, Yahya A.; Magesa, Stephen M.

    2014-01-01

    BackgroundLymphatic filariasis (LF) control started in Tanga Region of Tanzania in 2004, with annual ivermectin/albendazole mass drug administration (MDA). Since then, the current project has monitored the effect in communities and schools in rural areas of Tanga District. In 2013, after 8 rounds...

  18. Pdgfrb-Cre targets lymphatic endothelial cells of both venous and non-venous origins.

    Science.gov (United States)

    Ulvmar, Maria H; Martinez-Corral, Ines; Stanczuk, Lukas; Mäkinen, Taija

    2016-06-01

    The Pdgfrb-Cre line has been used as a tool to specifically target pericytes and vascular smooth muscle cells. Recent studies showed additional targeting of cardiac and mesenteric lymphatic endothelial cells (LECs) by the Pdgfrb-Cre transgene. In the heart, this was suggested to provide evidence for a previously unknown nonvenous source of LECs originating from yolk sac (YS) hemogenic endothelium (HemEC). Here we show that Pdgfrb-Cre does not, however, target YS HemEC or YS-derived erythro-myeloid progenitors (EMPs). Instead, a high proportion of ECs in embryonic blood vessels of multiple organs, as well as venous-derived LECs were targeted. Assessment of temporal Cre activity using the R26-mTmG double reporter suggested recent occurrence of Pdgfrb-Cre recombination in both blood and lymphatic ECs. It thus cannot be excluded that Pdgfrb-Cre mediated targeting of LECs is due to de novo expression of the Pdgfrb-Cre transgene or their previously established venous endothelial origin. Importantly, Pdgfrb-Cre targeting of LECs does not provide evidence for YS HemEC origin of the lymphatic vasculature. Our results highlight the need for careful interpretation of lineage tracing using constitutive Cre lines that cannot discriminate active from historical expression. The early vascular targeting by the Pdgfrb-Cre also warrants consideration for its use in studies of mural cells. genesis 54:350-358, 2016. © 2016 The Authors. Genesis Published by Wiley Periodicals, Inc. © 2016 The Authors. Genesis Published by Wiley Periodicals, Inc.

  19. Short time effects of radiotherapy on lymphatic vessels and restorative lymphatic pathways: experimental approaches ina mouse model.

    Science.gov (United States)

    Pastouret, F; Lievens, P; Leduc, O; Bourgeois, P; Tournel, K; Lamote, J; Zirak, C; Leduc, A

    2014-06-01

    Radiotherapy (RT) is an important component in the therapeutic approach to oncologic conditions. This study presents the investigative results on the impact of RT on lymphatic vessels and on the regenerative response of the lymphatic system in a mouse model. We first irradiated 3 groups of ten mice using brachytherapy in a single treatment of 20 Gy. We then performed morphological examination of the irradiated lymphatic vessels using an in vivo microscopic transillumination technique at 2, 4, and 6 weeks. Next we evaluated lymphatic flow using lymphoscintigraphy and in vivo microscopy at 6 to 11 weeks in: 10 additional mice following irradiation as above (IR), in 10 mice following incision of a lymphatic vessel (I), and in a non-treated control group of 10 mice (N). Intact lymphatic vessels were observed in all mice at 2, 4, and 8 weeks following the single dose of radiotherapy in the first group of mice and normal lymphatic flow was fully restored in the irradiated (IR) and incised (I) mice indicating that the reparative substitution lymphatic pathways are functioning normally. We found that following irradiation with one dose of 20 Gy, lymphatic vessels were not visibly damaged and also that lymphatic flow was consistently restored and substitutive lymphatic pathways formed.

  20. Computational lymphatic node models in pediatric and adult hybrid phantoms for radiation dosimetry

    International Nuclear Information System (INIS)

    Lee, Choonsik; Lamart, Stephanie; Moroz, Brian E

    2013-01-01

    We developed models of lymphatic nodes for six pediatric and two adult hybrid computational phantoms to calculate the lymphatic node dose estimates from external and internal radiation exposures. We derived the number of lymphatic nodes from the recommendations in International Commission on Radiological Protection (ICRP) Publications 23 and 89 at 16 cluster locations for the lymphatic nodes: extrathoracic, cervical, thoracic (upper and lower), breast (left and right), mesentery (left and right), axillary (left and right), cubital (left and right), inguinal (left and right) and popliteal (left and right), for different ages (newborn, 1-, 5-, 10-, 15-year-old and adult). We modeled each lymphatic node within the voxel format of the hybrid phantoms by assuming that all nodes have identical size derived from published data except narrow cluster sites. The lymph nodes were generated by the following algorithm: (1) selection of the lymph node site among the 16 cluster sites; (2) random sampling of the location of the lymph node within a spherical space centered at the chosen cluster site; (3) creation of the sphere or ovoid of tissue representing the node based on lymphatic node characteristics defined in ICRP Publications 23 and 89. We created lymph nodes until the pre-defined number of lymphatic nodes at the selected cluster site was reached. This algorithm was applied to pediatric (newborn, 1-, 5-and 10-year-old male, and 15-year-old males) and adult male and female ICRP-compliant hybrid phantoms after voxelization. To assess the performance of our models for internal dosimetry, we calculated dose conversion coefficients, called S values, for selected organs and tissues with Iodine-131 distributed in six lymphatic node cluster sites using MCNPX2.6, a well validated Monte Carlo radiation transport code. Our analysis of the calculations indicates that the S values were significantly affected by the location of the lymph node clusters and that the values increased for

  1. Functional photoacoustic microscopy of diabetic vasculature

    Science.gov (United States)

    Krumholz, Arie; Wang, Lidai; Yao, Junjie; Wang, Lihong V.

    2012-06-01

    We used functional photoacoustic microscopy to image diabetes-induced damage to the microvasculature. To produce an animal model for Type 1 diabetes, we used streptozotocin (STZ), which is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. A set number of ND4 Swiss Webster mice received intraperitoneal injections of STZ for five consecutive days at 50 mg/kg. Most mice developed a significant rise in blood glucose level (~400 mg/dL) within three weeks of the first injection. Changes in vasculature and hemodynamics were monitored for six weeks. The mouse ear was imaged with an optical-resolution photoacoustic microscope at a main blood vessel branch from the root of the ear. There are noticeable and measurable changes associated with the disease, including decreased vessel diameter and possible occlusion due to vessel damage and polyurea. We also observed an increase in the blood flow speed in the vein and a decrease in the artery, which could be due to compensation for the dehydration and vessel diameter changes. Functional and metabolic parameters such as hemoglobin oxygen saturation, oxygen extraction fraction, and oxygen consumption rate were also measured, but showed no significant change.

  2. Non-endemic cases of lymphatic filariasis.

    Science.gov (United States)

    Jones, Robert T

    2014-11-01

    Several cases of lymphatic filariasis (LF) have been reported in non-endemic countries due to travellers, military personnel and expatriates spending time in and returning from endemic areas, as well as immigrants coming from these regions. These cases are reviewed to assess the scale and context of non-endemic presentations and to consider the biological factors underlying their relative paucity. Cases reported in the English, French, Spanish and Portuguese literature during the last 30 years were examined through a search of the PubMed, ProMED-mail and TropNet resources. The literature research revealed 11 cases of lymphatic filariasis being reported in non-endemic areas. The extent of further infections in recent migrants to non-endemic countries was also revealed through the published literature. The life-cycle requirements of Wuchereria and Brugia species limit the extent of transmission of LF outside of tropical regions. However, until elimination, programmes are successful in managing the disease, there remains a possibility of low rates of infection being reported in non-endemic areas, and increased international travel can only contribute to this phenomenon. Physicians need to be aware of the signs and symptoms of lymphatic filariasis, and infection should be considered in the differential diagnosis of people with a relevant travel history. © 2014 John Wiley & Sons Ltd.

  3. Development and plasticity of meningeal lymphatic vessels.

    Science.gov (United States)

    Antila, Salli; Karaman, Sinem; Nurmi, Harri; Airavaara, Mikko; Voutilainen, Merja H; Mathivet, Thomas; Chilov, Dmitri; Li, Zhilin; Koppinen, Tapani; Park, Jun-Hee; Fang, Shentong; Aspelund, Aleksanteri; Saarma, Mart; Eichmann, Anne; Thomas, Jean-Léon; Alitalo, Kari

    2017-12-04

    The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect. Surprisingly, in adult mice, the LVs showed regression after VEGF-C or VEGFR3 deletion, administration of the tyrosine kinase inhibitor sunitinib, or expression of VEGF-C/D trap, which also compromised the lymphatic drainage function. Conversely, an excess of VEGF-C induced meningeal lymphangiogenesis. The plasticity and regenerative potential of meningeal LVs should allow manipulation of cerebrospinal fluid drainage and neuropathological processes in the CNS. © 2017 Antila et al.

  4. The lymphatics of the cardia of stomach

    International Nuclear Information System (INIS)

    Yonemura, Yutaka; Katayama, Kanji; Sawa, Toshiharu

    1985-01-01

    The lymphatics of the cardia of stomach was examined using lymphoscintigraphy with technetium 99m colloid in 98 patients with gastric cancer and 4 patients with esophageal cancer. The colloidal Tc-99m was injected into the submucosa of stomach 12 hr before operation with the aid of endoscopy. Each lymph node dissected from the specimens was measured by scintillation counter. Lymph nodes located along the left gastric, splenic and left inferior phrenic arteries were mainly involved in the lymphatics of the cardia of stomach. There was strong relationship between the cardia and the node of number 16. The lymphatics was also present in the mediastinum. These results suggest the necessities of the complete removal of the gastropancreatic mesenteriolum including the left inferior phrenic artery and the extirpation of the regional lymph nodes around the aorta above and below the left renal artery, in addition to the removal of both pancreas and spleen in cases of cardia tumors. Furthermore, in cases of squamous cell carcinoma or adenocarcinoma metastasizing to the intraperitoneal lymph nodes, it seems necessary to extirpate the complete mediastinal lymph nodes. (Namekawa, K.)

  5. Lymphatic microangiopathy of the skin in systemic sclerosis.

    Science.gov (United States)

    Leu, A J; Gretener, S B; Enderlin, S; Brühlmann, P; Michel, B A; Kowal-Bielecka, O; Hoffmann, U; Franzeck, U K

    1999-03-01

    The cutaneous capillary lymphatic system in patients with systemic sclerosis was investigated using fluorescence microlymphography. The distal upper limbs of 16 healthy controls (mean age 62.3+/-13.1 yr) and 16 patients with systemic sclerosis (mean age 58.9+/-13.6 yr) were examined and the following parameters were evaluated: (a) single lymphatic capillaries; (b) lymphatic capillary network and cutaneous backflow; (c) extension of the stained lymphatics; (d) diameter of single lymphatic capillaries. At the finger level, lymphatic capillaries were lacking in five patients, while they were present in all controls (P < 0.05). Extension of the stained lymphatics was increased in 11 patients (8.1+/-6.0 mm) compared to the 16 healthy controls (2.0+/-1.2 mm) (P < 0.0001). Cutaneous backflow was observed in three patients (P < 0.05). At the hand level, lymphatic network extension was significantly different between patients (3.8+/-2.4 mm) and controls (1.2+/-0.8 mm) (P < 0.01); however, no significant differences were found at the forearm level. Lesional skin in patients with systemic sclerosis exhibits evidence of lymphatic microangiopathy.

  6. Lymphatic imaging: Lymphography, computed tomography and scintigraphy, 2nd ed

    International Nuclear Information System (INIS)

    Close, M.E.; Wallace, S.

    1985-01-01

    The latest addition to the Golden's Diagnostic Radiology series deals not only with imaging of the lymphatic system but also with lymphatic anatomy, its pathophysiology, and treatment of disorders. The first two chapters deal with the history of the discovery of the lymphatic system and its normal anatomy. The section on technique contains practical information and discussion of lymphatic physiology and the pathology of lymphomas. Half of the book's 16 chapters are devoted to problems encountered in clinical imaging. The approach is both by anatomy (thorax, neck, abdomen) and pathology (benign disease, lymphoma, solid tumors)

  7. Lymphatic Leak Occurring After Surgical Lymph Node Dissection: A Preliminary Study Assessing the Feasibility and Outcome of Lymphatic Embolization

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Yoolim; Won, Je Hwan [Ajou University School of Medicine, Department of Radiology, Ajou University Hospital (Korea, Republic of); Kong, Tae-Wook; Paek, Jiheum; Chang, Suk-Joon; Ryu, Hee-Sug [Ajou University School of Medicine, Department of Obstetrics and Gynecology, Gynecologic Cancer Center (Korea, Republic of); Kim, Jinoo, E-mail: jinoomail@gmail.com [Ajou University School of Medicine, Department of Radiology, Ajou University Hospital (Korea, Republic of)

    2016-12-15

    PurposeTo analyze imaging findings of lymphatic leakage associated with surgical lymph node dissection on lymphangiography and assess the outcome of lymphatic embolization.Materials and MethodsThis retrospective study comprised 21 consecutive patients who were referred for lymphatic intervention between March 2014 and April 2015 due to postsurgical lymphatic leaks. Lymphangiography was performed through inguinal lymph nodes to identify the leak. When a leak was found, lymphatic embolization was performed by fine-needle injection of N-butyl cyanoacrylate into the site of leakage or into an inflow lymphatic vessel or into a pelvic lymph node located below the leakage. Electronic medical records and imaging studies were reviewed to assess the outcome.ResultLymphangiography revealed single or multiple leaks in all but one patient. Lymphatic embolization was performed in 20 patients with leaks. Including the patient who did not undergo embolization, 17 patients (81.0 %) showed initial response to treatment. Three patients underwent repeated embolization with successful results. The overall success rate was 95.2 %. The mean duration of hospitalization after lymphatic intervention was 5.9 days. During a mean follow-up period of 11 months, two patients developed localized swelling in the groin following lipiodol injection. There were no complications related to lymphatic embolization. Three patients were found to have developed small, asymptomatic lymphoceles on CT or MRI that did not require further treatment.ConclusionLymphangiography is useful for detecting lymphatic leakage occurring after lymph node dissection. Furthermore, lymphatic embolization is feasible, effective, and safe for managing leaks demonstrated on lymphangiography.

  8. Investigations of lymphatic drainage from the interstitial space

    Science.gov (United States)

    Jayathungage Don, Tharanga; Richard Clarke Collaboration; John Cater Collaboration; Vinod Suresh Collaboration

    2017-11-01

    The lymphatic system is a highly complex biological system that facilitates the drainage of excess fluid in body tissues. In addition, it is an integral part of the immunological control system. Understanding the mechanisms of fluid absorption from the interstitial space and flow through the initial lymphatics is important to treat several pathological conditions. The main focus of this study is to computationally model the lymphatic drainage from the interstitial space. The model has been developed to consider a 3D lymphatic network and uses biological data to inform the creation of realistic geometries for the lymphatic capillary networks. We approximate the interstitial space as a porous region and the lymphatic vessel walls as permeable surfaces. The dynamics of the flow is approximated by Darcy's law in the interstitium and the Navier-Stokes equations in the lymphatic capillary lumen. The proposed model examines lymph drainage as a function of pressure gradient. In addition, we have examined the effects of interstitial and lymphatic wall permeabilities on the lymph drainage and the solute transportation in the model. The computational results are in accordance with the available experimental measurements.

  9. The Glymphatic-Lymphatic Continuum: Opportunities for Osteopathic Manipulative Medicine.

    Science.gov (United States)

    Hitscherich, Kyle; Smith, Kyle; Cuoco, Joshua A; Ruvolo, Kathryn E; Mancini, Jayme D; Leheste, Joerg R; Torres, German

    2016-03-01

    The brain has long been thought to lack a lymphatic drainage system. Recent studies, however, show the presence of a brain-wide paravascular system appropriately named the glymphatic system based on its similarity to the lymphatic system in function and its dependence on astroglial water flux. Besides the clearance of cerebrospinal fluid and interstitial fluid, the glymphatic system also facilitates the clearance of interstitial solutes such as amyloid-β and tau from the brain. As cerebrospinal fluid and interstitial fluid are cleared through the glymphatic system, eventually draining into the lymphatic vessels of the neck, this continuous fluid circuit offers a paradigm shift in osteopathic manipulative medicine. For instance, manipulation of the glymphatic-lymphatic continuum could be used to promote experimental initiatives for nonpharmacologic, noninvasive management of neurologic disorders. In the present review, the authors describe what is known about the glymphatic system and identify several osteopathic experimental strategies rooted in a mechanistic understanding of the glymphatic-lymphatic continuum.

  10. Cutaneous Nocardiosis Simulating Cutaneous Lymphatic Sporotrichosis.

    Science.gov (United States)

    Secchin, Pedro; Trope, Beatriz Moritz; Fernandes, Larissa Araujo; Barreiros, Glória; Ramos-E-Silva, Marcia

    2017-01-01

    Sporotrichosis is the subcutaneous mycosis caused by several species of the Sporothrix genus. With worldwide occurrence, the State of Rio de Janeiro is presently undergoing a zoonotic sporotrichosis epidemic. The form of lymphocutaneous nocardiosis is rare, being caused especially by Nocardia brasiliensis. It appears as a nodular or ulcerated lesion, with multiple painful erythematous nodules or satellite pustules distributed along the lymphatic tract, similar to the lymphocutaneous variant of sporotrichosis. We present a 61-year-old man who, after an insect bite in the left leg, developed an ulcerated lesion associated with ascending lymphangitis, nonresponsive to previous antibiotic therapies. The patient was admitted for investigation, based on the main diagnostic hypothesis of lymphatic cutaneous sporotrichosis entailed by the highly suggestive morphology, associated with the epidemiologic information that he is a resident of the city of Rio de Janeiro. While culture results were being awaited, the patient was medicated with sulfamethoxazole-trimethoprim to cover CA-MRSA and evolved with total healing of the lesions. After hospital discharge, using an ulcer fragment, an Actinomyces sp. was cultivated and N. brasiliensis was identified by molecular biology. The objective of this report is to demonstrate a case of lymphocutaneous nocardiosis caused by N. brasiliensis after a probable insect bite. Despite the patient being a resident of the State of Rio de Janeiro (endemic region for sporotrichosis), it is highlighted that it is necessary to be aware of the differential diagnoses of an ulcerated lesion with lymphangitis, favoring an early diagnosis and appropriate treatment of the illness.

  11. Inflammatory manifestations of experimental lymphatic insufficiency.

    Directory of Open Access Journals (Sweden)

    Raymond Tabibiazar

    2006-07-01

    Full Text Available BACKGROUND: Sustained lymph stagnation engenders a pathological response that is complex and not well characterized. Tissue inflammation in lymphedema may reflect either an active or passive consequence of impaired immune traffic. METHODS AND FINDINGS: We studied an experimental model of acute post-surgical lymphedema in the tails of female hairless, immunocompetent SKH-1 mice. We performed in vivo imaging of impaired immune traffic in experimental, murine acquired lymphatic insufficiency. We demonstrated impaired mobilization of immunocompetent cells from the lymphedematous region. These findings correlated with histopathological alterations and large-scale transcriptional profiling results. We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response. CONCLUSIONS: We have characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging and histopathological correlation. The model closely simulates the volume response, histopathology, and lymphoscintigraphic characteristics of human acquired lymphedema, and the response is accompanied by an increase in the number and size of microlymphatic structures in the lymphedematous cutaneous tissues. Molecular characterization through clustering of genes with known functions provides insights into processes and signaling pathways that compose the acute tissue response to lymph stagnation. Further study of genes identified through this effort will continue to elucidate the molecular mechanisms and lead to potential therapeutic strategies for lymphatic vascular insufficiency.

  12. Lymphatic albumin clearance from psoriatic skin

    International Nuclear Information System (INIS)

    Staberg, B.; Klemp, P.; Aasted, M.; Worm, A.M.; Lund, P.

    1983-01-01

    In nine patients with untreated psoriasis vulgaris, human serum albumin labelled with 125 I or 131 I was injected intradermally in symmetrically located involved and uninvolved skin. The activity of the depots was followed by external detection, and the arrival of labelled albumin in plasma was monitored. In involved psoriatic skin the local mean half-time (T1/2) for tracer disappearance was 20.8 +/- 8.2 (S.D.) hr and in clinically normal skin, 29.1 +/- 9.6 (S.D.) hr. The difference was significant (p less than 0.002). Accordingly, the tracer from involved skin reached higher plasma levels than the tracer from uninvolved skin. However, under slight lymphatic stasis the appearance rate of radiolabelled albumin in plasma from both tissues was minimal during 1 to 2 hours after the injection, indicating that a local direct transvascular drainage of plasma albumin from the interstitium of diseased and normal skin was negligible. We conclude that the previously demonstrated increased extravasation of plasma proteins in involved psoriatic skin is compensated by an increased lymphatic drainage of plasma proteins, and not by an increased local transvascular return

  13. Scholars and scientists in the history of the lymphatic system.

    Science.gov (United States)

    Natale, Gianfranco; Bocci, Guido; Ribatti, Domenico

    2017-09-01

    The discovery of the lymphatic system has a long and fascinating history. The interest in anatomy and physiology of this system paralleled that of the blood cardiocirculatory system and has been maybe obscured by the latter. Paradoxically, if the closed blood system appeared open in Galen's anatomy and physiology, and took a very long time to be correctly described in terms of pulmonary and general circulation by ibn Al-Nafis/Michael Servetus/Realdo Colombo and William Harvey, respectively, the open lymphatic system was incorrectly described as a closed circuit connected with arteries and veins. In ancient times only macroscopic components of the lymphatic system have been described, although misinterpreted, including lymph nodes and lacteals, the latter being easily identified because of their milk-like content. For about 15 centuries the dogmatic acceptance of Galen's notions did not allow a significant progress in medicine. After Vesalius' revolution in anatomical studies, new knowledge was accumulated, and the 17th century was the golden age for the investigation of the lymphatic system with several discoveries: gut lacteals (Gaspare Aselli), cloacal bursa (Hieronimus Fabricius of Acquapendente), reservoir of the chyle (Jean Pecquet), extra-intestinal lymphatic vessels (Thomas Bartholin and Olaus Rudbeck dispute), hepatic lymph circulation (Francis Glisson). In the Enlightenment century Frederik Ruysch described the function of lymphatic valves, and Paolo Mascagni provided a magnificent iconography of the lymphatic network in humans. In recent times, Leonetto Comparini realized three-dimensional reconstructions of the liver lymphatic vessels, and Kari Alitalo discovered the lymphatic growth factor/receptor system. Far from a complete understanding of its anatomy and function, the lymphatic system still needs to be profoundly examined. © 2017 Anatomical Society.

  14. Persistent fetal vasculature: ocular features, management of cataract and outcomes

    Directory of Open Access Journals (Sweden)

    Marcia Beatriz Tartarella

    2013-06-01

    Full Text Available PURPOSES: To describe ocular features, management of cataract and functional outcomes in patients with persistent fetal vasculature. METHODS: Retrospective, descriptive case series of patients with persistent fetal vasculature. Data were recorded from the Congenital Cataract Section of Federal University of São Paulo, Brazil from 2001 to 2012. All patients were evaluated for sex, age at diagnosis, systemic findings, laterality, age at surgery, and initial and final follow-up visual acuities. Follow-up and complications after cataract surgery were recorded. Ultrasound was performed in all cases and ocular eco-Doppler was performed in most. RESULTS: The study comprised 53 eyes from 46 patients. Age at diagnosis ranged from 5 days of life to 10 years-old (mean 22.7 months. Twenty-seven patients were male (58.7%. Persistent fetal vasculature was bilateral in 7 patients (15.2%. Forty-two eyes (79.2% had combined (anterior and posterior forms PFV presentation, 5 eyes (9.4% had only anterior persistent fetal vasculature presentation and 6 eyes (11.3% had posterior persistent fetal vasculature presentation. Thirty-eight eyes (71.7% were submitted to cataract surgery. Lensectomy combined with anterior vitrectomy was performed in 18 eyes (47.4%. Phacoaspiration with intraocular lens implantation was performed in 15 eyes (39.5%, and without lens implantation in 5 eyes (13.2%. Mean follow-up after surgery was 44 months. Postoperative complications were posterior synechiae (3 cases, retinal detachment (2 cases, phthisis (3 cases, posterior capsular opacification (8 cases, inflammatory pupillary membrane (5 cases, glaucoma (4 cases, intraocular lens implantation displacement (1 case and vitreous hemorrhage (2 cases. Complications were identified in 19 (50% of the 38 operated eyes. Visual acuity improved after cataract surgery in 83% of the eyes. CONCLUSIONS: Patients with persistent fetal vasculature have variable clinical presentation. There is an

  15. Triptans and CGRP blockade - impact on the cranial vasculature

    DEFF Research Database (Denmark)

    Benemei, Silvia; Cortese, Francesca; Labastida-Ramírez, Alejandro

    2017-01-01

    and vascular tone. Thirty years after discovery of agonists for serotonin 5-HT1B and 5-HT1D receptors (triptans) and less than fifteen after the proof of concept of the gepant class of CGRP receptor antagonists, we are still a long way from understanding their precise site and mode of action in migraine....... The effect on cranial vasculature is relevant, because all specific anti-migraine drugs and migraine pharmacological triggers may act in perivascular space. This review reports the effects of triptans and CGRP blocking molecules on cranial vasculature in humans, focusing on their specific relevance...

  16. The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems.

    Science.gov (United States)

    Wu, Min; Frieboes, Hermann B; Chaplain, Mark A J; McDougall, Steven R; Cristini, Vittorio; Lowengrub, John S

    2014-08-21

    Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the response

  17. The prognostic significance of lymphatics in colorectal liver metastases.

    Science.gov (United States)

    Muralidharan, Vijayaragavan; Nguyen, Linh; Banting, Jonathan; Christophi, Christopher

    2014-01-01

    Background. Colorectal Cancer (CRC) is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%-60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM) as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM) and surrounding host tissue. Lymphatic vessel density (LVD) was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P = 0.01, P > 0.01, and P = 0.05, resp.). Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P = 0.05). Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.

  18. The Prognostic Significance of Lymphatics in Colorectal Liver Metastases

    Directory of Open Access Journals (Sweden)

    Vijayaragavan Muralidharan

    2014-01-01

    Full Text Available Background. Colorectal Cancer (CRC is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%–60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM and surrounding host tissue. Lymphatic vessel density (LVD was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P=0.01, P>0.01, and P=0.05, resp.. Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P=0.05. Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.

  19. Primary Intestinal Lymphangiectasia and its Association With Generalized Lymphatic Anomaly

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    Victoria María Díaz Marugán

    2016-01-01

    Full Text Available Background: Lymph is a fluid originating in the interstitial spaces of the body that contains cells, proteins, particles, chylomicrons, and sometimes bacteria. Objectives: The aim of the present study is to demonstrate that primary intestinal lymphangiectasia (PIL results from a disruption of lymphatic circulation, thus corresponding to a secondary rather than a primary event in the context of generalized lymphatic anomaly. Materials and Methods: In this case series and record review, an analysis of intestinal lymphatic involvement was performed on patients diagnosed with PIL between 1965 and 2013. Of the 21 patients included in the study, 10 had been diagnosed before 5 years of age (1 prenatal, 8 between 5 and 18 years of age, and 3 while older than 18 years of age. The follow-up period varied between 1 and 34 years. Clinical data, blood and fecal parameters, imaging studies, endoscopy results, biopsy analyses, treatment details, and outcome information were collected from medical records. Endoscopy, histological studies, magnetic resonance imaging, and lymphoscintigraphy were performed on all patients. Dynamic intranodal lymphangiography was performed on 8 patients. Results: Central lymphatic channel obstruction was identified in 12 patients (57%. Associated lymphatic malformation (LM was present in 16, diarrhea in 10, chylothorax in 11, chylous ascites in 10, pericardial effusion in 6, coagulopathy in 3, and osteolysis in 7. Conclusions: We consider intestinal lymphangiectasia not as an entity in itself, but as a consequence of lymphatic flow impairment in the thoracic duct, producing chylous reflux into the intestinal lymphatics.

  20. Thermal modelling using discrete vasculature for thermal therapy: a review

    Science.gov (United States)

    Kok, H.P.; Gellermann, J.; van den Berg, C.A.T.; Stauffer, P.R.; Hand, J.W.; Crezee, J.

    2013-01-01

    Reliable temperature information during clinical hyperthermia and thermal ablation is essential for adequate treatment control, but conventional temperature measurements do not provide 3D temperature information. Treatment planning is a very useful tool to improve treatment quality and substantial progress has been made over the last decade. Thermal modelling is a very important and challenging aspect of hyperthermia treatment planning. Various thermal models have been developed for this purpose, with varying complexity. Since blood perfusion is such an important factor in thermal redistribution of energy in in vivo tissue, thermal simulations are most accurately performed by modelling discrete vasculature. This review describes the progress in thermal modelling with discrete vasculature for the purpose of hyperthermia treatment planning and thermal ablation. There has been significant progress in thermal modelling with discrete vasculature. Recent developments have made real-time simulations possible, which can provide feedback during treatment for improved therapy. Future clinical application of thermal modelling with discrete vasculature in hyperthermia treatment planning is expected to further improve treatment quality. PMID:23738700

  1. Contractile Changes in the Vasculature After Subchronic Smoking

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Kruse, Lars Schack; Johansson, Helle Wulf

    2016-01-01

    clearance in the lungs and knock-out (KO) mice for this protein develop emphysema. SP-D is also weakly expressed in the vasculature. We aimed to investigate whether SP-D was important in the cardiovascular response to cigarette smoke exposure (CSE), by utilizing SP-D KO mice and a myograph setup. METHODS...

  2. 3D morphological measurement of whole slide histological vasculature reconstructions

    Science.gov (United States)

    Xu, Yiwen; Pickering, J. G.; Nong, Zengxuan; Ward, Aaron D.

    2016-03-01

    Properties of the microvasculature that contribute to tissue perfusion can be assessed using immunohistochemistry on 2D histology sections. However, the vasculature is inherently 3D and the ability to measure and visualize the vessel wall components in 3D will aid in detecting focal pathologies. Our objectives were (1) to develop a method for 3D measurement and visualization of microvasculature in 3D, (2) to compare the normal and regenerated post-ischemia mouse hind limb microvasculature, and (3) to compare the 2D and 3D vessel morphology measures. Vessels were stained for smooth muscle using 3,3'-Diaminobenzidine (DAB) immunostain for both normal (n = 6 mice) and regenerated vasculature (n = 5 mice). 2D vessel segmentations were reconstructed into 3D using landmark based registration. No substantial bias was found in the 2D measurements relative to 3D, but larger differences were observed for individual vessels oriented non-orthogonally to the plane of sectioning. A larger value of area, perimeter, and vessel wall thickness was found in the normal vasculature as compared to the regenerated vasculature, for both the 2D and 3D measurements (p pathologies on a whole slide level.

  3. Cutaneous Nocardiosis Simulating Cutaneous Lymphatic Sporotrichosis

    Directory of Open Access Journals (Sweden)

    Pedro Secchin

    2017-08-01

    Full Text Available Sporotrichosis is the subcutaneous mycosis caused by several species of the Sporothrix genus. With worldwide occurrence, the State of Rio de Janeiro is presently undergoing a zoonotic sporotrichosis epidemic. The form of lymphocutaneous nocardiosis is rare, being caused especially by Nocardia brasiliensis. It appears as a nodular or ulcerated lesion, with multiple painful erythematous nodules or satellite pustules distributed along the lymphatic tract, similar to the lymphocutaneous variant of sporotrichosis. We present a 61-year-old man who, after an insect bite in the left leg, developed an ulcerated lesion associated with ascending lymphangitis, nonresponsive to previous antibiotic therapies. The patient was admitted for investigation, based on the main diagnostic hypothesis of lymphatic cutaneous sporotrichosis entailed by the highly suggestive morphology, associated with the epidemiologic information that he is a resident of the city of Rio de Janeiro. While culture results were being awaited, the patient was medicated with sulfamethoxazole-trimethoprim to cover CA-MRSA and evolved with total healing of the lesions. After hospital discharge, using an ulcer fragment, an Actinomyces sp. was cultivated and N. brasiliensis was identified by molecular biology. The objective of this report is to demonstrate a case of lymphocutaneous nocardiosis caused by N. brasiliensis after a probable insect bite. Despite the patient being a resident of the State of Rio de Janeiro (endemic region for sporotrichosis, it is highlighted that it is necessary to be aware of the differential diagnoses of an ulcerated lesion with lymphangitis, favoring an early diagnosis and appropriate treatment of the illness.

  4. Mapping lymphatic nodes: Role of thrombospondin

    International Nuclear Information System (INIS)

    Spana, G.S.; Liu, J.; Rao, P.S.; Thakur, M.L.

    2002-01-01

    Aim: Lymphatic (sentinel) node (SN) mapping determines the status of lymphatic basin draining a primary tumor, provides staging information of systemic spread of malignancy, and is vital in the management of breast cancer and melanoma. Thrombospondin (TSP), a matrix bound adhesive glycoprotein, promotes cell proliferation and angiogenesis. TSP receptors are expressed on lymphocytes, and on the cells of breast cancer and melanoma. We hypothesized that Tc-99m-CSVTCR, a small, soluble, and TSP specific peptide, can image SN. Method: CSVTCR was modified at the N terminus with Aba-G(D) AGG (TP1300) and labeled with Tc-99m. Female New Zealand rabbits were anesthetized and 125 μCi TP1300 was given into the plantar/palmer surface of each foot pad in the metacarpal/metatarsal region, followed by dynamic imaging for 2 hrs and quantification of Tc-99m in SN and injection site by ROI. Control rabbits received Tc-99m-O 4 - and TP1300>Tc-99mO- 4 . Tc-99m clearance from injection site was Tc-99m-O 4 >TP1300>>TSC. % ID/g in the axillary SN was greater in than the popliteal SN for all agents. For TP1300, SN to muscle Tc-99m ratios were 552 for axillary and 140 for popliteal nodes. With infiltrating tumor cells higher uptake in SN is expected. Summary: Due to high SN uptake, rapid clearance from injection site delivering low radiation dose at injection site and ease of handling, targeting TSP receptors with Tc-99m-TP1300, a soluble, receptor specific, small biomolecule for efficient imaging of SN is promising

  5. Characterization of tumor vasculature in mouse brain by USPIO contrast-enhanced MRI.

    NARCIS (Netherlands)

    Gambarota, G.; Leenders, W.P.J.

    2011-01-01

    Detailed characterization of the tumor vasculature provides a better understanding of the complex mechanisms associated with tumor development and is especially important to evaluate responses to current therapies which target the tumor vasculature. Magnetic resonance imaging (MRI) studies of tumors

  6. Optical coherent tomography and fluorescent microscopy for the study of meningeal lymphatic systems

    Science.gov (United States)

    Semyachkina-Glushkovskaya, O.; Abdurashitov, A.; Namykin, A.; Fedosov, I.; Pavlov, A.; Karavaev, A.; Sindeeva, O.; Shirokov, A.; Ulanova, M.; Shushunova, N.; Khorovodov, A.; Agranovich, I.; Bodrova, A.; Sagatova, M.; Shareef, Ali Esmat; Saranceva, E.; Dvoryatkina, M.; Tuchin, V.

    2018-04-01

    The development of novel technologies for the imaging of meningeal lymphatic vessels is one of the amazing trends of biophotonics thanks to discovery of brain lymphatics over several years ago. However, there is the limited technologies exist for the study of lymphatics in vivo because lymphatic vessels are transparent with a low speed flow of lymph. Here we demonstrate the successful application of fluorescent microscopy for the imaging of lymphatic system in the mouse brain in vivo.

  7. Isolation and Characterization of Human Lung Lymphatic Endothelial Cells

    Science.gov (United States)

    Lorusso, Bruno; Falco, Angela; Madeddu, Denise; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Gervasi, Andrea; Rinaldi, Laura; Lagrasta, Costanza; Maselli, Davide; Gnetti, Letizia; Silini, Enrico M.; Quaini, Eugenio; Ampollini, Luca; Carbognani, Paolo; Quaini, Federico

    2015-01-01

    Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL-LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy. PMID:26137493

  8. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  9. C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma.

    Science.gov (United States)

    Kawamata, Futoshi; Homma, Shigenori; Kamachi, Hirofumi; Einama, Takahiro; Kato, Yasutaka; Tsuda, Masumi; Tanaka, Shinya; Maeda, Masahiro; Kajino, Kazunori; Hino, Okio; Takahashi, Norihiko; Kamiyama, Toshiya; Nishihara, Hiroshi; Taketomi, Akinobu; Todo, Satoru

    2014-01-01

    Lymph node metastasis is a key event of colorectal cancer (CRC) progression. Mesothelin is expressed in various types of malignant tumor and associated with an unfavorable prognosis. The full-length mesothelin (Full-ERC) is cleaved by protease into membrane-bound C-ERC/mesothelin and N-ERC/mesothelin which is secreted into the blood. The aim of this study was to examine the biological role of mesothelin in CRC by clinicopathological analysis and in vitro lymphatic invasion assay. Ninety-one cases of CRC specimens were immunohistochemically examined and the localization of mesothelin in luminal membrane and/or cytoplasm was also evaluated. Lymphatic invasion assay was also performed using the human CRC cell line, WiDr, which was transfected with Full-, N- and C-ERC/mesothelin expression plasmids (Full-WiDr, N-WiDr and C-WiDr). Immunohistochemically, "luminal membrane positive" of mesothelin was identified in 37.4 %, and correlated with lymphatic permeation and lymph node metastasis, but not with patients' prognosis. Interestingly, among the patients with lymph node metastasis (N = 38), "luminal membrane positive" of mesothelin significantly correlated with unfavorable patients' outcome. In addition, lymphatic invasion assay revealed that Full-WiDr and C-WiDr more significantly invaded human lymphatic endothelial cells than the Mock-WiDr (P ERC/mesothelin associated with lymphatic invasion of cancer in vitro.

  10. Quantum dots trace lymphatic drainage from the mouse eye

    Energy Technology Data Exchange (ETDEWEB)

    Tam, Alex L C; Gupta, Neeru; Zhang Zhexue; Yuecel, Yeni H, E-mail: yucely@smh.ca [Department of Ophthalmology and Vision Sciences, University of Toronto, M5T 2S8 (Canada)

    2011-10-21

    Glaucoma is a leading cause of blindness in the world, often associated with elevated eye pressure. Currently, all glaucoma treatments aim to lower eye pressure by improving fluid exit from the eye. We recently reported the presence of lymphatics in the human eye. The lymphatic circulation is known to drain fluid from organ tissues and, as such, lymphatics may also play a role in draining fluid from the eye. We investigated whether lymphatic drainage from the eye is present in mice by visualizing the trajectory of quantum dots once injected into the eye. Whole-body hyperspectral fluorescence imaging was performed in 17 live mice. In vivo imaging was conducted prior to injection, and 5, 20, 40 and 70 min, and 2, 6 and 24 h after injection. A quantum dot signal was observed in the left neck region at 6 h after tracer injection into the eye. Examination of immunofluorescence-labelled sections using confocal microscopy showed the presence of a quantum dot signal in the left submandibular lymph node. This is the first direct evidence of lymphatic drainage from the mouse eye. The use of quantum dots to image this lymphatic pathway in vivo is a novel tool to stimulate new treatments to reduce eye pressure and prevent blindness from glaucoma.

  11. Quantum dots trace lymphatic drainage from the mouse eye

    International Nuclear Information System (INIS)

    Tam, Alex L C; Gupta, Neeru; Zhang Zhexue; Yuecel, Yeni H

    2011-01-01

    Glaucoma is a leading cause of blindness in the world, often associated with elevated eye pressure. Currently, all glaucoma treatments aim to lower eye pressure by improving fluid exit from the eye. We recently reported the presence of lymphatics in the human eye. The lymphatic circulation is known to drain fluid from organ tissues and, as such, lymphatics may also play a role in draining fluid from the eye. We investigated whether lymphatic drainage from the eye is present in mice by visualizing the trajectory of quantum dots once injected into the eye. Whole-body hyperspectral fluorescence imaging was performed in 17 live mice. In vivo imaging was conducted prior to injection, and 5, 20, 40 and 70 min, and 2, 6 and 24 h after injection. A quantum dot signal was observed in the left neck region at 6 h after tracer injection into the eye. Examination of immunofluorescence-labelled sections using confocal microscopy showed the presence of a quantum dot signal in the left submandibular lymph node. This is the first direct evidence of lymphatic drainage from the mouse eye. The use of quantum dots to image this lymphatic pathway in vivo is a novel tool to stimulate new treatments to reduce eye pressure and prevent blindness from glaucoma.

  12. Multidetector CT angiography of renal vasculature: normal anatomy and variants

    International Nuclear Information System (INIS)

    Tuerkvatan, Aysel; Oezdemir, Mustafa; Cumhur, Turhan; Oelcer, Tuelay

    2009-01-01

    Knowledge of the variations in renal vascular anatomy is important before laparoscopic donor or partial nephrectomy and vascular reconstruction for renal artery stenosis or abdominal aortic aneurysm. Recently, multidetector computed tomographic (MDCT) angiography has become a principal imaging investigation for assessment of the renal vasculature and has challenged the role of conventional angiography. It is an excellent imaging technique because it is a fast and non-invasive tool that provides highly accurate and detailed evaluation of normal renal vascular anatomy and variants. The number, size and course of the renal arteries and veins are easily identified by MDCT angiography. The purpose of this pictorial essay is to illustrate MDCT angiographic appearance of normal anatomy and common variants of the renal vasculature. (orig.)

  13. Multidetector CT angiography of renal vasculature: normal anatomy and variants

    Energy Technology Data Exchange (ETDEWEB)

    Tuerkvatan, Aysel; Oezdemir, Mustafa; Cumhur, Turhan; Oelcer, Tuelay [Tuerkiye Yueksek ihtisas Hospital, Department of Radiology, Sihhiye, Ankara (Turkey)

    2009-01-15

    Knowledge of the variations in renal vascular anatomy is important before laparoscopic donor or partial nephrectomy and vascular reconstruction for renal artery stenosis or abdominal aortic aneurysm. Recently, multidetector computed tomographic (MDCT) angiography has become a principal imaging investigation for assessment of the renal vasculature and has challenged the role of conventional angiography. It is an excellent imaging technique because it is a fast and non-invasive tool that provides highly accurate and detailed evaluation of normal renal vascular anatomy and variants. The number, size and course of the renal arteries and veins are easily identified by MDCT angiography. The purpose of this pictorial essay is to illustrate MDCT angiographic appearance of normal anatomy and common variants of the renal vasculature. (orig.)

  14. Development of Antibody-Based Vaccines Targeting the Tumor Vasculature.

    Science.gov (United States)

    Zhuang, Xiaodong; Bicknell, Roy

    2016-01-01

    A functional vasculature is essential for tumor progression and malignant cell metastasis. Endothelial cells lining blood vessels in the tumor are exposed to a unique microenvironment, which in turn induces expression of specific proteins designated as tumor endothelial markers (TEMs). TEMs either localized at the plasma membrane or secreted into the extracellular matrix are accessible for antibody targeting, which can be either infused or generated de novo via vaccination. Recent studies have demonstrated vaccines against several TEMs can induce a strong antibody response accompanied by a potent antitumor effect in animal models. These findings present an exciting field for novel anticancer therapy development. As most of the TEMs are self-antigens, breaking tolerance is necessary for a successful vaccine. This chapter describes approaches to efficiently induce a robust antibody response against the tumor vasculature.

  15. Selective alpha-particle mediated depletion of tumor vasculature with vascular normalization.

    Directory of Open Access Journals (Sweden)

    Jaspreet Singh Jaggi

    2007-03-01

    Full Text Available Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature.Actinium-225 ((225Ac-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, (225Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in (225Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following (225Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following (225Ac-E4G10 therapy.The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy.

  16. Effects of dietary amines on the gut and its vasculature

    OpenAIRE

    Broadley, Kenneth John; Anwar, Mohammad Akhtar; Herbert, Amy Angharad; Fehler, Martina; Jones, Elen M.; Davies, W. E.; Kidd, Emma Jane; Ford, William Richard

    2009-01-01

    Trace amines, including tyramine and β-phenylethylamine (β-PEA), are constituents of many foods including chocolate, cheeses and wines and are generated by so-called ‘friendly’ bacteria such as Lactobacillus, Lactococcus and Enterococcus species, which are found in probiotics. We therefore examined whether these dietary amines could exert pharmacological effects on the gut and its vasculature. In the present study we examined the effects of tyramine and β-PEA on the contractile activity of gu...

  17. Effect of tamsulosin on iris vasculature and morphology.

    Science.gov (United States)

    Shtein, Roni M; Hussain, Munira T; Cooney, Theresa M; Elner, Victor M; Hood, Christopher T

    2014-05-01

    To determine whether preoperative iris vasculature and morphology are altered in patients who have taken tamsulosin (Flomax). Academic multispecialty practice. Case series. Patients with current or past tamsulosin use and age- and sex-matched control patients were included. Anterior segment optical coherence tomography (AS-OCT) and iris fluorescein angiography were performed to measure iris vasculature and thickness before cataract surgery. Data collected at surgery included pupil diameter, clinical signs of intraoperative floppy-iris syndrome, and surgical complications. Tamsulosin was currently used by 16 patients and in the past by 4 patients; the control group comprised 10 patients. Pharmacologically dilated pupil diameter was statistically significantly smaller preoperatively and immediately postoperatively in the tamsulosin group than in the control group (P=.009 and P=.003, respectively). There was a statistically significant decrease in pupil size intraoperatively in the tamsulosin group (P=.05) but not in the control group (P=.3). Iris-vasculature parameters, specifically time to first vessel fill and percentage of vessel fill on iris fluorescein angiography, were not significantly different between the 2 groups. The AS-OCT measurements of iris morphology were not statistically significantly different between the groups. No surgical complications occurred. No fluorescein dye leakage, staining, or other vascular anomalies were observed. Although there were differences in pupil measurements and intraoperative iris behavior between patients who had been on tamsulosin and control patients, there were no significant differences in iris vasculature on iris fluorescein angiography or in iris morphology on AS-OCT. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  18. Effect of tamsulosin on iris vasculature and morphology

    Science.gov (United States)

    Shtein, Roni M.; Hussain, Munira T.; Cooney, Theresa M.; Elner, Victor M.; Hood, Christopher T.

    2015-01-01

    PURPOSE To determine whether preoperative iris vasculature and morphology are altered in patients who have taken tamsulosin (Flomax). SETTING Academic multispecialty practice. DESIGN Case series. METHODS Patients with current or past tamsulosin use and age- and sex-matched control patients were included. Anterior segment optical coherence tomography (AS-OCT) and iris fluorescein angiography were performed to measure iris vasculature and thickness before cataract surgery. Data collected at surgery included pupil diameter, clinical signs of intraoperative floppy-iris syndrome, and surgical complications. RESULTS Tamsulosin was currently used by 16 patients and in the past by 4 patients; the control group comprised 10 patients. Pharmacologically dilated pupil diameter was significantly smaller preoperatively and immediately postoperatively in the tamsulosin group than in the control group (P = .009 and P = .003, respectively). There was a statistically significant decrease in pupil size intraoperatively in the tamsulosin group (P = .05) but not in the control group (P = .3). Iris-vasculature parameters, specifically time to first vessel fill and percentage of vessel fill on iris fluorescein angiography, were not significantly different between the 2 groups. The AS-OCT measurements of iris morphology were not statistically significantly different between the groups. No surgical complications occurred. No fluorescein dye leakage, staining, or other vascular anomalies were observed. CONCLUSIONS Although there were differences in pupil measurements and intraoperative iris behavior between patients who had been on tamsulosin and control patients, there were no significant differences in iris vasculature on iris fluorescein angiography or in iris morphology on AS-OCT. PMID:24631201

  19. Effects of dietary amines on the gut and its vasculature.

    Science.gov (United States)

    Broadley, Kenneth J; Akhtar Anwar, M; Herbert, Amy A; Fehler, Martina; Jones, Elen M; Davies, Wyn E; Kidd, Emma J; Ford, William R

    2009-06-01

    Trace amines, including tyramine and beta-phenylethylamine (beta-PEA), are constituents of many foods including chocolate, cheeses and wines and are generated by so-called 'friendly' bacteria such as Lactobacillus, Lactococcus and Enterococcus species, which are found in probiotics. We therefore examined whether these dietary amines could exert pharmacological effects on the gut and its vasculature. In the present study we examined the effects of tyramine and beta-PEA on the contractile activity of guinea-pig and rat ileum and upon the isolated mesenteric vasculature and other blood vessels. Traditionally, these amines are regarded as sympathomimetic amines, exerting effects through the release of noradrenaline from sympathetic nerve endings, which should relax the gut. A secondary aim was therefore to confirm this mechanism of action. However, contractile effects were observed in the gut and these were independent of noradrenaline, acetylcholine, histamine and serotonin receptors. They were therefore probably due to the recently described trace amine-associated receptors. These amines relaxed the mesenteric vasculature. In contrast, the aorta and coronary arteries were constricted, a response that was also independent of a sympathomimetic action. From these results, we propose that after ingestion, trace amines could stimulate the gut and improve intestinal blood flow. Restriction of blood flow elsewhere diverts blood to the gut to aid digestion. Thus, trace amines in the diet may promote the digestive process through stimulation of the gut and improved gastrointestinal circulation.

  20. Localization and proliferation of lymphatic vessels in the tympanic membrane in normal state and regeneration

    International Nuclear Information System (INIS)

    Miyashita, Takenori; Burford, James L.; Hong, Young-Kwon; Gevorgyan, Haykanush; Lam, Lisa; Mori, Nozomu; Peti-Peterdi, Janos

    2013-01-01

    Highlights: •We newly developed the whole-mount imaging method of the tympanic membrane. •Lymphatic vessel loops were localized around the malleus handle and annulus tympanicus. •In regeneration, abundant lymphatic vessels were observed in the pars tensa. •Site-specific lymphatic vessels may play an important role in the tympanic membrane. -- Abstract: We clarified the localization of lymphatic vessels in the tympanic membrane and proliferation of lymphatic vessels during regeneration after perforation of the tympanic membrane by using whole-mount imaging of the tympanic membrane of Prox1 GFP mice. In the pars tensa, lymphatic vessel loops surrounded the malleus handle and annulus tympanicus. Apart from these locations, lymphatic vessel loops were not observed in the pars tensa in the normal tympanic membrane. Lymphatic vessel loops surrounding the malleus handle were connected to the lymphatic vessel loops in the pars flaccida and around the tensor tympani muscle. Many lymphatic vessel loops were detected in the pars flaccida. After perforation of the tympanic membrane, abundant lymphatic regeneration was observed in the pars tensa, and these regenerated lymphatic vessels extended from the lymphatic vessels surrounding the malleus at day 7. These results suggest that site-specific lymphatic vessels play an important role in the tympanic membrane

  1. Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos

    DEFF Research Database (Denmark)

    Dunworth, William P; Cardona-Costa, Jose; Bozkulak, Esra Cagavi

    2014-01-01

    : Our aim was to delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic development. METHODS AND RESULTS: BMP2 signaling negatively regulates the formation of LECs. Developing LECs lack any detectable BMP signaling activity in both zebrafish and mouse embryos, and excess BMP2...... signaling in zebrafish embryos and mouse embryonic stem cell-derived embryoid bodies substantially decrease the emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31 and miR-181a in a SMAD-dependent mechanism, which in turn results in attenuated expression of prospero homeobox...

  2. Cross-talk between cardiac muscle and coronary vasculature.

    Science.gov (United States)

    Westerhof, Nico; Boer, Christa; Lamberts, Regis R; Sipkema, Pieter

    2006-10-01

    The cardiac muscle and the coronary vasculature are in close proximity to each other, and a two-way interaction, called cross-talk, exists. Here we focus on the mechanical aspects of cross-talk including the role of the extracellular matrix. Cardiac muscle affects the coronary vasculature. In diastole, the effect of the cardiac muscle on the coronary vasculature depends on the (changes in) muscle length but appears to be small. In systole, coronary artery inflow is impeded, or even reversed, and venous outflow is augmented. These systolic effects are explained by two mechanisms. The waterfall model and the intramyocardial pump model are based on an intramyocardial pressure, assumed to be proportional to ventricular pressure. They explain the global effects of contraction on coronary flow and the effects of contraction in the layers of the heart wall. The varying elastance model, the muscle shortening and thickening model, and the vascular deformation model are based on direct contact between muscles and vessels. They predict global effects as well as differences on flow in layers and flow heterogeneity due to contraction. The relative contributions of these two mechanisms depend on the wall layer (epi- or endocardial) and type of contraction (isovolumic or shortening). Intramyocardial pressure results from (local) muscle contraction and to what extent the interstitial cavity contracts isovolumically. This explains why small arterioles and venules do not collapse in systole. Coronary vasculature affects the cardiac muscle. In diastole, at physiological ventricular volumes, an increase in coronary perfusion pressure increases ventricular stiffness, but the effect is small. In systole, there are two mechanisms by which coronary perfusion affects cardiac contractility. Increased perfusion pressure increases microvascular volume, thereby opening stretch-activated ion channels, resulting in an increased intracellular Ca2+ transient, which is followed by an increase in Ca

  3. Imaging of the interaction of cancer cells and the lymphatic system.

    Science.gov (United States)

    Tran Cao, Hop S; McElroy, Michele; Kaushal, Sharmeela; Hoffman, Robert M; Bouvet, Michael

    2011-09-10

    A thorough understanding of the lymphatic system and its interaction with cancer cells is crucial to our ability to fight cancer metastasis. Efforts to study the lymphatic system had previously been limited by the inability to visualize the lymphatic system in vivo in real time. Fluorescence imaging can address these limitations and allow for visualization of lymphatic delivery and trafficking of cancer cells and potentially therapeutic agents as well. Here, we review recent articles in which antibody-fluorophore conjugates are used to label the lymphatic network and fluorescent proteins to label cancer cells in the evaluation of lymphatic delivery and imaging. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. A model to measure lymphatic drainage from the eye.

    Science.gov (United States)

    Kim, Minhui; Johnston, Miles G; Gupta, Neeru; Moore, Sara; Yücel, Yeni H

    2011-11-01

    Intraocular pressure (IOP) is the most important risk factor for glaucoma development and progression. Most anti-glaucoma treatments aim to lower IOP by enhancing aqueous humor drainage from the eye. Aqueous humor drainage occurs via well-characterized trabecular meshwork (TM) and uveoscleral (UVS) pathways, and recently described ciliary body lymphatics. The relative contribution of the lymphatic pathway to aqueous drainage is not known. We developed a sheep model to quantitatively assess lymphatic drainage along with TM and UVS outflows. This study describes that model and presents our initial findings. Following intracameral injection of (125)I-bovine serum albumin (BSA), lymph was continuously collected via cannulated cervical lymphatic vessels and the thoracic lymphatic duct over either a 3-h or 5-h time period. In the same animals, blood samples were collected from the right jugular vein every 15 min. Lymphatic and TM drainage were quantitatively assessed by measuring (125)I-BSA in lymph and plasma, respectively. Radioactive tracer levels were also measured in UVS and "other" ocular tissue, as well as periocular tissue harvested 3 and 5 h post-injection. Tracer recovered from UVS tissue was used to estimate UVS drainage. The amount of (125)I-BSA recovered from different fluid and tissue compartments was expressed as a percentage of total recovered tracer. Three hours after tracer injection, percentage of tracer recovered in lymph and plasma was 1.64% ± 0.89% and 68.86% ± 9.27%, respectively (n = 8). The percentage of tracer in UVS, other ocular and periocular tissues was 19.87% ± 5.59%, 4.30% ± 3.31% and 5.32% ± 2.46%, respectively. At 5 h (n = 2), lymphatic drainage was increased (6.40% and 4.96% vs. 1.64%). On the other hand, the percentage of tracer recovered from UVS and other ocular tissue had decreased, and the percentage from periocular tissue showed no change. Lymphatic drainage increased steadily over the 3 h post-injection period, while TM

  5. Study on enhanced lymphatic tracing of isosulfan blue injection by influence of osmotic pressure on lymphatic exposure.

    Science.gov (United States)

    Ye, Tiantian; He, Rui; Wu, Yue; Shang, Lei; Wang, Shujun

    2018-04-01

    Isosulfan blue (IB) is being used as a lymphatic tracer has been approved by the FDA in 1981. This study aimed at improving lymphatic exposure of IB injection by osmotic pressure regulation to achieve step-by step lymphatic tracing. First, IB injection with appropriate osmotic pressure, stability, and suitable pH was prepared. Next, the lymphatic tracing ability of different osmotic pressure was studied to determine the blue-stained state of IB in three-level lymph nodes after subcutaneous administration. Furthermore, pharmacokinetics of lymphatic drainage, lymph node uptake, and plasma concentration was investigate to explore the improving law of the lymphatic tracing by osmotic pressure, and combined with tissue irritation to determine the optimal osmotic pressure. At last, the tissue distribution in mice of IB injection which had the property of optimal osmotic pressure was investigated. The results showed that increasing osmotic pressure could significantly reduce injection site retention and increase IB concentration of lymph node. The lymph nodes could be obviously blue-stained by IB injection which had 938 mmol/kg osmotic pressure and would not cause inflammatory reaction and blood exposure. The tissue distribution study suggested that IB injection which had 938 mmol/kg osmotic pressure was mainly distributed into gallbladder and duodenum that verified the reports that 90% IB was excreted through the feces through biliary excretion. In conclusion, this study provides the basic study to improve lymphatic exposure of IB injection by regulate the osmotic pressure and have the potential to be the helpful guidance for the elective lymph node dissection.

  6. Supplementary oxygen and risk of childhood lymphatic leukaemia.

    Science.gov (United States)

    Naumburg, E; Bellocco, R; Cnattingius, S; Jonzon, A; Ekbom, A

    2002-01-01

    Childhood leukaemia has been linked to several factors, such as asphyxia and birthweight, which in turn are related to newborn resuscitation. Based on the findings from a previous study a population-based case-control study was performed to investigate the association between childhood leukaemia and exposure to supplementary oxygen and other birth-related factors. Children born in Sweden and diagnosed with lymphatic leukaemia between 1973 and 1989 (578 cases) were individually matched by gender and date of birth to a randomly selected control. Children with Down's syndrome were excluded. Exposure data were blindly gathered from antenatal, obstetric and other standardized medical records. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by conditional logistic regression. Resuscitation with 100% oxygen with a facemask and bag immediately postpartum was significantly associated with an increased risk of childhood lymphatic leukaemia (OR = 2.57, 95% Cl 1.21-6.82). The oxygen-related risk further increased if the manual ventilation lasted for 3 min or more (OR = 3.54, 95% CI 1.16-10.80). Low Apgar scores at 1 and 5 min were associated with a non-significantly increased risk of lymphatic leukaemia. There were no associations between lymphatic leukaemia and supplementary oxygen later in the neonatal period or other birth-related factors. Resuscitation with 100% oxygen immediately postpartum is associated with childhood lymphatic leukaemia, but further studies are warranted to confirm the findings.

  7. Altered Pulmonary Lymphatic Development in Infants with Chronic Lung Disease

    Science.gov (United States)

    McNellis, Emily M.; Mabry, Sherry M.; Taboada, Eugenio; Ekekezie, Ikechukwu I.

    2014-01-01

    Pulmonary lymphatic development in chronic lung disease (CLD) has not been investigated, and anatomy of lymphatics in human infant lungs is not well defined. Hypothesis. Pulmonary lymphatic hypoplasia is present in CLD. Method. Autopsy lung tissues of eighteen subjects gestational ages 22 to 40 weeks with and without history of respiratory morbidity were stained with monoclonal antipodoplanin and reviewed under light microscopy. Percentage of parenchyma podoplanin stained at the acinar level was determined using computerized image analysis; 9 CLD and 4 control subjects gestational ages 27 to 36 weeks were suitable for the analysis. Results. Distinct, lymphatic-specific staining with respect to other vascular structures was appreciated in all gestations. Infants with and without respiratory morbidity had comparable lymphatic distribution which extended to the alveolar ductal level. Podoplanin staining per parenchyma was increased and statistically significant in the CLD group versus controls at the alveolar ductal level (0.06% ± 0.02% versus 0.04% ± 0.01%, 95% CI −0.04% to −0.002%, P CLD. It is suggested that the findings, by expanding current knowledge of CLD pathology, may offer insight into the development of more effective therapies to tackle CLD. PMID:24527433

  8. Indirect measurement of lymphatic absorption in CAPD patients is not influenced by trapping

    NARCIS (Netherlands)

    Struijk, D. G.; Koomen, G. C.; Krediet, R. T.; Arisz, L.

    1992-01-01

    The disappearance rate of intraperitoneally administered macromolecules is often used to calculate lymphatic absorption during CAPD. The possible contribution of local accumulation (trapping) of such solutes in the tissues surrounding the peritoneal cavity, leading to overestimation of lymphatic

  9. The lymphatic mechanisms of brain cleaning: application of optical coherence tomography and fluorescence microscopy

    Science.gov (United States)

    Glushkovskaya-Semyachkina, O.; Abdurashitov, A.; Fedosov, I.; Namykin, A.; Pavlov, A.; Shirokov, A.; Shushunova, N.; Sindeeva, O.; Khorovodov, A.; Ulanova, M.; Sagatova, V.; Agranovich, I.; Bodrova, A.; Kurths, J.

    2018-04-01

    Here we studied the role of cerebral lymphatic system in the brain clearing using intraparenchymal injection of Evans Blue and gold nanorods assessed by optical coherent tomography and fluorescence microscopy. Our data clearly show that the cerebral lymphatic system plays an important role in the brain cleaning via meningeal lymphatic vessels but not cerebral veins. Meningeal lymphatic vessels transport fluid from the brain into the deep cervical node, which is the first anatomical "station" for lymph outflow from the brain. The lymphatic processes underlying brain clearing are more slowly vs. peripheral lymphatics. These results shed light on the lymphatic mechanisms responsible for brain clearing as well as interaction between the intra- and extracranial lymphatic compartment.

  10. MR imaging of edematous limbs in lymphatic and nonlymphatic edema

    International Nuclear Information System (INIS)

    Fujii, K.

    1994-01-01

    To evaluate the role of MR imaging in the diagnosis of edema, various types of edema were examined with MR imaging. MR imaging of edematous limbs was performed on 60 patients (lymphatic edema 48, nonlymphatic edema 12) using. T1-and T2-weighted spin-echo and shot inversion time inversion recovery sequences. Thickness and signal intensity of the cutis, subcutis and subfascia were evaluated in the images. In all 48 cases with lymphatic edema, trabecular structures suggesting dilated collateral lymphatic vessels were observed in the swollen subcutis. Two cases with nephrotic syndrome showed similar findings. In 6 cases with venous edema, fatty intensity was found in the subfascia. In the remaining 4 cases, the subcutis exhibited only water intensity. MR imaging is a potential contributor to the diagnosis of various edematous diseases. (orig./MG)

  11. Unusual persistent fetal vasculature presentation in a premature baby

    Directory of Open Access Journals (Sweden)

    Alon Zahavi

    2015-11-01

    Full Text Available Persistent fetal vasculature (PFV is a congenital developmental disorder manifesting as a fibrovascular remnant of the embryonal hyaloid vascular system within the vitreal space. Retinopathy of prematurity (ROP presents as varying degrees of non-vascularized retinal tissue with potentially devastating ocular complications. Both pathologies arise from ocular vascular system abnormalities, and various treatment modalities have been attempted in the past. In this report we describe a unique case of a late manifesting PFV that may be associated with the development of ROP, complicated by a visually significant cataract.

  12. Thoracic involvement in generalised lymphatic anomaly (or lymphangiomatosis

    Directory of Open Access Journals (Sweden)

    Francesca Luisi

    2016-06-01

    Full Text Available Generalised lymphatic anomaly (GLA, also known as lymphangiomatosis, is a rare disease caused by congenital abnormalities of lymphatic development. It usually presents in childhood but can also be diagnosed in adults. GLA encompasses a wide spectrum of clinical manifestations ranging from single-organ involvement to generalised disease. Given the rarity of the disease, most of the information regarding it comes from case reports. To date, no clinical trials concerning treatment are available. This review focuses on thoracic GLA and summarises possible diagnostic and therapeutic approaches.

  13. Lymphatic vessel assessment by podoplanin (D2-40 immunohistochemistry in breast cancer

    Directory of Open Access Journals (Sweden)

    Shailja Puri Wahal

    2015-01-01

    Conclusion: Taking into account our small sample size, we conclude that a further large-sized study should be carried out to further prove the role of lymphatics in tumor dissemination. New therapeutic options can be developed targeting the lymphatic channels to arrest the lymphatic spread of the breast cancer.

  14. Sphingosine-1-phosphate in the lymphatic fluid determined by novel methods

    Directory of Open Access Journals (Sweden)

    Masayuki Nagahashi

    2016-12-01

    Conclusions: In agreement with the previous theory, our results confirm “S1P gradient” among blood, lymphatic fluid and peripheral lymphatic tissues. Convenient methods for collection and measurement of sphingolipids in lymphatic fluid are expected to provide new insights on functions of sphingolipids.

  15. In Vitro Study of Directly Bioprinted Perfusable Vasculature Conduits.

    Science.gov (United States)

    Zhang, Yahui; Yu, Yin; Akkouch, Adil; Dababneh, Amer; Dolati, Farzaneh; Ozbolat, Ibrahim T

    2015-01-01

    The ability to create three dimensional (3D) thick tissues is still a major tissue engineering challenge. It requires the development of a suitable vascular supply for an efficient media exchange. An integrated vasculature network is particularly needed when building thick functional tissues and/or organs with high metabolic activities, such as the heart, liver and pancreas. In this work, human umbilical vein smooth muscle cells (HUVSMCs) were encapsulated in sodium alginate and printed in the form of vasculature conduits using a coaxial deposition system. Detailed investigations were performed to understand the dehydration, swelling and degradation characteristics of printed conduits. In addition, because perfusional, permeable and mechanical properties are unique characteristics of natural blood vessels, for printed conduits these properties were also explored in this work. The results show that cells encapsulated in conduits had good proliferation activities and that their viability increased during prolonged in vitro culture. Deposition of smooth muscle matrix and collagen was observed around the peripheral and luminal surface in long-term cultured cellular vascular conduit through histology studies.

  16. Three-dimensional stereotactic atlas of the extracranial vasculature correlated with the intracranial vasculature, cranial nerves, skull and muscles.

    Science.gov (United States)

    Nowinski, Wieslaw L; Shoon Let Thaung, Thant; Choon Chua, Beng; Hnin Wut Yi, Su; Yang, Yili; Urbanik, Andrzej

    2015-04-01

    Our objective was to construct a 3D, interactive, and reference atlas of the extracranial vasculature spatially correlated with the intracranial blood vessels, cranial nerves, skull, glands, and head muscles.The atlas has been constructed from multiple 3T and 7T magnetic resonance angiogram (MRA) brain scans, and 3T phase contrast and inflow MRA neck scans of the same specimen in the following steps: vessel extraction from the scans, building 3D tubular models of the vessels, spatial registration of the extra- and intracranial vessels, vessel editing, vessel naming and color-coding, vessel simplification, and atlas validation.This new atlas contains 48 names of the extracranial vessels (25 arterial and 23 venous) and it has been integrated with the existing brain atlas.The atlas is valuable for medical students and residents to easily get familiarized with the extracranial vasculature with a few clicks; is useful for educators to prepare teaching materials; and potentially can serve as a reference in the diagnosis of vascular disease and treatment, including craniomaxillofacial surgeries and radiologic interventions of the face and neck. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  17. Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects

    DEFF Research Database (Denmark)

    Arngrim, Nanna Bjørkbom; Simonsen, L; Holst, J J

    2013-01-01

    The aim of this study was to investigate subcutaneous adipose tissue lymphatic drainage (ATLD) of macromolecules in lean and obese subjects and, furthermore, to evaluate whether ATLD may change in parallel with adipose tissue blood flow. Lean and obese male subjects were studied before and after ...... online publication, 3 July 2012; doi:10.1038/ijo.2012.98....

  18. Expression of Lymphatic Markers in the Adult Rat Spinal Cord.

    Science.gov (United States)

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  19. The Hepatic Lymphatic Vascular System: Structure, Function, Markers, and LymphangiogenesisSummary

    Directory of Open Access Journals (Sweden)

    Masatake Tanaka

    2016-11-01

    Full Text Available The lymphatic vascular system has been minimally explored in the liver despite its essential functions including maintenance of tissue fluid homeostasis. The discovery of specific markers for lymphatic endothelial cells has advanced the study of lymphatics by methods including imaging, cell isolation, and transgenic animal models and has resulted in rapid progress in lymphatic vascular research during the last decade. These studies have yielded concrete evidence that lymphatic vessel dysfunction plays an important role in the pathogenesis of many diseases. This article reviews the current knowledge of the structure, function, and markers of the hepatic lymphatic vascular system as well as factors associated with hepatic lymphangiogenesis and compares liver lymphatics with those in other tissues. Keywords: VEGF, Inflammation, Cirrhosis, Portal Hypertension

  20. Postnatal Deletion of Podoplanin in Lymphatic Endothelium Results in Blood Filling of the Lymphatic System and Impairs Dendritic Cell Migration to Lymph Nodes.

    Science.gov (United States)

    Bianchi, Roberta; Russo, Erica; Bachmann, Samia B; Proulx, Steven T; Sesartic, Marko; Smaadahl, Nora; Watson, Steve P; Buckley, Christopher D; Halin, Cornelia; Detmar, Michael

    2017-01-01

    The lymphatic vascular system exerts major physiological functions in the transport of interstitial fluid from peripheral tissues back to the blood circulation and in the trafficking of immune cells to lymph nodes. Previous studies in global constitutive knockout mice for the lymphatic transmembrane molecule podoplanin reported perinatal lethality and a complex phenotype with lung abnormalities, cardiac defects, lymphedema, blood-filled lymphatic vessels, and lack of lymph node organization, reflecting the importance of podoplanin expression not only by the lymphatic endothelium but also by a variety of nonendothelial cell types. Therefore, we aimed to dissect the specific role of podoplanin expressed by adult lymphatic vessels. We generated an inducible, lymphatic-specific podoplanin knockout mouse model (Pdpn ΔLEC ) and induced gene deletion postnatally. Pdpn ΔLEC mice were viable, and their lymphatic vessels appeared morphologically normal with unaltered fluid drainage function. Intriguingly, Pdpn ΔLEC mice had blood-filled lymph nodes and vessels, most frequently in the neck and axillary region, and displayed a blood-filled thoracic duct, suggestive of retrograde filling of blood from the blood circulation into the lymphatic system. Histological and fluorescence-activated cell sorter analyses revealed normal lymph node organization with the presence of erythrocytes within lymph node lymphatic vessels but not surrounding high endothelial venules. Moreover, fluorescein isothiocyanate painting experiments revealed reduced dendritic cell migration to lymph nodes in Pdpn ΔLEC mice. These results reveal an important role of podoplanin expressed by lymphatic vessels in preventing postnatal blood filling of the lymphatic vascular system and in contributing to efficient dendritic cell migration to the lymph nodes. © 2016 American Heart Association, Inc.

  1. Effects of lymphatic drainage on cellulitis assessed by magnetic resonance

    International Nuclear Information System (INIS)

    Meyer, Patricia Froes; Martins, Nara Mendes; Martins, Flavia Mendes; Monteiro, Rosimary Araujo; Mendonca, Karla Morganna Pereira Pinto de

    2008-01-01

    The aim of this study was to assess the use of magnetic resonance as a new method for evaluating the manual lymphatic drainage technique in treating cellulitis. Cellulitis is one of the main esthetic problems that lead women toward seeking guidance and specific treatments. There are various therapeutic approaches, owing to the multifactorial nature of its pathogen, although the effectiveness of most of these has not been definitively proven, given that the assessment methods used are mostly subjective or do not provide enough information on subcutaneous tissue. The introduction of magnetic resonance as a means of assessing a lymphatic drainage technique in cellulitis treatment makes the evaluation more accurate, since it enables a detailed study of subcutaneous architecture. (author)

  2. Effects of lymphatic drainage on cellulitis assessed by magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, Patricia Froes; Martins, Nara Mendes; Martins, Flavia Mendes; Monteiro, Rosimary Araujo; Mendonca, Karla Morganna Pereira Pinto de [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Centro de Ciencias da Saude

    2008-12-15

    The aim of this study was to assess the use of magnetic resonance as a new method for evaluating the manual lymphatic drainage technique in treating cellulitis. Cellulitis is one of the main esthetic problems that lead women toward seeking guidance and specific treatments. There are various therapeutic approaches, owing to the multifactorial nature of its pathogen, although the effectiveness of most of these has not been definitively proven, given that the assessment methods used are mostly subjective or do not provide enough information on subcutaneous tissue. The introduction of magnetic resonance as a means of assessing a lymphatic drainage technique in cellulitis treatment makes the evaluation more accurate, since it enables a detailed study of subcutaneous architecture. (author)

  3. Core content for training in venous and lymphatic medicine.

    Science.gov (United States)

    Zimmet, Steven E; Min, Robert J; Comerota, Anthony J; Meissner, Mark H; Carman, Teresa L; Rathbun, Suman W; Jaff, Michael R; Wakefield, Thomas W; Feied, Craig F

    2014-10-01

    The major venous societies in the United States share a common mission to improve the standards of medical practitioners, the educational goals for teaching and training programs in venous disease, and the quality of patient care related to the treatment of venous disorders. With these important goals in mind, a task force made up of experts from the specialties of dermatology, interventional radiology, phlebology, vascular medicine, and vascular surgery was formed to develop a consensus document describing the Core Content for venous and lymphatic medicine and to develop a core educational content outline for training. This outline describes the areas of knowledge considered essential for practice in the field, which encompasses the study, diagnosis, and treatment of patients with acute and chronic venous and lymphatic disorders. The American Venous Forum and the American College of Phlebology have endorsed the Core Content. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  4. Primary disorders of the lymphatic vessels--a unified concept.

    Science.gov (United States)

    Levine, C

    1989-03-01

    Congenital defects of lymphatics constitute a spectrum of disorders that may manifest with a variety of clinical presentations including lymphedema, chylous effusions, lymphangiomatous malformations with cystic masses and localized gigantism, and intestinal lymphangiectasia with malabsorption. These entities constitute a relatively rare group of disorders, the origin of which remains somewhat controversial, but in some it appears to be due to early lymphatic obstruction. Five cases are described, which demonstrate the anatomical pathology of these entities. A classification and description of the defects is also presented. An attempt is made to present a unified theory of origin for this seemingly diverse group of diseases. While these entities may be challenging from a diagnostic and therapeutic standpoint, a wide variety of imaging modalities, which includes lymphography, computed tomography scanning, and ultrasound, may be used to diagnose the extent and internal structural characteristics of the abnormalities.

  5. Lymphoscintigraphic studies of lymphatic drainage from the testes

    International Nuclear Information System (INIS)

    Yeh, S.D.; Morse, M.J.; Grando, R.; Kleinert, E.L.; Whitmore, W.F. Jr.

    1986-01-01

    Two colloidal radiopharmaceuticals, Au-198 and Tc-99m antimony, were used to evaluate the lymphatic drainage of the testis in experimental animals and humans. One to 24 hours after direct intratesticular injection of Au-198 colloid in dogs and 4-6 hours after injection of Tc-99m antimony colloid in men, distribution within retroperitoneal lymph nodes was demonstrated. Uptake within the para-aortic lymph nodes primarily draining the testis was decreased following proximal ligation of the spermatic vessels in dogs. Testicular lymphoscintigraphy successfully demonstrated an intact spermatic cord lymphatic communication to the para-aortic nodes in five of six patients with chronic lower-extremity lymphedema. When the intact testicle and spermatic cord were transposed to the thigh in a patient with chronic lymphedema of the lower extremity, percutaneous pedal lymphoscintigraphy successfully demonstrated uptake within the para-aortic lymph nodes draining the ipsilateral testis

  6. PMab-48 Recognizes Dog Podoplanin of Lymphatic Endothelial Cells.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

    2018-02-01

    Podoplanin, a type I transmembrane glycoprotein, is a specific marker of lymphatic endothelial cells (LECs). Recently, we developed PMab-38, an anti-dog podoplanin monoclonal antibody that did not stain canine LECs. In this study, we newly developed PMab-48 against dog podoplanin. Immunohistochemical analysis revealed that PMab-48 reacts not only with canine squamous cell carcinoma cells but also with LECs of the normal colon. Therefore, PMab-48 may be useful in investigating the function of dog podoplanin in LECs.

  7. Studies of lymphatic drainage from testes by lymphoscintigraphy

    International Nuclear Information System (INIS)

    Yeh, S.D.J.; Morse, M.J.; Grando, R.; Kleinert, E.L.; Whitmore, W.F. Jr.

    1985-01-01

    Severe lymphedema of lower extremity may cause functional disability and foster recurrent lymphangitis. Surgical transportation of the testis to the thigh offers the possibility of enhancing lymphatic drainage from the leg via spermatic cord lymphatics. Testicular lymphoscintigraphy was employed to assess the quality of testicular lymphatic drainage prior to testis transposition. Images of abdomen and measurement of testis radioactivity were made serially after injection of Au 198 colloid into the testis of dogs before and after litigation of the spermatic cord. In the intact dogs, the residual radioactivities in the testis (5 dogs) were 53.5 +- 13.25, 41.6 +- 7.80 and 26.3 +- 5.66% at 2, 4 and 24 hours post injection. After ligation of spermatic cord, the residual activities in the testis were 95.0 +- 3.33, 86.4 +- 6.49 and 74.2 +- 6.28% at corresponding intervals post injection. Paraaortic nodes and liver were visualized in the abdominal images 1 hour after injection in the intact animals but only poorly seen in dogs following ligation. /sup 99m/Tc antimony colloid was used similarly in 5 patients who had severe lymphedema and abnormal pelvic lymphoscintigraphy following bipedal injection. With intratesticular injection, paraaortic lymph nodes and liver were visualized in 7 studies between 3 to 5 hours. Poor visualization was noted in two studies in patients who had previous radiation to the abdomen. The findings suggest that this simple technic can aid in the assessment of testicular lymphatic drainage and help to select patients for appropriate surgical intervention

  8. Follicular thyroid carcinoma invades venous rather than lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Liu Yulin

    2010-01-01

    Full Text Available Abstract Follicular thyroid carcinoma (FTC tends to metastasize to remote organs rather than local lymph nodes. Separation of FTC from follicular thyroid adenoma (FTA relies on detection of vascular and/or capsular invasion. We investigated which vascular markers, CD31, CD34 and D2-40 (lymphatic vessel marker, can best evaluate vascular invasion and why FTC tends to metastasize via blood stream to remote organs. Thirty two FTCs and 34 FTAs were retrieved for evaluation. The average age of patients with FTA was 8 years younger than FTC (p = 0.02. The female to male ratio for follicular neoplasm was 25:8. The average size of FTC was larger than FTA (p = 0.003. Fourteen of 32 (44% FTCs showed venous invasion and none showed lymphatic invasion, with positive CD31 and CD34 staining and negative D2-40 staining of the involved vessels. The average number of involved vessels was 0.88 ± 1.29 with a range from 0 to 5, and the average diameter of involved vessels was 0.068 ± 0.027 mm. None of the 34 FTAs showed vascular invasion. CD31 staining demonstrated more specific staining of vascular endothelial cells than CD34, with less background staining. We recommended using CD31 rather than CD34 and/or D2-40 in confirming/excluding vascular invasion in difficult cases. All identified FTCs with vascular invasions showed involvement of venous channels, rather than lymphatic spaces, suggesting that FTCs prefer to metastasize via veins to distant organs, instead of lymphatic vessels to local lymph nodes, which correlates with previous clinical observations.

  9. Facial nerve mapping and monitoring in lymphatic malformation surgery.

    Science.gov (United States)

    Chiara, Jospeh; Kinney, Greg; Slimp, Jefferson; Lee, Gi Soo; Oliaei, Sepehr; Perkins, Jonathan A

    2009-10-01

    Establish the efficacy of preoperative facial nerve mapping and continuous intraoperative EMG monitoring in protecting the facial nerve during resection of cervicofacial lymphatic malformations. Retrospective study in which patients were clinically followed for at least 6 months postoperatively, and long-term outcome was evaluated. Patient demographics, lesion characteristics (i.e., size, stage, location) were recorded. Operative notes revealed surgical techniques, findings, and complications. Preoperative, short-/long-term postoperative facial nerve function was standardized using the House-Brackmann Classification. Mapping was done prior to incision by percutaneously stimulating the facial nerve and its branches and recording the motor responses. Intraoperative monitoring and mapping were accomplished using a four-channel, free-running EMG. Neurophysiologists continuously monitored EMG responses and blindly analyzed intraoperative findings and final EMG interpretations for abnormalities. Seven patients collectively underwent 8 lymphatic malformation surgeries. Median age was 30 months (2-105 months). Lymphatic malformation diagnosis was recorded in 6/8 surgeries. Facial nerve function was House-Brackmann grade I in 8/8 cases preoperatively. Facial nerve was abnormally elongated in 1/8 cases. EMG monitoring recorded abnormal activity in 4/8 cases--two suggesting facial nerve irritation, and two with possible facial nerve damage. Transient or long-term facial nerve paresis occurred in 1/8 cases (House-Brackmann grade II). Preoperative facial nerve mapping combined with continuous intraoperative EMG and mapping is a successful method of identifying the facial nerve course and protecting it from injury during resection of cervicofacial lymphatic malformations involving the facial nerve.

  10. Synchronization and Random Triggering of Lymphatic Vessel Contractions

    Science.gov (United States)

    Baish, James W.; Kunert, Christian; Padera, Timothy P.; Munn, Lance L.

    2016-01-01

    The lymphatic system is responsible for transporting interstitial fluid back to the bloodstream, but unlike the cardiovascular system, lacks a centralized pump-the heart–to drive flow. Instead, each collecting lymphatic vessel can individually contract and dilate producing unidirectional flow enforced by intraluminal check valves. Due to the large number and spatial distribution of such pumps, high-level coordination would be unwieldy. This leads to the question of how each segment of lymphatic vessel responds to local signals that can contribute to the coordination of pumping on a network basis. Beginning with elementary fluid mechanics and known cellular behaviors, we show that two complementary oscillators emerge from i) mechanical stretch with calcium ion transport and ii) fluid shear stress induced nitric oxide production (NO). Using numerical simulation and linear stability analysis we show that the newly identified shear-NO oscillator shares similarities with the well-known Van der Pol oscillator, but has unique characteristics. Depending on the operating conditions, the shear-NO process may i) be inherently stable, ii) oscillate spontaneously in response to random disturbances or iii) synchronize with weak periodic stimuli. When the complementary shear-driven and stretch-driven oscillators interact, either may dominate, producing a rich family of behaviors similar to those observed in vivo. PMID:27935958

  11. Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

    Science.gov (United States)

    Lerner, Thomas R.; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R.G.; Borel, Sophie; Diedrich, Collin R.; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M.; Wilkinson, Robert J.; Griffiths, Gareth; Gutierrez, Maximiliano G.

    2016-01-01

    In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID:26901813

  12. Lymphatics of the cardia of stomach. Examination using RI lymphoscintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yonemura, Yutaka; Katayama, Kanji; Sawa, Toshiharu

    1985-01-01

    The lymphatics of the cardia of stomach was examined using lymphoscintigraphy with technetium 99m colloid in 98 patients with gastric cancer and 4 patients with esophageal cancer. The colloidal Tc-99m was injected into the submucosa of stomach 12 hr before operation with the aid of endoscopy. Each lymph node dissected from the specimens was measured by scintillation counter. Lymph nodes located along the left gastric, splenic and left inferior phrenic arteries were mainly involved in the lymphatics of the cardia of stomach. There was strong relationship between the cardia and the node of number 16. The lymphatics was also present in the mediastinum. These results suggest the necessities of the complete removal of the gastropancreatic mesenteriolum including the left inferior phrenic artery and the extirpation of the regional lymph nodes around the aorta above and below the left renal artery, in addition to the removal of both pancreas and spleen in cases of cardia tumors. Furthermore, in cases of squamous cell carcinoma or adenocarcinoma metastasizing to the intraperitoneal lymph nodes, it seems necessary to extirpate the complete mediastinal lymph nodes. (Namekawa, K.).

  13. Acidic microenvironments induce lymphangiogenesis and IL-8 production via TRPV1 activation in human lymphatic endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Masako, E-mail: n-masako@wakayama-med.ac.jp [Department of Pathology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Morita, Yoshihiro [Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871 (Japan); Department of Oral and Maxillofacial Surgery, Seichokai Hannan Municipal Hospital, Hannan, Osaka 599-0202 (Japan); Hata, Kenji [Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871 (Japan); Muragaki, Yasuteru, E-mail: ymuragak@wakayama-med.ac.jp [Department of Pathology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509 (Japan)

    2016-07-15

    Local acidosis is one of the characteristic features of the cancer microenvironment. Many reports indicate that acidosis accelerates the proliferation and invasiveness of cancer cells. However, whether acidic conditions affect lymphatic metastasis is currently unknown. In the present study, we focused on the effects of acidosis on lymphatic endothelial cells (LECs) to assess the relationship between acidic microenvironments and lymph node metastasis. We demonstrated that normal human LECs express various acid receptors by immunohistochemistry and reverse transcriptase-polymerase chain reaction (PCR). Acidic stimulation with low pH medium induced morphological changes in LECs to a spindle shape, and significantly promoted cellular growth and tube formation. Moreover, real-time PCR revealed that acidic conditions increased the mRNA expression of interleukin (IL)-8. Acidic stimulation increased IL-8 production in LECs, whereas a selective transient receptor potential vanilloid subtype 1 (TRPV1) antagonist, 5′-iodoresiniferatoxin, decreased IL-8 production. IL-8 accelerated the proliferation of LECs, and inhibition of IL-8 diminished tube formation and cell migration. In addition, phosphorylation of nuclear factor (NF)-κB was induced by acidic conditions, and inhibition of NF-κB activation reduced acid-induced IL-8 expression. These results suggest that acidic microenvironments in tumors induce lymphangiogenesis via TRPV1 activation in LECs, which in turn may promote lymphatic metastasis. - Highlights: • Acidity accelerates the growth, migration, and tube formation of LECs. • Acidic condition induces IL-8 expression in LECs. • IL-8 is critical for the changes of LECs. • IL-8 expression is induced via TRPV1 activation.

  14. A hybrid discrete-continuum mathematical model of pattern prediction in the developing retinal vasculature.

    Science.gov (United States)

    McDougall, S R; Watson, M G; Devlin, A H; Mitchell, C A; Chaplain, M A J

    2012-10-01

    Pathological angiogenesis has been extensively explored by the mathematical modelling community over the past few decades, specifically in the contexts of tumour-induced vascularisation and wound healing. However, there have been relatively few attempts to model angiogenesis associated with normal development, despite the availability of animal models with experimentally accessible and highly ordered vascular topologies: for example, growth and development of the vascular plexus layers in the murine retina. The current study aims to address this issue through the development of a hybrid discrete-continuum mathematical model of the developing retinal vasculature in neonatal mice that is closely coupled with an ongoing experimental programme. The model of the functional vasculature is informed by a range of morphological and molecular data obtained over a period of several days, from 6 days prior to birth to approximately 8 days after birth. The spatio-temporal formation of the superficial retinal vascular plexus (RVP) in wild-type mice occurs in a well-defined sequence. Prior to birth, astrocytes migrate from the optic nerve over the surface of the inner retina in response to a chemotactic gradient of PDGF-A, formed at an earlier stage by migrating retinal ganglion cells (RGCs). Astrocytes express a variety of chemotactic and haptotactic proteins, including VEGF and fibronectin (respectively), which subsequently induce endothelial cell sprouting and modulate growth of the RVP. The developing RVP is not an inert structure; however, the vascular bed adapts and remodels in response to a wide variety of metabolic and biomolecular stimuli. The main focus of this investigation is to understand how these interacting cellular, molecular, and metabolic cues regulate RVP growth and formation. In an earlier one-dimensional continuum model of astrocyte and endothelial migration, we showed that the measured frontal velocities of the two cell types could be accurately reproduced

  15. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI.

    Science.gov (United States)

    Absinta, Martina; Ha, Seung-Kwon; Nair, Govind; Sati, Pascal; Luciano, Nicholas J; Palisoc, Maryknoll; Louveau, Antoine; Zaghloul, Kareem A; Pittaluga, Stefania; Kipnis, Jonathan; Reich, Daniel S

    2017-10-03

    Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent with high propensity to extravasate across a permeable capillary endothelial barrier, but not with gadofosveset, a blood-pool contrast agent. The topography of these vessels, running alongside dural venous sinuses, recapitulates the meningeal lymphatic system of rodents. In primates, meningeal lymphatics display a typical panel of lymphatic endothelial markers by immunohistochemistry. This discovery holds promise for better understanding the normal physiology of lymphatic drainage from the central nervous system and potential aberrations in neurological diseases.

  16. Optical coherence tomographic view of persistent primary fetal vasculature

    International Nuclear Information System (INIS)

    Shenoy, R.; Al-Kharousi, Nadia S.; Bialasiewicz, Alexander A.

    2006-01-01

    Purpose was to report on the posterior segment changes in a patient with bilateral persistent primary fetal vasculature as detected by optical coherence tomography. An 18-year-old lady with poor vision, left esotropia and bilateral posterior polar cataract was found to have dysplasia of the macula in the both eyes. Fundus fluorescein angiography, optical coherence tomography, ''A'' scan biometry and genetic work up was performed as a part of investigation. There was increase in thickness of the macular area in both the eyes (450-500mm). The left eye showed a ''sail like'' fold extending over macula, from nasal to temporal side. The tissue had the same sensitivity and thickness as inner the retinal layers (180-200). There was no detectable nerve fibre layer in the macula of either eye. Fundus fluorescein angiography was normal in the right eye, and showed hyperfluorescence at the inferior pole of the disk in the left eye corresponding to the Bergmeister papilla. There was no staining of the membrane with the dye. Evaluation of the posterior segment is important in predicting the visual outcome in patients with any from of PFV. Optical coherence tomography is an adjuvant to direct visualization and aids in further delineating posterior segment changes seen in this condition. (author)

  17. Lymphographic criteria of lymphatic edema of the limbs in terms of microsurgery

    International Nuclear Information System (INIS)

    Rabkin, I.Kh.; Krylov, V.S.; Milanov, N.O.; Lein, A.P.; Ermakov, N.P.

    1980-01-01

    Based on the assessment of the results of 126 lymphographic studies, performed on patients with lymphatic edema of the limbs of various genesis, an important role has been assigned to lymphography as the criterion for establishing indications and contra-indications for microsurgical lymphovenous anastomosis. A special technique of pre-operation lymphophlebographic examination of patients with lymphatic edema of the limbds has been developed. A working scheme of primary lymphatic edemas, as well as the detailed interpretation of lymphographic appearance of primary and secondary lymphatic edemas are also provided

  18. A New Technique to Map the Lymphatic Distribution and Alignment of the Penis.

    Science.gov (United States)

    Long, Liu Yan; Qiang, Pan Fu; Ling, Tao; Wei, Zhang Yan; Long, Zhang Yu; Shan, Meng; Rong, Li Shi; Li, Li Hong

    2015-08-01

    The present study was to examine the distribution of lymphatic vessels in the penis of normal adult males, which could provide an anatomical basis for improvement of incisions in penile lengthening surgery, and may also help to prevent postoperative refractory edema. Thirteen normal adult male volunteers were recruited for this study. Contrast agent was injected subcutaneously in the foreskin of the penis, and after two minutes magnetic resonance lymphangiography (MRL) was performed. The acquired magnetic resonance images were analyzed to determine the changes in the number and diameter of lymphatic vessels in different parts of the penis. Maximum intensity projections (MIP) and materializes interactive medical image control system (MIMICS) were applied to analyze the overall distribution of lymphatic vessels in the penis. Magnetic resonance imaging (MRI) showed that the lymphatic vessels were in conspicuous contrast with surrounding tissues and could be clearly identified. Penile lymphatic vessels were clearly visible in the root of the penis. At the junction of the penis and the abdominal wall, all lymphatic vessels were found to be concentrated in the dorsal part of the penis. MIP two-dimensional reconstruction showed that the overall distribution of relatively large lymphatic vessels in the dorsal and ventral parts of the penis could be seen clearly on bilateral 45° position, but not inside the abdominal wall because some of lymphatic vessels were overlapped by other tissues in the abdomen. MIMICS three-dimensional reconstruction was able to reveal the overall spatial distribution of lymphatic vessels in the penis from any angle. The reconstruction results showed that there were 1-2 main lymphatic vessels on the root of dorsal penis, which coursed along the cavernous to the first physiological curvature of the penis. Lymphatic vessels merged on both sides of the ventral penis. At the root of the penis, lymphatic vessels gradually coursed to the dorsal surface

  19. Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node.

    Science.gov (United States)

    Srinivasan, Swetha; Vannberg, Fredrik O; Dixon, J Brandon

    2016-04-18

    It is well documented that cells secrete exosomes, which can transfer biomolecules that impact recipient cells' functionality in a variety of physiologic and disease processes. The role of lymphatic drainage and transport of exosomes is as yet unknown, although the lymphatics play critical roles in immunity and exosomes are in the ideal size-range for lymphatic transport. Through in vivo near-infrared (NIR) imaging we have shown that exosomes are rapidly transported within minutes from the periphery to the lymph node by lymphatics. Using an in vitro model of lymphatic uptake, we have shown that lymphatic endothelial cells actively enhanced lymphatic uptake and transport of exosomes to the luminal side of the vessel. Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow. Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake. Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

  20. The interaction between the meningeal lymphatics and blood-brain barrier

    Science.gov (United States)

    Semyachkina-Glushkovskaya, O.; Abdurashitov, A.; Dubrovsky, A.; Pavlov, A.; Shushunova, N.; Maslyakova, G.; Navolokin, N.; Bucharskaya, A.; Tuchin, V.; Kurths, J.

    2018-02-01

    Here we show the interaction between the meningeal lymphatic system and the blood-brain barrier (BBB) function. In normal state, the meningeal lymphatic vessels are invisible on optical coherent tomography (OCT), while during the opening of the BBB, meningeal lymphatic vessels are clearly visualized by OCT in the area of cerebral venous sinuses. These results give a significant impulse in the new application of OCT for the study of physiology of meningeal lymphatic system as well as sheds light on novel strategies in the prognosis of the opening of the BBB related with many central nervous system diseases, such as stroke, brain trauma, Alzheimers disease, etc.

  1. The potential role of perivascular lymphatic vessels in preservation of kidney allograft function.

    Science.gov (United States)

    Tsuchimoto, Akihiro; Nakano, Toshiaki; Hasegawa, Shoko; Masutani, Kosuke; Matsukuma, Yuta; Eriguchi, Masahiro; Nagata, Masaharu; Nishiki, Takehiro; Kitada, Hidehisa; Tanaka, Masao; Kitazono, Takanari; Tsuruya, Kazuhiko

    2017-08-01

    Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear. This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed. There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized β = -0.30, P = 0.019). High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.

  2. NORMALIZATION OF THE VASCULATURE FOR TREATMENT OF CANCER AND OTHER DISEASES

    Science.gov (United States)

    Goel, Shom; Duda, Dan G.; Xu, Lei; Munn, Lance L.; Boucher, Yves; Fukumura, Dai; Jain, Rakesh K.

    2012-01-01

    New vessel formation (angiogenesis) is an essential physiological process for embryologic development, normal growth, and tissue repair. Angiogenesis is tightly regulated at the molecular level. Dysregulation of angiogenesis occurs in various pathologies and is one of the hallmarks of cancer. The imbalance of pro- and anti-angiogenic signaling within tumors creates an abnormal vascular network that is characterized by dilated, tortuous, and hyperpermeable vessels. The physiological consequences of these vascular abnormalities include temporal and spatial heterogeneity in tumor blood flow and oxygenation and increased tumor interstitial fluid pressure. These abnormalities and the resultant microenvironment fuel tumor progression, and also lead to a reduction in the efficacy of chemotherapy, radiotherapy, and immunotherapy. With the discovery of vascular endothelial growth factor (VEGF) as a major driver of tumor angiogenesis, efforts have focused on novel therapeutics aimed at inhibiting VEGF activity, with the goal of regressing tumors by starvation. Unfortunately, clinical trials of anti-VEGF monotherapy in patients with solid tumors have been largely negative. Intriguingly, the combination of anti-VEGF therapy with conventional chemotherapy has improved survival in cancer patients compared with chemotherapy alone. These seemingly paradoxical results could be explained by a “normalization” of the tumor vasculature by anti-VEGF therapy. Preclinical studies have shown that anti-VEGF therapy changes tumor vasculature towards a more “mature” or “normal” phenotype. This “vascular normalization” is characterized by attenuation of hyperpermeability, increased vascular pericyte coverage, a more normal basement membrane, and a resultant reduction in tumor hypoxia and interstitial fluid pressure. These in turn can lead to an improvement in the metabolic profile of the tumor microenvironment, the delivery and efficacy of exogenously administered therapeutics

  3. Characterization of Receptors for Peptides Homing to the Vasculature of the Breast Carcinomas by Display Cloning

    National Research Council Canada - National Science Library

    Zhang, Lianglin

    2004-01-01

    .... The homing peptide technology provides a new targeting strategy that aims at physically concentrating therapeutic agents in tumor tissue by making use of the unique features of tumor vasculature...

  4. In vivo 3-dimensional photoacoustic imaging of the renal vasculature in preclinical rodent models

    OpenAIRE

    Ogunlade, O.; Connell, J. J.; Huang, J. L.; Zhang, E.; Lythgoe, M. F.; Long, D. A.; Beard, P.

    2017-01-01

    Non-invasive imaging of the kidney vasculature in preclinical murine models is important for studying renal development, diseases and evaluating new therapies, but is challenging to achieve using existing imaging modalities. Photoacoustic imaging is a promising new technique that is particularly well suited to visualising the vasculature and could provide an alternative to existing preclinical imaging methods for studying renal vascular anatomy and function. To investigate this, an all-optica...

  5. Normal Doppler velocimetry of renal vasculature in Persian cats.

    Science.gov (United States)

    Carvalho, Cibele F; Chammas, Maria C

    2011-06-01

    Renal diseases are common in older cats. Decreased renal blood flow may be the first sign of dysfunction and can be evaluated by Doppler ultrasound. But previous studies suggest that the resistive index (RI) has a low sensitivity for detecting renal disease. Doppler waveforms of renal and intrarenal arteries demonstrate decreased blood flow before there are any changes in the RI. The purpose of this study was to evaluate the normal Doppler flowmetrics parameters of renal arteries (RAs), interlobar arteries (IAs) and abdominal aorta (AO) in adult healthy, Persian cats. Twenty-five Persian cats (13 females and 12 males with mean age of 30 months and an age range 12-60 months) with normal clinical examinations and biochemical tests and normal systemic blood pressure were given B-mode ultrasonographies in order to exclude all nephropathies, including polycystic kidney disease. All measurements were performed on both kidneys. Both kidneys (n=50) were examined by color mapping of the renal vasculature. Pulsed Doppler was used to examine both RAs, the IAs at cranial, middle and caudal sites, and the AO. The RI was calculated for all of the vessels. Early systolic acceleration (ESA) of RA and IA was obtained with Doppler spectral analysis. Furthermore, the ratio indices between RA/AO, and IA/RA velocities were calculated. The mean values of peak systolic velocity (PSV) and the diameter for AO were 53.17±13.46 cm/s and 0.38±0.08 cm, respectively. The mean RA diameter for all 50 kidneys was 0.15±0.02 cm. Considering the velocimetric values in both RAs, the mean PSV and RI that were obtained were 41.17±9.40 cm/s and 0.54±0.07. The RA had a mean ESA of 1.12±1.14 m/s(2) and the calculated upper limit of the reference value was 3.40 m/s(2). The mean renal-aortic ratio was 0.828±0.296. The IA showed PSV and RI values of 32.16±9.33 cm/s and 0.52±0.06, respectively. The mean ESA of all IAs was 0.73±0.61 m/s(2). The calculated upper limit of the reference value was 2.0m

  6. Radiologic Assessment of Native Renal Vasculature: A Multimodality Review.

    Science.gov (United States)

    Al-Katib, Sayf; Shetty, Monisha; Jafri, Syed Mohammad A; Jafri, Syed Zafar H

    2017-01-01

    A wide range of clinically important anatomic variants and pathologic conditions may affect the renal vasculature, and radiologists have a pivotal role in the diagnosis and management of these processes. Because many of these entities may not be suspected clinically, renal artery and vein assessment is an essential application of all imaging modalities. An understanding of the normal vascular anatomy is essential for recognizing clinically important anatomic variants. An understanding of the protocols used to optimize imaging modalities also is necessary. Renal artery stenosis is the most common cause of secondary hypertension and is diagnosed by using both direct ultrasonographic (US) findings at the site of stenosis and indirect US findings distal to the stenosis. Fibromuscular dysplasia, while not as common as atherosclerosis, remains an important cause of renal artery hypertension, especially among young female individuals. Fibromuscular dysplasia also predisposes individuals to renal artery aneurysms and dissection. Although most renal artery dissections are extensions of aortic dissections, on rare occasion they occur in isolation. Renal artery aneurysms often are not suspected clinically before imaging, but they can lead to catastrophic outcomes if they are overlooked. Unlike true aneurysms, pseudoaneurysms are typically iatrogenic or posttraumatic. However, multiple small pseudoaneurysms may be seen with underlying vasculitis. Arteriovenous fistulas also are commonly iatrogenic, whereas arteriovenous malformations are developmental (ie, congenital). Both of these conditions involve a prominent feeding artery and draining vein; however, arteriovenous malformations contain a nidus of tangled vessels. Nutcracker syndrome should be suspected when there is distention of the left renal vein with abrupt narrowing as it passes posterior to the superior mesenteric artery. Filling defects in a renal vein can be due to a bland or tumor thrombus. A tumor thrombus is

  7. A microarray analysis of two distinct lymphatic endothelial cell populations

    Directory of Open Access Journals (Sweden)

    Bernhard Schweighofer

    2015-06-01

    Full Text Available We have recently identified lymphatic endothelial cells (LECs to form two morphologically different populations, exhibiting significantly different surface protein expression levels of podoplanin, a major surface marker for this cell type. In vitro shockwave treatment (IVSWT of LECs resulted in enrichment of the podoplaninhigh cell population and was accompanied by markedly increased cell proliferation, as well as 2D and 3D migration. Gene expression profiles of these distinct populations were established using Affymetrix microarray analyses. Here we provide additional details about our dataset (NCBI GEO accession number GSE62510 and describe how we analyzed the data to identify differently expressed genes in these two LEC populations.

  8. Imagery of the abdominal reticulo-histiocytary system [lymphatic nodes

    International Nuclear Information System (INIS)

    Ruel, Y.; Begon, D.

    1996-01-01

    Radiography and ultrasonography used together provide useful help in the clinical exploration of spleen and of abdominal lymphatic node abnormalities. These organs are difficult to examine by other techniques. Examination by radiography and ultrasonography often allows the abnormality to be localized and described, to visualize its spread and to observe its extension to other organs. Although these examinations do not allow this aspect they are invaluable in effective diagnosis. The information provided by these studies should avoid some exploratory laparotomies, to prepare for future surgical operations, to help in the prognostic (observation of metastasis,..), even to complete direct visual pre-operation examination (intra-hepatic metastasis)

  9. Survival of Lymphatic Cells after X-Irradiation in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Vos, O. [Medical Biological Laboratory, National Defense Research Organization TNO, Ruswuk, Z.H. (Netherlands)

    1967-07-15

    Lymphatic tissues are generally classified among the most radiosensitive tissues of the body. The main reason for this is that histologically extensive destruction is found within a few hours after irradiation. We tried to estimate the degree of cellular degeneration by making cell suspensions from lymph nodes and thymus of mice at different times after X-irradiation with 800 R or at 24 h after radiation with different doses. The numbers of normal viable cells we obtained were expressed as percentages of the cells recovered from unirradiated control mice.

  10. Mathematical models and lymphatic filariasis control: monitoring and evaluating interventions.

    Science.gov (United States)

    Michael, Edwin; Malecela-Lazaro, Mwele N; Maegga, Bertha T A; Fischer, Peter; Kazura, James W

    2006-11-01

    Monitoring and evaluation are crucially important to the scientific management of any mass parasite control programme. Monitoring enables the effectiveness of implemented actions to be assessed and necessary adaptations to be identified; it also determines when management objectives are achieved. Parasite transmission models can provide a scientific template for informing the optimal design of such monitoring programmes. Here, we illustrate the usefulness of using a model-based approach for monitoring and evaluating anti-parasite interventions and discuss issues that need addressing. We focus on the use of such an approach for the control and/or elimination of the vector-borne parasitic disease, lymphatic filariasis.

  11. An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas.

    Science.gov (United States)

    Korsgren, Erik; Korsgren, Olle

    2016-04-01

    The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. Immunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet-exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  12. Smooth muscle cell recruitment to lymphatic vessels requires PDGFB and impacts vessel size but not identity.

    Science.gov (United States)

    Wang, Yixin; Jin, Yi; Mäe, Maarja Andaloussi; Zhang, Yang; Ortsäter, Henrik; Betsholtz, Christer; Mäkinen, Taija; Jakobsson, Lars

    2017-10-01

    Tissue fluid drains through blind-ended lymphatic capillaries, via smooth muscle cell (SMC)-covered collecting vessels into venous circulation. Both defective SMC recruitment to collecting vessels and ectopic recruitment to lymphatic capillaries are thought to contribute to vessel failure, leading to lymphedema. However, mechanisms controlling lymphatic SMC recruitment and its role in vessel maturation are unknown. Here, we demonstrate that platelet-derived growth factor B (PDGFB) regulates lymphatic SMC recruitment in multiple vascular beds. PDGFB is selectively expressed by lymphatic endothelial cells (LECs) of collecting vessels. LEC-specific deletion of Pdgfb prevented SMC recruitment causing dilation and failure of pulsatile contraction of collecting vessels. However, vessel remodelling and identity were unaffected. Unexpectedly, Pdgfb overexpression in LECs did not induce SMC recruitment to capillaries. This was explained by the demonstrated requirement of PDGFB extracellular matrix (ECM) retention for lymphatic SMC recruitment, and the low presence of PDGFB-binding ECM components around lymphatic capillaries. These results demonstrate the requirement of LEC-autonomous PDGFB expression and retention for SMC recruitment to lymphatic vessels, and suggest an ECM-controlled checkpoint that prevents SMC investment of capillaries, which is a common feature in lymphedematous skin. © 2017. Published by The Company of Biologists Ltd.

  13. Erratum: PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis

    DEFF Research Database (Denmark)

    Cao, R.H.; Bjorndahl, M.A.; Religa, P.

    2006-01-01

    This corrects the article "PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis", Cancer Cell, 2004, vol. 6(4), pg 333-45.......This corrects the article "PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis", Cancer Cell, 2004, vol. 6(4), pg 333-45....

  14. Anatomy and physiology of lymphatic drainage of the breast from the perspective of sentinel node biopsy

    NARCIS (Netherlands)

    Tanis, P. J.; Nieweg, O. E.; Valdés Olmos, R. A.; Kroon, B. B.

    2001-01-01

    Knowledge of the anatomy and physiology of the lymphatic system is helpful when considering a particular sentinel node biopsy technique. The delicate balance between internal and external pressures in a lymphatic channel can be influenced by the injection volume and by massage in a negative or

  15. Development and validation of a custom made indocyanine green fluorescence lymphatic vessel imager

    Science.gov (United States)

    Pallotta, Olivia J.; van Zanten, Malou; McEwen, Mark; Burrow, Lynne; Beesley, Jack; Piller, Neil

    2015-06-01

    Lymphoedema is a chronic progressive condition often producing significant morbidity. An in-depth understanding of an individual's lymphatic architecture is valuable both in the understanding of underlying pathology and for targeting and tailoring treatment. Severe lower limb injuries resulting in extensive loss of soft tissue require transposition of a flap consisting of muscle and/or soft tissue to close the defect. These patients are at risk of lymphoedema and little is known about lymphatic regeneration within the flap. Indocyanine green (ICG), a water-soluble dye, has proven useful for the imaging of lymphatic vessels. When injected into superficial tissues it binds to plasma proteins in lymph. By exposing the dye to specific wavelengths of light, ICG fluoresces with near-infrared light. Skin is relatively transparent to ICG fluorescence, enabling the visualization and characterization of superficial lymphatic vessels. An ICG fluorescence lymphatic vessel imager was manufactured to excite ICG and visualize real-time fluorescence as it travels through the lymphatic vessels. Animal studies showed successful ICG excitation and detection using this imager. Clinically, the imager has assisted researchers to visualize otherwise hidden superficial lymphatic pathways in patients postflap surgery. Preliminary results suggest superficial lymphatic vessels do not redevelop in muscle flaps.

  16. Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice.

    Science.gov (United States)

    Agollah, Germaine D; Wu, Grace; Peng, Ho-Lan; Kwon, Sunkuk

    2015-12-07

    To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired

  17. [Study of Chinese herbal medicine in treating ascites and their mechanism in regulating lymphatic stomata].

    Science.gov (United States)

    Wu, Y; Li, J C; Mao, L G

    2001-09-01

    To study the therapeutic effect of Chinese herbal medicines (CHM) in treating ascites to elucidate its mechanism in regulating the lymphatic stomata and promoting the absorption of ascites from the peritoneal cavity. Using scanning electron microscope (SEM) and computerized image processing and quantitative analysis assays, the CHM extract consisting of Atractylodes macrocephala, Salvia miltiorrhiza, Codonopsis pilosula, Alismatis orientale and Leonurus heterophyllus were studied. Intraperitoneal injection of nitric oxide (NO) supplier or CHM administration could cause the average area of lymphatic stomata obviously enlarged (P inverted obviously, i.e. the average area and the density of lymphatic stomata were markedly reduced (P < 0.01). CHM might treat ascites through increasing the endogenous NO concentration to open the lymphatic stomata and in turn to conduct the peritoneal water through lymphatic path.

  18. Hydraulic control of tuna fins: A role for the lymphatic system in vertebrate locomotion.

    Science.gov (United States)

    Pavlov, Vadim; Rosental, Benyamin; Hansen, Nathaniel F; Beers, Jody M; Parish, George; Rowbotham, Ian; Block, Barbara A

    2017-07-21

    The lymphatic system in teleost fish has genetic and developmental origins similar to those of the mammalian lymphatic system, which is involved in immune response and fluid homeostasis. Here, we show that the lymphatic system of tunas functions in swimming hydrodynamics. Specifically, a musculo-vascular complex, consisting of fin muscles, bones, and lymphatic vessels, is involved in the hydraulic control of median fins. This specialization of the lymphatic system is associated with fish in the family Scombridae and may have evolved in response to the demand for swimming and maneuvering control in these high-performance species. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  19. In-vivo imaging of retinal nerve fiber layer vasculature: imaging – histology comparison

    Directory of Open Access Journals (Sweden)

    Libby Richard T

    2009-08-01

    Full Text Available Abstract Background Although it has been suggested that alterations of nerve fiber layer vasculature may be involved in the etiology of eye diseases, including glaucoma, it has not been possible to examine this vasculature in-vivo. This report describes a novel imaging method, fluorescence adaptive optics (FAO scanning laser ophthalmoscopy (SLO, that makes possible for the first time in-vivo imaging of this vasculature in the living macaque, comparing in-vivo and ex-vivo imaging of this vascular bed. Methods We injected sodium fluorescein intravenously in two macaque monkeys while imaging the retina with an FAO-SLO. An argon laser provided the 488 nm excitation source for fluorescence imaging. Reflectance images, obtained simultaneously with near infrared light, permitted precise surface registration of individual frames of the fluorescence imaging. In-vivo imaging was then compared to ex-vivo confocal microscopy of the same tissue. Results Superficial focus (innermost retina at all depths within the NFL revealed a vasculature with extremely long capillaries, thin walls, little variation in caliber and parallel-linked structure oriented parallel to the NFL axons, typical of the radial peripapillary capillaries (RPCs. However, at a deeper focus beneath the NFL, (toward outer retina the polygonal pattern typical of the ganglion cell layer (inner and outer retinal vasculature was seen. These distinguishing patterns were also seen on histological examination of the same retinas. Furthermore, the thickness of the RPC beds and the caliber of individual RPCs determined by imaging closely matched that measured in histological sections. Conclusion This robust method demonstrates in-vivo, high-resolution, confocal imaging of the vasculature through the full thickness of the NFL in the living macaque, in precise agreement with histology. FAO provides a new tool to examine possible primary or secondary role of the nerve fiber layer vasculature in retinal

  20. Lymphatic drainage and sentinel node location in breast cancer

    International Nuclear Information System (INIS)

    Uren, R.F.; Howman-Giles, R.B.; Roberts, J.; Renwick, S.; Gillett, D.; Neische, F.; Ramsay-Stewart, G.

    1999-01-01

    Full text: Mammary lymphoscintigraphy using small volume (0.1-0.2 ml) peritumoral injections of 99 Tc m -antimony sulphide colloid provided a map of the lymph drainage of a breast cancer to its draining sentinel lymph nodes in 92 of 102 patients (over 90%). Non-migration of tracer is reduced by post-injection massage for 5 min but may occur especially if the lymphatics are blocked by metastases. Drainage included the axilla in 92%, internal mammary nodes in 43%, supraclavicular nodes in 12% and intramammary interval nodes in 10% of patients. One patient drained to an interpectoral node. Drainage across the centre-line of the breast occurred in 46% of patients but direct drainage to the contralateral side of the patient was not seen. Lymphatic drainage occurred to 1 node field in 52 patients, 2 node fields in 34 patients and 3 node fields in 6 patients, so that 43% of patients had multiple draining node fields. Drainage to non-axillary sites occurred in 51% of patients. In conclusion, mammary lymphoscintigraphy accurately maps sentinel node location in breast cancer. Approximately half of the patients will have sentinel nodes outside the axilla. To achieve complete lymph node staging in patients with breast cancer, it is logical to biopsy these non-axillary sentinel nodes as well as the sentinel nodes in the axilla. Failure to do so will potentially understage the node status in 50% of patients

  1. Histopathologic aspects of radiation effects on lymphatic tissues and malignancies

    International Nuclear Information System (INIS)

    Lushbaugh, C.C.; Swartzendruber, D.C.

    1976-01-01

    Morphologic study with the light microscope remains our most facile and rapid means of tissue identification, diagnosis and staging of diseases, and demonstration of radiation-induced and other toxic effects. The inadequacy of its use alone, however, for the solution of biologic problems is nowhere better illustrated than in such studies on lymphatic tissues as are reported in this symposium. Nearly every classical concept concerning lymphocyte biology and disease derived by morphologic methods has been challenged or disproved in recent years by applications of nonmorphologic technologies. Studies with light and electron microscopy in combination with cell-labeling techniques, histochemical methodology, virology, immunology, and radiation biology have corrected many of our misconceptions and provided unifying concepts of lymphatic-tissue structure and function which explain anew our observations of the past. For example, nearly everyone now accepts the biologic role of viruses in what once were considered radiation-caused neoplasms in rodents, although whether the role of radiation and other physical and chemical insults in human carcinogenesis is direct or indirect is still to be elucidated. Also, the exact relations that obtain between radiation and cancer induction via viruses even in well-studied rodent systems remain to be determined; and here morphologic studies continue to play an important integrating role for the multidisciplinary studies that are required

  2. [The mantle zone in lymphatic follicles and its stratification].

    Science.gov (United States)

    Bednár, B

    1993-04-01

    Ten inguinal lymph nodes and spleens from autopsies were chosen according to age decades in order to get an idea about usual appearance of follicular structures. The group was complemented by 4 palatine tonsils from routine biopsies. Phenotype was ascertained by using about 30 standard markers and results were compared with a basic histocytological picture. The appearance of lymphatic tissue was quite different according to location and age categories, nevertheless, there were common immunophenotypic and structural features of follicular mantle in younger persons. It mostly comprised four cellular layers, more conspicuous at the upper pole of the follicle. An innermost layer was small-celled blastic, MB 2 and IgD positive, the next B monocytoid layer had medium sized cells of a similar phenotype but more alc, phosphatase positive. An inconstant plasmacytoid layer and a clarocellular layer used to be incomplete. It was cytostructurally characteristic but immunohistologically non-standard (faint CD 19 et CD 20 positivity). T 4 lymphocytes and perhaps some other elements leaving germinal centres were admixed into the inner mantle layer. Various small lymphoid cells, especially T 8 lymphocytes and sometimes litoral cells, were admixed into mantle periphery. Mutual exchange of lymphatic cells between the germinal and mantle zones was very scant. The mantle zone is presumed therefore to be independent from the structural and functional point of view as well.

  3. A series of parapharyngeal glial heterotopia mimicking lymphatic malformation.

    Science.gov (United States)

    Haloob, Nora; Pepper, Christopher; Hartley, Benjamin

    2015-12-01

    Otolaryngologists will most frequently encounter extra-cranial glial tissue within the nasal cavity, where it is known as a 'nasal glioma', and may communicate with the dura. However, glial tissue can also present extra-nasally in the form of a neck mass with no intracranial connection. In these rare cases, they can present soon after birth as an enlarging neck mass, causing compressive symptoms with airway obstruction and feeding difficulties. In this way, it is often initially misdiagnosed as a more common lesion such as a lymphatic malformation, teratoma, branchial anomaly or vascular malformation. As with many congenital head and neck masses, offering the most the appropriate management relies heavily on radiological imaging and, where possible, histopathology from a diagnostic biopsy. Once the diagnosis of extra-nasal glial heterotopia has been confirmed, the gold standard management is complete surgical excision. We review three cases of extra-nasal glial heterotopia presenting to our institution over an eleven year period as a large neck mass, which mimicked other congenital neck lumps, and discuss them in the context of those in the literature. We highlight how their clinical and radiological features can easily be confused with lymphatic malformations, and the potential implications of misdiagnosis. Raising awareness of this diagnostic confusion will highlight the need for management of these cases within an appropriate paediatric multidisciplinary setting. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Sclerotherapy for lymphatic malformations in children: a scoping review.

    Science.gov (United States)

    Churchill, Paige; Otal, Damanjot; Pemberton, Julia; Ali, Abdullah; Flageole, Helene; Walton, J Mark

    2011-05-01

    This scoping review assesses the literature and summarizes the current evidence on sclerotherapy for the treatment of lymphatic malformations in pediatric patients. A comprehensive search of published and unpublished literature was conducted using multiple databases. Title, abstract, and full-text screening was conducted by 2 independent clinicians. All discrepancies were resolved during consensus meetings. A total of 182 articles were retrieved. Forty-four articles were removed as duplicates, and 11 articles were added after reviewing prominent studies. After full-text abstraction, 44 articles and 2 conference proceedings (N = 882 patients) were included in the final results. Twelve articles were classified as level II and 34 articles as level IV evidence. Picibanil (OK-432) was the primary agent used in most included studies. Postinjection symptoms with OK-432 were primarily fever, swelling, and erythema at the site. Life-threatening complications were uncommon and involved postinjection swelling of cervical lesions causing airway compromise. The literature regarding sclerotherapy for lymphatic malformations is of a low level of evidence and suffers from a lack of standardization. Randomized clinical trials focused on OK-432, bleomycin, or alcoholic solution of zein; standardized dosing protocols; and consistent and reliable outcome reporting will be necessary for further development of treatment guidelines. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Estimation of lymphatic conductance. A model based on protein-kinetic studies and haemodynamic measurements in patients with cirrhosis of the liver and in pigs

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl

    1985-01-01

    A model of lymphatic conductivity (i.e. flow rate per unit pressure difference = conductance) based on protein-kinetic and haemodynamic measurements is described. The model is applied to data from patients with cirrhosis and from pigs with different haemodynamic abnormalities in the hepatosplanch......A model of lymphatic conductivity (i.e. flow rate per unit pressure difference = conductance) based on protein-kinetic and haemodynamic measurements is described. The model is applied to data from patients with cirrhosis and from pigs with different haemodynamic abnormalities...... compatible with increased sinusoidal wall tightening and fibrosis in the interstitial space of the liver. The model presented supports the so-called 'lymph-imbalance' theory of ascites formation according to which a relatively insufficient lymph drainage is important in the pathogenesis of hepatic ascites....

  6. Ccbe1 regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis

    NARCIS (Netherlands)

    Le Guen, Ludovic; Karpanen, Terhi; Schulte, Dörte; Harris, Nicole C; Koltowska, Katarzyna; Roukens, Guy; Bower, Neil I; van Impel, Andreas; Stacker, Steven A; Achen, Marc G; Schulte-Merker, Stefan; Hogan, Benjamin M

    The VEGFC/VEGFR3 signaling pathway is essential for lymphangiogenesis (the formation of lymphatic vessels from pre-existing vasculature) during embryonic development, tissue regeneration and tumor progression. The recently identified secreted protein CCBE1 is indispensible for lymphangiogenesis

  7. Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer

    Directory of Open Access Journals (Sweden)

    Kim Wun-Jae

    2011-04-01

    Full Text Available Abstract Background Most bladder cancer patients experience lymphatic metastasis in the course of disease progression, yet the relationship between lymphangiogenesis and lymphatic metastasis is not well known. The aim of this study is to elucidate underlying mechanisms of how expanded lymphatic vessels and tumor microenvironment interacts each other and to find effective therapeutic options to inhibit lymphatic metastasis. Results The orthotopic urinary bladder cancer (OUBC model was generated by intravesical injection of MBT-2 cell lines. We investigated the angiogenesis, lymphangiogenesis, and CD11b+/CD68+ tumor-associated macrophages (TAM by using immunofluorescence staining. OUBC displayed a profound lymphangiogenesis and massive infiltration of TAM in primary tumor and lymphatic metastasis in lymph nodes. TAM flocked near lymphatic vessels and express higher levels of VEGF-C/D than CD11b- cells. Because VEGFR-3 was highly expressed in lymphatic vascular endothelial cells, TAM could assist lymphangiogenesis by paracrine manner in bladder tumor. VEGFR-3 expressing adenovirus was administered to block VEGF-C/D signaling pathway and clodronate liposome was used to deplete TAM. The blockade of VEGF-C/D with soluble VEGF receptor-3 markedly inhibited lymphangiogenesis and lymphatic metastasis in OUBC. In addition, the depletion of TAM with clodronate liposome exerted similar effects on OUBC. Conclusion VEGF-C/D are the main factors of lymphangiogenesis and lymphatic metastasis in bladder cancer. Moreover, TAM plays an important role in these processes by producing VEGF-C/D. The inhibition of lymphangiogenesis could provide another therapeutic target to inhibit lymphatic metastasis and recurrence in patients with invasive bladder cancer.

  8. Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

    Science.gov (United States)

    Sun, Bao-Liang; Wang, Li-Hua; Yang, Tuo; Sun, Jing-Yi; Mao, Lei-Lei; Yang, Ming-Feng; Yuan, Hui; Colvin, Robert A; Yang, Xiao-Yi

    2017-09-10

    The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange. Copyright © 2017. Published by Elsevier Ltd.

  9. Lymphatic endothelial cells efferent to inflamed joints produce iNOS and inhibit lymphatic vessel contraction and drainage in TNF-induced arthritis in mice.

    Science.gov (United States)

    Liang, Qianqian; Ju, Yawen; Chen, Yan; Wang, Wensheng; Li, Jinlong; Zhang, Li; Xu, Hao; Wood, Ronald W; Schwarz, Edward M; Boyce, Brendan F; Wang, Yongjun; Xing, Lianping

    2016-03-12

    In this study, we sought to determine the cellular source of inducible nitric oxide synthase (iNOS) induced in lymphatic endothelial cells (LECs) in response to tumor necrosis factor (TNF), the effects of iNOS on lymphatic smooth muscle cell (LSMC) function and on the development of arthritis in TNF-transgenic (TNF-Tg) mice, and whether iNOS inhibitors improve lymphatic function and reduce joint destruction in inflammatory erosive arthritis. We used quantitative polymerase chain reactions, immunohistochemistry, histology, and near-infrared imaging to examine (1) iNOS expression in podoplanin + LECs and lymphatic vessels from wild-type (WT) and TNF-Tg mice, (2) iNOS induction by TNF in WT LECs, (3) the effects of iNOS inhibitors on expression of functional muscle genes in LSMCs, and (4) the effects of iNOS inhibitors on lymphatic vessel contraction and drainage, as well as the severity of arthritis, in TNF-Tg mice. LECs from TNF-Tg mice had eight fold higher iNOS messenger RNA levels than WT cells, and iNOS expression was confirmed immunohistochemically in podoplanin + LECs in lymphatic vessels from inflamed joints. TNF (0.1 ng/ml) increased iNOS levels 40-fold in LECs. LSMCs cocultured with LECs pretreated with TNF had reduced expression of functional muscle genes. This reduction was prevented by ferulic acid, which blocked nitric oxide production. Local injection of L-N(6)-(1-iminoethyl)lysine 5-tetrazole-amide into inflamed paws of TNF-Tg mice resulted in recovery of lymphatic vessel contractions and drainage. Treatment of TNF-Tg mice with ferulic acid reduced synovial inflammation as well as cartilage and bone erosion, and it also restored lymphatic contraction and drainage. iNOS is produced primarily by LECs in lymphatic vessel efferent from inflamed joints of TNF-Tg mice in response to TNF and inhibits LSMC contraction and lymph drainage. Ferulic acid represents a potential new therapy to restore lymphatic function and thus improve inflammatory

  10. ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor

    Energy Technology Data Exchange (ETDEWEB)

    Inagaki, Junko; Takahashi, Katsuyuki; Ogawa, Hiroko; Asano, Keiichi; Faruk Hatipoglu, Omer; Zeynel Cilek, Mehmet; Obika, Masanari; Ohtsuki, Takashi [Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); Hofmann, Matthias [Department of Dermatology, Venereology and Allergology, Goethe University, Frankfurt (Germany); Kusachi, Shozo [Department of Medical Technology, Okayama University Graduate School of Health Sciences, Okayama (Japan); Ninomiya, Yoshifumi [Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); Hirohata, Satoshi, E-mail: hirohas@cc.okayama-u.ac.jp [Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); International Center, Okayama University, Okayama (Japan)

    2014-05-01

    Angiogenesis and lymphangiogenesis play roles in malignant tumor progression, dissemination, and metastasis. ADAMTS1, a member of the matrix metalloproteinase family, is known to inhibit angiogenesis. Recombinant ADAMTS1 was shown to strongly inhibit angiogenesis. We investigated whether ADAMTS1 inhibited lymphangiogenesis in the present study. We examined cell proliferation and cell migration in normal human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) transduced with or without adenoviral human ADAMTS1 gene therapy. We then examined the VEGFC/VEGFR3 signal transduction pathway in ADAMTS1-transduced HMVEC-dLy. Cell proliferation and tube formation in Matrigel were significantly lower with transduced ADAMTS1 than with control (non-transduced HMVEC-dLy). The phosphorylation of VEGFR3 was also attenuated by ADAMTS1 gene therapy in HMVEC-dLy. Immunoprecipitation assays revealed that ADAMTS1 formed a complex with VEGFC. Our results demonstrated that ADAMTS1 inhibited lymphangiogenesis in vitro. The data highlight the new function of ADAMTS1 in the regulation of lymphangiogenesis and the therapeutic potential of ADAMTS1 in cancer therapy. - Highlights: • ADAMTS1 significantly inhibited tube formation and cell proliferation in HMVEC-dLy. • Reduced lymph endothelial cell migration in ADAMTS1 transduced co-culture systems. • VEGFC-stimulated phosphorylation of VEGFR3 is attenuated by ADAMTS1. • Reduced phosphorylation of Akt and ERK1/2 in ADAMTS1 treated HMVEC-dLy. • ADAMTS1 binds directly to VEGFC.

  11. ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor

    International Nuclear Information System (INIS)

    Inagaki, Junko; Takahashi, Katsuyuki; Ogawa, Hiroko; Asano, Keiichi; Faruk Hatipoglu, Omer; Zeynel Cilek, Mehmet; Obika, Masanari; Ohtsuki, Takashi; Hofmann, Matthias; Kusachi, Shozo; Ninomiya, Yoshifumi; Hirohata, Satoshi

    2014-01-01

    Angiogenesis and lymphangiogenesis play roles in malignant tumor progression, dissemination, and metastasis. ADAMTS1, a member of the matrix metalloproteinase family, is known to inhibit angiogenesis. Recombinant ADAMTS1 was shown to strongly inhibit angiogenesis. We investigated whether ADAMTS1 inhibited lymphangiogenesis in the present study. We examined cell proliferation and cell migration in normal human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) transduced with or without adenoviral human ADAMTS1 gene therapy. We then examined the VEGFC/VEGFR3 signal transduction pathway in ADAMTS1-transduced HMVEC-dLy. Cell proliferation and tube formation in Matrigel were significantly lower with transduced ADAMTS1 than with control (non-transduced HMVEC-dLy). The phosphorylation of VEGFR3 was also attenuated by ADAMTS1 gene therapy in HMVEC-dLy. Immunoprecipitation assays revealed that ADAMTS1 formed a complex with VEGFC. Our results demonstrated that ADAMTS1 inhibited lymphangiogenesis in vitro. The data highlight the new function of ADAMTS1 in the regulation of lymphangiogenesis and the therapeutic potential of ADAMTS1 in cancer therapy. - Highlights: • ADAMTS1 significantly inhibited tube formation and cell proliferation in HMVEC-dLy. • Reduced lymph endothelial cell migration in ADAMTS1 transduced co-culture systems. • VEGFC-stimulated phosphorylation of VEGFR3 is attenuated by ADAMTS1. • Reduced phosphorylation of Akt and ERK1/2 in ADAMTS1 treated HMVEC-dLy. • ADAMTS1 binds directly to VEGFC

  12. Label-free imaging of developing vasculature in zebrafish with phase variance optical coherence microscopy

    Science.gov (United States)

    Chen, Yu; Fingler, Jeff; Trinh, Le A.; Fraser, Scott E.

    2016-03-01

    A phase variance optical coherence microscope (pvOCM) has been created to visualize blood flow in the vasculature of zebrafish embryos, without using exogenous labels. The pvOCM imaging system has axial and lateral resolutions of 2 μm in tissue, and imaging depth of more than 100 μm. Imaging of 2-5 days post-fertilization zebrafish embryos identified the detailed structures of somites, spinal cord, gut and notochord based on intensity contrast. Visualization of the blood flow in the aorta, veins and intersegmental vessels was achieved with phase variance contrast. The pvOCM vasculature images were confirmed with corresponding fluorescence microscopy of a zebrafish transgene that labels the vasculature with green fluorescent protein. The pvOCM images also revealed functional information of the blood flow activities that is crucial for the study of vascular development.

  13. Tolerogenic properties of lymphatic endothelial cells are controlled by the lymph node microenvironment.

    Directory of Open Access Journals (Sweden)

    Jarish N Cohen

    Full Text Available Peripheral self-tolerance eliminates lymphocytes specific for tissue-specific antigens not encountered in the thymus. Recently, we demonstrated that lymphatic endothelial cells in mice directly express peripheral tissue antigens, including tyrosinase, and induce deletion of specific CD8 T cells via Programmed Death Ligand-1 (PD-L1. Here, we demonstrate that high-level expression of peripheral tissue antigens and PD-L1 is confined to lymphatic endothelial cells in lymph nodes, as opposed to tissue (diaphragm and colon lymphatics. Lymphatic endothelial cells in the lymph node medullary sinus express the highest levels of peripheral tissue antigens and PD-L1, and are the only subpopulation that expresses tyrosinase epitope. The representation of lymphatic endothelial cells in the medullary sinus expressing high-level PD-L1, which is necessary for normal CD8 T cell deletion kinetics, is controlled by lymphotoxin-β receptor signaling and B cells. Lymphatic endothelial cells from neonatal mice do not express high-level PD-L1 or present tyrosinase epitope. This work uncovers a critical role for the lymph node microenvironment in endowing lymphatic endothelial cells with potent tolerogenic properties.

  14. Corpus callosum vasculature predicts white matter microstructure abnormalities following pediatric mild traumatic brain injury.

    Science.gov (United States)

    Wendel, Kara M; Lee, Jeong Bin; Affeldt, Bethann; Hamer, Mary; Harahap-Carrillo, Indira S; Pardo, Andrea C; Obenaus, Andre

    2018-05-09

    Emerging data suggest that pediatric traumatic brain injury (TBI) is associated with impaired developmental plasticity and poorer neuropsychological outcomes than adults with similar head injuries. Unlike adult mild TBI (mTBI), the effects of mTBI on white matter (WM) microstructure and vascular supply are not well-understood in the pediatric population. The cerebral vasculature plays an important role providing necessary nutrients and removing waste. To address this critical element, we examined the microstructure of the corpus callosum (CC) following pediatric mTBI using diffusion tensor imaging (DTI), and investigated myelin, oligodendrocytes, and vasculature of WM with immunohistochemistry. We hypothesized that pediatric mTBI leads to abnormal WM microstructure and impacts the vasculature within the CC, and that these alterations to WM vasculature contribute to the long-term altered microstructure. We induced a closed head injury mTBI at postnatal day 14, then at 4, 14, and 60 days post injury (DPI) mice were sacrificed for analysis. We observed persistent changes in apparent diffusion coefficient (ADC) within the ipsilateral CC following mTBI, indicating microstructural changes, but surprisingly changes in myelin and oligodendrocyte densities were minimal. However, vasculature features of the ipsilateral CC such as vessel density, length, and number of junctions were persistently altered following mTBI. Correlative analysis showed a strong inverse relationship between ADC and vessel density at 60 DPI, suggesting increased vessel density following mTBI may restrict WM diffusion characteristics. Our findings suggest that WM vasculature contributes to the long-term microstructural changes within the ipsilateral CC following mTBI.

  15. Expression of receptor-type protein tyrosine phosphatase in developing and adult renal vasculature.

    Directory of Open Access Journals (Sweden)

    Keiko Takahashi

    Full Text Available Renal vascular development is a coordinated process that requires ordered endothelial cell proliferation, migration, intercellular adhesion, and morphogenesis. In recent decades, studies have defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs in the development and maintenance of renal vasculature. However, the expression and the role of receptor tyrosine phosphatases (RPTPs in renal endothelium are poorly understood, though coupled and counterbalancing roles of RPTKs and RPTPs are well defined in other systems. In this study, we evaluated the promoter activity and immunolocalization of two endothelial RPTPs, VE-PTP and PTPμ, in developing and adult renal vasculature using the heterozygous LacZ knock-in mice and specific antibodies. In adult kidneys, both VE-PTP and PTPμ were expressed in the endothelium of arterial, glomerular, and medullary vessels, while their expression was highly limited in peritubular capillaries and venous endothelium. VE-PTP and PTPμ promoter activity was also observed in medullary tubular segments in adult kidneys. In embryonic (E12.5, E13.5, E15.5, E17.5 and postnatal (P0, P3, P7 kidneys, these RPTPs were expressed in ingrowing renal arteries, developing glomerular microvasculature (as early as the S-shaped stage, and medullary vessels. Their expression became more evident as the vasculatures matured. Peritubular capillary expression of VE-PTP was also noted in embryonic and postnatal kidneys. Compared to VE-PTP, PTPμ immunoreactivity was relatively limited in embryonic and neonatal renal vasculature and evident immunoreactivity was observed from the P3 stage. These findings indicate 1 VE-PTP and PTPμ are expressed in endothelium of arterial, glomerular, and medullary renal vasculature, 2 their expression increases as renal vascular development proceeds, suggesting that these RPTPs play a role in maturation and maintenance of these vasculatures, and 3 peritubular capillary VE-PTP expression

  16. Podoplanin immunopositive lymphatic vessels at the implant interface in a rat model of osteoporotic fractures.

    Directory of Open Access Journals (Sweden)

    Katrin Susanne Lips

    Full Text Available Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of

  17. Podoplanin Immunopositive Lymphatic Vessels at the Implant Interface in a Rat Model of Osteoporotic Fractures

    Science.gov (United States)

    Lips, Katrin Susanne; Kauschke, Vivien; Hartmann, Sonja; Thormann, Ulrich; Ray, Seemun; Kampschulte, Marian; Langheinrich, Alexander; Schumacher, Matthias; Gelinsky, Michael; Heinemann, Sascha; Hanke, Thomas; Kautz, Armin R.; Schnabelrauch, Matthias; Schnettler, Reinhard; Heiss, Christian; Alt, Volker; Kilian, Olaf

    2013-01-01

    Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of lymphocytes, macrophages

  18. Initial afferent lymphatic vessels controlling outbound leukocyte traffic from skin to lymph nodes.

    Directory of Open Access Journals (Sweden)

    Ignacio eMelero

    2013-12-01

    Full Text Available Tissue drains fluid and macromolecules through lymphatic vessels, which are lined by a specialized endothelium that expresses peculiar differentiation proteins, not found in blood vessels (i.e: LYVE-1, Podoplanin, PROX-1 and VEGFR-3. Lymphatic capillaries are characteristically devoid of a continuous basal membrane and are anchored to the ECM by elastic fibers that act as pulling ropes which open the vessel to avoid oedema if tissue volume increases, as it occurs upon inflammation. Lymphatic vessels are also crucial for the transit of T lymphocytes and antigen presenting cells from tissue to draining lymph nodes. Importantly, cell traffic control across lymphatic endothelium is differently regulated under resting and inflammatory conditions. Under steady-state non-inflammatory conditions, leukocytes enter into the lymphatic capillaries through basal membrane gaps (portals. This entrance is integrin-independent and seems to be mainly guided by CCL21 chemokine gradients acting on leukocytes expressing CCR7. In contrast, inflammatory processes in lymphatic capillaries involve a plethora of cytokines, chemokines, leukocyte integrins and other adhesion molecules. Importantly, under inflammation a role for integrins and their ligands becomes apparent and, as a consequence, the number of leukocytes entering the lymphatic capillaries multiplies several-fold. Enhancing transmigration of dendritic cells en route to lymph nodes is conceivably useful for vaccination and cancer immunotherapy, whereas interference with such key mechanisms may ameliorate autoimmunity or excessive inflammation. Recent findings illustrate how, transient cell-to-cell interactions between lymphatic endothelial cells and leukocytes contribute to shape the subsequent behaviour of leukocytes and condition the lymphatic vessel for subsequent trans-migratory events.

  19. Fallopian tube cancer: incidence and role of lymphatic spread.

    Science.gov (United States)

    di Re, E; Grosso, G; Raspagliesi, F; Baiocchi, G

    1996-08-01

    Lymphatic spread pattern in 17 cases of adenocarcinoma of fallopian tube is reported. Median age of the patients was 48 years. All patients underwent surgical staging including total abdominal hysterectomy, bilateral salpingo-oopherectomy omentectomy, and appendectomy. Systematic pelvic and paraaortic lymphadenectomy was feasible in 15 cases. Majority of the patients (11 of 17 cases, 64%) had advanced disease and showed serous adenocarcinoma (83%). Lymph nodes were involved in 10 of 17 cases (59%). Node metastases rate increased significantly (P < 0.01) with intraperitoneal stage of disease and with grading. Interestingly, positive nodes were also found in 2 cases (33%) of 6 patients with disease still limited to fallopian tube. Overall, patients with negative nodes had a median survival of 76 months, compared with only 33 months if node metastases were found. In conclusion, combined pelvic and para-aortic lymphadenectomy seems to be necessary for staging and perhaps for prognosis of this disease.

  20. Total lymphatic irradiation and bone marrow in human heart transplantation

    International Nuclear Information System (INIS)

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-01-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem

  1. Efficacy and safety of OK-432 immunotherapy of lymphatic malformations.

    Science.gov (United States)

    Smith, Mark C; Zimmerman, M Bridget; Burke, Diane K; Bauman, Nancy M; Sato, Yutaka; Smith, Richard J H

    2009-01-01

    To determine the efficacy and safety of the immunostimulant OK-432 (Picibanil) as a treatment option in the management of children with cervicofacial lymphatic malformations. A prospective, randomized, multi-institutional phase II clinical trial at 27 U.S. academic medical centers. 182 patients with lymphatic malformations (LM) were enrolled between January 1998 and November 2004. Of the 151 patients with complete case report forms, 117 patients were randomized into immediate or delayed treatment groups; 34 patients were nonrandomized and assigned to the open-label group. Treatment consisted of a four-dose intralesional injection series of OK-432 at eight-week intervals. Patients randomized into the delayed treatment group served as observational controls for spontaneous regression. Response to therapy was measured radiographically by quantitating change in lesion size and graded as complete (90%-100%), substantial (60%-89%), intermediate (20%-59%), or none (<20%). Of 117 patients randomized with intent-to-treat, 68% demonstrated a complete or substantial response to OK-432 immunotherapy. Response data for macrocystic LM were higher, with a complete or substantial response in 94% of patients; 63% of patients with mixed macrocystic-microcystic LM responded to treatment; no patients with microcystic LM responded to treatment. Spontaneous resolution occurred in less than 2% of patients. Median follow-up of 2.9 years demonstrated a 9% recurrence rate. Major adverse effects related to therapy occurred in 11 patients. As compared to historical surgical data on LM, OK-432 immunotherapy is more effective (P < .001) and has a lower morbidity (P < .001). OK-432 immunotherapy is an effective, safe, and simple treatment option for the management of macrocystic cervicofacial LM. ClinicalTrials.gov Identifier: NCT00010452.

  2. Antenatal hemorrhage of a cervical lymphatic malformation presenting as a draining neck mass: An unusual presentation.

    Science.gov (United States)

    Haricharan, R N; Nawaz, M; Bettolli, M; Ferretti, E

    2014-01-01

    Lymphatic malformations in the neck can present as large fetal neck masses causing airway obstructions with potential perinatal demise and can pose a therapeutic challenge. We present a rare case of prenatally diagnosed large fetal neck mass with features of lymphatic malformation with intralesional hemorrhage of uncertain origin. Postnatal evaluation showed a complex cystic-solid lesion eroding through the skin with an open wound that made it clinically hard to differentiate from a teratoma. Given that malignancy could not be completely ruled out, surgery was favored. Final pathology showed a complex lymphatic malformation with intralesional hemorrhage, despite having no associated capillary, venous or arterial malformations.

  3. Normal anatomy of the lymphatic system in the CT-image

    International Nuclear Information System (INIS)

    Steinbrich, W.; Peters, P.E.

    1982-01-01

    To evaluate a pathologic process of a lymphatic node, detailed knowledge is required of the normal anatomy of the lumphatic system in an axial CT image. The anatomy is demonstrated in a comparative study before and after lymphography with CT-scans of patients with normal lymphadenographs. Hereby it appears that with the high-resolution scanning method and favourable imaging conditions even small lymphatic nodes can be differentiated without a lymphographic contrast technique. However, nerves and vessels cannot be differentiated. The extreme variability in the size of normal lymphatic nodes makes the differentiation of pathologic processes very difficult. (orig.) [de

  4. Short report: documentation of iodine deficiency in Haitian schoolchildren: implication for lymphatic filariasis elimination in Haiti.

    Science.gov (United States)

    Beach, M J; Streit, T G; Houston, R; May, W A; Addiss, D G; Lammie, P J

    2001-01-01

    In this study we documented unexpected moderate-to-severe iodine deficiency in Haitian schoolchildren although they live in a coastal community where presumably they have access to iodine-containing seafood. This fact combined with the lack of an iodized salt supply and endemic lymphatic filariasis makes community distribution of diethylcarbamazine-fortified, iodized salt an attractive strategy for elimination of lymphatic filariasis and iodine deficiency disorders in this area of Haiti. Combining lymphatic filariasis elimination with other public health interventions is one strategy to increase its public health benefit and maximize the impact of limited public health resources.

  5. Assessment of peripheral vessels and of the lymphatic system by means of gamma-camera scintiscan (gamma-scintigraphy of the whole body)

    Energy Technology Data Exchange (ETDEWEB)

    Ennis, J T

    1981-01-01

    For diagnosing pathologies of the peripheric vessels or of the lymphatic system, albumin aggregates marked with sup(99m) technetium (MAA) or antimonocolloids were used. The radionuclide venography is useful in diagnosing thrombosis, venous insufficiency, and permits a high degree of accuracy, comparable with that of phlebography. In the most cases the radionuclide lymphoscintigraphy is required for the diagnosis of lymphoedema and allows by distribution analysis an adequate morphological representation of the lymphatic ducts and glands. Contrary to lymphography, lymphoscintigraphy presents a completely physiological radionuclide transport and does not cause any reactive lymphatic node hyperplasia by contrast media. Increased capillary perfusion is found in collateral vessel formation in cases of arterial obstruction and ischaemic ulcus, whereas hypoperfusion is seen in obstructions of the larger arteries having no collateral vessels, and in bad circulatory states. Particularly in diabetics with microangiopathy, a peripheral distribution with hyperfusion of the skon presents itself as piece-meal necrosis. The importance and relevance of the perfusion scans of the extremities for the diagnostic assessment within the field of resection surgery is explained.

  6. The Effect of Irradiation on the Structure of Vasculature Experimentally Induced Rat Salivary Gland Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hyo Shick [Dept. of Oral Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1990-02-15

    after a lapse of time. 6. The change of the vascular structure after irradiation such as vasculitis, endothelial swelling and thrombosis on histologic section were coincided with the microangiographic changes. 7. It is suggestive that the mechanisms of the post-irradiation changes of vasculature in the center or periphery of the tumor mass is the destruction of tumor cells and capillaries caused by direct radiation effect, and the progressive degenerative and destructive changes are due to usual residual tissue damage by irradiation. 8. The vascular alterations by irradiation can cause the disruption of blood flow and it can be considered as one of the most effective suppressive factor of tumor growth. 9. The post-irradiative hyalinzation of the connectivie tissue surrounding the tumor tissue was one of the inhibitory factor of the tumor dissemination and the cause of decrease of vascularity. 10. The granulation tissue formation outward the hyalinized zone surrounding the tumor tissue was the reactive feature against the post irradiative central tumor necrosis.

  7. The Effect of Irradiation on the Structure of Vasculature Experimentally Induced Rat Salivary Gland Carcinoma

    International Nuclear Information System (INIS)

    Kang, Hyo Shick

    1990-01-01

    after a lapse of time. 6. The change of the vascular structure after irradiation such as vasculitis, endothelial swelling and thrombosis on histologic section were coincided with the microangiographic changes. 7. It is suggestive that the mechanisms of the post-irradiation changes of vasculature in the center or periphery of the tumor mass is the destruction of tumor cells and capillaries caused by direct radiation effect, and the progressive degenerative and destructive changes are due to usual residual tissue damage by irradiation. 8. The vascular alterations by irradiation can cause the disruption of blood flow and it can be considered as one of the most effective suppressive factor of tumor growth. 9. The post-irradiative hyalinzation of the connectivie tissue surrounding the tumor tissue was one of the inhibitory factor of the tumor dissemination and the cause of decrease of vascularity. 10. The granulation tissue formation outward the hyalinized zone surrounding the tumor tissue was the reactive feature against the post irradiative central tumor necrosis.

  8. Minilaparoscopic varicocelectomy with preservation of testicular artery and lymphatic vessels by using intracorporeal knot-tying technique: five-year experience.

    Science.gov (United States)

    Chung, Shiu-Dong; Wu, Chia-Chang; Lin, Victor Chia-Hsiang; Ho, Chen-Hsun; Yang, Stephen Shei Dei; Tsai, Yao-Chou

    2011-08-01

    In this study we present our experience using minilaparoscopic intracorporeal knot tying to ligate internal spermatic veins (ISV) while sparing the spermatic artery and lymphatics. Minilaparoscopic varicocelectomies were performed in 87 patients between January 2004 and January 2009. All varicoceles were detected clinically according to the World Health Organization (WHO) classification and confirmed by scrotal color Doppler ultrasonography. The surgical indications were scrotal symptoms in 71, infertility in 16, and both conditions in 2. Three 3.5 mm minilaparoscopic ports were used for the operation. The ISVs were dissected and then ligated with intracorporeal knot-tying. The testicular artery and lymphatic vessels were carefully preserved to minimize procedure-related complications. Unilateral laparoscopic varicocelectomy was performed in 21 (24.2%) patients and bilateral in 66 (75.8%). Mean operative time was 71.1 ± 29.2 and 46.8 ± 12.6 min for bilateral and unilateral varicocelectomies, respectively. All patients were discharged within 24 h after surgery. Neither immediate major nor late procedure-related complications were noted. Of the 71 patients with scrotal symptoms, the symptoms completely subsided in 55 (77.5%) and partially subsided in 10 (14.1%). Only one (1.2%) recurrent varicocele was detected within a mean follow-up of 21 months (range = 3-42). Neither hydrocele formation nor testicular atrophy was found during the follow-up period. Our 5-year experience revealed that minilaparoscopic varicocelectomy with sparing of artery and lymphatic vessels could safely and effectively ligate all spermatic veins and preserve spermatic arteries and lymphatic channels without leading to a high varicocele persistence or recurrence.

  9. Treatment of Lymphatic Malformations With OK-432 (Picibanil) : Review of the Literature

    NARCIS (Netherlands)

    Poldervaart, Michelle T.; Breugem, Corstiaan C.; Speleman, Lucienne; Pasmans, Suzanne

    Introduction: Lymphatic malformations (LM) are benign structural defects that call cause serious complications because of their size and location. Traditionally surgical removal was the first treatment modality, but this Could be associated with many complications and risks. Since Ogita introduced

  10. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

    NARCIS (Netherlands)

    Temming, K; Molema, G; Kok, RJ

    2005-01-01

    During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to a(v)beta(3)-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to

  11. Comparison of anterior segment optical coherence tomography angiography and fluorescein angiography for iris vasculature analysis.

    Science.gov (United States)

    Zett, Claudio; Stina, Deborah M Rosa; Kato, Renata Tiemi; Novais, Eduardo Amorim; Allemann, Norma

    2018-04-01

    The aim of this study is to perform imaging of irises of different colors using spectral domain anterior segment optical coherence tomography angiography (AS-OCTA) and iris fluorescein angiography (IFA) and compare their effectiveness in examining iris vasculature. This is a cross-sectional observational clinical study. Patients with no vascular iris alterations and different pigmentation levels were recruited. Participants were imaged using OCTA adapted with an anterior segment lens and IFA with a confocal scanning laser ophthalmoscope (cSLO) adapted with an anterior segment lens. AS-OCTA and IFA images were then compared. Two blinded readers classified iris pigmentation and compared the percentage of visible vessels between OCTA and IFA images. Twenty eyes of 10 patients with different degrees of iris pigmentation were imaged using AS-OCTA and IFA. Significantly more visible iris vessels were observed using OCTA than using FA (W = 5.22; p Iris pigmentation was negatively correlated to the percentage of visible vessels in both imaging methods (OCTA, rho = - 0.73, p iris vasculature. In both AS-OCTA and IFA, iris pigmentation caused vasculature imaging blockage, but AS-OCTA provided more detailed iris vasculature images than IFA. Additional studies including different iris pathologies are needed to determine the most optimal scanning parameters in OCTA of the anterior segment.

  12. Tumour vasculature and angiogenic profile of paediatric pilocytic astrocytoma; is it much different from glioblastoma?

    NARCIS (Netherlands)

    Sie, M.; de Bont, E. S. J. M.; Scherpen, F. J. G.; Hoving, E. W.; den Dunnen, W. F. A.

    2010-01-01

    Aims: Pilocytic astrocytomas are the most frequent brain tumours in children. Because of their high vascularity, this study aimed to obtain insights into potential angiogenic related therapeutic targets in these tumours by characterization of the vasculature and the angiogenic profile. In this study

  13. A New Presentation and Exploration of Human Cerebral Vasculature Correlated with Surface and Sectional Neuroanatomy

    Science.gov (United States)

    Nowinski, Wieslaw L.; Thirunavuukarasuu, Arumugam; Volkau, Ihar; Marchenko, Yevgen; Aminah, Bivi; Gelas, Arnaud; Huang, Su; Lee, Looi Chow; Liu, Jimin; Ng, Ting Ting; Nowinska, Natalia G.; Qian, Guoyu Yu; Puspitasari, Fiftarina; Runge, Val M.

    2009-01-01

    The increasing complexity of human body models enabled by advances in diagnostic imaging, computing, and growing knowledge calls for the development of a new generation of systems for intelligent exploration of these models. Here, we introduce a novel paradigm for the exploration of digital body models illustrating cerebral vasculature. It enables…

  14. The presence and absence of lymphatic vessels in the adult human intervertebral disc: relation to disc pathology

    International Nuclear Information System (INIS)

    Kliskey, Karolina; Williams, Kelly; Yu, J.; Urban, Jill; Athanasou, Nick; Jackson, David

    2009-01-01

    Although the normal adult human intervertebral disc is considered to be avascular, vascularised cellular fibrous tissue can be found in pathological conditions involving the disc such as disc herniation. Whether lymphatics vessels form a component of this reparative tissue is not known as the presence or absence of lymphatics in herniated and normal disc tissue is not known. We examined spinal tissues and discectomy specimens for the presence of lymphatics. The examination used immunohistochemistry to identify the specific lymphatic endothelial cell markers, podoplanin and LYVE1. Lymphatic vessels were not found in the nucleus pulposus or annulus fibrosus of intact, non-herniated lumbar and thoracic discs but were present in the surrounding ligaments. Ingrowth of fibrous tissue was seen in 73% of herniated disc specimens of which 36% contained LYVE1+/podoplanin + lymphatic vessels. Lymphatic vessels were not seen in the sacrum and coccyx or biopsies of four sacrococcygeal chordomas, but they were noted in surrounding extra-osseous fat and fibrous tissue at the edge of the infiltrating tumour. Our findings indicate that lymphatic vessels are not present in the normal adult intervertebral disc but that, when there is extrusion of disc material into surrounding soft tissue, there is ingrowth of reparative fibrous tissue containing lymphatic vessels. Our findings also indicate that chordoma, a tumour of notochordal origin, spreads to regional lymph nodes via lymphatics in para-spinal soft tissues. (orig.)

  15. Flow rates in the head and neck lymphatics after food stimulation in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Thommesen, P.; Buhl, J.; Jansen, K.; Funch-Jensen, P.

    1981-02-01

    In 22 healthy subjects lymph transport flow rates was studied in the head lymphatics after food stimulation, mastication (chewing) and taste. After food stimulation there was a significantly higher transport rate (0.67 meter/hour) than after taste (0.57 meter/hour) and mastication (0.55 meter/hour). The calculation of transport flow rate was independent of quantitative distribution of radioactivity in the head and neck lymphatics, and it could therefore perhaps be of clinical value.

  16. Lymphatic drainage of lung segments in the visceral pleura: a cadaveric study.

    Science.gov (United States)

    Fourdrain, Alex; Lafitte, Sophie; Iquille, Jules; De Dominicis, Florence; Havet, Eric; Peltier, Johann; Bagan, Patrick; Berna, Pascal

    2018-01-01

    Although peribronchial lymphatic drainage of the lung has been well characterized, lymphatic drainage in the visceral pleura is less well understood. The objective of the present study was to evaluate the lymphatic drainage of lung segments in the visceral pleura. Adult, European cadavers were examined. Cadavers with a history of pleural or pulmonary disease were excluded. The cadavers had been refrigerated but not embalmed. The lungs were surgically removed and re-warmed. Blue dye was injected into the subpleural area and into the first draining visceral pleural lymphatic vessel of each lung segment. Twenty-one cadavers (7 males and 14 females; mean age 80.9 years) were dissected an average of 9.8 day postmortem. A total of 380 dye injections (in 95 lobes) were performed. Lymphatic drainage of the visceral pleura followed a segmental pathway in 44.2% of the injections (n = 168) and an intersegmental pathway in 55.8% (n = 212). Drainage was found to be both intersegmental and interlobar in 2.6% of the injections (n = 10). Lymphatic drainage in the visceral pleura followed an intersegmental pathway in 22.8% (n = 13) of right upper lobe injections, 57.9% (n = 22) of right middle lobe injections, 83.3% (n = 75) of right lower lobe injections, 21% (n = 21) of left upper lobe injections, and 85.3% (n = 81) of left lower lobe injections. In the lung, lymphatic drainage in the visceral pleura appears to be more intersegmental than the peribronchial pathway is-especially in the lower lobes. The involvement of intersegmental lymphatic drainage in the visceral pleura should now be evaluated during pulmonary resections (and especially sub-lobar resections) for lung cancer.

  17. Lymphatic deletion of calcitonin receptor–like receptor exacerbates intestinal inflammation

    Science.gov (United States)

    Davis, Reema B.; Kechele, Daniel O.; Blakeney, Elizabeth S.; Pawlak, John B.

    2017-01-01

    Lymphatics play a critical role in maintaining gastrointestinal homeostasis and in the absorption of dietary lipids, yet their roles in intestinal inflammation remain elusive. Given the increasing prevalence of inflammatory bowel disease, we investigated whether lymphatic vessels contribute to, or may be causative of, disease progression. We generated a mouse model with temporal and spatial deletion of the key lymphangiogenic receptor for the adrenomedullin peptide, calcitonin receptor–like receptor (Calcrl), and found that the loss of lymphatic Calcrl was sufficient to induce intestinal lymphangiectasia, characterized by dilated lacteals and protein-losing enteropathy. Upon indomethacin challenge, Calcrlfl/fl/Prox1-CreERT2 mice demonstrated persistent inflammation and failure to recover and thrive. The epithelium and crypts of Calcrlfl/fl/Prox1-CreERT2 mice exhibited exacerbated hallmarks of disease progression, and the lacteals demonstrated an inability to absorb lipids. Furthermore, we identified Calcrl/adrenomedullin signaling as an essential upstream regulator of the Notch pathway, previously shown to be critical for intestinal lacteal maintenance and junctional integrity. In conclusion, lymphatic insufficiency and lymphangiectasia caused by loss of lymphatic Calcrl exacerbates intestinal recovery following mucosal injury and underscores the importance of lymphatic function in promoting recovery from intestinal inflammation. PMID:28352669

  18. Investigating the Lymphatic System by Dual-Color Elemental Mass Spectrometry Imaging

    Directory of Open Access Journals (Sweden)

    Ann-Christin Niehoff

    2017-01-01

    Full Text Available Secondary lymphedema accompanied with strong restrictions in quality of life is still major side effects in cancer therapy. Therefore, dedicated diagnostic tools and further investigation of the lymphatic system are crucial to improve lymphedema therapy. In this pilot study, a method for quantitative analysis of the lymphatic system in a rat model by laser ablation (LA with inductively coupled plasma mass spectrometry imaging (ICP-MSI is presented. As a possible lymph marker, thulium(III(1R,4R,7R,10R-α,α′,α′′,α′′′-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (Tm-DOTMA is introduced and compared to the clinically used magnetic resonance imaging contrast agent gadolinium(III2,2′,2′′-(10-((2R,3S-1,3,4-trihydroxybutan-2-yl-1,4,7,10-tetraazacyclododecane-1,4,7-triyltriacetate (Gd-DO3A-butrol. Gadobutrol functioned as standard contrast media in MRI lymphangiography to detect lymphatic flow qualitatively. Thus, Tm-DOTMA was investigated as lymphatic marker to detect lymphatic flow quantitatively. Both contrast agents were successfully used to visualize the lymphatic flow in successive lymph nodes in LA-ICP-MS due to lower limits of detection compared to MRI. Furthermore, the distribution of contrast agents by multicolored imaging showed accumulation in specific areas (sectors of the lymph nodes after application of contrast agents in different areas.

  19. Correlation between blood and lymphatic vessel density and results of contrast-enhanced spectral mammography.

    Science.gov (United States)

    Luczynska, Elzbieta; Niemiec, Joanna; Ambicka, Aleksandra; Adamczyk, Agnieszka; Walasek, Tomasz; Ryś, Janusz; Sas-Korczyńska, Beata

    2015-09-01

    Contrast-enhanced spectral mammography (CESM) is a novel technique used for detection of tumour vascularity by imaging the moment in which contrast, delivered to the lesion by blood vessels, leaks out of them, and flows out through lymphatic vessels. In our study, we included 174 women for whom spectral mammography was performed for diagnostic purposes. The relationship between enhancement in CESM and blood vessel density (BVD), lymphatic vessel density (LVD) or the percentage of fields with at least one lymphatic vessel (distribution of podoplanin-positive vessels - DPV) and other related parameters was assessed in 55 cases. BVD, LVD and DPV were assessed immunohistochemically, applying podoplanin and CD31/CD34 as markers of lymphatic and blood vessels, respectively. The sensitivity (in detection of malignant lesions) of CESM was 100%, while its specificity - 39%. We found a significant positive correlation between the intensity of enhancement in CESM and BVD (p = 0.007, r = 0.357) and a negative correlation between the intensity of enhancement in CESM and DPV (p = 0.003, r = -0.390). Lesions with the highest enhancement in CESM showed a high number of blood vessels and a low number of lymphatics. 1) CESM is a method characterized by high sensitivity and acceptable specificity; 2) the correlation between CESM results and blood/lymphatic vessel density confirms its utility in detection of tissue angiogenesis and/or lymphangiogenesis.

  20. Comparison of the Blood and Lymphatic Microvessel Density of Pleomorphic Adenoma and Basal Cell Adenoma

    Directory of Open Access Journals (Sweden)

    Andresa Borges Soares

    2015-01-01

    Full Text Available Background Pleomorphic adenoma (PA is the most common tumor of the salivary gland, while basal cell adenoma (BCA is an uncommon neoplasm. Blood and lymphatic vessels are crucial for tumor metabolism. The aim of this study was to compare the blood and lymphatic vascular density and vascular and endothelial growth factor (VEGF expression in PA and BCA tumors. In addition, cell proliferation was evaluated in these tumors. Methods Blood and lymphatic vessel content, VEGF expression, and cell proliferation were analyzed in 30 cases of PA and 13 cases of BCA by immu-nohistochemistry using antibodies for CD34, CD105, D2-40, VEGF, and Mcm -2. Results Regarding CD34 and CD105 expression, PA demonstrated a high vascularity and a low number of positive vessels, respectively. D2-40-positive lymphatic vessels were mainly located in the tumor capsules, with small intratumoral lymphatic vessels observed occasionally. VEGF expression revealed a remarkably heterogeneous immunoreactivity, alternating from weak or negative to positive or intense. BCA presented significantly higher CD34, CD34, CD105, D2-40, and VEGF expression compared to PA. No significant difference was found in cell proliferation between the tumors. Conclusion Although PA and BCA are considered part of the same spectrum of differentiation, this study showed that the blood and lymphatic vascularization of these tumors is different.

  1. Lymphangiogenesis and lymphatic remodeling induced by filarial parasites: implications for pathogenesis.

    Directory of Open Access Journals (Sweden)

    Sasisekhar Bennuru

    2009-12-01

    Full Text Available Even in the absence of an adaptive immune system in murine models, lymphatic dilatation and dysfunction occur in filarial infections, although severe irreversible lymphedema and elephantiasis appears to require an intact adaptive immune response in human infections. To address how filarial parasites and their antigens influence the lymphatics directly, human lymphatic endothelial cells were exposed to filarial antigens, live parasites, or infected patient serum. Live filarial parasites or filarial antigens induced both significant LEC proliferation and differentiation into tube-like structures in vitro. Moreover, serum from patently infected (microfilaria positive patients and those with longstanding chronic lymphatic obstruction induced significantly increased LEC proliferation compared to sera from uninfected individuals. Differentiation of LEC into tube-like networks was found to be associated with significantly increased levels of matrix metalloproteases and inhibition of their TIMP inhibitors (Tissue inhibitors of matrix metalloproteases. Comparison of global gene expression induced by live parasites in LEC to parasite-unexposed LEC demonstrated that filarial parasites altered the expression of those genes involved in cellular organization and development as well as those associated with junction adherence pathways that in turn decreased trans-endothelial transport as assessed by FITC-Dextran. The data suggest that filarial parasites directly induce lymphangiogenesis and lymphatic differentiation and provide insight into the mechanisms underlying the pathology seen in lymphatic filariasis.

  2. CAVAREV-an open platform for evaluating 3D and 4D cardiac vasculature reconstruction

    International Nuclear Information System (INIS)

    Rohkohl, Christopher; Hornegger, Joachim; Lauritsch, Guenter; Keil, Andreas

    2010-01-01

    The 3D reconstruction of cardiac vasculature, e.g. the coronary arteries, using C-arm CT (rotational angiography) is an active and challenging field of research. There are numerous publications on different reconstruction techniques. However, there is still a lack of comparability of achieved results for several reasons: foremost, datasets used in publications are not open to public and thus experiments are not reproducible by other researchers. Further, the results highly depend on the vasculature motion, i.e. cardiac and breathing motion patterns which are also not comparable across publications. We aim to close this gap by providing an open platform, called Cavarev (CArdiac VAsculature Reconstruction EValuation). It features two simulated dynamic projection datasets based on the 4D XCAT phantom with contrasted coronary arteries which was derived from patient data. In the first dataset, the vasculature undergoes a continuous periodic motion. The second dataset contains aperiodic heart motion by including additional breathing motion. The geometry calibration and acquisition protocol were obtained from a real-world C-arm system. For qualitative evaluation of the reconstruction results, the correlation of the morphology is used. Two segmentation-based quality measures are introduced which allow us to assess the 3D and 4D reconstruction quality. They are based on the spatial overlap of the vasculature reconstruction with the ground truth. The measures enable a comprehensive analysis and comparison of reconstruction results independent from the utilized reconstruction algorithm. An online platform (www.cavarev.com) is provided where the datasets can be downloaded, researchers can manage and publish algorithm results and download a reference C++ and Matlab implementation.

  3. Optical imaging of the chorioretinal vasculature in the living human eye.

    Science.gov (United States)

    Kim, Dae Yu; Fingler, Jeff; Zawadzki, Robert J; Park, Susanna S; Morse, Lawrence S; Schwartz, Daniel M; Fraser, Scott E; Werner, John S

    2013-08-27

    Detailed visualization of microvascular changes in the human retina is clinically limited by the capabilities of angiography imaging, a 2D fundus photograph that requires an intravenous injection of fluorescent dye. Whereas current angiography methods enable visualization of some retinal capillary detail, they do not adequately reveal the choriocapillaris or other microvascular features beneath the retina. We have developed a noninvasive microvascular imaging technique called phase-variance optical coherence tomography (pvOCT), which identifies vasculature three dimensionally through analysis of data acquired with OCT systems. The pvOCT imaging method is not only capable of generating capillary perfusion maps for the retina, but it can also use the 3D capabilities to segment the data in depth to isolate vasculature in different layers of the retina and choroid. This paper demonstrates some of the capabilities of pvOCT imaging of the anterior layers of choroidal vasculature of a healthy normal eye as well as of eyes with geographic atrophy (GA) secondary to age-related macular degeneration. The pvOCT data presented permit digital segmentation to produce 2D depth-resolved images of the retinal vasculature, the choriocapillaris, and the vessels in Sattler's and Haller's layers. Comparisons are presented between en face projections of pvOCT data within the superficial choroid and clinical angiography images for regions of GA. Abnormalities and vascular dropout observed within the choriocapillaris for pvOCT are compared with regional GA progression. The capability of pvOCT imaging of the microvasculature of the choriocapillaris and the anterior choroidal vasculature has the potential to become a unique tool to evaluate therapies and understand the underlying mechanisms of age-related macular degeneration progression.

  4. Pharmacologic Activation of Wnt Signaling by Lithium Normalizes Retinal Vasculature in a Murine Model of Familial Exudative Vitreoretinopathy.

    Science.gov (United States)

    Wang, Zhongxiao; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Favazza, Tara L; Morss, Peyton C; Saba, Nicholas J; Fredrick, Thomas W; He, Xi; Akula, James D; Chen, Jing

    2016-10-01

    Familial exudative vitreoretinopathy (FEVR) is characterized by delayed retinal vascular development, which promotes hypoxia-induced pathologic vessels. In severe cases FEVR may lead to retinal detachment and visual impairment. Genetic studies linked FEVR with mutations in Wnt signaling ligand or receptors, including low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we investigated ocular pathologies in a Lrp5 knockout (Lrp5(-/-)) mouse model of FEVR and explored whether treatment with a pharmacologic Wnt activator lithium could bypass the genetic defects, thereby protecting against eye pathologies. Lrp5(-/-) mice displayed significantly delayed retinal vascular development, absence of deep layer retinal vessels, leading to increased levels of vascular endothelial growth factor and subsequent pathologic glomeruloid vessels, as well as decreased inner retinal visual function. Lithium treatment in Lrp5(-/-) mice significantly restored the delayed development of retinal vasculature and the intralaminar capillary networks, suppressed formation of pathologic glomeruloid structures, and promoted hyaloid vessel regression. Moreover, lithium treatment partially rescued inner-retinal visual function and increased retinal thickness. These protective effects of lithium were largely mediated through restoration of canonical Wnt signaling in Lrp5(-/-) retina. Lithium treatment also substantially increased vascular tubular formation in LRP5-deficient endothelial cells. These findings suggest that pharmacologic activation of Wnt signaling may help treat ocular pathologies in FEVR and potentially other defective Wnt signaling-related diseases. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  5. Biology of Bone: The Vasculature of the Skeletal System.

    Science.gov (United States)

    Watson, Emma C; Adams, Ralf H

    2017-09-11

    Blood vessels are essential for the distribution of oxygen, nutrients, and immune cells, as well as the removal of waste products. In addition to this conventional role as a versatile conduit system, the endothelial cells forming the innermost layer of the vessel wall also possess important signaling capabilities and can control growth, patterning, homeostasis, and regeneration of the surrounding organ. In the skeletal system, blood vessels regulate developmental and regenerative bone formation as well as hematopoiesis by providing vascular niches for hematopoietic stem cells. Here we provide an overview of blood vessel architecture, growth and properties in the healthy, aging, and diseased skeletal system. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  6. Temperature-dependent modulation of regional lymphatic contraction frequency and flow.

    Science.gov (United States)

    Solari, Eleonora; Marcozzi, Cristiana; Negrini, Daniela; Moriondo, Andrea

    2017-11-01

    Lymph drainage and propulsion are sustained by an extrinsic mechanism, based on mechanical forces acting from the surrounding tissues against the wall of lymphatic vessels, and by an intrinsic mechanism attributable to active spontaneous contractions of the lymphatic vessel muscle. Despite being heterogeneous, the mechanisms underlying the generation of spontaneous contractions share a common biochemical nature and are thus modulated by temperature. In this study, we challenged excised tissues from rat diaphragm and hindpaw, endowed with spontaneously contracting lymphatic vessels, to temperatures from 24°C (hindpaw) or 33°C (diaphragmatic vessels) to 40°C while measuring lymphatic contraction frequency ( f c ) and amplitude. Both vessel populations displayed a sigmoidal relationship between f c and temperature, each centered around the average temperature of surrounding tissue (36.7 diaphragmatic and 32.1 hindpaw lymphatics). Although the slope factor of the sigmoidal fit to the f c change of hindpaw vessels was 2.3°C·cycles -1 ·min -1 , a value within the normal range displayed by simple biochemical reactions, the slope factor of the diaphragmatic lymphatics was 0.62°C·cycles -1 ·min -1 , suggesting the added involvement of temperature-sensing mechanisms. Lymph flow calculated as a function of temperature confirmed the relationship observed on f c data alone and showed that none of the two lymphatic vessel populations would be able to adapt to the optimal working temperature of the other tissue district. This poses a novel question whether lymphatic vessels might not adapt their function to accommodate the change if exposed to a surrounding temperature, which is different from their normal condition. NEW & NOTEWORTHY This study demonstrates to what extent lymphatic vessel intrinsic contractility and lymph flow are modulated by temperature and that this modulation is dependent on the body district that the vessels belong to, suggesting a possible

  7. Mortality from lymphatic and haematopoietic cancer in Scottish coastal towns

    International Nuclear Information System (INIS)

    Lloyd, O.Ll.; Macdonald, J.; Lloyd, M.M.

    1984-01-01

    Using annual Scottish registration data, the authors have been examining mortality from cancers including all leukaemias, classified within malignant neoplasm of lymphatic and haematopoietic tissue, from 1969/73. The results showed: (1) Coastal burghs had a higher standardised mortality than did inland burghs; (2) the SMRs in communities of the east coast as a whole were consistently higher than those in west-coast communities, whether small burghs, large burghs, or cities were considered; (3) all segments of the eastern coastline, other than the open coastline stretching from Aberdeenshire to Angus, showed relatively high SMRs; (4) on the west coast, the highest SMRs (of only 100) were in Ayrshire and Glasgow; (5) in terms of statistical significance at the level p<=0.5, mortality in inland burghs was significantly low, while in east-coast burghs, in Edinburgh, and in Aberdeen it was significantly high. The geographical distribution cannot be explained in terms of nuclear power stations, and differs importantly from that given by registration data for leukaemia alone (Heasman et al, May 26, p.1188). (U.K.)

  8. Nanoradioliposomes molecularly modulated to study the lung deep lymphatic drainage

    Directory of Open Access Journals (Sweden)

    Maria Filomena Rabaça Roque Botelho

    2009-03-01

    Full Text Available Lung deep lymphatic drainage (LDLD plays an important role in the removal of foreign materials from lungs being alveolar macrophages the first line of phagocytic defence with high affinity for pathogenic microorganisms. Bacillus subtilis is a well-known genome- decoded saprophyte of the human respiratory tract used in research and in the biotechnology industry.Lung deep lymphatic chains (LDLC constitute one of the first sites of lung tumours’ dissemination. In this work we intended to develop and validate a non-invasive method for assessing LDLC by nanoradioliposomes aerosolised modulated on the Bacillus subtilis spore wall. The final goal was to produce a nanoradioliposome formulation that can mimics the dynamics of preferential removal of spores by LDLD and present the ideal properties as a tracer for molecular imaging studies.Seven different liposomal formulations were tested, and the formulation-F demonstrated physicochemical and radiopharmaceutical properties that make it an ideal candidate as an in vivo probe for molecular imaging studies of the LDLC.Nanoradioliposomes of the formulation-F after labelling with 99mTc-HMPAO were administered as aerosols to 20 Sus scrofa. Hilar and interpulmonary communications were visualized in first 5 minutes post-inhalation, infradiaphragmatic chains between 10 and 20 minutes, the ganglia of the aortic chain at 20 minutes and those of the renal hilar region at 30 minutes. Conclusion: the proposed method enables visualization of deep lymphatic lung network and lymph nodes. Besides, this technique involving the modulation of nanoradioliposomes targeting specific organs or tissues may be an important tool for diagnostic or even for therapeutic purposes. Resumo: A drenagem linfática pulmonar profunda (DLPP desempenha um papel importante na remoção de materiais estranhos, constituindo os macrófagos alveolares a primeira linha de defesa fagocitária, dada a grande afinidade para

  9. [Cytostructure of the mantle zone in lymphatic tissue].

    Science.gov (United States)

    Bednár, B

    1993-04-01

    Four cellular layers of the follicular mantle zone in palatine tonsil lymphatic tissue were studied by electron microscopy after simultaneous immunophenotypical investigation. The first layer of the mantle zone consisting of small blastic cells was analogous to the small (centrocytoid) blastic layer of germinal centres. The second B monocytoid layer was lacking analogy in basic series of lymphocytes and seemed to be an independent morphological and probably functional unit. Plasmacytoid and clarocellular elements in outer layers of follicular mantle zone were in a way similar to T plasmacytoid and clarocellular components of Sézary syndrome infiltrates but considering transitional forms they had a local origin from incompletely transformed elements of B monocytoid layer. Inner follicular mantle zone was discussed as a source of incompletely transformed B lymphocytes for further mantle layers where their immunophenotypical modulation is taking place according to actual need. Outer mantle layers are aggressive against damaged epithelial and litoral structures and may be instrumental in a common reaction of B and T components.

  10. Malignant T cells express lymphotoxin alpha and drive endothelial activation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Lauenborg, Britt; Christensen, Louise; Ralfkiaer, Ulrik

    2015-01-01

    Lymphotoxin α (LTα) plays a key role in the formation of lymphatic vasculature and secondary lymphoid structures. Cutaneous T cell lymphoma (CTCL) is the most common primary lymphoma of the skin and in advanced stages, malignant T cells spreads through the lymphatic to regional lymph nodes...

  11. Dynamics of pleural fluid effusion and chylothorax in the fetus and newborn: role of the lymphatic system.

    Science.gov (United States)

    Bellini, C; Ergaz, Z; Boccardo, F; Bellini, T; Campisi, C C; Bonioli, E; Ramenghi, L A

    2013-06-01

    Pleural fluid effusion particularly chylothorax is a relatively rare occurrence in the newborn, but when it occurs it is often life-threatening. In this article, we describe and illustrate the morphologic features of the visceral and parietal pleura including pleural lymphatics and the physiology and pathophysiology of pleural fluid balance. The role and function of the lymphatic system in controlling the volume and composition of pleural liquid are detailed and a conceptual scheme presented. Finally, the crucial role of inadequate lymphatic drainage (either functional overload from an imbalance in Starling forces or mechanical insufficiency from lymphatic dysplasia) is emphasized.

  12. Immunohistochemical Examination on the Distribution of Cells Expressed Lymphatic Endothelial Marker Podoplanin and LYVE-1 in the Mouse Tongue Tissue

    Science.gov (United States)

    Noda, Yuya; Amano, Ikuko; Hata, Minoru; Kojima, Hiroshi; Sawa, Yoshihiko

    2010-01-01

    The clinical study for lingual disease requires the detailed investigation of the lingual lymphatic network and lymphatic marker-positive cells. Recently, it has been reported that several tissue cells and leukocytes express lymphatic markers, LYVE-1 and podoplanin. This study was aimed to clarify the lingual distribution of cells expressing LYVE-1 and podoplanin. In the mouse tongue, podoplanin is expressed in nerve sheaths, lingual gland myoepithelial cells, and lymphatic vessels. LYVE-1 is expressed in the macrophage marker Mac-1-positive cells as well as lymphatic vessels, while factor-VIII was detected in only blood endothelial cells. α-SMA was detected in vascular smooth muscle and myoepithelial cells. Therefore, identification of lymphatic vessels in lingual glands, the combination of LYVE-1 and factor-VIII, or LYVE-1 and Mac-1 is useful because myoepithelial cells express podoplanin and α-SMA. The immunostaining of factor-VIII on lymphatic vessels was masked by the immunostaining to LYVE-1 or podoplanin because lymphatic vessels express factor-VIII to a far lesser extent than blood vessels. Therefore, except for the salivary glands, the combination of podoplanin and α-SMA, or factor-VIII is useful to identify lymphatic vessels and blood vessels with smooth muscle, or blood capillaries. PMID:20514293

  13. Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads

    International Nuclear Information System (INIS)

    Ruddell, Alanna; Croft, Alexandra; Kelly-Spratt, Karen; Furuya, Momoko; Kemp, Christopher J

    2014-01-01

    Tumors drive blood vessel growth to obtain oxygen and nutrients to support tumor expansion, and they also can induce lymphatic vessel growth to facilitate fluid drainage and metastasis. These processes have generally been studied separately, so that it is not known how peritumoral blood and lymphatic vessels grow relative to each other. The murine B16-F10 melanoma and chemically-induced squamous cell carcinoma models were employed to analyze large red-colored vessels growing between flank tumors and draining lymph nodes. Immunostaining and microscopy in combination with dye injection studies were used to characterize these vessels. Each peritumoral red-colored vessel was found to consist of a triad of collecting lymphatic vessel, vein, and artery, that were all enlarged. Peritumoral veins and arteries were both functional, as detected by intravenous dye injection. The enlarged lymphatic vessels were functional in most mice by subcutaneous dye injection assay, however tumor growth sometimes blocked lymph drainage to regional lymph nodes. Large red-colored vessels also grew between benign papillomas or invasive squamous cell carcinomas and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of the red-colored vessels again identified the clustered growth of enlarged collecting lymphatics, veins, and arteries in the vicinity of these spontaneously arising tumors. Implanted and spontaneously arising tumors induce coordinate growth of blood and lymphatic vessel triads. Many of these vessel triads are enlarged over several cm distance between the tumor and regional lymph nodes. Lymphatic drainage was sometimes blocked in mice before lymph node metastasis was detected, suggesting that an unknown mechanism alters lymph drainage patterns before tumors reach draining lymph nodes

  14. Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads.

    Science.gov (United States)

    Ruddell, Alanna; Croft, Alexandra; Kelly-Spratt, Karen; Furuya, Momoko; Kemp, Christopher J

    2014-05-21

    Tumors drive blood vessel growth to obtain oxygen and nutrients to support tumor expansion, and they also can induce lymphatic vessel growth to facilitate fluid drainage and metastasis. These processes have generally been studied separately, so that it is not known how peritumoral blood and lymphatic vessels grow relative to each other. The murine B16-F10 melanoma and chemically-induced squamous cell carcinoma models were employed to analyze large red-colored vessels growing between flank tumors and draining lymph nodes. Immunostaining and microscopy in combination with dye injection studies were used to characterize these vessels. Each peritumoral red-colored vessel was found to consist of a triad of collecting lymphatic vessel, vein, and artery, that were all enlarged. Peritumoral veins and arteries were both functional, as detected by intravenous dye injection. The enlarged lymphatic vessels were functional in most mice by subcutaneous dye injection assay, however tumor growth sometimes blocked lymph drainage to regional lymph nodes. Large red-colored vessels also grew between benign papillomas or invasive squamous cell carcinomas and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of the red-colored vessels again identified the clustered growth of enlarged collecting lymphatics, veins, and arteries in the vicinity of these spontaneously arising tumors. Implanted and spontaneously arising tumors induce coordinate growth of blood and lymphatic vessel triads. Many of these vessel triads are enlarged over several cm distance between the tumor and regional lymph nodes. Lymphatic drainage was sometimes blocked in mice before lymph node metastasis was detected, suggesting that an unknown mechanism alters lymph drainage patterns before tumors reach draining lymph nodes.

  15. Human Lymphatic Mesenteric Vessels: Morphology and Possible Function of Aminergic and NPY-ergic Nerve Fibers.

    Science.gov (United States)

    D'Andrea, Vito; Panarese, Alessandra; Taurone, Samanta; Coppola, Luigi; Cavallotti, Carlo; Artico, Marco

    2015-09-01

    The lymphatic vessels have been studied in different organs from a morphological to a clinical point of view. Nevertheless, the knowledge of the catecholaminergic control of the lymphatic circulation is still incomplete. The aim of this work is to study the presence and distribution of the catecholaminergic and NPY-ergic nerve fibers in the whole wall of the human mesenteric lymphatic vessels in order to obtain knowledge about their morphology and functional significance. The following experimental procedures were performed: 1) drawing of tissue containing lymphatic vessels; 2) cutting of tissue; 3) staining of tissue; 4) staining of nerve fibers; 5) histofluorescence microscopy for the staining of catecholaminergic nerve fibers; 6) staining of neuropeptide Y like-immune reactivity; 7) biochemical assay of proteins; 8) measurement of noradrenaline; 9) quantitative analysis of images; 10) statistical analysis of data. Numerous nerve fibers run in the wall of lymphatic vessels. Many of them are catecholaminergic in nature. Some nerve fibers are NPY-positive. The biochemical results on noradrenaline amounts are in agreement with morphological results on catecholaminergic nerve fibers. Moreover, the morphometric results, obtained by the quantitative analysis of images and the subsequent statistical analysis of data, confirm all our morphological and biochemical data. The knowledge of the physiological or pathological mechanism regulating the functions of the lymphatic system is incomplete. Nevertheless the catecholaminergic nerve fibers of the human mesenteric lymphatic vessels come from the adrenergic periarterial plexuses of the mesenterial arterial bed. NPY-ergic nerve fibers may modulate the microcirculatory mesenterial bed in different pathological conditions.

  16. In vivo microCT imaging of rodent cerebral vasculature

    International Nuclear Information System (INIS)

    Seo, Youngho; Hasegawa, Bruce H; Hashimoto, Tomoki; Nuki, Yoshitsugu

    2008-01-01

    Computed tomography (CT) remains a critical diagnostic tool for evaluating patients with cerebrovascular disease, and the advent of specialized systems for imaging rodents has extended these techniques to small animal models of these diseases. We therefore have evaluated in vivo methods of imaging rat models of hemorrhagic stroke using a high resolution compact computed tomography ('microCT') system (FLEX(tm) X-O(tm), Gamma Medica-Ideas, Northridge, CA). For all in vivo studies, the head of the anesthetized rat was secured in a custom immobilization device for microCT imaging with 512 projections over 2 min at 60 kVp and 0.530 mA (I tube x t/rotation = 63.6 mAs). First, imaging without iodinated contrast was performed (a) to differentiate the effect of contrast agent in contrast-enhanced CT and (b) to examine the effectiveness of the immobilization device between two time points of CT acquisitions. Then, contrast-enhanced CT was performed with continuous administration of iopromide (300 mgI ml -1 at 1.2 ml min -1 ) to visualize aneurysms and other vascular formations in the carotid and cerebral arteries that may precede subarachnoid hemorrhage. The accuracy of registration between the noncontrast and contrast-enhanced CT images with the immobilization device was compared against the images aligned with normalized mutual information using FMRIB's linear image registration tool (FLIRT). Translations and rotations were examined between the FLIRT-aligned noncontrast CT image and the nonaligned noncontrast CT image. These two data sets demonstrated translational and rotational differences of less than 0.5 voxel (∼85 μm) and 0.5 deg., respectively. Noncontrast CT demonstrated a very small volume (0.1 ml) of femoral arterial blood introduced surgically into the rodent brain. Continuous administration of iopromide during the CT acquisition produced consistent vascular contrast in the reconstructed CT images. As a result, carotid arteries and major cerebral blood vessels

  17. In vivo microCT imaging of rodent cerebral vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Youngho; Hasegawa, Bruce H [Center for Molecular and Functional Imaging, Department of Radiology, University of California, San Francisco, CA 94143 (United States); Hashimoto, Tomoki; Nuki, Yoshitsugu [Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143 (United States)], E-mail: youngho.seo@radiology.ucsf.edu

    2008-04-07

    Computed tomography (CT) remains a critical diagnostic tool for evaluating patients with cerebrovascular disease, and the advent of specialized systems for imaging rodents has extended these techniques to small animal models of these diseases. We therefore have evaluated in vivo methods of imaging rat models of hemorrhagic stroke using a high resolution compact computed tomography ('microCT') system (FLEX(tm) X-O(tm), Gamma Medica-Ideas, Northridge, CA). For all in vivo studies, the head of the anesthetized rat was secured in a custom immobilization device for microCT imaging with 512 projections over 2 min at 60 kVp and 0.530 mA (I{sub tube} x t/rotation = 63.6 mAs). First, imaging without iodinated contrast was performed (a) to differentiate the effect of contrast agent in contrast-enhanced CT and (b) to examine the effectiveness of the immobilization device between two time points of CT acquisitions. Then, contrast-enhanced CT was performed with continuous administration of iopromide (300 mgI ml{sup -1} at 1.2 ml min{sup -1}) to visualize aneurysms and other vascular formations in the carotid and cerebral arteries that may precede subarachnoid hemorrhage. The accuracy of registration between the noncontrast and contrast-enhanced CT images with the immobilization device was compared against the images aligned with normalized mutual information using FMRIB's linear image registration tool (FLIRT). Translations and rotations were examined between the FLIRT-aligned noncontrast CT image and the nonaligned noncontrast CT image. These two data sets demonstrated translational and rotational differences of less than 0.5 voxel ({approx}85 {mu}m) and 0.5 deg., respectively. Noncontrast CT demonstrated a very small volume (0.1 ml) of femoral arterial blood introduced surgically into the rodent brain. Continuous administration of iopromide during the CT acquisition produced consistent vascular contrast in the reconstructed CT images. As a result, carotid

  18. Partial corrosion casting to assess cochlear vasculature in mouse models of presbycusis and CMV infection.

    Science.gov (United States)

    Carraro, Mattia; Park, Albert H; Harrison, Robert V

    2016-02-01

    Some forms of sensorineural hearing loss involve damage or degenerative changes to the stria vascularis and/or other vascular structures in the cochlea. In animal models, many methods for anatomical assessment of cochlear vasculature exist, each with advantages and limitations. One methodology, corrosion casting, has proved useful in some species, however in the mouse model this technique is difficult to achieve because digestion of non vascular tissue results in collapse of the delicate cast specimen. We have developed a partial corrosion cast method that allows visualization of vasculature along much of the cochlear length but maintains some structural integrity of the specimen. We provide a detailed step-by-step description of this novel technique. We give some illustrative examples of the use of the method in mouse models of presbycusis and cytomegalovirus (CMV) infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. The shell vasculature of Trachemys turtles investigated by modern 3D imaging techniques

    DEFF Research Database (Denmark)

    Hansen, Kasper; Thygesen, Jesper; Nielsen, Tobias Wang

    Many freshwater turtles are extremely tolerant to the lack of oxygen and can survive the winter submerged in anoxic mud in ice-covered lakes. The pronounced anoxia-tolerance resides with a considerable depression of cellular metabolism and the ability to use the shell to buffer the acidosis arising...... from anaerobic metabolism (1). Infusion of microspheres has shown that the shell receives almost half of the cardiac output in turtles made anoxic at low temperatures (2). However, the vasculature of the turtle shell remains to be described. To visualise the vasculature within the carapace and plastron...... of the turtle Trachemys scripta, we perfused terminally anaesthetised turtles with different contrast enhancing agents (Microfil [lead n/a]), barium sulphate [250 mg/kg], and iodine [15-250 mg/kg]), and the animals were then scanned by both single source as well as dual energy Computed Tomographic systems...

  20. The combined effect of diabetes and ionising radiation on the retinal vasculature of the rat

    International Nuclear Information System (INIS)

    Gardiner, T.A.; Amoaku, W.M.K.; Archer, D.B.

    1993-01-01

    The clinical impression that pre-existing diabetes exacerbates radiation injury to the retinal vasculature was studied in STZ diabetic rats. Half of 2 groups of streptozotocin (STZ)-induced diabetic rats and 1 group of normal animals had their right eyes irradiated with 1000 cGy of 90 KVP x-rays. The prevalence of acellular capillaries in trypsin digests of the retinal vasculature was quantified for each of the 6 groups of animals at 6.5 months post-irradiation. The prevalence of acellular capillaries in both non-irradiated diabetic groups was significantly higher than in controls while the irradiated animals in each of the three main categories showed a statistically significant increase compared to their non-irradiated equivalents. (author)

  1. Magnetic resonance angiography of fetal vasculature at 3.0 T.

    Science.gov (United States)

    Neelavalli, Jaladhar; Krishnamurthy, Uday; Jella, Pavan K; Mody, Swati S; Yadav, Brijesh K; Hendershot, Kelly; Hernandez-Andrade, Edgar; Yeo, Lami; Cabrera, Maria D; Haacke, Ewart M; Hassan, Sonia S; Romero, Roberto

    2016-12-01

    Magnetic resonance angiography has not been used much previously for visualizing fetal vessels in utero for reasons that include a contraindication for the use of exogenous contrast agents, maternal respiratory motion and fetal motion. In this work, we report the feasibility of using an appropriately modified clinical time-of-flight magnetic resonance imaging sequence for non-contrast angiography of human fetal and placental vessels at 3.0 T. Using this 2D angiography technique, it is possible to visualize fetal vascular networks in late pregnancy. • 3D-visualization of fetal vasculature is feasible using non-contrast MRA at 3.0 T. • Visualization of placental vasculature is also possible with this method. • Fetal MRA can serve as a vascular localizer for quantitative MRI studies. • This method can be extended to 1.5 T.

  2. Probenecid inhibits α-adrenergic receptor-mediated vasoconstriction in the human leg vasculature

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Piil, Peter Bergmann; Kiehn, Oliver Thistrup

    2018-01-01

    to α1- and α2-adrenergic receptor stimulation in the human forearm and leg vasculature of young healthy male subjects (23±3 years). By use of immunolabeling and confocal microscopy, Panx1 channels were found to be expressed in vascular smooth muscle cells of arterioles in human leg skeletal muscle....... Probenecid treatment increased (Padrenergic receptor stimulation) by ≈15%, whereas the response to the α1-agonist phenylephrine was unchanged. Inhibition...

  3. Role of the Norrie disease pseudoglioma gene in sprouting angiogenesis during development of the retinal vasculature.

    Science.gov (United States)

    Luhmann, Ulrich F O; Lin, Jihong; Acar, Niyazi; Lammel, Stefanie; Feil, Silke; Grimm, Christian; Seeliger, Mathias W; Hammes, Hans-Peter; Berger, Wolfgang

    2005-09-01

    To characterize developmental defects and the time course of Norrie disease in retinal and hyaloid vasculature during retinal development and to identify underlying molecular angiogenic pathways that may be affected in Norrie disease, exudative vitreoretinopathy, retinopathy of prematurity, and Coats' disease. Norrie disease pseudoglioma homologue (Ndph)-knockout mice were studied during retinal development at early postnatal (p) stages (p5, p10, p15, and p21). Histologic techniques, quantitative RT-PCR, ELISA, and Western blot analyses provided molecular data, and scanning laser ophthalmoscopy (SLO) angiography and electroretinography (ERG) were used to obtain in vivo data. The data showed that regression of the hyaloid vasculature of Ndph-knockout mice occurred but was drastically delayed. The development of the superficial retinal vasculature was strongly delayed, whereas the deep retinal vasculature did not form because of the blockage of vessel outgrowth into the deep retinal layers. Subsequently, microaneurysm-like lesions formed. Several angiogenic factors were differentially transcribed during retinal development. Increased levels of hypoxia inducible factor-1alpha (HIF1alpha) and VEGFA, as well as a characteristic ERG pattern, confirmed hypoxic conditions in the inner retina of the Ndph-knockout mouse. These data provide evidence for a crucial role of Norrin in hyaloid vessel regression and in sprouting angiogenesis during retinal vascular development, especially in the development of the deep retinal capillary networks. They also suggest an early and a late phase of Norrie disease and may provide an explanation for similar phenotypic features of allelic retinal diseases in mice and patients as secondary consequences of pathologic hypoxia.

  4. Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake

    Directory of Open Access Journals (Sweden)

    Fang Li

    2017-05-01

    Full Text Available Huperzine A (Hup-A is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration–time curve (AUC of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (P<0.01. The absorption rate constant (Ka and the apparent permeability coefficient (Papp for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values of Ka and Papp of Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration (Cmax of the blocking model were significantly lower than those of the control model (P<0.05. The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%, respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.

  5. PEGylation of polylysine dendrimers improves absorption and lymphatic targeting following SC administration in rats.

    Science.gov (United States)

    Kaminskas, Lisa M; Kota, Jagannath; McLeod, Victoria M; Kelly, Brian D; Karellas, Peter; Porter, Christopher Jh

    2009-12-03

    Polylysine dendrimers have potential as highly flexible, biodegradable nanoparticular carriers that may also promote lymphatic transport. The current study was undertaken to determine the impact of PEGylation on the absorption and lymphatic transport of polylysine dendrimers modified by surface derivatisation with PEG (200, 570 or 2000Da) or 4-benzene sulphonate following SC or IV dosing. PEGylation led to the PEG(200) derived dendrimer being rapidly and completely absorbed into the blood after SC administration, however only 3% of the administered dose was recovered in pooled thoracic lymph over 30h. Increasing the PEG chain length led to a systematic decrease in absorption into the blood and an enhancement of the proportion recovered in the lymphatics (up to 29% over 30h). For the PEG(570) and PEG(2000) derived dendrimers, indirect access to the lymph via equilibration across the capillary beds also appeared to play a role in lymphatic targeting after both IV and SC dosing. In contrast, the anionic benzene sulphonate-capped dendrimer was not well absorbed from the SC injection site (26% bioavailability) into either the blood or the lymph. The data suggest that PEGylated poly-L-lysine dendrimers are well absorbed from SC injection sites and that the extent of lymphatic transport may be enhanced by increasing the size of the PEGylated dendrimer complex.

  6. Prediction of melanoma metastasis by the Shields index based on lymphatic vessel density

    Directory of Open Access Journals (Sweden)

    Metcalfe Chris

    2010-05-01

    Full Text Available Abstract Background Melanoma usually presents as an initial skin lesion without evidence of metastasis. A significant proportion of patients develop subsequent local, regional or distant metastasis, sometimes many years after the initial lesion was removed. The current most effective staging method to identify early regional metastasis is sentinel lymph node biopsy (SLNB, which is invasive, not without morbidity and, while improving staging, may not improve overall survival. Lymphatic density, Breslow's thickness and the presence or absence of lymphatic invasion combined has been proposed to be a prognostic index of metastasis, by Shields et al in a patient group. Methods Here we undertook a retrospective analysis of 102 malignant melanomas from patients with more than five years follow-up to evaluate the Shields' index and compare with existing indicators. Results The Shields' index accurately predicted outcome in 90% of patients with metastases and 84% without metastases. For these, the Shields index was more predictive than thickness or lymphatic density. Alternate lymphatic measurement (hot spot analysis was also effective when combined into the Shields index in a cohort of 24 patients. Conclusions These results show the Shields index, a non-invasive analysis based on immunohistochemistry of lymphatics surrounding primary lesions that can accurately predict outcome, is a simple, useful prognostic tool in malignant melanoma.

  7. Lymphatic filariasis among the Yakurr people of Cross River State, Nigeria

    Directory of Open Access Journals (Sweden)

    Iboh Cletus I

    2012-09-01

    Full Text Available Abstract Background In order to initiate a disease elimination programme for lymphatic filariasis based on mass drug administration, a proper understanding of the geographical distribution and degree of risk is essential. Methods An investigation of lymphatic filariasis due to Wuchereria bancrofti was carried out among 785 people in four communities of Yakurr Local Government Area of Cross River State, Nigeria between March and August, 2009. Finger prick blood smear samples collected from the subjects were examined for W. bancrofti using standard parasitological protocol. The subjects were also screened for clinical manifestations of lymphatic filariasis. Results Of the 785 persons examined, 48 (6.1% were positive for microfilariae in their thick blood smear. There was a significant difference in the prevalence of lymphatic filariasis among the various age groups (P  0.05. The overall mean microfilarial density of the infected individuals was 5.6mf/50 μl. There was a significant variation (P  Conclusions The National Lymphatic Filariasis Elimination Programme should intervene by expanding the distribution of albendazole and ivermectin to all endemic areas including Yakurr Local Government Area of Cross River State, Nigeria.

  8. Rice Ovate Family Protein 2 (OFP2) alters hormonal homeostasis and vasculature development.

    Science.gov (United States)

    Schmitz, Aaron J; Begcy, Kevin; Sarath, Gautam; Walia, Harkamal

    2015-12-01

    OFP (Ovate Family Protein) is a transcription factor family found only in plants. In dicots, OFPs control fruit shape and secondary cell wall biosynthesis. OFPs are also thought to function through interactions with KNOX and BELL transcription factors. Here, we have functionally characterized OsOFP2, a member of the OFP subgroup associated with regulating fruit shape. OsOFP2 was found to localize to the nucleus and to the cytosol. A putative nuclear export signal was identified within the OVATE domain and was required for the localization of OsOFP2 to distinct cytosolic spots. Rice plants overexpressing OsOFP2 were reduced in height and exhibited altered leaf morphology, seed shape, and positioning of vascular bundles in stems. Transcriptome analysis indicated disruptions of genes associated with vasculature development, lignin biosynthesis, and hormone homeostasis. Reduced expression of the gibberellin biosynthesis gene GA 20-oxidase 7 coincided with lower gibberellin content in OsOFP2 overexpression lines. Also, we found that OsOFP2 was expressed in plant vasculature and determined that putative vascular development KNOX and BELL proteins interact with OsOFP2. KNOX and BELL genes are known to suppress gibberellin biosynthesis through GA20ox gene regulation and can restrict lignin biosynthesis. We propose that OsOFP2 could modulate KNOX-BELL function to control diverse aspects of development including vasculature development. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. In vivo preclinical photoacoustic imaging of tumor vasculature development and therapy

    Science.gov (United States)

    Laufer, Jan; Johnson, Peter; Zhang, Edward; Treeby, Bradley; Cox, Ben; Pedley, Barbara; Beard, Paul

    2012-05-01

    The use of a novel all-optical photoacoustic scanner for imaging the development of tumor vasculature and its response to a therapeutic vascular disrupting agent is described. The scanner employs a Fabry-Perot polymer film ultrasound sensor for mapping the photoacoustic waves and an image reconstruction algorithm based upon attenuation-compensated acoustic time reversal. The system was used to noninvasively image human colorectal tumor xenografts implanted subcutaneously in mice. Label-free three-dimensional in vivo images of whole tumors to depths of almost 10 mm with sub-100-micron spatial resolution were acquired in a longitudinal manner. This enabled the development of tumor-related vascular features, such as vessel tortuosity, feeding vessel recruitment, and necrosis to be visualized over time. The system was also used to study the temporal evolution of the response of the tumor vasculature following the administration of a therapeutic vascular disrupting agent (OXi4503). This revealed the well-known destruction and recovery phases associated with this agent. These studies illustrate the broader potential of this technology as an imaging tool for the preclinical and clinical study of tumors and other pathologies characterized by changes in the vasculature.

  10. Assessment of variability in cerebral vasculature for neuro-anatomical surgery planning in rodent brain

    Science.gov (United States)

    Rangarajan, J. R.; Van Kuyck, K.; Himmelreich, U.; Nuttin, B.; Maes, F.; Suetens, P.

    2011-03-01

    Clinical and pre-clinical studies show that deep brain stimulation (DBS) of targeted brain regions by neurosurgical techniques ameliorate psychiatric disorder such as anorexia nervosa. Neurosurgical interventions in preclinical rodent brain are mostly accomplished manually with a 2D atlas. Considering both the large number of animals subjected to stereotactic surgical experiments and the associated imaging cost, feasibility of sophisticated pre-operative imaging based surgical path planning and/or robotic guidance is limited. Here, we spatially normalize vasculature information and assess the intra-strain variability in cerebral vasculature for a neurosurgery planning. By co-registering and subsequently building a probabilistic vasculature template in a standard space, we evaluate the risk of a user defined electrode trajectory damaging a blood vessel on its path. The use of such a method may not only be confined to DBS therapy in small animals, but also could be readily applicable to a wide range of stereotactic small animal surgeries like targeted injection of contrast agents and cell labeling applications.

  11. A systematic review of factors that shape implementation of mass drug administration for lymphatic filariasis in sub-Saharan Africa.

    Science.gov (United States)

    Silumbwe, Adam; Zulu, Joseph Mumba; Halwindi, Hikabasa; Jacobs, Choolwe; Zgambo, Jessy; Dambe, Rosalia; Chola, Mumbi; Chongwe, Gershom; Michelo, Charles

    2017-05-22

    Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF) elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA) region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs) through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Mass drug administration for lymphatic filariasis elimination programmes should design their implementation strategies differently based on specific contextual factors to

  12. A systematic review of factors that shape implementation of mass drug administration for lymphatic filariasis in sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Adam Silumbwe

    2017-05-01

    Full Text Available Abstract Background Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. Methods A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. Results The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Conclusion Mass drug administration for lymphatic filariasis elimination programmes should design their implementation

  13. Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

    DEFF Research Database (Denmark)

    Louveau, Antoine; Plog, Benjamin A.; Antila, Salli

    2017-01-01

    Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss...... the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges...... and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems....

  14. Classification of the lymphatic drainage status of a primary tumor: a proposal

    International Nuclear Information System (INIS)

    Munz, D.L.; Maza, S.; Ivancevic, V.; Geworski, L.

    2000-01-01

    Aim: Creation of a classification of the lymphatic drainage status of a primary tumour. It shall enable comparison of different approaches, standardisation and quality control. Methods: Identification and topographic localisation of the sentinel node(s) using lymphatic radionuclide gamma camera imaging and/or gamma probe detection and/or vital dye mapping. Results: A classification comprising four classes (D-Class I-IV) and distinct subclasses (A-E) proved to be simply to be learned and applicable as well as reliably reproducible. It is based on the number of sentinel lymph nodes and their locations and can be combined with the pathological and molecular biological lymph node status. D-classes/subclasses obtained in 420 patients with malignant melanoma of the skin are presented. Conclusions: The classification is applicable to different approaches. Its diagnostic, therapeutic and prognostic value should be studied prospectively in those primary tumours which preferably metastasise via their draining lymphatic vessels. (orig.) [de

  15. Treatment of lymphatic nodes metastasis in advanced cancer with interventional chemotherapy combined radiotherapy

    International Nuclear Information System (INIS)

    Xia Shian; Guo Weijian; Wu Guohua; Lin Qing; Jiang Mawei; Yao Yuan

    2000-01-01

    Objective: To evaluate the clinical effects of treatment with interventional chemotherapy combined radiotherapy for lymphatic nodes metastasis in advanced cancer. Methods: Treated with interventional chemotherapy for 27 cases of lymphatic rode metastasis once a month with average 2-3 times totally. Simultaneously treated with linear accelerator radiotherapy with average dose of 40-50 Gy/20-25 times/4-5 weeks. Results: To evaluate the clinical effects after finished the whole treatment program two months later. CR + PR reached 77.8% (24/27). All patients showed tolerance to accept the treatment. Conclusion: Treatment for lymphatic node metastasis in advanced cancer with interventional chemotherapy combined radiation therapy seems to be a valuable way

  16. Application of trans-lymphatic interventional bio-chemotherapy in the treatment of malignant tumors

    International Nuclear Information System (INIS)

    Zhang Qingfan; Jiang Zhaohui; Miao Jianliang; Lu Xuehua; Yang Sheng

    1998-01-01

    Purpose: To investigate the effectiveness of intralymphatic infusion of anticancerous and biologic agents in the treatment of malignancy. Methods: Forty-one patients suffering from advanced metastatic cancers and 2 patients with primary lymphoma, resistant to standard therapies or intra-arterial chemotherapy, were treated with lymphatic injections of anticancerous drugs or combined with biochemotherapy. Results: Follow-up about one month after the therapy, comparison was made based on the findings of lymphatic radiography and CT, decrease in size of lymph-odes was demonstrated in all 40 cases. Conclusion: This therapeutic approach proved to be an effective and safe method for the palliative treatment of advanced lymphatic metastases and lymphomas. The procedure was feasible without serious complications

  17. Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver- Re-evaluations of microlymphatic abnormalities

    Science.gov (United States)

    2010-01-01

    Background From the morphological appearance, it was impossible to distinguish terminal portal venules from small lymphatic vessels in the portal tract even using histochemical microscopic techniques. Recently, D2-40 was found to be expressed at a high level in lymphatic endothelial cells (LECs). This study was undertaken to elucidate hepatic lymphatic vessels during progression of cirrhosis by examining the expression of D2-40 in LECs. Methods Surgical wedge biopsy specimens were obtained from non-cirrhotic portions of human livers (normal control) and from cirrhotic livers (LC) (Child A-LC and Child C-LC). Immunohistochemical (IHC), Western blot, and immunoelectron microscopic studies were conducted using D2-40 as markers for lymphatic vessels, as well as CD34 for capillary blood vessels. Results Imunostaining of D2-40 produced a strong reaction in lymphatic vessels only, especially in Child C-LC. It was possible to distinguish the portal venules from the small lymphatic vessels using D-40. Immunoelectron microscopy revealed strong D2-40 expression along the luminal and abluminal portions of the cell membrane of LECs in Child C-LC tissue. Conclusion It is possible to distinguish portal venules from small lymphatic vessels using D2-40 as marker. D2-40- labeling in lymphatic capillary endothelial cells is related to the degree of fibrosis in cirrhotic liver. PMID:21059220

  18. Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver- Re-evaluations of microlymphatic abnormalities

    Directory of Open Access Journals (Sweden)

    Yoshimura Kazunori

    2010-11-01

    Full Text Available Abstract Background From the morphological appearance, it was impossible to distinguish terminal portal venules from small lymphatic vessels in the portal tract even using histochemical microscopic techniques. Recently, D2-40 was found to be expressed at a high level in lymphatic endothelial cells (LECs. This study was undertaken to elucidate hepatic lymphatic vessels during progression of cirrhosis by examining the expression of D2-40 in LECs. Methods Surgical wedge biopsy specimens were obtained from non-cirrhotic portions of human livers (normal control and from cirrhotic livers (LC (Child A-LC and Child C-LC. Immunohistochemical (IHC, Western blot, and immunoelectron microscopic studies were conducted using D2-40 as markers for lymphatic vessels, as well as CD34 for capillary blood vessels. Results Imunostaining of D2-40 produced a strong reaction in lymphatic vessels only, especially in Child C-LC. It was possible to distinguish the portal venules from the small lymphatic vessels using D-40. Immunoelectron microscopy revealed strong D2-40 expression along the luminal and abluminal portions of the cell membrane of LECs in Child C-LC tissue. Conclusion It is possible to distinguish portal venules from small lymphatic vessels using D2-40 as marker. D2-40- labeling in lymphatic capillary endothelial cells is related to the degree of fibrosis in cirrhotic liver.

  19. Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

    International Nuclear Information System (INIS)

    Schultheiss, Timothy E.; Wong, Jeffrey; Liu, An; Olivera, Gustavo; Somlo, George

    2007-01-01

    Purpose: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. Methods and Materials: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribs and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. Results: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. Conclusion: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk

  20. Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer.

    Science.gov (United States)

    Paik, E Sun; Choi, Hyun Jin; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo; Choi, Chel Hun

    2018-04-01

    We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation,we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. We identified 21 mRNAs, and seven methylated DNAs from primary EOC tissues that predicted lymphatic invasion and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (p < 0.001 and p=0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (log-rank p-value=0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients' survival. Molecular signature model predicting lymphatic invasion was well performed and also associated with survival of EOC patients.

  1. Mapping the distinctive populations of lymphatic endothelial cells in different zones of human lymph nodes.

    Directory of Open Access Journals (Sweden)

    Saem Mul Park

    Full Text Available The lymphatic sinuses in human lymph nodes (LNs are crucial to LN function yet their structure remains poorly defined. Much of our current knowledge of lymphatic sinuses derives from rodent models, however human LNs differ substantially in their sinus structure, most notably due to the presence of trabeculae and trabecular lymphatic sinuses that rodent LNs lack. Lymphatic sinuses are bounded and traversed by lymphatic endothelial cells (LECs. A better understanding of LECs in human LNs is likely to improve our understanding of the regulation of cell trafficking within LNs, now an important therapeutic target, as well as disease processes that involve lymphatic sinuses. We therefore sought to map all the LECs within human LNs using multicolor immunofluorescence microscopy to visualize the distribution of a range of putative markers. PROX1 was the only marker that uniquely identified the LECs lining and traversing all the sinuses in human LNs. In contrast, LYVE1 and STAB2 were only expressed by LECs in the paracortical and medullary sinuses in the vast majority of LNs studied, whilst the subcapsular and trabecular sinuses lacked these molecules. These data highlight the existence of at least two distinctive populations of LECs within human LNs. Of the other LEC markers, we confirmed VEGFR3 was not specific for LECs, and CD144 and CD31 stained both LECs and blood vascular endothelial cells (BECs; in contrast, CD59 and CD105 stained BECs but not LECs. We also showed that antigen-presenting cells (APCs in the sinuses could be clearly distinguished from LECs by their expression of CD169, and their lack of expression of PROX1 and STAB2, or endothelial markers such as CD144. However, both LECs and sinus APCs were stained with DCN46, an antibody commonly used to detect CD209.

  2. Site-specific induction of lymphatic malformations in a rat model for image-guided therapy

    Energy Technology Data Exchange (ETDEWEB)

    Short, Robert F.; Shiels, William E. [Ohio State University College of Medicine and Public Health, Department of Radiology, The Children' s Radiological Institute, Children' s Hospital, Columbus, OH (United States); Sferra, Thomas J. [Ohio State University College of Medicine and Public Health, Department of Gastroenterology, The Columbus Children' s Research Institute, Children' s Hospital, Columbus, OH (United States); Nicol, Kathleen K. [Ohio State University College of Medicine and Public Health, Department of Pathology, Children' s Hospital, Columbus, OH (United States); Schofield, Minka; Wiet, Gregory J. [Ohio State University College of Medicine and Public Health, Department of Otolaryngology, Children' s Hospital, Columbus, OH (United States)

    2007-06-15

    Lymphatic malformation is a common benign mass in children and adults and is representative of a derangement in lymphangiogenesis. These lesions have high recurrence rates and significant morbidity associated with surgery. Several sclerotherapy regimens have been developed clinically to treat lymphatic malformations; however, an animal model has not been developed that is adequate to test the efficacy of image-guided therapeutic interventions. To develop an animal model suitable for evaluation of percutaneous treatments of lymphatic malformations. Male Harlan Sprague-Dawley rats (n = 9) received two US-guided injections of Incomplete Freund's Adjuvant (IFA) over a 2-week period. All nine rats were injected twice into the peritoneum (IP); a subgroup (n = 3) received additional injections into the neck. Three animals that received IP injections of saline were used as controls. The injection sites were monitored for the development of lesions by high-resolution ultrasonography at 2-week intervals for 100 days. High-resolution (4.7 Tesla) magnetic resonance imaging was then performed on two animals noted to have developed masses. The rats were sacrificed and histologic examination of the identified lesions was performed, including immunohistochemical staining for vascular (CD31) and lymphatic (Flt-4 and Prox-1) endothelium. All animals injected with IFA developed cystic lesions. The three animals injected at dual sites were noted to have both microcystic and macrocystic malformations in the neck and microcystic plaque-like lesions in the peritoneum. The macrocystic malformations ({>=}5 mm) in the neck were detected by ultrasonography and grossly later during necropsy. Histopathologic analysis revealed the cystic spaces to be lined by lymphatic endothelium supported by a connective tissue stroma. Control animals did not exhibit detectable lesions with either ultrasonography or necropsy. This model represents a promising tool for translational development of image

  3. Intravital two-photon microscopy of immune cell dynamics in corneal lymphatic vessels.

    Directory of Open Access Journals (Sweden)

    Philipp Steven

    Full Text Available BACKGROUND: The role of lymphatic vessels in tissue and organ transplantation as well as in tumor growth and metastasis has drawn great attention in recent years. METHODOLOGY/PRINCIPAL FINDINGS: We now developed a novel method using non-invasive two-photon microscopy to simultaneously visualize and track specifically stained lymphatic vessels and autofluorescent adjacent tissues such as collagen fibrils, blood vessels and immune cells in the mouse model of corneal neovascularization in vivo. The mouse cornea serves as an ideal tissue for this technique due to its easy accessibility and its inducible and modifiable state of pathological hem- and lymphvascularization. Neovascularization was induced by suture placement in corneas of Balb/C mice. Two weeks after treatment, lymphatic vessels were stained intravital by intrastromal injection of a fluorescently labeled LYVE-1 antibody and the corneas were evaluated in vivo by two-photon microscopy (TPM. Intravital TPM was performed at 710 nm and 826 nm excitation wavelengths to detect immunofluorescence and tissue autofluorescence using a custom made animal holder. Corneas were then harvested, fixed and analyzed by histology. Time lapse imaging demonstrated the first in vivo evidence of immune cell migration into lymphatic vessels and luminal transport of individual cells. Cells immigrated within 1-5.5 min into the vessel lumen. Mean velocities of intrastromal corneal immune cells were around 9 µm/min and therefore comparable to those of T-cells and macrophages in other mucosal surfaces. CONCLUSIONS: To our knowledge we here demonstrate for the first time the intravital real-time transmigration of immune cells into lymphatic vessels. Overall this study demonstrates the valuable use of intravital autofluorescence two-photon microscopy in the model of suture-induced corneal vascularizations to study interactions of immune and subsequently tumor cells with lymphatic vessels under close as possible

  4. Site-specific induction of lymphatic malformations in a rat model for image-guided therapy

    International Nuclear Information System (INIS)

    Short, Robert F.; Shiels, William E.; Sferra, Thomas J.; Nicol, Kathleen K.; Schofield, Minka; Wiet, Gregory J.

    2007-01-01

    Lymphatic malformation is a common benign mass in children and adults and is representative of a derangement in lymphangiogenesis. These lesions have high recurrence rates and significant morbidity associated with surgery. Several sclerotherapy regimens have been developed clinically to treat lymphatic malformations; however, an animal model has not been developed that is adequate to test the efficacy of image-guided therapeutic interventions. To develop an animal model suitable for evaluation of percutaneous treatments of lymphatic malformations. Male Harlan Sprague-Dawley rats (n = 9) received two US-guided injections of Incomplete Freund's Adjuvant (IFA) over a 2-week period. All nine rats were injected twice into the peritoneum (IP); a subgroup (n = 3) received additional injections into the neck. Three animals that received IP injections of saline were used as controls. The injection sites were monitored for the development of lesions by high-resolution ultrasonography at 2-week intervals for 100 days. High-resolution (4.7 Tesla) magnetic resonance imaging was then performed on two animals noted to have developed masses. The rats were sacrificed and histologic examination of the identified lesions was performed, including immunohistochemical staining for vascular (CD31) and lymphatic (Flt-4 and Prox-1) endothelium. All animals injected with IFA developed cystic lesions. The three animals injected at dual sites were noted to have both microcystic and macrocystic malformations in the neck and microcystic plaque-like lesions in the peritoneum. The macrocystic malformations (≥5 mm) in the neck were detected by ultrasonography and grossly later during necropsy. Histopathologic analysis revealed the cystic spaces to be lined by lymphatic endothelium supported by a connective tissue stroma. Control animals did not exhibit detectable lesions with either ultrasonography or necropsy. This model represents a promising tool for translational development of image

  5. Lymphatic drainage pathways from the cervix uteri: implications for radical hysterectomy?

    Science.gov (United States)

    Kraima, A C; Derks, M; Smit, N N; Van Munsteren, J C; Van der Velden, J; Kenter, G G; DeRuiter, M C

    2014-01-01

    Radical hysterectomy with pelvic lymphadenectomy is the treatment of choice for early-stage cervical cancer. Wertheim's original technique has been often modified, mainly in the extent of parametrectomy. Okabayashi's technique is considered as the most radical variant regarding removal of the ventral parametrium and paracolpal tissues. Surgical outcome concerning recurrence and survival is good, but morbidity is high due to autonomic nerve damage. While the autonomic network has been studied extensively, the lymphatic system is less understood. This study describes the lymphatic drainage pathways of the cervix uteri and specifically the presence of lymphatics in the vesico-uterine ligament (VUL). A developmental series of 10 human female fetal pelves was studied. Paraffin embedded blocks were sliced in transverse sections of 8 or 10 μm. Analysis was performed by staining with antibodies against LYVE-1 (lymphatic endothelium), S100 (Schwann cells), alpha-Smooth Muscle Actin (smooth muscle cells) and CD68 (macrophages). The results were three-dimensionally represented. Two major pathways drained the cervix uteri: a supra-ureteral pathway, running in the cardinal ligament superior to the ureter, and a dorsal pathway, running in the utero-sacral ligament towards the rectal pillars. No lymph vessels draining the cervix uteri were detected in the VUL. In the paracolpal parametrium lymph vessels draining the upper vagina fused with those from the bladder. The VUL does not contain lymphatics from the cervix uteri. Hence, the favorable survival outcomes of the Okabayashi technique cannot be explained by radical removal of lymphatic pathways in the ventrocaudal parametrium. © 2013.

  6. The effect of defibrotide on thromboembolism in the pulmonary vasculature of mice and rabbits and in the cerebral vasculature of rabbits.

    Science.gov (United States)

    Paul, W.; Gresele, P.; Momi, S.; Bianchi, G.; Page, C. P.

    1993-01-01

    1. Administration of bovine thrombin (100 u kg-1) into the carotid artery of rabbits induces a sustained accumulation of 111 Indium-labelled platelets within the cranial vasculature over the subsequent 3 h. 2. Intracarotid (i.c.) administration of defibrotide (64 mg kg-1 bolus plus 64 mg kg-1 h-1 for 1 h) prior to i.c. thrombin (100 u kg-1) significantly reduces the ability of thrombin to induce cranial thromboembolism in rabbits. 3. Intravenous (i.v.) administration of thrombin (20 u kg-1) in rabbits induces a reversible accumulation of radiolabelled platelets into the thoracic circulation which is significantly reduced by i.v. administration of defibrotide (64 mg kg-1 bolus plus 64 mg kg-1 h-1 for 1 h) prior to i.v. thrombin. In contrast, platelet accumulation in response to adenosine diphosphate (ADP; 20 micrograms kg-1, i.v.) or platelet activating factor (PAF; 50 ng kg-1, i.v.) is not significantly affected by this treatment. 4. Intravenous administration of the nitric oxide (NO)-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 mg kg-1) potentiates platelet accumulation induced by low dose thrombin (10 u kg-1, i.v.) within the pulmonary vasculature of rabbits. The potentiated response is significantly abrogated following pretreatment with defibrotide (64 mg kg-1 bolus plus 64 mg kg-1 h-1 for 1 h, i.v.). 5. Intravenous injection of human thrombin (1250 u kg-1) to mice induces death within the majority of animals which is significantly reduced by pretreatment with defibrotide (150-175 mg kg-1, i.v.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8306102

  7. Prolonged lymphatic leak after retroperitoneal lymph node dissection: a case report

    Directory of Open Access Journals (Sweden)

    Browne Katherine M

    2009-08-01

    Full Text Available Abstract Introduction Persistent lymphatic drainage following retroperitoneal lymph node dissection for testicular tumor is an uncommon complication. Case presentation We describe a 21-year old man of Caucasian origin who had metastatic non-seminomatous germ cell tumor of the testis, and underwent retroperitoneal lymph node dissection, nephrectomy and partial inferior vena cava excision for a residual mass. The patient subsequently developed persistent lymphatic drainage causing foot drop that eventually responded to conservative medical and surgical measures. Conclusion This postoperative condition usually responds well to conservative measures but has the potential for serious morbidity if it is not managed appropriately.

  8. Flow rates in the head and neck lymphatics after food stimulation in healthy subjects

    International Nuclear Information System (INIS)

    Thommesen, P.; Buhl, J.; Jansen, K.; Funch-Jensen, P.; Central Hospital Randers; Municipal Hospital Aarhus

    1981-01-01

    In 22 healthy subjects lymph transport flow rates was studied in the head lymphatics after food stimulation, mastication (chewing) and taste. After food stimulation there was a significantly higher transport rate (0.67 meter/hour) than after taste (0.57 meter/hour) and mastication (0.55 meter/hour). The calculation of transport flow rate was independent of quantitative distribution of radioactivity in the head and neck lymphatics, and it could therefore perhaps be of clinical value. (orig.) [de

  9. Lymphatic endothelial cell line (CH3) from a recurrent retroperitoneal lymphangioma.

    Science.gov (United States)

    Way, D; Hendrix, M; Witte, M; Witte, C; Nagle, R; Davis, J

    1987-09-01

    An endothelial cell line derived from a massive recurrent chyle-containing retroperitoneal lymphangioma was isolated in monolayer culture. Scanning and transmission electron microscopy and immunohistochemistry confirmed a close resemblance to blood vascular endothelium with typical cobblestone morphology, positive immunofluorescence staining for endothelial marker Factor VIII-associated antigen and fibronectin, and prominent Weibel-Palade bodies. The endothelial cells also exhibited other ultrastructural features characteristic of lymphatic endothelium, including sparse microvillous surface projections, overlapping intercellular junctions, and abundant intermediate filaments. This endothelial cell line represents a new source of proliferating lymphatic endothelium for future study, including structural and functional comparison to blood vascular endothelium.

  10. Laparoscopic management of abdominal lymphatic cyst in children.

    Science.gov (United States)

    Tran, Ngoc Son; Nguyen, Thanh Liem

    2012-06-01

    The aim of this study is to investigate the feasibility and effectiveness of laparoscopic surgery (LS) in management of abdominal lymphatic cyst (ALC) in children. Medical records of all patients undergoing LS for ALC at the National Hospital of Pediatrics, Hanoi, Vietnam, from May 2007 to June 2011 were reviewed. For LS, one umbilical port of 10 mm and up to three other 3-5-mm ports were used. Cystic fluid was aspirated prior to removal of the cyst. When intestinal resection was indicated, the mesenteric cyst with the bowel loop was delivered out of the abdomen through a minimally enlarged umbilical incision; resection of the intestinal segment together with the cyst and the bowel anastomosis were both performed extracorporally. Forty-seven patients were identified, with a mean age of 4.3 ± 3.7 years. The most common symptoms were abdominal pain (72.3%) and abdominal distention (34.0%). Four patients presented with acute abdomen due to infection or hemorrhage of the cyst. Mean size of the ALC was 9.5 ± 5.5 cm (range, 3.4-30 cm). In 12 cases the ALC was omental, and in 35 cases it was mesenteric. Laparoscopic cyst excision was performed in 36 cases (76.6%) versus laparoscopy-assisted bowel resection en bloc with the cyst in 8 cases (17.0%); in 3 patients (6.4%), conversion to open surgery was required. Mean operative time was 79 ± 39 minutes. There were no intra- or postoperative complications. Mean length of hospital stay after laparoscopic management was 3.8 ± 1.6 days. The results of pathologic investigation showed benign cystic lymphangioma in all cases. During follow-up ranging from 1 month to 4 years, recurrence was seen in 1 patient (2.1%) with complex mesenteric cyst. All other patients remained in good health. Laparoscopic management is safe, feasible, and effective and should be the treatment of choice for most cases of ALC in children.

  11. Direct lymphangiography as treatment option of lymphatic leakage: Indications, outcomes and role in patient's management

    Energy Technology Data Exchange (ETDEWEB)

    Gruber-Rouh, Tatjana, E-mail: tgruberrouh@googlemail.com [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Naguib, Nagy N.N. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Department of Radiology, Faculty of Medicine, Alexandria University, Alexandria (Egypt); Lehnert, Thomas; Harth, Marc; Thalhammer, Axel; Beeres, Martin [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Tsaur, Igor [Department of Urology, Johann Wolfgang Goethe University Frankfurt, Frankfurt am Main (Germany); Hammersting, Renate; Wichmann, Julian L.; Vogl, Thomas J.; Jacobi, Volkmar [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany)

    2014-12-15

    Background: To evaluate the effectiveness of lymphography as a minimally invasive treatment option of lymphatic leakage in terms of local control and to investigate which parameters influence the success rate. Method: This retrospective study protocol was approved by the ethic committee. Patient history, imaging data, therapeutic options and follow-up were recorded and retrospectively analyzed. Between June 1998 and February 2013, 71 patients (m:w = 42:29, mean age, 52.4; range 42–75 years) with lymphatic leakage in form of lymphatic fistulas (n = 37), lymphocele (n = 11), chylothorax (n = 13) and chylous ascites (n = 10) underwent lymphography. Sixty-four patients (90.1%) underwent successful lymphography while lymphography failed in 7 cases. Therapeutic success was evaluated and correlated to the volume of lymphatic leakage and to the volume of the applied iodized oil. Result: Signs of leakage or contrast extravasation were directly detected in 64 patients. Of 64 patients, 45 patients (70.3%) were treated and cured after lymphography. Based on the lymphography findings, 19 patients (29.7%) underwent surgical intervention with a completely occlusion of lymphatic leakage. The lymphatic leak could be completely occluded in 96.8% of patients when the lymphatic drainage volume was less than 200 mL/day (n = 33). Even when lymphatic drainage was higher than 200 mL/day (n = 31), therapeutic lymphography was still successful in 58.1% of the patients. Conclusion: Lymphography is an effective, minimally invasive method in the detection and treatment of lymphatic leakage. The volume of lymphatic drainage per day is a significant predictor of the therapeutic success rate.

  12. Direct lymphangiography as treatment option of lymphatic leakage: Indications, outcomes and role in patient's management

    International Nuclear Information System (INIS)

    Gruber-Rouh, Tatjana; Naguib, Nagy N.N.; Lehnert, Thomas; Harth, Marc; Thalhammer, Axel; Beeres, Martin; Tsaur, Igor; Hammersting, Renate; Wichmann, Julian L.; Vogl, Thomas J.; Jacobi, Volkmar

    2014-01-01

    Background: To evaluate the effectiveness of lymphography as a minimally invasive treatment option of lymphatic leakage in terms of local control and to investigate which parameters influence the success rate. Method: This retrospective study protocol was approved by the ethic committee. Patient history, imaging data, therapeutic options and follow-up were recorded and retrospectively analyzed. Between June 1998 and February 2013, 71 patients (m:w = 42:29, mean age, 52.4; range 42–75 years) with lymphatic leakage in form of lymphatic fistulas (n = 37), lymphocele (n = 11), chylothorax (n = 13) and chylous ascites (n = 10) underwent lymphography. Sixty-four patients (90.1%) underwent successful lymphography while lymphography failed in 7 cases. Therapeutic success was evaluated and correlated to the volume of lymphatic leakage and to the volume of the applied iodized oil. Result: Signs of leakage or contrast extravasation were directly detected in 64 patients. Of 64 patients, 45 patients (70.3%) were treated and cured after lymphography. Based on the lymphography findings, 19 patients (29.7%) underwent surgical intervention with a completely occlusion of lymphatic leakage. The lymphatic leak could be completely occluded in 96.8% of patients when the lymphatic drainage volume was less than 200 mL/day (n = 33). Even when lymphatic drainage was higher than 200 mL/day (n = 31), therapeutic lymphography was still successful in 58.1% of the patients. Conclusion: Lymphography is an effective, minimally invasive method in the detection and treatment of lymphatic leakage. The volume of lymphatic drainage per day is a significant predictor of the therapeutic success rate

  13. Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons, megavoltage photons, and kilovoltage photons

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yuting, E-mail: yutingl188@gmail.com; Paganetti, Harald; Schuemann, Jan [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States); McMahon, Stephen J. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 and Center for Cancer Research and Cell Biology, Queen’s University Belfast, 97 Lisburn Road, Belfast BT97AE, Northern Ireland (United Kingdom)

    2015-10-15

    Purpose: The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) photon, and kilovoltage (kV) photon irradiation. Methods: Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 μm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV photon beam, and two kV photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 μm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. Results: These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1% for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached

  14. Co-localization of lymphoid aggregates and lymphatic networks in nose- (NALT) and lacrimal duct-associated lymphoid tissue (LDALT) of mice.

    Science.gov (United States)

    Lohrberg, Melanie; Pabst, Reinhard; Wilting, Jörg

    2018-01-25

    The lymphatic vascular pattern in the head of mice has rarely been studied, due to problems of sectioning and immunostaining of complex bony structures. Therefore, the association of head lymphoid tissues with the lymphatics has remained unknown although the mouse is the most often used species in immunology. Here, we studied the association of nasal and nasolacrimal duct lymphatics with lymphoid aggregates in 14-day-old and 2-month-old mice. We performed paraffin sectioning of whole, decalcified heads, and immunostaining with the lymphatic endothelial cell-specific antibodies Lyve-1 and Podoplanin. Most parts of the nasal mucous membrane do not contain any lymphatics. Only the region of the inferior turbinates contains lymphatic networks, which are connected to those of the palatine. Nose-associated lymphoid tissue (NALT) is restricted to the basal parts of the nose, which contain lymphatics. NALT is continued occipitally and can be found at both sides along the sphenoidal sinus, again in close association with lymphatic networks. Nasal lymphatics are connected to those of the ocular region via a lymphatic network along the nasolacrimal duct (NLD). By this means, lacrimal duct-associated lymphoid tissue (LDALT) has a dense supply with lymphatics. NALT and LDALT play a key role in the immune system of the mouse head, where they function as primary recognition sites for antigens. Using the dense lymphatic networks along the NLD described in this study, these antigens reach lymphatics near the palatine and are further drained to lymph nodes of the head and neck region. NALT and LDALT develop in immediate vicinity of lymphatic vessels. Therefore, we suggest a causative connection of lymphatic vessels and the development of lymphoid tissues.

  15. A Comparison between Gadofosveset Trisodium and Gadobenate Dimeglumine for Steady State MRA of the Thoracic Vasculature

    OpenAIRE

    Camren, G. Paul; Wilson, Gregory J.; Bamra, Vikram R.; Nguyen, Khahn Q.; Hippe, Daniel S.; Maki, Jeffrey H.

    2014-01-01

    Purpose. Retrospective comparison between gadofosveset trisodium and gadobenate dimeglumine steady state magnetic resonance angiography (SS-MRA) of the thoracic vasculature at 1.5T using signal-to-noise ratio (SNR) and vessel edge sharpness (ES) as markers of image quality. Materials and Methods. IRB approval was obtained. Twenty separate patients each underwent SS-MRA using high-resolution 3D ECG-triggered coronal IR-TFE at 1.5T approximately 3-4 minutes following 10 or 15 mL gadofosveset or...

  16. Bilateral persistent fetal vasculature due to a mutation in the Norrie disease protein gene.

    Science.gov (United States)

    Payabvash, Seyedmehdi; Anderson, Jill S; Nascene, David R

    2015-12-01

    We report a case of a 7-week-old boy with bilateral leukocoria and asymmetric microphthalmia who was found to have Norrie disease. Symmetrically hyperdense globes with no evidence of calcification were seen on CT scan. The MRI showed bilateral retinal hemorrhages resulting in conical vitreous chambers-narrow at the optic disc and widened toward the lens-characteristic of persistent fetal vasculature. Genetic evaluation revealed a previously undescribed mutation in the Norrie disease protein gene. © The Author(s) 2015.

  17. Effect of Physical Methods of Lymphatic Drainage on Postexercise Recovery of Mixed Martial Arts Athletes.

    Science.gov (United States)

    Zebrowska, Aleksandra; Trybulski, Robert; Roczniok, Robert; Marcol, Wieslaw

    2017-08-16

    Physical methods are reported to be important for accelerating skeletal muscle regeneration, decreasing muscle soreness, and shortening of the recovery time. The aim of the study was to assess the effect of the physical methods of lymphatic drainage (PMLD) such as manual lymphatic drainage (MLD), the Bodyflow (BF) therapy, and lymphatic drainage by deep oscillation (DO) on postexercise regeneration of the forearm muscles of mixed martial arts (MMA) athletes. Eighty MMA athletes aged 27.5 ± 6.4 years were allocated to 4 groups: MLD, the BF device, DO therapy, and the control group. Blood flow velocity in the cephalic vein was measured with the ultrasound Doppler velocity meter. Maximal strength of the forearm muscles (Fmax), muscle tissue tension, pain threshold, blood lactate concentration (LA), and activity of creatine kinase were measured in all groups at rest, after the muscle fatigue test (post-ex) and then 20 minutes, 24, and 48 hours after the application of PMLD. The muscle fatigue test reduced Fmax in all subjects, but in the groups receiving MLD, DO, and BF significantly higher Fmax was observed at recovery compared with post-ex values. The application of MDL reduced the postexercise blood LA and postexercise muscle tension. The lymphatic drainage methods, whether manual or using electro-stimulation and DO, improve postexercise regeneration of the forearm muscles of MMA athletes. The methods can be an important element of therapeutic management focused on optimizing training effects and reducing the risk of injuries of the combat sports athletes.

  18. Hobnail hemangioma reclassified as superficial lymphatic malformation: a study of 52 cases.

    Science.gov (United States)

    Trindade, Felicidade; Kutzner, Heinz; Tellechea, Óscar; Requena, Luis; Colmenero, Isabel

    2012-01-01

    Hobnail hemangioma (HH) is currently classified as a benign vascular tumor, although it is not well understood whether this lesion differentiates toward blood or lymphatic endothelial cells. Immunostaining with the endothelial marker Wilms tumor 1 (WT1) helps distinguish between vascular neoplasms and malformations, being positive in the former and negative in the latter. We sought to investigate WT1, human herpesvirus 8 latent nuclear antigen, D2-40, and Ki-67 immunoprofile in HH, to gain further insight into its histogenesis. We evaluated 52 HHs collected in Dermatohistopathologische Gemeinschaftslabor, Friedrichshafen, Germany. Immunohistochemical expression of WT1 was performed in all cases. Ten of 52 lesions were also studied for D2-40 and Ki-67 staining and 12 lesions were stained for human herpesvirus 8 latent nuclear antigen. All 52 HHs were completely negative for WT1 immunostaining. Immunohistochemistry performed in 10 HHs showed diffuse and strong positive staining for D2-40 in 8 lesions and focal positivity in two. All cases tested showed negative staining for Ki-67 and human herpesvirus 8 latent nuclear antigen. There are no limitations. Although the exact histogenesis of HH is unknown, most of the performed immunohistochemical studies support a lymphatic line of differentiation. However, on the basis of the WT1 negativity, we believe that HH is better considered as a lymphatic malformation rather than a lymphatic neoplasm. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  19. Indirect measurement of lymphatic absorption with inulin in continuous ambulatory peritoneal dialysis (CAPD) patients

    NARCIS (Netherlands)

    Struijk, D. G.; Krediet, R. T.; Koomen, G. C.; Boeschoten, E. W.; vd Reijden, H. J.; Arisz, L.

    1990-01-01

    To elucidate the importance of possible trapping of macromolecules in peritoneal tissue on the calculation of peritoneal lymphatic drainage, we compared the transport of inulin administered i.v. and i.p. in nine continuous ambulatory peritoneal dialysis (CAPD) patients on two separate days. In the

  20. IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression

    DEFF Research Database (Denmark)

    Nielsen, Sebastian Rune; Hammer, Troels; Gibson, Josefine

    2013-01-01

    OBJECTIVE: IL-27 belongs to the IL-12 family of cytokines and is recognized for its role in Th cell differentiation and as an inhibitor of tumor-angiogenesis. The purpose of this study was to investigate the effect of IL-27 on proliferation of lymphatic endothelial cells to gain insight into the ...

  1. Lymphangiography: Forgotten Tool or Rising Star in the Diagnosis and Therapy of Postoperative Lymphatic Vessel Leakage

    International Nuclear Information System (INIS)

    Kos, Sebastian; Haueisen, Harald; Lachmund, Ulrich; Roeren, Thomas

    2007-01-01

    Since the advent of computed tomography, numbers and expertise in Lymphangiography (LAG) have markedly dropped. The intention of our study was to demonstrate the persisting diagnostic and therapeutic impact of LAG on the postoperative patient with known or suspected lymphatic vessel leakage. Between May 1, 1999, and April 30, 2006, we investigated pedal lipiodol-LAGs (18 monopedal, 2 bipedal) on 22 patients (16 male, 6 female) with known or suspected postoperative chylothorax, chylaskos, lymphocele, or lymphatic fistula. Ages varied from 26 to 81 years. The spectrum of operative procedures was broad: 6 thoracic, 5 abdominal, and 11 peripheral operations were performed. In 20 patients who underwent mono- or bipedal LAG for lymphatic vessel injury, we were able to demonstrate the specific site of leakage in 15 cases (75%) and found signs of extravasation in 5 patients (25%). Furthermore, in 11 patients (55%) we were able to avoid surgery because of closure of the leak after LAG. As the conservative therapeutic approach usually takes 2-3 weeks to reveal its therapeutic effects, 73.3% (11/15) of the patients who were not reoperated before this hallmark was passed did not need any further operation. Our study clearly demonstrates that even in the decades of modern cross-sectional imaging, classic LAG is a powerful and highly reliable tool to visualize and even assist occlusion of the postoperatively damaged lymphatic vessel and may thereby avoid the need for reoperation

  2. Composition of the Extracellular Matrix of Lymphatic Novel Threadlike Structures: Is It Keratin?

    Directory of Open Access Journals (Sweden)

    Hyub Huh

    2013-01-01

    Full Text Available Background. The lumen of novel threadlike structures (NTSs is enclosed by a single layer of endothelial cells surrounded by extracellular matrix (ECM. We hypothesized that collagen may be a component of the ECM associated with lymphatic NTSs. Methods. Six female New Zealand white rabbits were anesthetized, and the NTS structures within lymphatic vessels were identified by contrast-enhanced stereomicroscopy or alcian blue staining. Isolated NTS specimens were stained with acridine orange, YOYO-1, and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI. The structural and molecular composition of the ECM was investigated using transmission electron microscopy (TEM, electrospray ionization-mass spectrometry, and proteomic analysis. Results. The lymph vessel wall was stained red by DiI, and rod-shaped nuclei were stained green by YOYO-1. The area surrounding the NTS was also stained red and contained green rod-shaped nuclei. TEM images showed that the NTS consisted of many ECM fibers and the ECM fibers appeared to be ~100 nm in diameter and had narrowly spaced striated bands. Proteomic analysis of the lymphatic NTS-associated ECM identified 4 proteins: keratin 10, cytokeratin 3, cytokeratin 12, and soluble adenylyl cyclase. Conclusion. The TEM study suggested that the lymphatic NTS-associated ECM did not contain collagen. This was confirmed by proteomic analysis, which showed that keratin was the major component of the ECM.

  3. Impact of Surgical Route in Influencing the Risk of Lymphatic Complications After Ovarian Cancer Staging.

    Science.gov (United States)

    Bogani, Giorgio; Borghi, Chiara; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Chiappa, Valentina; Scaffa, Cono; Perotto, Stefania; Leone Roberti Maggiore, Umberto; Montanelli, Luca; Di Donato, Violante; Infantino, Carmelo; Lorusso, Domenica; Raspagliesi, Francesco

    Lymphatic complications are a common occurrence after staging surgery for early-stage ovarian cancer (eEOC). We investigated whether the introduction of minimally invasive surgery influences the risk of developing lymphoceles and lymphorrhea in patients undergoing staging for eEOC. For this purpose, data of consecutive patients affected by eEOC undergoing staging surgery between January 1980 and January 2016 were retrospectively reviewed, and a systematic review and meta-analysis was performed. This systematic review was registered in the International Prospective Register of Systematic Review. Among 341 patients included in the present study, 47 severe postoperative complications occurred (13.7%), including 40 lymphatic complications: 31 symptomatic lymphoceles (9%) and 9 cases of lymphorrhea (2.6%), respectively. Laparoscopic staging correlated with a lower risk of developing any severe lymphatic complications in comparison with open surgery (p = .02). In particular, the laparoscopic approach and para-aortic node involvement were associated with a trend toward lower lymphoceles (odds ratio, .13; 95% confidence interval, .07-2.20; p = .05) and a trend toward higher risk of lymphorrhea developing (odds ratio, 4.02; 95% confidence interval, .93-17.3; p = .06), respectively. In conclusion, the implementation of a minimally invasive approach might result in a slight reduction of lymphatic complications after eEOC staging. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

  4. Vascular, glial, and lymphatic immune gateways of the central nervous system

    NARCIS (Netherlands)

    Engelhardt, Britta; Carare, Roxana O.; Bechmann, Ingo; Fluegel, Alexander; Laman, Jon D.; Weller, Roy O.

    Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system.

  5. Lymph Nodes and Cancer Metastasis: New Perspectives on the Role of Intranodal Lymphatic Sinuses

    Directory of Open Access Journals (Sweden)

    Rui-Cheng Ji

    2016-12-01

    Full Text Available The lymphatic system is essential for transporting interstitial fluid, soluble antigen, and immune cells from peripheral tissues to lymph nodes (LNs. Functional integrity of LNs is dependent on intact lymphatics and effective lymph drainage. Molecular mechanisms that facilitate interactions between tumor cells and lymphatic endothelial cells (LECs during tumor progression still remain to be identified. The cellular and molecular structures of LNs are optimized to trigger a rapid and efficient immune response, and to participate in the process of tumor metastasis by stimulating lymphangiogenesis and establishing a premetastatic niche in LNs. Several molecules, e.g., S1P, CCR7-CCL19/CCL21, CXCL12/CXCR4, IL-7, IFN-γ, TGF-β, and integrin α4β1 play an important role in controlling the activity of LN stromal cells including LECs, fibroblastic reticular cells (FRCs and follicular dendritic cells (DCs. The functional stromal cells are critical for reconstruction and remodeling of the LN that creates a unique microenvironment of tumor cells and LECs for cancer metastasis. LN metastasis is a major determinant for the prognosis of most human cancers and clinical management. Ongoing work to elucidate the function and molecular regulation of LN lymphatic sinuses will provide insight into cancer development mechanisms and improve therapeutic approaches for human malignancy.

  6. [Value of CT lymphangiography in the detection of lymphatic leakage: a report of nine cases].

    Science.gov (United States)

    Safar, K; Aouaifia, A; Oudjit, A; Le Pimpec-Barthes, F; Riquet, M; Legmann, P

    2011-01-01

    To demonstrate the value of CT lymphangiography to detect lymphatic leakage, especially at the thoracic level, prior to therapeutic intervention. Between 2004 and 2008, nine patients underwent lymphangiography, followed by CT for the evaluation of intractable lymphatic leakage in spite of optimal medical management. Patients included seven females and two males, with age ranging between 25 and 58 years. Lymphangiography was performed after unilateral or bilateral foot injection(s) of Lipiodol ultrafluid followed by standard radiographs of the chest and abdomen and CT of the chest, abdomen and pelvis. The images were reviewed by two experienced radiologists. Lipiodol leakage was observed in six patients, while three patients showed evidence of lymphangiectasia of the abdominal and/or thoracic lymphatics. Spontaneous resolution of leakage after lymphangiography occurred in three cases. CT lymphangiography allows direct evaluation of lymphatics, from pelvis to chest, in order to detect the site of leakage at the origin of a chylous effusion and assist in its management. Copyright © 2010 Elsevier Masson SAS and Éditions françaises de radiologie. All rights reserved.

  7. Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: A modelling study

    NARCIS (Netherlands)

    M.A. Irvine (Michael A.); W.A. Stolk (Wilma); Smith, M.E. (Morgan E); S.V. Subramanian; B.K. Singh (Brajendra K.); G.J. Weil (Gary); E. Michael (Edwin); T.D. Hollingsworth (T. Déirdre)

    2017-01-01

    textabstractBackground: Lymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen

  8. Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration

    DEFF Research Database (Denmark)

    Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo

    2013-01-01

    Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached...

  9. A Lymphatic dwelling filarioid nematode, Rumenfilaria andersoni (Filarioidea; Splendidofilariinae), is an emerging parasite in Finnish cervids

    Science.gov (United States)

    Background-Recent studies revealed expansion of filarioid nematodes into the northern Finland. In addition to Setaria tundra, unidentified and very abundant filarioids, representing Rumenfilaria andersoni, were found inhabiting the lymphatic vessels of reindeer. Our study explores the biology and d...

  10. The effect of interstitial pressure on tumor growth: coupling with the blood and lymphatic vascular systems

    Science.gov (United States)

    Wu, Min; Frieboes, Hermann B.; McDougall, Steven R.; Chaplain, Mark A.J.; Cristini, Vittorio; Lowengrub, John

    2013-01-01

    The flow of interstitial fluid and the associated interstitial fluid pressure (IFP) in solid tumors and surrounding host tissues have been identified as critical elements in cancer growth and vascularization. Both experimental and theoretical studies have shown that tumors may present elevated IFP, which can be a formidable physical barrier for delivery of cell nutrients and small molecules into the tumor. Elevated IFP may also exacerbate gradients of biochemical signals such as angiogenic factors released by tumors into the surrounding tissues. These studies have helped to understand both biochemical signaling and treatment prognosis. Building upon previous work, here we develop a vascular tumor growth model by coupling a continuous growth model with a discrete angiogenesis model. We include fluid/oxygen extravasation as well as a continuous lymphatic field, and study the micro-environmental fluid dynamics and their effect on tumor growth by accounting for blood flow, transcapillary fluid flux, interstitial fluid flow, and lymphatic drainage. We thus elucidate further the non-trivial relationship between the key elements contributing to the effects of interstitial pressure in solid tumors. In particular, we study the effect of IFP on oxygen extravasation and show that small blood/lymphatic vessel resistance and collapse may contribute to lower transcapillary fluid/oxygen flux, thus decreasing the rate of tumor growth. We also investigate the effect of tumor vascular pathologies, including elevated vascular and interstitial hydraulic conductivities inside the tumor as well as diminished osmotic pressure differences, on the fluid flow across the tumor capillary bed, the lymphatic drainage, and the IFP. Our results reveal that elevated interstitial hydraulic conductivity together with poor lymphatic function is the root cause of the development of plateau profiles of the IFP in the tumor, which have been observed in experiments, and contributes to a more uniform

  11. Lymphatic Vessel Density as Prognostic Factor in Breast Carcinoma: Relation to Clinico pathologic Parameters

    International Nuclear Information System (INIS)

    El-Gendi, S.; Abdel-Hadi, M.

    2009-01-01

    Angiogenesis and lymphangiogenesis are essential for breast cancer growth and progression. This study aimed at investigating lymphatic micro vessel density (LVD) and microvessel density (MVD) as prognostic markers in breast carcinoma. Forty breast carcinomas were immuno stained for D2-40, CD31 and VEGF. Median lymphatic and blood micro vessel densities, as well as VEGF expression, were related to each other and to clinico pathologic parameters including lymph node (Ln) status. The efficacy of haematoxylin and eosin (H and E) in detecting lymphatic vessel invasion (LVI) compared to D2-40 immunostaining was also investigated. D2-40 stained normal lymphatic endothelium and myoepithelial cells, but with different staining patterns. D2-40 LVD related significantly to CD31 counts (r=0.470; p=0.002), and LN metastasis (Mann-Whitney U=101.500; p=0.043); however, it did not relate to age, tumor grade, tumor size or LVI. D2-40 identified LVI in 3 more cases (7.5%) than those detected by H and E. VEGF was expressed in 85% of cases, and was significantly related to CD31 and D2-40 counts (p=0.033 and 0.007, respectively). In conclusion, D2-40 LVD showed a significant association with LN metastasis, and can be considered to segregate patients with positive from those with negative LNs. D2-40 enhances the detection of LVI relative to H and E staining reflecting a potential for lymphatic metastatic spread and possible poor prognosis

  12. Lymphatic pump treatment mobilizes leukocytes from the gut associated lymphoid tissue into lymph.

    Science.gov (United States)

    Hodge, Lisa M; Bearden, Melissa K; Schander, Artur; Huff, Jamie B; Williams, Arthur; King, Hollis H; Downey, H Fred

    2010-06-01

    Lymphatic pump techniques (LPT) are used clinically by osteopathic practitioners for the treatment of edema and infection; however, the mechanisms by which LPT enhances lymphatic circulation and provides protection during infection are not understood. Rhythmic compressions on the abdomen during LPT compress the abdominal area, including the gut-associated lymphoid tissues (GALT), which may facilitate the release of leukocytes from these tissues into the lymphatic circulation. This study is the first to document LPT-induced mobilization of leukocytes from the GALT into the lymphatic circulation. Catheters were inserted into either the thoracic or mesenteric lymph ducts of dogs. To determine if LPT enhanced the release of leukocytes from the mesenteric lymph nodes (MLN) into lymph, the MLN were fluorescently labeled in situ. Lymph was collected during 4 min pre-LPT, 4 min LPT, and 10 min following cessation of LPT. LPT significantly increased lymph flow and leukocytes in both mesenteric and thoracic duct lymph. LPT had no preferential effect on any specific leukocyte population, since neutrophil, monocyte, CD4+ T cell, CD8+ T cell, IgG+B cell, and IgA+B cell numbers were similarly increased. In addition, LPT significantly increased the mobilization of leukocytes from the MLN into lymph. Lymph flow and leukocyte counts fell following LPT treatment, indicating that the effects of LPT are transient. LPT mobilizes leukocytes from GALT, and these leukocytes are transported by the lymphatic circulation. This enhanced release of leukocytes from GALT may provide scientific rationale for the clinical use of LPT to improve immune function.

  13. Octreotide in Intestinal Lymphangiectasia: Lack of a Clinical Response and Failure to Alter Lymphatic Function in a Guinea Pig Model

    Directory of Open Access Journals (Sweden)

    S Makhija

    2004-01-01

    Full Text Available Intestinal lymphangiectasia, which can be classified as primary or secondary, is an unusual cause of protein-losing enteropathy. The main clinical features include edema, fat malabsorption, lymphopenia and hypoalbuminemia. Clinical management generally includes a low-fat diet and supplementation with medium chain triglycerides. A small number of recent reports advocate the use of octreotide in intestinal lymphangiectasia. It is unclear why octreotide was used in these studies; although octreotide can alter splanchnic blood flow and intestinal motility, its actions on lymphatic function has never been investigated. A case of a patient with intestinal lymphangiectasia who required a shunt procedure after failing medium chain triglycerides and octreotide therapy is presented. During the management of this case, all existing literature on intestinal lymphangiectasia and all the known actions of octreotide were reviewed. Because some of the case reports suggested that octreotide may improve the clinical course of intestinal lymphangiectasia by altering lymphatic function, a series of experiments were undertaken to assess this. In an established guinea pig model, the role of octreotide in lymphatic function was examined. In this model system, the mesenteric lymphatic vessels responded to 5-hydroxytryptamine with a decrease in constriction frequency, while histamine administration markedly increased lymphatic constriction frequency. Octreotide failed to produce any change in lymphatic function when a wide range of concentrations were applied to the mesenteric lymphatic vessel preparation. In conclusion, in this case, octreotide failed to induce a clinical response and laboratory studies showed that octreotide did not alter lymphatic function. Thus, the mechanisms by which octreotide induced clinical responses in the cases reported elsewhere in the literature remain unclear, but the present study suggests that it does not appear to act via increasing

  14. Functional anatomy of the footpad vasculature of dogs: scanning electron microscopy of vascular corrosion casts.

    Science.gov (United States)

    Ninomiya, Hiroyoshi; Akiyama, Emi; Simazaki, Kanae; Oguri, Atsuko; Jitsumoto, Momoko; Fukuyama, Takaaki

    2011-12-01

    Dogs are well adapted to cold climates and they can stand, walk and run on snow and ice for long periods of time. In contrast to the body trunk, which has, dense fur, the paws are more exposed to the cold due to the lack of fur insulation. The extremities have a high surface area-to-volume ratio, so they lose heat very easily. We offer anatomical evidence for a heat-conserving structure associated with dog footpad vasculature. Methylmethacrylate vascular corrosion casts for scanning electron microscopy, Indian ink-injected whole-mount and histological specimens were each prepared, in a series of 16 limbs from four adult dogs. Vascular casts and Indian ink studies showed that abundant venules were arranged around the arteries supplying the pad surface and formed a vein-artery-vein triad, with the peri-arterial venous network intimately related to the arteries. In addition, numerous arteriovenous anastomoses and well-developed venous plexuses were found throughout the dermal vasculature. The triad forms a counter-current heat exchanger. When the footpad is exposed to a cold environment, the counter-current heat exchanger serves to prevent heat loss by recirculating heat back to the body core. Furthermore, the arteriovenous anastomoses shift blood flow, draining blood to the skin surface, and the venous plexuses retain warm blood in the pad surface. Hence, the appropriate temperature for the footpad can be maintained in cold environments. © 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.

  15. Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability

    Science.gov (United States)

    Palomba, R.; Parodi, A.; Evangelopoulos, M.; Acciardo, S.; Corbo, C.; De Rosa, E.; Yazdi, I. K.; Scaria, S.; Molinaro, R.; Furman, N. E. Toledano; You, J.; Ferrari, M.; Salvatore, F.; Tasciotti, E.

    2016-10-01

    Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability, and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are composed of a surface coating containing multiple receptors that are critical in the cross-talk with the endothelium, mediating cellular accumulation in the tumor microenvironment while decreasing vascular barrier function. We previously demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Herein, we provide a more comprehensive analysis of the working mechanism of LLV in vitro in activating this pathway and in vivo in enhancing vascular permeability. Our results suggest the biological activity of the leukocyte membrane can be retained upon transplant onto NPS and is critical in providing the particles with complex biological functions towards tumor vasculature.

  16. Characterization of an Isolated Kidney's Vasculature for Use in Bio-Thermal Modeling

    Science.gov (United States)

    Payne, Allison H.; Parker, Dennis L.; Moellmer, Jeff; Roemer, Robert B.; Clifford, Sarah

    2007-05-01

    Accurate bio-thermal modeling requires site-specific modeling of discrete vascular anatomy. Presented herewith are several steps that have been developed to describe the vessel network of isolated canine and bovine kidneys. These perfused, isolated kidneys provide an environment to repeatedly test and improve acquisition methods to visualize the vascular anatomy, as well as providing a method to experimentally validate discrete vasculature thermal models. The organs are preserved using a previously developed methodology that keeps the vasculature intact, allowing for the organ to be perfused. It also allows for the repeated fixation and re-hydration of the same organ, permitting the comparison of various methods and models. The organ extraction, alcohol preservation, and perfusion of the organ are described. The vessel locations were obtained through a high-resolution time-of-flight (TOF) magnetic resonance angiography (MRA) technique. Sequential improvements of both the experimental setup used for this acquisition, as well as MR sequence development are presented. The improvements in MR acquisition and experimental setup improved the number of vessels seen in both the raw data and segmented images by 50%. An automatic vessel centerline extraction algorithm describes both vessel location and genealogy. Centerline descriptions also allows for vessel diameter and flow rate determination, providing valuable input parameters for the discrete vascular thermal model. Characterized vessels networks of both canine and bovine kidneys are presented. While these tools have been developed in an ex vivo environment, all steps can be applied to in vivo applications.

  17. Cancer cells remodel themselves and vasculature to overcome the endothelial barrier.

    Science.gov (United States)

    Shenoy, Anitha K; Lu, Jianrong

    2016-10-01

    Metastasis refers to the spread of cancer cells from a primary tumor to distant organs mostly via the bloodstream. During the metastatic process, cancer cells invade blood vessels to enter circulation, and later exit the vasculature at a distant site. Endothelial cells that line blood vessels normally serve as a barrier to the movement of cells into or out of the blood. It is thus critical to understand how metastatic cancer cells overcome the endothelial barrier. Epithelial cancer cells acquire increased motility and invasiveness through epithelial-to-mesenchymal transition (EMT), which enables them to move toward vasculature. Cancer cells also express a variety of adhesion molecules that allow them to attach to vascular endothelium. Finally, cancer cells secrete or induce growth factors and cytokines to actively prompt vascular hyperpermeability that compromises endothelial barrier function and facilitates transmigration of cancer cells through the vascular wall. Elucidation of the mechanisms underlying metastatic dissemination may help develop new anti-metastasis therapeutics. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Residual motion compensation in ECG-gated interventional cardiac vasculature reconstruction

    International Nuclear Information System (INIS)

    Schwemmer, C; Müller, K; Hornegger, J; Rohkohl, C; Lauritsch, G

    2013-01-01

    Three-dimensional reconstruction of cardiac vasculature from angiographic C-arm CT (rotational angiography) data is a major challenge. Motion artefacts corrupt image quality, reducing usability for diagnosis and guidance. Many state-of-the-art approaches depend on retrospective ECG-gating of projection data for image reconstruction. A trade-off has to be made regarding the size of the ECG-gating window. A large temporal window is desirable to avoid undersampling. However, residual motion will occur in a large window, causing motion artefacts. We present an algorithm to correct for residual motion. Our approach is based on a deformable 2D–2D registration between the forward projection of an initial, ECG-gated reconstruction, and the original projection data. The approach is fully automatic and does not require any complex segmentation of vasculature, or landmarks. The estimated motion is compensated for during the backprojection step of a subsequent reconstruction. We evaluated the method using the publicly available CAVAREV platform and on six human clinical datasets. We found a better visibility of structure, reduced motion artefacts, and increased sharpness of the vessels in the compensated reconstructions compared to the initial reconstructions. At the time of writing, our algorithm outperforms the leading result of the CAVAREV ranking list. For the clinical datasets, we found an average reduction of motion artefacts by 13 ± 6%. Vessel sharpness was improved by 25 ± 12% on average. (paper)

  19. Residual motion compensation in ECG-gated interventional cardiac vasculature reconstruction

    Science.gov (United States)

    Schwemmer, C.; Rohkohl, C.; Lauritsch, G.; Müller, K.; Hornegger, J.

    2013-06-01

    Three-dimensional reconstruction of cardiac vasculature from angiographic C-arm CT (rotational angiography) data is a major challenge. Motion artefacts corrupt image quality, reducing usability for diagnosis and guidance. Many state-of-the-art approaches depend on retrospective ECG-gating of projection data for image reconstruction. A trade-off has to be made regarding the size of the ECG-gating window. A large temporal window is desirable to avoid undersampling. However, residual motion will occur in a large window, causing motion artefacts. We present an algorithm to correct for residual motion. Our approach is based on a deformable 2D-2D registration between the forward projection of an initial, ECG-gated reconstruction, and the original projection data. The approach is fully automatic and does not require any complex segmentation of vasculature, or landmarks. The estimated motion is compensated for during the backprojection step of a subsequent reconstruction. We evaluated the method using the publicly available CAVAREV platform and on six human clinical datasets. We found a better visibility of structure, reduced motion artefacts, and increased sharpness of the vessels in the compensated reconstructions compared to the initial reconstructions. At the time of writing, our algorithm outperforms the leading result of the CAVAREV ranking list. For the clinical datasets, we found an average reduction of motion artefacts by 13 ± 6%. Vessel sharpness was improved by 25 ± 12% on average.

  20. Recombinant human endostatin improves tumor vasculature and alleviates hypoxia in Lewis lung carcinoma

    International Nuclear Information System (INIS)

    Peng Fang; Wang Jin; Zou Yi; Bao Yong; Huang Wenlin; Chen Guangming; Luo Xianrong; Chen Ming

    2011-01-01

    Objective: To investigate whether recombinant human endostatin can create a time window of vascular normalization prior to vascular pruning to alleviate hypoxia in Lewis lung carcinoma in mice. Methods: Kinetic changes in morphology of tumor vasculature in response to recombinant human endostatin were detected under a confocal microscope with immunofluorescent staining in Lewis lung carcinomas in mice. The hypoxic cell fraction of different time was assessed with immunohistochemical staining . Effects on tumor growth were monitored as indicated in the growth curve of tumors . Results: Compared with the control group vascularity of the tumors was reduced over time by recombinant human endostatin treatment and significantly regressed for 9 days. During the treatment, pericyte coverage increased at day 3, increased markedly at day 5, and fell again at day 7. The vascular basement membrane was thin and closely associated with endothelial cells after recombinant human endostatin treatment, but appeared thickened, loosely associated with endothelial cells in control tumors. The decrease in hypoxic cell fraction at day 5 after treatment was also found. Tumor growth was not accelerated 5 days after recombinant human endostatin treatment. Conclusions: Recombinant human endostatin can normalize tumor vasculature within day 3 to 7, leading to improved tumor oxygenation. The results provide important experimental basis for combining recombinant human endostatin with radiation therapy in human tumors. (authors)

  1. The role of vasculature in bone development, regeneration and proper systemic functioning.

    Science.gov (United States)

    Filipowska, Joanna; Tomaszewski, Krzysztof A; Niedźwiedzki, Łukasz; Walocha, Jerzy A; Niedźwiedzki, Tadeusz

    2017-08-01

    Bone is a richly vascularized connective tissue. As the main source of oxygen, nutrients, hormones, neurotransmitters and growth factors delivered to the bone cells, vasculature is indispensable for appropriate bone development, regeneration and remodeling. Bone vasculature also orchestrates the process of hematopoiesis. Blood supply to the skeletal system is provided by the networks of arteries and arterioles, having distinct molecular characteristics and localizations within the bone structures. Blood vessels of the bone develop through the process of angiogenesis, taking place through different, bone-specific mechanisms. Impaired functioning of the bone blood vessels may be associated with the occurrence of some skeletal and systemic diseases, i.e., osteonecrosis, osteoporosis, atherosclerosis or diabetes mellitus. When a disease or trauma-related large bone defects appear, bone grafting or bone tissue engineering-based strategies are required. However, a successful bone regeneration in both approaches largely depends on a proper blood supply. In this paper, we review the most recent data on the functions, molecular characteristics and significance of the bone blood vessels, with a particular emphasis on the role of angiogenesis and blood vessel functioning in bone development and regeneration, as well as the consequences of its impairment in the course of different skeletal and systemic diseases.

  2. Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis.

    Science.gov (United States)

    Bisoendial, Radjesh; Tabet, Fatiha; Tak, Paul P; Petrides, Francine; Cuesta Torres, Luisa F; Hou, Liming; Cook, Adam; Barter, Philip J; Weninger, Wolfgang; Rye, Kerry-Anne

    2015-11-01

    Lymphatic endothelial dysfunction underlies the pathogenesis of many chronic inflammatory disorders. The proinflammatory cytokine tumor necrosis factor (TNF) is known for its role in disrupting the function of the lymphatic vasculature. This study investigates the ability of apolipoprotein (apo) A-I, the principal apolipoprotein of high-density lipoproteins, to preserve the normal function of lymphatic endothelial cells treated with TNF. TNF decreased the ability of lymphatic endothelial cells to form tube-like structures. Preincubation of lymphatic endothelial cells with apoA-I attenuated the TNF-mediated inhibition of tube formation in a concentration-dependent manner. In addition, apoA-I reversed the TNF-mediated suppression of lymphatic endothelial cell migration and lymphatic outgrowth in thoracic duct rings. ApoA-I also abrogated the negative effect of TNF on lymphatic neovascularization in an ATP-binding cassette transporter A1-dependent manner. At the molecular level, this involved downregulation of TNF receptor-1 and the conservation of prospero-related homeobox gene-1 expression, a master regulator of lymphangiogenesis. ApoA-I also re-established the normal phenotype of the lymphatic network in the diaphragms of human TNF transgenic mice. ApoA-I restores the neovascularization capacity of the lymphatic system during TNF-mediated inflammation. This study provides a proof-of-concept that high-density lipoprotein-based therapeutic strategies may attenuate chronic inflammation via its action on lymphatic vasculature. © 2015 American Heart Association, Inc.

  3. Functional transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 channels along different segments of the renal vasculature

    DEFF Research Database (Denmark)

    Chen, L; Kaßmann, M; Sendeski, M

    2015-01-01

    with functional TRPV1 having a narrow, discrete distribution in the resistance vasculature and TRPV4 having more universal, widespread distribution along different vascular segments. We suggest that TRPV1/4 channels are potent therapeutic targets for site-specific vasodilation in the kidney.......AIM: Transient receptor potential vanilloid 1 (TRPV1) and vanilloid 4 (TRPV4) cation channels have been recently identified to promote endothelium-dependent relaxation of mouse mesenteric arteries. However, the role of TRPV1 and TRPV4 in the renal vasculature is largely unknown. We hypothesized...... that TRPV1/4 plays a role in endothelium-dependent vasodilation of renal blood vessels. METHODS: We studied the distribution of functional TRPV1/4 along different segments of the renal vasculature. Mesenteric arteries were studied as control vessels. RESULTS: The TRPV1 agonist capsaicin relaxed mouse...

  4. Etonogestrel implant migration to the vasculature, chest wall, and distant body sites: cases from a pharmacovigilance database.

    Science.gov (United States)

    Kang, Sarah; Niak, Ali; Gada, Neha; Brinker, Allen; Jones, S Christopher

    2017-12-01

    To describe clinical outcomes of etonogestrel implant patients with migration to the vasculature, chest wall and other distant body sites spontaneously reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. We performed a standardized Medical Dictionary for Regulatory Activities (MedDRA) query in the FAERS database (through November 15, 2015), with reports coded with one or more MedDRA preferred terms that indicate complications with device placement or migration of the device from the original site of insertion to the vasculature, chest wall and other distant body sites. We excluded any cases previously described in the medical literature. We identified 38 cases of pronounced etonogestrel implant migration. Migration locations included the lung/pulmonary artery (n=9), chest wall (n=1), vasculature at locations other than the lung/pulmonary artery (n=14) and extravascular migrations (n=14) to other body sites (e.g., the axilla and clavicle/neck line/shoulder). The majority of cases were asymptomatic and detected when the patient desired implant removal; however, seven cases reported symptoms such as pain, discomfort and dyspnea in association with implant migration. Three cases also describe pulmonary fibrosis and skin reactions as a result of implant migration to the vasculature, chest wall and other distant body sites. Sixteen cases reported surgical removal in an operating room setting. Our FAERS case series demonstrates etonogestrel implant migration to the vasculature, chest wall and other body sites distant from the site of original insertion. As noted by the sponsor in current prescribing information, a key determinant in the risk for etonogestrel contraceptive implant migration appears to be improper insertion technique. Although migration of etonogestrel implants to the vasculature is rare, awareness of migration and education on proper insertion technique may reduce the risk. Published by Elsevier Inc.

  5. Noise-immune complex correlation for vasculature imaging based on standard and Jones-matrix optical coherence tomography

    Science.gov (United States)

    Makita, Shuichi; Kurokawa, Kazuhiro; Hong, Young-Joo; Li, En; Miura, Masahiro; Yasuno, Yoshiaki

    2016-03-01

    A new optical coherence angiography (OCA) method, called correlation mapping OCA (cmOCA), is presented by using the SNR-corrected complex correlation. An SNR-correction theory for the complex correlation calculation is presented. The method also integrates a motion-artifact-removal method for the sample motion induced decorrelation artifact. The theory is further extended to compute more reliable correlation by using multi- channel OCT systems, such as Jones-matrix OCT. The high contrast vasculature imaging of in vivo human posterior eye has been obtained. Composite imaging of cmOCA and degree of polarization uniformity indicates abnormalities of vasculature and pigmented tissues simultaneously.

  6. Lymphangiogenesis and Lymphatic Absorption Are Related and Increased in Chronic Kidney Failure, Independent of Exposure to Dialysis Solutions

    NARCIS (Netherlands)

    Vlahu, Carmen A.; de Graaff, Marijke; Aten, Jan; Struijk, Dirk G.; Krediet, Raymond T.

    2015-01-01

    Increased lymphatic absorption might contribute to ultrafiltration failure in peritoneal dialysis (PD). Lymphangiogenesis develops during PD, but little is known about the relationship between its morphologic and functional parameters. The relationships between lymph vessel density, the effective

  7. Development of a Tissue-Engineered Lymphatic Graft Using Nanocomposite Polymer for the Treatment of Secondary Lymphedema.

    Science.gov (United States)

    Kanapathy, Muholan; Kalaskar, Deepak; Mosahebi, Afshin; Seifalian, Alexander M

    2016-03-01

    Damage of the lymphatic vessels, commonly due to surgical resection for cancer treatment, leads to secondary lymphedema. Tissue engineering approach offers a possible solution to reconstruct this damage with the use of lymphatic graft to re-establish the lymphatic flow, hence preventing lymphedema. The aim of this study is to develop a tissue-engineered lymphatic graft using nanocomposite polymer and human dermal lymphatic endothelial cells (HDLECs). A nanocomposite polymer, the polyhedral oligomeric silsequioxane-poly(carbonate-urea)urethane (POSS-PCU), which has enhanced mechanical, chemical, and physical characteristics, was used to develop the lymphatic graft. POSS-PCU has been used clinically for the world's first synthetic trachea, lacrimal duct, and is currently undergoing clinical trial for coronary artery bypass graft. Two designs and fabrication methods were used to manufacture the conduits. The fabrication method, the mechanical and physical properties, as well as the hydraulic conductivity were tested. This is followed by in vitro cell culture analysis to test the cytocompatibility of HDLEC with the polymer surface. Using the casted extrusion method, the nanocomposite lymphatic graft demonstrates desirable mechanical property and hydraulic conductivity to re-establish the lymphatic flow. The conduit has high tensile strength (casted: 74.86 ± 5.74 MPa vs. coagulated: 31.33 ± 3.71 MPa; P nanocomposite polymer. It displays excellent mechanical property and cytocompatibility to HDLECs, offering much promise for clinical applications and as a new treatment option for secondary lymphedema. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  8. Study Regarding the Effectiveness of Manual Lymphatic Drainage in the Case of Patients with Breast Cancer that Present Lymphedema

    OpenAIRE

    Alexandru MIOC; Corina PANTEA

    2013-01-01

    Lymphedema is defined as a persistent increase of tissue volume caused by the blocked or absent lymphatic drainage. The purpose of this study is to analyse the effectiveness of lymphatic drainage in the treatment of lymphedema after a mastectomy, with the aim of reducing the volume of the lymphedema and improving overall symptomatology, as well as providing information regarding the impact of this treatment on quality-of-life and the physical limitations of these patients. With these objectiv...

  9. Characterization of biosynthesis and modes of action of prostaglandin E2 and prostacyclin in guinea pig mesenteric lymphatic vessels.

    Science.gov (United States)

    Rehal, Sonia; Blanckaert, Pauline; Roizes, Simon; von der Weid, Pierre-Yves

    2009-12-01

    Rhythmical transient constrictions of the lymphatic vessels provide the means for efficient lymph drainage and interstitial tissue fluid balance. This activity is critical during inflammation, to avoid or limit oedema resulting from increased vascular permeability, mediated by the release of various inflammatory mediators. In this study, we investigated the mechanisms by which prostaglandin E(2) (PGE(2)) and prostacyclin modulate lymphatic contractility in isolated guinea pig mesenteric lymphatic vessels. Quantitative RT-PCR was used to assess the expression of mRNA for enzymes and receptors involved in the production and action of PGE(2) and prostacyclin in mesenteric collecting lymphatic vessels. Frequency and amplitude of lymphatic vessel constriction were measured in the presence of these prostaglandins and the role of their respective EP and IP receptors assessed. Prostaglandin E(2) and prostacyclin decreased concentration-dependently the frequency, without affecting the amplitude, of lymphatic constriction. Data obtained in the presence of the EP(4) receptor antagonists, GW627368x (1 microM) and AH23848B (30 microM) and the IP receptor antagonist CAY10441 (0.1 microM) suggest that PGE(2) predominantly activates EP(4), whereas prostacyclin mainly stimulates IP receptors. Inhibition of responses to either prostaglandin with H89 (10 microM) or glibenclamide (1 microM) suggested a role for the activation of protein kinase A and ATP-sensitive K(+) channels. Our findings characterized the inhibition of lymphatic pumping induced by PGE(2) or prostacyclin in guinea pig mesenteric lymphatics. This action is likely to impair oedema resolution and to contribute to the pro-inflammatory actions of these prostaglandins.

  10. Changes of the vasculature and innervation in the anterior segment of the RCS rat eye.

    Science.gov (United States)

    May, Christian Albrecht

    2011-12-01

    Investigating the anterior eye segment vasculature and innervation of dystrophic RCS rats, two major unique findings were observed: in the iris, young adult animals with retinal dystrophy showed an increase in substance P nerve fibres and a dilation of arterioles and capillaries. This finding continued during ageing. In the pars plana region, the surface covered by venules decreased continuously with age. In older animals, this decrease was parallelled by a local decrease of sympathetic TH-positive nerve fibres supplying these venules. For both conditions, no comparable data exists so far in the literature. They might point to a unique situation in the anterior eye segment of the dystrophic RCS rat. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. From the Cover: Adipose tissue mass can be regulated through the vasculature

    Science.gov (United States)

    Rupnick, Maria A.; Panigrahy, Dipak; Zhang, Chen-Yu; Dallabrida, Susan M.; Lowell, Bradford B.; Langer, Robert; Judah Folkman, M.

    2002-08-01

    Tumor growth is angiogenesis dependent. We hypothesized that nonneoplastic tissue growth also depends on neovascularization. We chose adipose tissue as an experimental system because of its remodeling capacity. Mice from different obesity models received anti-angiogenic agents. Treatment resulted in dose-dependent, reversible weight reduction and adipose tissue loss. Marked vascular remodeling was evident in adipose tissue sections, which revealed decreased endothelial proliferation and increased apoptosis in treated mice compared with controls. Continuous treatment maintained mice near normal body weights for age without adverse effects. Metabolic adaptations in food intake, metabolic rate, and energy substrate utilization were associated with anti-angiogenic weight loss. We conclude that adipose tissue mass is sensitive to angiogenesis inhibitors and can be regulated by its vasculature.

  12. Lymphatic compensation during the postoperative period after breast cancer treatment with axillary dissection

    Directory of Open Access Journals (Sweden)

    Mariana Maia Freire de Oliveira

    2015-06-01

    Full Text Available Lymphedema secondary to breast cancer causes physical and psychological morbidity and compromises quality of life. The objective of this literature review was to study lymphatic compensation after surgery for breast cancer and the factors that influence this process, with a view to understanding the etiopathogenesis of lymphedema. Articles indexed on Pubmed published from 1985 to 2012 were reviewed. According to the literature, lymphangiogenesis reduces damage to lymph vessels; there is little evidence that Vascular Endothelial Growth Factor is elevated in women with lymphedema; lymphovenous communications can be observed 60 days after surgery; women without lymphedema have acquired alternative mechanisms for removal of proteins from the interstitial space; and active exercise stimulates lymphatic and venous pumping. Health professionals should teach these patients about the risk factors for lymphedema. The effects of lymphangiogenesis, proteolysis and lymphovenous communications on development of lymphedema should be studied, since these events are intimately related.

  13. Effects of lymphatic drainage and cryotherapy on indirect markers of muscle damage.

    Science.gov (United States)

    Behringer, Michael; Jedlicka, Diana; Mester, Joachim

    2018-06-01

    Muscle enzymes are cleared from the extracellular space by the lymphatic system, while smaller proteins enter the bloodstream directly. We investigated if manual lymphatic drainage (MLD), local cryotherapy (CRY), and rest (RST) differently affect the time course of creatine kinase (CK, 84 kDa) and heart-type fatty acid binding protein (h-FABP, 15 kDa) in the blood. Randomized controlled trial. After 4x20 unilateral, eccentric accentuated knee extensions (with one-third of the maximal isometric force) 30 sports students randomly received either a 30 min MLD, CRY or they rested (RST) for the same amount of time. CK, h-FABP, neutrophil granulocytes, and the perceived muscle soreness were assessed before, immediately after, and 1 hour, 4 hours, and 24 hours after the exercise. All measures increased significantly (Psports physicians and conditioning specialists who use biochemical muscle damage markers to adjust the training load and volume of athletes.

  14. Twin infant with lymphatic dysplasia diagnosed with Noonan syndrome by molecular genetic testing.

    Science.gov (United States)

    Mathur, Deepan; Somashekar, Santhosh; Navarrete, Cristina; Rodriguez, Maria M

    2014-08-01

    Noonan Syndrome is an autosomal dominant disorder characterized by short stature, congenital heart defects, developmental delay, dysmorphic facial features and occasional lymphatic dysplasias. The features of Noonan Syndrome change with age and have variable expression. The diagnosis has historically been based on clinical grounds. We describe a child that was born with congenital refractory chylothorax and subcutaneous edema suspected to be secondary to pulmonary lymphangiectasis. The infant died of respiratory failure and anasarca at 80 days. The autopsy confirmed lymphatic dysplasia in lungs and mesentery. The baby had no dysmorphic facial features and was diagnosed postmortem with Noonan syndrome by genomic DNA sequence analysis as he had a heterozygous mutation for G503R in the PTPN11 gene.

  15. Role of the paraventricular nucleus in the reflex diuresis to pulmonary lymphatic obstruction in rabbits.

    Science.gov (United States)

    Choudhary, Rishabh Charan; Sharma, Ravindra Kumar; Gulati, Kavita; Ravi, Krishnan

    2016-01-01

    The changes in urine flow and renal sympathetic nerve activity (RSNA) due to pulmonary lymphatic obstruction (PLO) were examined in anesthetized, artificially ventilated New Zealand white rabbits. PLO was produced by pressurizing an isolated pouch created in the right external jugular vein at the points of entry of the right lymphatic ducts. During this maneuver, urine flow increased from 8.5 ± 0.3 mL/10 min to 12 ± 0.5 mL/10 min (P acid microinjections into the PVN. The results show that (i) neurons in the PVN are an important relay site in the reflex arc, which is activated by PLO; and (ii) this activation is regulated by glutamatergic and partly by GABAergic input to the PVN.

  16. Use of Magnetic Nanoparticles to Visualize Threadlike Structures inside Lymphatic Vessels of Rats

    Directory of Open Access Journals (Sweden)

    Hyeon-Min Johng

    2007-01-01

    Full Text Available A novel application of fluorescent magnetic nanoparticles was made to visualize a new tissue which had not been detectable by using simple stereomicroscopes. This unfamiliar threadlike structure inside the lymphatic vessels of rats was demonstrated in vivo by injecting nanoparticles into lymph nodes and applying magnetic fields on the collecting lymph vessels so that the nanoparticles were taken up by the threadlike structures. Confocal laser scanning microscope images of cryosectioned specimens exhibited that the nanoparticles were absorbed more strongly by the threadlike structure than by the lymphatic vessels. Further examination using a transmission electron microscope revealed that the nanoparticles had been captured between the reticular fibers in the extracellular matrix of the threadlike structures. The emerging technology of nanoparticles not only allows the extremely elusive threadlike structures to be visualized but also is expected to provide a magnetically controllable means to investigate their physiological functions.

  17. Semaphorin 3G Provides a Repulsive Guidance Cue to Lymphatic Endothelial Cells via Neuropilin-2/PlexinD1.

    Science.gov (United States)

    Liu, Xinyi; Uemura, Akiyoshi; Fukushima, Yoko; Yoshida, Yutaka; Hirashima, Masanori

    2016-11-22

    The vertebrate circulatory system is composed of closely related blood and lymphatic vessels. It has been shown that lymphatic vascular patterning is regulated by blood vessels during development, but its molecular mechanisms have not been fully elucidated. Here, we show that the artery-derived ligand semaphorin 3G (Sema3G) and the endothelial cell receptor PlexinD1 play a role in lymphatic vascular patterning. In mouse embryonic back skin, genetic inactivation of Sema3G or PlexinD1 results in abnormal artery-lymph alignment and reduced lymphatic vascular branching. Conditional ablation in mice demonstrates that PlexinD1 is primarily required in lymphatic endothelial cells (LECs). In vitro analyses show that Sema3G binds to neuropilin-2 (Nrp2), which forms a receptor complex with PlexinD1. Sema3G induces cell collapse in an Nrp2/PlexinD1-dependent manner. Our findings shed light on a molecular mechanism by which LECs are distributed away from arteries and form a branching network during lymphatic vascular development. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Autoradiographic investigations on the prednisolone-induced atrophy and on interdependent reactions in different lymphatic tissues of rabbit

    International Nuclear Information System (INIS)

    Steigueber, F.

    1980-01-01

    Under the application of 3 H-thymidine the method of organ extirpation (thymectomy and appendectomy) was combined with the cell labeling technique. By autoradiographic evaluation of histologic specimens the content of labelled lymphocytes in the examined tissues was determined. Thymus, appendix, subcutaneous lymphatic nodes and spleen were examined. In the thymus the application of prednisolone induced organ atrophy. Appendectomy leads in the thymic marrow to an increase of the mitotic activity. In the appendix the application of prednisolone causes the emptying of basal lymphatic follicles. Thymectomy induces a large increase of the mitotic activity of the lymphatic tissue. Not all lymphatic nodes show identical changes after organ extirpation and after prednisolone application, but considerable differences. Only a decreased proliferation of labled lymphocytes, occuring under prednisolone application, can be detected in the marrow of the mesenteric lymphatic nodes and of the red splenic pulp in the animal with thymectomy. This result is also valid for the marrow of the remaining deep lymphatic nodes, after thymectomy and appendectomy. The lymphocyte counting in the peripheral blood done during prednisolone treatment, does not indicate that the lymphocyte values depend to a notable extent on the previous surgical treatment of the animals. (orig./MG) [de

  19. Immune Consequences of Decreasing Tumor Vasculature with Antiangiogenic Tyrosine Kinase Inhibitors in Combination with Therapeutic Vaccines

    Science.gov (United States)

    Farsaci, Benedetto; Donahue, Renee N.; Coplin, Michael A.; Grenga, Italia; Lepone, Lauren M.; Molinolo, Alfredo A.; Hodge, James W.

    2014-01-01

    This study investigated the effects on the tumor microenvironment of combining antiangiogenic tyrosine kinase inhibitors (TKI) with therapeutic vaccines, and in particular, how vascular changes affect tumor-infiltrating immune cells. We conducted studies using a TKI (sunitinib or sorafenib) in combination with recombinant vaccines in 2 murine tumor models: colon carcinoma (MC38-CEA) and breast cancer (4T1). Tumor vasculature was measured by immunohistochemistry using 3 endothelial cell markers: CD31 (mature), CD105 (immature/proliferating), and CD11b (monocytic). We assessed oxygenation, tight junctions, compactness, and pressure within tumors, along with the frequency and phenotype of tumor-infiltrating T lymphocytes (TIL), myeloid-derived suppressor cells (MDSC), and tumor-associated macrophages (TAM) following treatment with antiangiogenic TKIs alone, vaccine alone, or the combination of a TKI with vaccine. The combined regimen decreased tumor vasculature, compactness, tight junctions, and pressure, leading to vascular normalization and increased tumor oxygenation. This combination therapy also increased TILs, including tumor antigen-specific CD8 T cells, and elevated the expression of activation markers FAS-L, CXCL-9, CD31, and CD105 in MDSCs and TAMs, leading to reduced tumor volumes and an increase in the number of tumor-free animals. The improved antitumor activity induced by combining antiangiogenic TKIs with vaccine may be the result of activated lymphoid and myeloid cells in the tumor microenvironment, resulting from vascular normalization, decreased tumor-cell density, and the consequent improvement in vascular perfusion and oxygenation. Therapies that alter tumor architecture can thus have a dramatic impact on the effectiveness of cancer immunotherapy. PMID:25092771

  20. A comparative study of Cyclofem and depot medroxyprogesterone acetate (DMPA) effects on endometrial vasculature.

    Science.gov (United States)

    Simbar, Masoumeh; Tehrani, Fahimeh Ramezani; Hashemi, Zeinab; Zham, Hananeh; Fraser, Ian S

    2007-10-01

    The most common reason for discontinuation of long-acting progestogen-only contraceptives is irregular bleeding following local endometrial vascular changes. To reduce unpredictable bleeding episodes among depot medroxyprogesterone acetate (DMPA) users, the combined injectable contraceptive, Cyclofem, was offered as an alternative. However, there is a gap in our knowledge about the effects of Cyclofem on the endometrial vasculature and patterns of bleeding. This study aimed to compare the effects of Cyclofem and DMPA on endometrial vascular density, endometrial histology and pattern of bleeding. Sixty-eight healthy women with regular menstrual bleeding and seeking injectable long-acting contraceptives were recruited. Two endometrial samples (before and 3 to 6 months after initial exposure to DMPA or Cyclofem) were collected from each participant. The samples were stained using an immunohistochemical method and anti-CD34 to visualise the endometrial vasculature. Endometrial vascular density was assessed using standard techniques. Sixty-eight women were randomly assigned to Cyclofem (38 women) or DMPA (30 women). Endometrial vascular density was 149.3 +/- 6.7 (mean +/- SD)/mm(2) before injection. This significantly decreased to 132.4 +/- 12.2 after DMPA use, and from 151.9 +/- 5.8 to 131.8 +/- 12.8 vessels/mm(2) following Cyclofem use (paired t-test, p Spotting was the most common type of bleeding experienced, and atrophic endometrium was the most common histological pattern observed in both groups. This study demonstrated that both Cyclofem and DMPA use are associated with decreased endometrial vascular density and atrophic endometrium, in addition to irregular bleeding, mainly spotting. There was no significant difference in bleeding patterns or endometrial findings observed for these two injectable contraceptives in Iranian women.

  1. Identification of thioaptamer ligand against E-selectin: potential application for inflamed vasculature targeting.

    Directory of Open Access Journals (Sweden)

    Aman P Mann

    Full Text Available Active targeting of a drug carrier to a specific target site is crucial to provide a safe and efficient delivery of therapeutics and imaging contrast agents. E-selectin expression is induced on the endothelial cell surface of vessels in response to inflammatory stimuli but is absent in the normal vessels. Thus, E-selectin is an attractive molecular target, and high affinity ligands for E-selectin could be powerful tools for the delivery of therapeutics and/or imaging agents to inflamed vessels. In this study, we identified a thiophosphate modified aptamer (thioaptamer, TA against E-selectin (ESTA-1 by employing a two-step selection strategy: a recombinant protein-based TA binding selection from a combinatorial library followed by a cell-based TA binding selection using E-selectin expressing human microvascular endothelial cells. ESTA-1 selectively bound to E-selectin with nanomolar binding affinity (K(D = 47 nM while exhibiting minimal cross reactivity to P- and L-selectin. Furthermore, ESTA-1 binding to E-selectin on the endothelial cells markedly antagonized the adhesion (over 75% inhibition of sLe(x positive HL-60 cells at nanomolar concentration. ESTA-1 also bound specifically to the inflamed tumor-associated vasculature of human carcinomas derived from breast, ovarian, and skin but not to normal organs, and this binding was highly associated with the E-selectin expression level. Similarly, intravenously injected ESTA-1 demonstrated distinct binding to the tumor vasculature in a breast cancer xenograft model. Together, our data substantiates the discovery of a thioaptamer (ESTA-1 that binds to E-selectin with high affinity and specificity, thereby highlighting the potential application of ESTA-1 for E-selectin targeted delivery.

  2. Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

    DEFF Research Database (Denmark)

    Louveau, Antoine; Plog, Benjamin A; Antila, Salli

    2017-01-01

    to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege...... and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems....

  3. Conjugated Linoleic Triacylglycerols Exhibit Superior Lymphatic Absorption Than Free Conjugate Linoleic Acids and Have Antiobesity Properties.

    Science.gov (United States)

    Woo, Hyunjoon; Chung, Min-Yu; Kim, Juyeon; Kong, Daecheol; Min, Jinyoung; Choi, Hee-Don; Choi, In-Wook; Kim, In-Hwan; Noh, Sang K; Kim, Byung Hee

    2016-05-01

    This study aimed to compare lymphatic absorption of conjugated linoleic acids (CLAs) in the triacylglycerol (TAG) or free fatty acid (FFA) form and to examine the antiobesity effects of different doses of CLAs in the TAG form in animals. Conjugated linoleic TAGs (containing 70.3 wt% CLAs; CLA-TAG) were prepared through lipase-catalyzed esterification of glycerol with commercial CLA mixtures (CLA-FFA). Lymphatic absorption of CLA-TAG and CLA-FFA was compared in a rat model of lymphatic cannulation. Greater amounts of cis-9,trans-11 and trans-10,cis-12 CLAs were detected in the collected lymph from a lipid emulsion containing CLA-TAG. This result suggests that CLA-TAG has greater capacity for lymphatic absorption than does CLA-FFA. The antiobesity efficacy of CLA-TAG at different doses was examined in mice with diet-induced obesity. A high-fat diet (HFD) for 12 weeks caused a significant increase in body weight and epididymal and retroperitoneal fat weights, which were significantly decreased by 2% dietary supplementation (w/w) with CLA-TAG. CLA-TAG at 2% significantly attenuated the HFD-induced upregulation of serum TAG, but led to hepatomegaly and exacerbated HFD-induced hypercholesterolemia. CLA-TAG at 1% significantly attenuated upregulation of retroperitoneal fat weight and significantly increased liver weight, which was decreased by the HFD. Nonetheless, the liver weight in group "HFD +1% CLA-TAG" was not significantly different from that of normal diet controls. CLA-TAG at 1% significantly reduced serum TAG levels and did not exacerbate HFD-induced hypercholesterolemia. Thus, 1% dietary supplementation with CLA-TAG reduces retroperitoneal fat weight without apparent hepatomegaly, a known side-effect of CLAs in mouse models of obesity.

  4. The Role of Lymphatic Niches in T Cell Differentiation

    Science.gov (United States)

    Capece, Tara; Kim, Minsoo

    2016-01-01

    Long-term immunity to many viral and bacterial pathogens requires CD8+ memory T cell development, and the induction of long-lasting CD8+ memory T cells from a naïve, undifferentiated state is a major goal of vaccine design. Formation of the memory CD8+ T cell compartment is highly dependent on the early activation cues received by naïve CD8+ T cells during primary infection. This review aims to highlight the cellularity of various niches within the lymph node and emphasize recent evidence suggesting that distinct types of T cell activation and differentiation occur within different immune contexts in lymphoid organs. PMID:27306645

  5. RIP1 regulates TNF-α-mediated lymphangiogenesis and lymphatic metastasis in gallbladder cancer by modulating the NF-κB-VEGF-C pathway.

    Science.gov (United States)

    Li, Cheng-Zong; Jiang, Xiao-Jie; Lin, Bin; Hong, Hai-Jie; Zhu, Si-Yuan; Jiang, Lei; Wang, Xiao-Qian; Tang, Nan-Hong; She, Fei-Fei; Chen, Yan-Ling

    2018-01-01

    for TNF-α-mediated NF-κB activation in GBC cells and can regulate TNF-α-mediated VEGF-C expression at the protein and transcriptional levels through the NF-κB pathway. RIP1 can regulate TNF-α-mediated lymphatic tube formation and metastasis in GBC cells both in vitro and vivo. The average optical density of RIP1 was linearly related to that of TNF-α protein and the lymphatic vessel density in GBC tissues. We conclude that RIP1 regulates TNF-α-mediated lymphangiogenesis and lymph node metastasis in GBC by modulating the NF-κB-VEGF-C pathway.

  6. Maternal separation diminishes α-adrenergic receptor density and function in renal vasculature from male Wistar-Kyoto rats.

    Science.gov (United States)

    Loria, Analia S; Osborn, Jeffrey L

    2017-07-01

    Adult rats exposed to maternal separation (MatSep) are normotensive but display lower glomerular filtration rate and increased renal neuroadrenergic drive. The aim of this study was to determine the renal α-adrenergic receptor density and the renal vascular responsiveness to adrenergic stimulation in male rats exposed to MatSep. In addition, baroreflex sensitivity was assessed to determine a component of neural control of the vasculature. Using tissue collected from 4-mo-old MatSep and control rats, α 1 -adrenergic receptors (α 1 -ARs) were measured in renal cortex and isolated renal vasculature using receptor binding assay, and the α-AR subtype gene expression was determined by RT-PCR. Renal cortical α 1 -AR density was similar between MatSep and control tissues (B max = 44 ± 1 vs. 42 ± 2 fmol/mg protein, respectively); however, MatSep reduced α 1 -AR density in renal vasculature (B max = 47 ± 4 vs. 62 ± 4 fmol/mg protein, P adrenergic receptor expression and function in the renal vasculature could develop secondary to MatSep-induced overactivation of the renal neuroadrenergic tone. Copyright © 2017 the American Physiological Society.

  7. Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Irene Vergara

    2016-03-01

    Full Text Available The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to β-neurotoxins (β-NTx. The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main β-NTx of M. fulvius venom. β-NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was 60%–78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD50 and PLA2 activity of bioconjugated β-NTx decreased 3 and 2.5 times, respectively, in comparison with native β-NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of β-NTx-DTPA-67Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with 67Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of β-NTx-DTPA-67Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of β-NTx-DTPA-67Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming.

  8. [Neck lymphatic metastasis, surgical methods and prognosis in early tongue squamous cell carcinoma].

    Science.gov (United States)

    Wang, L S; Zhou, F T; Han, C B; He, X P; Zhang, Z X

    2018-02-09

    Objective: To investigate the different pattern of neck lymph node metastasis, the choice of surgical methods and prognosis in early tongue squamous cell carcinoma. Methods: A total of 157 patients with early oral tongue squamous cell carcinoma were included in this study. Statistical analysis was performed to identify the pattern of lymph node metastasis, to determine the best surgical procedure and to analyze the prognosis. Results: The occurrence of cervical lymph node metastasis rate was 31%(48/157). Neck lymphatic metastasis was significantly related to tumor size ( P= 0.026) and histology differentiation type ( P= 0.022). The rate of metastasis was highest in level Ⅱ [33% (16/48)]. In level Ⅳ, the incidence of lymph node metastasis was 5%(7/157), and there was no skip metastases. The possibility of level Ⅳ metastasis was higher, when level Ⅱ ( P= 0.000) or Ⅲ ( P= 0.000) involved. The differentiation tumor recurrence, neck lymphatic metastasis and adjuvant radiotherapy were prognostic factors ( Psquamous cell carcinoma, simultaneous glossectomy and neck dissection should be performed. Level Ⅳ metastasis rate is extremely low, so supraomohyoid neck dissection is sufficient for most of the time. The histology differentiation type, neck lymphatic metastasis and adjuvant radiotherapy are independent prognostic factors.

  9. Lymphatic recovery of exogenous oleic acid in rats on long chain or specific structured triacylglycerol diets

    DEFF Research Database (Denmark)

    Vistisen, Bodil; Mu, Huiling; Høy, Carl-Erik

    2006-01-01

    Specific structured triacylglycerols, MLM (M = medium-chain fatty acid, L = long-chain fatty acid), rapidly deliver energy and long-chain fatty acids to the body and are used for longer periods in human enteral feeding. In the present study rats were fed diets of 10 wt% MLM or LLL (L = oleic acid......% and 45%, respectively). However, the recovery of exogenous 18:1 n-9 was higher after a single bolus of MLM compared with a bolus of LLL in rats on the MLM diet (40% and 24%, respectively, P = 0.009). The recovery of lymphatic 18:1 n-9 of the LLL bolus tended to depend on the diet triacylglycerol...... structure and composition (P = 0.07). This study demonstrated that with a diet containing specific structured triacylglycerol, the lymphatic recovery of 18:1 n-9 after a single bolus of fat was dependent on the triacylglycerol structure of the bolus. This indicates that the lymphatic recovery of long...

  10. Refinements of the radiographic cadaver injection technique for investigating minute lymphatic vessels.

    Science.gov (United States)

    Suami, Hiroo; Taylor, G Ian; O'Neill, Jennifer; Pan, Wei-Ren

    2007-07-01

    The authors previously reported a new technique with which to delineate the lymphatic vessels, using hydrogen peroxide to identify them and a lead oxide suspension to demonstrate them on radiographs. This technique provided excellent studies of the lymph vessels in human cadavers, but there was still room for improvement. Lymph collecting vessels run superficially in some regions, where they may be damaged while the surgeon is attempting to find them. Vessels smaller than 0.3 mm in diameter could not be cannulated with a 30-gauge needle, which was the smallest the authors had available, and the lead oxide suspension often blocked this cannula. The authors also encountered problems holding the cannula steady. The authors solved these problems by using a mixture of hydrogen peroxide and ink to better identify the lymphatics, an extruded glass tube instead of a metal needle to cannulate them, an agate pestle and mortar to grind the lead oxide into finer particles, powdered milk to suspend the lead oxide, and a micromanipulator to facilitate accurate and steady cannulation of the vessels. This study developed these modifications to focus on tributaries of the collecting lymphatic channels that are smaller than 0.3 mm in diameter.

  11. Manual lymphatic drainage therapy in patients with breast cancer related lymphoedema

    Directory of Open Access Journals (Sweden)

    Martínez Helena

    2011-03-01

    Full Text Available Abstract Background Lymphoedema is a common and troublesome condition that develops following breast cancer treatment. The aim of this study is to analyze the effectiveness of Manual Lymphatic Drainage in the treatment of postmastectomy lymphoedema in order to reduce the volume of lymphoedema and evaluate the improvement of the concomitant symptomatology. Methods A randomized, controlled clinical trial in 58 women with post-mastectomy lymphoedema. The control group includes 29 patients with standard treatment (skin care, exercise and compression measures, bandages for one month and, subsequently, compression garnments. The experimental group includes 29 patients with standard treatment plus Manual Lymphatic Drainage. The therapy will be administered daily for four weeks and the patient's condition will be assessed one, three and six months after treatment. The primary outcome parameter is volume reduction of the affected arm after treatment, expressed as a percentage. Secondary outcome parameters include: duration of lymphoedema reduction and improvement of the concomitant symptomatology (degree of pain, sensation of swelling and functional limitation in the affected extremity, subjective feeling of being physically less atractive and less feminine, difficulty looking at oneself naked and dissatisfaction with the corporal image. Discussion The results of this study will provide information on the effectiveness of Manual Lymphatic Drainage and its impact on the quality of life and physical limitations of these patients. Trial registration ClinicalTrials (NCT: NCT01152099

  12. Understanding the three-dimensional anatomy of the superficial lymphatics of the limbs.

    Science.gov (United States)

    Tourani, Saam S; Taylor, G Ian; Ashton, Mark W

    2014-11-01

    There are minimal data in the current literature regarding the depth of the superficial lymphatic collectors of the limbs in relation to the various subcutaneous tissue layers. Injection, microdissection, radiographic, and histologic studies of the superficial lymphatics and the subcutaneous tissues of 32 limbs from 15 human cadavers were performed. Five layers were consistently identified in the integument of all the upper and lower limb specimens: (1) skin, (2) subcutaneous fat, (3) superficial fascia, (4) loose areolar tissue, and (5) deep fascia. Layer 2 was further divided into superficial (2a) and deep (2c) compartments by a thin, transparent, horizontal septum (layer 2b). The main superficial veins and the superficial nerves coursed in layer 4. The lymphatic collectors were found at layer 2c and layer 4. The use of consistent nomenclature to describe the subcutaneous tissue layers facilitates a greater understanding and discussion of the anatomy. In lymphovenous anastomosis for the treatment of lymphedema, indocyanine green lymphography is an unreliable method for identification of the superficial collectors of the thigh. The medial proximal leg, the dorsum of the wrist over the anatomical snuffbox, and the volar proximal forearm provide suitable areas for locating superficial collectors with nearby matching size veins. In vertical medial thigh lift, choosing a dissection plane superficial to the great saphenous vein is unlikely to preserve the collectors of the ventromedial bundle.

  13. Endoscopically observable white nodule caused by distal intramural lymphatic spread of rectal cancer: a case report

    Directory of Open Access Journals (Sweden)

    Tsumura Ayako

    2012-10-01

    Full Text Available Abstract This report describes a case of rectal cancer with endoscopically observable white nodules caused by distal intramural lymphatic spread. A 57-year-old female presented to our hospital with frequent diarrhea and hemorrhoids. Computed tomography showed bilateral ovarian masses and three hepatic tumors diagnosed as rectal cancer metastases, and also showed multiple lymph node involvement. The patient was preoperatively diagnosed with stage IV rectal cancer. Colonoscopy demonstrated that primary rectal cancer existed 15 cm from the anal verge and that there were multiple white small nodules on the anal side of the primary tumor extending to the dentate line. Biopsies of the white spots were performed, and they were identified as adenocarcinoma. The patient underwent Hartmann’s procedure because of the locally advanced primary tumor. The white nodules were ultimately diagnosed as being caused by intramural lymphatic spreading because lymphatic permeation was strongly positive at the surrounding area. Small white nodules near a primary rectal cancer should be suspected of being intramural spreading. Endoscopic detection of white nodules may be useful for the diagnosis of distal intramural spread.

  14. Knowledge, attitudes and perceptions regarding lymphatic filariasis: study on systematic noncompliance with mass drug administration

    Directory of Open Access Journals (Sweden)

    Silvia Cabral

    Full Text Available ABSTRACT The aim of this study was to investigate the epidemiological characteristics, antigenic profile, perceptions, attitudes and practices of individuals who have been systematically non-compliant in mass drug administration (MDA campaigns targeting lymphatic filariasis, in the municipality of Olinda, State of Pernambuco, Northeastern Brazil. A pretested questionnaire was used to obtain information on socioenvironmental demographics, perceptions of lymphatic filariasis and MDA, and reasons for systematic noncompliance with treatment. A rapid immunochromatographic test (ICT was performed during the survey to screen for filariasis. It was found that the survey subjects knew about filariasis and MDA. Filariasis was identified as a disease (86.2% and 74.4% associated it with the presence of swelling in the legs. About 80% knew about MDA, and the main source of information was healthcare workers (68.3%. For men the main reasons for systematic noncompliance with MDA were that “the individual had not received the medication” (p=0.03 and for women “the individual either feared experiencing adverse reactions”. According to the ICT, the prevalence of lymphatic filariasis was 2%. The most important causes of systematic noncompliance were not receiving the drug and fear of side-effects. For successful implementation of MDA programs, good planning, educational campaigns promoting the benefits of MDA, adoption of measures to minimize the impact of adverse effects and improvement of drug distribution logistics are needed.

  15. Understanding the functions and relationships of the glymphatic system and meningeal lymphatics.

    Science.gov (United States)

    Louveau, Antoine; Plog, Benjamin A; Antila, Salli; Alitalo, Kari; Nedergaard, Maiken; Kipnis, Jonathan

    2017-09-01

    Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems.

  16. Low-cost microcontroller platform for studying lymphatic biomechanics in vitro.

    Science.gov (United States)

    Kornuta, Jeffrey A; Nipper, Matthew E; Dixon, J Brandon

    2013-01-04

    The pumping innate to collecting lymphatic vessels routinely exposes the endothelium to oscillatory wall shear stress and other dynamic forces. However, studying the mechanical sensitivity of the lymphatic endothelium remains a difficult task due to limitations of commercial or custom systems to apply a variety of time-varying stresses in vitro. Current biomechanical in vitro testing devices are very expensive, limited in capability, or highly complex; rendering them largely inaccessible to the endothelial cell biology community. To address these shortcomings, the authors propose a reliable, low-cost platform for augmenting the capabilities of commercially available pumps to produce a wide variety of flow rate waveforms. In particular, the Arduino Uno, a microcontroller development board, is used to provide open-loop control of a digital peristaltic pump using precisely timed serial commands. In addition, the flexibility of this platform is further demonstrated through its support of a custom-built cell-straining device capable of producing oscillatory strains with varying amplitudes and frequencies. Hence, this microcontroller development board is shown to be an inexpensive, precise, and easy-to-use tool for supplementing in vitro assays to quantify the effects of biomechanical forces on lymphatic endothelial cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. PEGylated polylysine dendrimers increase lymphatic exposure to doxorubicin when compared to PEGylated liposomal and solution formulations of doxorubicin.

    Science.gov (United States)

    Ryan, Gemma M; Kaminskas, Lisa M; Bulitta, Jürgen B; McIntosh, Michelle P; Owen, David J; Porter, Christopher J H

    2013-11-28

    Improved delivery of chemotherapeutic drugs to the lymphatic system has the potential to augment outcomes for cancer therapy by enhancing activity against lymph node metastases. Uptake of small molecule chemotherapeutics into the lymphatic system, however, is limited. Nano-sized drug carriers have the potential to promote access to the lymphatics, but to this point, this has not been examined in detail. The current study therefore evaluated the lymphatic exposure of doxorubicin after subcutaneous and intravenous administration as a simple solution formulation or when formulated as a doxorubicin loaded PEGylated poly-lysine dendrimer (hydrodynamic diameter 12 nm), a PEGylated liposome (100 nm) and various pluronic micellar formulations (~5 nm) to thoracic lymph duct cannulated rats. Plasma and lymph pharmacokinetics were analysed by compartmental pharmacokinetic modelling in S-ADAPT, and Berkeley Madonna software was used to predict the lymphatic exposure of doxorubicin over an extended period of time. The micelle formulations displayed poor in vivo stability, resulting in doxorubicin profiles that were similar to that observed after administration of the doxorubicin solution formulation. In contrast, the dendrimer formulation significantly increased the recovery of doxorubicin in the thoracic lymph after both intravenous and subcutaneous dosing when compared to the solution or micellar formulation. Dendrimer-doxorubicin also resulted in increases in lymphatic doxorubicin concentrations when compared to the liposome formulation, although liposomal doxorubicin did increase lymphatic transport when compared to the solution formulation. Specifically, the dendrimer formulation increased the recovery of doxorubicin in the lymph up to 30 h post dose by up to 685 fold and 3.7 fold when compared to the solution and liposomal formulations respectively. Using the compartmental model to predict lymphatic exposure to longer time periods suggested that doxorubicin exposure to

  18. Measurement of lymphatic function with technetium-99m-labelled polyclonal immunoglobulin

    International Nuclear Information System (INIS)

    Svensson, W.; Glass, D.M.; Bradley, D.; Peters, A.M.

    1999-01-01

    A reliable method for measuring lymph flow in physiological units would be valuable, especially in conditions in which it is uncertain whether lymph flow is increased or decreased. The requirements of a radiopharmaceutical for such measurement include stable radionuclide labelling and rapid access to lymphatic vessels following tissue injection but no access to blood vessels. A soluble macromolecule is likely to come closest to meeting these requirements. Technetium-99m- labelled human polyclonal immunoglobulin (HIG) was therefore investigated firstly in comparison with 99m Tc-labelled human serum albumin (HSA) in patients undergoing routine lymphoscintigraphy and secondly with respect to injection site in a group of volunteers with post-mastectomy oedema (PMO). Subcutaneous injection of 99m Tc-HIG into the web space of a distal extremity gave images in which lymphatic vessels were more clearly defined compared with images obtained after injection of 99m Tc-HSA. Lymph nodes were also more clearly defined, suggesting specific retention of HIG, possibly through Fc-mediated binding. Peripheral blood sampling showed a delayed arrival in blood of radioactivity after 99m Tc-HIG compared with 99m Tc-HSA, although ultimately, the blood recovery of 99m Tc-HIG was significantly higher (P 99m Tc-HSA. Clearance rates of radioactivity from the injection site were not sinificantly different, however, between the two agents. In patients with PMO, web space injection of 99m Tc-HIG gave excellent images of normal lymphatic vessels, of lymph nodes and of abnormal lymph drainage such as dermal backflow in swollen arms. In contrast, neither lymphatic vessels nor lymph nodes were visualised after injection into the skin of the dorsum of the distal forearm. Although there was no difference in clearance rates from the injection sites between normal and swollen arms with either agent in PMO, clearance was significantly faster following injection into the web space (0.11% per minute for

  19. Mapping the geographical distribution of lymphatic filariasis in Zambia

    DEFF Research Database (Denmark)

    Mwase, Enala T; Stensgaard, Anna-Sofie; Nsakashalo-Senkwe, Mutale

    2014-01-01

    to be an important determinant of medium-high prevalence levels. CONCLUSIONS/SIGNIFICANCE: LF was found to be surprisingly widespread in Zambia, although in most places with low prevalence. The produced maps and the identified environmental correlates of LF infection will provide useful guidance for planning...... volunteers from 108 geo-referenced survey sites across Zambia were examined for circulating filarial antigens (CFA) with rapid format ICT cards, and a map indicating the distribution of CFA prevalences in Zambia was prepared. 78% of survey sites had CFA positive cases, with prevalences ranging between 1......% and 54%. Most positive survey sites had low prevalence, but six foci with more than 15% prevalence were identified. The observed geographical variation in prevalence pattern was examined in more detail using a species distribution modeling approach to explore environmental requirements for parasite...

  20. Seventh meeting of the Global Alliance to Eliminate Lymphatic Filariasis: reaching the vision by scaling up, scaling down, and reaching out

    Science.gov (United States)

    2014-01-01

    This report summarizes the 7th meeting of the Global Alliance to Eliminate Lymphatic Filariasis (GAELF), Washington DC, November 18–19, 2012. The theme, “A Future Free of Lymphatic Filariasis: Reaching the Vision by Scaling Up, Scaling Down and Reaching Out”, emphasized new strategies and partnerships necessary to reach the 2020 goal of elimination of lymphatic filariasis (LF) as a public-health problem. PMID:24450283

  1. Finding an optimal method for imaging lymphatic vessels of the upper limb

    International Nuclear Information System (INIS)

    O'Mahony, Susan; Purushotham, Arnie D.; Rose, Sarah L.; Chilvers, Alison J.; Ballinger, James R.; Solanki, Chandra K.; Barber, Robert W.; Peters, A. Michael; Mortimer, Peter S.

    2004-01-01

    Lymphoscintigraphy involves interstitial injection of radiolabelled particulate materials or radioproteins. Although several variations in the technique have been described, their place in clinical practice remains controversial. Traditional diagnostic criteria are based primarily on lymph node appearances but in situations such as breast cancer, where lymph nodes may have been excised, these criteria are of limited use. In these circumstances, lymphatic vessel morphology takes on greater importance as a clinical endpoint, so a method that gives good definition of lymphatic vessels would be useful. In patients with breast cancer, for example, such a method, used before and after lymph node resection, may assist in predicting the development of breast cancer-related lymphoedema. The aim of this study was to optimise a method for the visualisation of lymphatic vessels. Subcutaneous (sc) and intradermal (id) injection sites were compared, and technetium-99m nanocolloid, a particulate material, was compared with 99m Tc-human immunoglobulin (HIG), which is a soluble macromolecule. Twelve normal volunteers were each studied on two occasions. In three subjects, id 99m Tc-HIG was compared with sc 99m Tc-HIG, in three id 99m Tc-nanocolloid was compared with sc 99m Tc-nanocolloid, in three id 99m Tc-HIG was compared with id 99m Tc-nanocolloid and in three sc 99m Tc-HIG was compared with sc 99m Tc-nanocolloid. Endpoints were quality of lymphatic vessel definition, the time after injection at which vessels were most clearly visualised, the rate constant of depot disappearance (k) and the systemic blood accumulation rate as measured by gamma camera imaging over the liver or cardiac blood pool. Excellent definition of lymphatic vessels was obtained following id injection of either radiopharmaceutical, an injection route that was clearly superior to sc. Differences between radiopharmaceuticals were less clear, although after id injection, 99m Tc-HIG gave images that were

  2. Evaluation of Persistent Lymphatic Fluid Leakage Using a Strategy of Placing a Drain After Kidney Transplantation: A Statistical Analysis to Assess Its Origin.

    Science.gov (United States)

    Inoue, T; Saito, M; Narita, S; Numakura, K; Tsuruta, H; Maeno, A; Tsuchiya, N; Satoh, S; Habuchi, T

    2017-10-01

    Using a strategy of placing a surgical drain after kidney transplantation, the duration of a lymphatic fluid leakage and prevalence of a symptomatic lymphocele were retrospectively analyzed. The risk factors for persistent lymphatic fluid leakage or asymptomatic lymphocele were evaluated using multivariate analysis to estimate the origin of the lymphatic fluid leakage. Patients with persistent lymphatic fluid leakage and symptomatic lymphocele were defined as those with lymphatic fluid drainage >50 mL for more than 15 days and those who required a percutaneous drainage of the lymphocele, respectively. Persistent lymphatic fluid leakage and symptomatic lymphocele were observed in 40 (16.4%) and 10 (4.1%) of a total of 244 patients, respectively. The maximum durations of lymphatic fluid drainage from the initial drain tube and the second drainage of the symptomatic lymphocele were 48 and 28 days, respectively. Anastomosis of the graft artery to the external iliac artery was an independent risk factor to predict persistent lymphatic fluid leakage or symptomatic lymphocele after kidney transplantation (odds = 2.597, P = .008). The findings of the study suggest that the lymphatic fluid originates from the recipient's iliac lymph trunk rather than from the graft kidney. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Comparison of three quality of life instruments in lymphatic filariasis: DLQI, WHODAS 2.0, and LFSQQ.

    Directory of Open Access Journals (Sweden)

    Cristina Thomas

    2014-02-01

    Full Text Available BACKGROUND: The Global Program to Eliminate Lymphatic Filariasis aims to interrupt transmission of lymphatic filariasis and manage morbidity in people currently living with the disease. A component of morbidity management is improving health-related quality of life (HRQoL in patients. Measurement of HRQoL in current management programs is varied because of the lack of a standard HRQoL tool for use in the lymphatic filariasis population. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the psychometric properties of three health status measures were compared when used in a group of lymphatic filariasis patients and healthy controls. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0, the Dermatology Life Quality Index (DLQI, and the Lymphatic Filariasis Quality of Life Questionnaire (LFSQQ were administered to 36 stage II and stage III lymphatic filariasis subjects and 36 age and sex matched controls in Kerala, India. All three tools yielded missing value rates lower than 10%, suggesting high feasibility. Highest internal consistency was seen in the LFSQQ (α = 0.97. Discriminant validity analysis demonstrated that HRQoL was significantly lower in the LF group than in controls for the WHODAS 2.0, DLQI, and LFSQQ, but total HRQoL scores did not differ between stage II and stage III lymphedema subjects. The LFSQQ total score correlated most strongly with the WHODAS 2.0 (r = 0.91, p<0.001 and DLQI (r = 0.81, p<0.001. CONCLUSIONS/SIGNIFICANCE: The WHODAS 2.0, DLQI, and LFSQQ demonstrate acceptable feasibility, internal consistency, discriminate validity, and construct validity. Based on our psychometric analyses, the LFSQQ performs the best and is recommended for use in the lymphatic filariasis population.

  4. Late radiation damage in bone, bone marrow and brain vasculature, with particular emphasis upon fractionation models

    International Nuclear Information System (INIS)

    Pitkaenen, Maunu.

    1986-04-01

    X-ray induced changes in rat and human bone and bone marrow vasculature and in rat brain vasculature were measured as a function of time after irradiation and absorbed dose. The absorbed dose in the organ varied from 5 to 25 Gy for single dose irradiations and from 19 to 58 Gy for fractionated irradiations.The number of fractions varied from 3 to 10 for the rats and from 12 to 25 for the human. Blood flow changes were measured using an ''1''2''5I antipyrine or ''8''6RbCl extraction technique. The red blood cell (RBC) volume was examined by ''5''1Cr labelled red cells. Different fractionation models have been compared. Radiation induced reduction of bone and bone marrow blood flow were both time and dose dependent. Reduced blood flow 3 months after irradiation would seem to be an important factor in the subsequent atrophy of bones. With a single dose of 10 Gy the bone marrow blood flow returned to the control level by 7 months after irradiation. In the irradiated bone the RBC volume was about same as that in the control side but in bone marrow the reduction was from 32 to 59%. The dose levels predicted by the nominal standard dose (NSD) formula produced about the same damage to the rat femur seven months after irradiation when the extraction of ''8''6Rb chloride and the dry weight were concerned as the end points. However, the results suggest that the NSB formula underestimates the late radiation damage in bone marrow when a small number of large fractions are used. In the irradiated brains of the rats the blood flow was on average 20.4% higher compared to that in the control group. There was no significant difference in brain blood flow between different fractionation schemes. The value of 0.42 for the exponent of N corresponds to the average value for central nervous system tolerance in the literature. The model used may be sufficiently accurate for clinical work provided the treatment schemes used do not depart too radically from standard practice

  5. Perceptions, knowledge, attitudes and practices for the prevention and control of lymphatic filariasis in Conakry, Republic of Guinea.

    Science.gov (United States)

    Kouassi, Bernard L; Barry, Aboulaye; Heitz-Tokpa, Kathrin; Krauth, Stefanie J; Goépogui, Andre; Baldé, Mamadou S; Barry, Oumar; Niamey, Marie L; Bockarie, Moses J; Koudou, Benjamin G; Utzinger, Jürg

    2018-03-01

    Little is known about the perceptions, attitudes and practices of lymphatic filariasis in Conakry, Republic of Guinea. Yet, such knowledge is important for an optimal design and implementation of setting-specific prevention and control measures. We conducted a cross-sectional study using a mixed methods approach. Qualitative data related to people's general experience with lymphatic filariasis, their perception of the causes of the disease, the onset of elephantiasis, care-seeking behaviour and the socioeconomic impact of lymphatic filariasis were collected through in-depth interviews with 85 respondents. Quantitative data related to strategies for prevention and the knowledge of the causes of the disease were collected by interviewing 429 people. A total of 514 individuals (313 females and 201 males), aged 10-84 years, participated. Most participants were well aware of lymphatic filariasis and they recognized the disease mainly by its disfiguring manifestation, collectively termed "elephantiasis" or "leg-swelling disease". Morbidity patterns due to filarial infection showed an increase with age (from 30 to 50 years) independent of sex. Most patients with lymphatic filariasis abandoned their jobs (73.9%) or sought other work (21.7%). The main perceived causes of acquiring lymphatic filariasis were of supernatural origin (as stated by 8.7% of patients and 5.7% of healthy subjects), while mosquito bites were mentioned by fewer participants (4.3% of patients and 4.2% of healthy subjects). A number of other causes were reported that relate to both medical and non-medical conceptions. The study also identified socioeconomic impairments and stigmatization due to elephantiasis. Taken together, community perception of lymphatic filariasis in Conakry is influenced by sociocultural conceptions. Appropriate health education campaigns aimed at enhancing community understanding of the transmission of lymphatic filariasis are required to increase the success of mass drug

  6. An evidence-based analysis of epidemiologic associations between lymphatic and hematopoietic cancers and occupational exposure to gasoline.

    Science.gov (United States)

    Keenan, J J; Gaffney, S; Gross, S A; Ronk, C J; Paustenbach, D J; Galbraith, D; Kerger, B D

    2013-10-01

    The presence of benzene in motor gasoline has been a health concern for potential increased risk of acute myelogenous leukemia and perhaps other lymphatic/hematopoietic cancers for approximately 40 years. Because of the widespread and increasing use of gasoline by consumers and the high exposure potential of occupational cohorts, a thorough understanding of this issue is important. The current study utilizes an evidence-based approach to examine whether or not the available epidemiologic studies demonstrate a strong and consistent association between occupational exposure to gasoline and lymphatic/hematopoietic cancers. Among 67 epidemiologic studies initially identified, 54 were ranked according to specific criteria relating to the relevance and robustness of each study for answering the research question. The 30 highest-ranked studies were sorted into three tiers of evidence and were analyzed for strength, specificity, consistency, temporality, dose-response trends and coherence. Meta statistics were also calculated for each general and specific lymphatic/hematopoietic cancer category with adequate data. The evidence-based analysis did not confirm any strong and consistent association between occupational exposure to gasoline and lymphatic/hematopoietic cancers based on the epidemiologic studies available to date. These epidemiologic findings, combined with the evidence showing relatively low occupational benzene vapor exposures associated with gasoline formulations during the last three decades, suggest that current motor gasoline formulations are not associated with increased lymphatic/hematopoietic cancer risks related to benzene.

  7. Ginsenoside Rg1 enhances lymphatic transport of intrapulmonary silica via VEGF-C/VEGFR-3 signaling in silicotic rats.

    Science.gov (United States)

    Yu, Jie; Mao, Lijun; Guan, Li; Zhang, Yanlin; Zhao, Jinyuan

    2016-03-25

    Ginsenoside Rg1, extracted mainly from Panax ginseng, has been shown to exert strong pro-angiogenic activities in vivo. But it is unclear whether ginsenoside Rg1 could promote lung lymphangiogenesis to improve lymphatic transport of intrapulmonary silica in silicotic rats. Here we investigated the effect of ginsenoside Rg1 on lymphatic transport of silica during experimental silicosis, and found that ginsenoside Rg1 treatment significantly raised the silicon content in tracheobronchial lymph nodes and serum to reduce the silicon level in lung interstitium, meanwhile increased pulmonary lymphatic vessel density by enhancing the protein and mRNA expressions of vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor-3 (VEGFR-3). The stimulative effect of ginsenoside Rg1 on lymphatic transport of silica was actively correlated with its pro-lymphangiogenic identity. And VEGFR-3 inhibitor SAR131675 blocked these above effects of ginsenoside Rg1. These findings suggest that ginsenoside Rg1 exhibits good protective effect against lung burden of silica during experimental silicosis through improving lymphatic transport of intrapulmonary silica, which is potentially associated with the activation of VEGF-C/VEGFR-3 signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Prediction of lymphatic metastasis based on gene expression profile analysis after brachytherapy for early-stage oral tongue carcinoma

    International Nuclear Information System (INIS)

    Watanabe, Hiroshi; Mogushi, Kaoru; Miura, Masahiko; Yoshimura, Ryo-ichi; Kurabayashi, Tohru; Shibuya, Hitoshi; Tanaka, Hiroshi; Noda, Shuhei; Iwakawa, Mayumi; Imai, Takashi

    2008-01-01

    Background and purpose: The management of lymphatic metastasis of early-stage oral tongue carcinoma patients is crucial for its prognosis. The purpose of this study was to evaluate the predictive ability of lymphatic metastasis after brachytherapy (BRT) for early-stage tongue carcinoma based on gene expression profiling. Patients and methods: Pre-therapeutic biopsies from 39 patients with T1 or T2 tongue cancer were analyzed for gene expression signatures using Codelink Uniset Human 20K Bioarray. All patients were treated with low dose-rate BRT for their primary lesions and underwent strict follow-up under a wait-and-see policy for cervical lymphatic metastasis. Candidate genes were selected for predicting lymph-node status in the reference group by the permutation test. Predictive accuracy was further evaluated by the prediction strength (PS) scoring system using an independent validation group. Results: We selected a set of 19 genes whose expression differed significantly between classes with or without lymphatic metastasis in the reference group. The lymph-node status in the validation group was predicted by the PS scoring system with an accuracy of 76%. Conclusions: Gene expression profiling using 19 genes in primary tumor tissues may allow prediction of lymphatic metastasis after BRT for early-stage oral tongue carcinoma

  9. Irradiation promotes Akt-targeting therapeutic gene delivery to the tumor vasculature

    International Nuclear Information System (INIS)

    Sonveaux, Pierre; Frerart, Francoise; Bouzin, Caroline; Brouet, Agnes; Wever, Julie de; Jordan, Benedicte F.; Gallez, Bernard; Feron, Olivier

    2007-01-01

    Purpose: To determine whether radiation-induced increases in nitric oxide (NO) production can influence tumor blood flow and improve delivery of Akt-targeting therapeutic DNA lipocomplexes to the tumor. Methods and Materials: The contribution of NO to the endothelial response to radiation was identified using NO synthase (NOS) inhibitors and endothelial NOS (eNOS)-deficient mice. Reporter-encoding plasmids complexed with cationic lipids were used to document the tumor vascular specificity and the efficacy of in vivo lipofection after irradiation. A dominant-negative Akt gene construct was used to evaluate the facilitating effects of radiotherapy on the therapeutic transgene delivery. Results: The abundance of eNOS protein was increased in both irradiated tumor microvessels and endothelial cells, leading to a stimulation of NO release and an associated increase in tumor blood flow. Transgene expression was subsequently improved in the irradiated vs. nonirradiated tumor vasculature. This effect was not apparent in eNOS-deficient mice and could not be reproduced in irradiated cultured endothelial cells. Finally, we combined low-dose radiotherapy with a dominant-negative Akt gene construct and documented synergistic antitumor effects. Conclusions: This study offers a new rationale to combine radiotherapy with gene therapy, by directly exploiting the stimulatory effects of radiation on NO production by tumor endothelial cells. The preferential expression of the transgene in the tumor microvasculature underscores the potential of such an adjuvant strategy to limit the angiogenic response of irradiated tumors

  10. A novel NDP mutation in an infant with unilateral persistent fetal vasculature and retinal vasculopathy.

    Science.gov (United States)

    Aponte, Elisabeth P; Pulido, Jose S; Ellison, Jay W; Quiram, Polly A; Mohney, Brian G

    2009-06-01

    Mutations in the Norrie Disease gene, Norrie Disease Pseudoglioma (NDP) lead to a phenotypically heterogeneous group of retinopathies. We report a novel mutation in the NDP gene identified in a patient whose clinical presentation was suggestive of unilateral persistent fetal vasculature (PFV). Ophthalmic examinations, ocular ultrasounds and sequence analysis of the exons of the NDP gene on peripheral blood DNA were performed. A four-month-old boy was referred to our institution for presumed unilateral retinoblastoma. The clinical and ultrasonographic exams were consistent with PFV and retinal detachment of the left eye as well as retinal fibrovascular changes in the right eye. A vitrectomy of the left eye revealed the absence of a retrolenticular stalk and mutation analysis of the NDP gene of the proband and mother demonstrated a novel missense mutation at codon 66, designated as c. 196G > A at the cDNA level and E66K at the protein level. We report a novel mutation in the NDP gene in a patient whose presentation demonstrates the phenotypic heterogeneity of NDP-related disorders.

  11. Cytomegalovirus (CMV) Infection Causes Degeneration of Cochlear Vasculature and Hearing Loss in a Mouse Model.

    Science.gov (United States)

    Carraro, Mattia; Almishaal, Ali; Hillas, Elaine; Firpo, Matthew; Park, Albert; Harrison, Robert V

    2017-04-01

    Cytomegalovirus (CMV) infection is one of the most common causes of congenital hearing loss in children. We have used a murine model of CMV infection to reveal functional and structural cochlear pathogenesis. The cerebral cortex of Balb/c mice (Mus musculus) was inoculated with 2000 pfu (plaque forming units) of murine CMV on postnatal day 3. At 6 weeks of age, cochlear function was monitored using auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measures. Histological assessment of cochlear vasculature using a corrosion cast technique was made at 8 weeks. Vascular casts of mCMV-damaged cochleas, and those of untreated control animals, were examined using scanning electron microscopy. We find very large variations in the degree of vascular damage in animals given identical viral injections (2000 pfu). The primary lesion caused by CMV infection is to the stria vascularis and to the adjacent spiral limbus capillary network. Capillary beds of the spiral ligament are generally less affected. The initial vascular damage is found in the mid-apical turn and appears to progress to more basal cochlear regions. After viral migration to the inner ear, the stria vascularis is the primary affected structure. We suggest that initial auditory threshold losses may relate to the poor development or maintenance of the endocochlear potential caused by strial dysfunction. Our increased understanding of the pathogenesis of CMV-related hearing loss is important for defining methods for early detection and treatment.

  12. Segmentation methods for breast vasculature in dual-energy contrast-enhanced digital breast tomosynthesis

    Science.gov (United States)

    Lau, Kristen C.; Lee, Hyo Min; Singh, Tanushriya; Maidment, Andrew D. A.

    2015-03-01

    Dual-energy contrast-enhanced digital breast tomosynthesis (DE CE-DBT) uses an iodinated contrast agent to image the three-dimensional breast vasculature. The University of Pennsylvania has an ongoing DE CE-DBT clinical study in patients with known breast cancers. The breast is compressed continuously and imaged at four time points (1 pre-contrast; 3 post-contrast). DE images are obtained by a weighted logarithmic subtraction of the high-energy (HE) and low-energy (LE) image pairs. Temporal subtraction of the post-contrast DE images from the pre-contrast DE image is performed to analyze iodine uptake. Our previous work investigated image registration methods to correct for patient motion, enhancing the evaluation of vascular kinetics. In this project we investigate a segmentation algorithm which identifies blood vessels in the breast from our temporal DE subtraction images. Anisotropic diffusion filtering, Gabor filtering, and morphological filtering are used for the enhancement of vessel features. Vessel labeling methods are then used to distinguish vessel and background features successfully. Statistical and clinical evaluations of segmentation accuracy in DE-CBT images are ongoing.

  13. A Comparison between Gadofosveset Trisodium and Gadobenate Dimeglumine for Steady State MRA of the Thoracic Vasculature

    Directory of Open Access Journals (Sweden)

    G. Paul Camren

    2014-01-01

    Full Text Available Purpose. Retrospective comparison between gadofosveset trisodium and gadobenate dimeglumine steady state magnetic resonance angiography (SS-MRA of the thoracic vasculature at 1.5T using signal-to-noise ratio (SNR and vessel edge sharpness (ES as markers of image quality. Materials and Methods. IRB approval was obtained. Twenty separate patients each underwent SS-MRA using high-resolution 3D ECG-triggered coronal IR-TFE at 1.5T approximately 3-4 minutes following 10 or 15 mL gadofosveset or 20 mL gadobenate. ROIs were placed in the right atrium, left ventricle, left atrium, ascending aorta, descending aorta, and right pulmonary artery to estimate SNR. Vessel ES was estimated as 20–80% rise distances from line intensity profiles in the left pulmonary vein, ascending aorta, and descending aorta. Data were analyzed using nonpaired Student’s t-test (threshold for significance set at P<0.05. Results. There was no significant difference in mean SNR for the gadofosveset or gadobenate groups (P values: 0.14 to 0.85. There was no significant difference in mean vessel ES for gadofosveset and gadobenate groups (P values: 0.17 to 0.78. Conclusion. High quality thoracic SS-MRA can be achieved with gadobenate dimeglumine, similar to that achieved with the blood pool agent gadofosveset trisodium provided that imaging is initiated quickly (3-4 min after contrast injection.

  14. A comparison between gadofosveset trisodium and gadobenate dimeglumine for steady state MRA of the thoracic vasculature.

    Science.gov (United States)

    Camren, G Paul; Wilson, Gregory J; Bamra, Vikram R; Nguyen, Khahn Q; Hippe, Daniel S; Maki, Jeffrey H

    2014-01-01

    Retrospective comparison between gadofosveset trisodium and gadobenate dimeglumine steady state magnetic resonance angiography (SS-MRA) of the thoracic vasculature at 1.5T using signal-to-noise ratio (SNR) and vessel edge sharpness (ES) as markers of image quality. IRB approval was obtained. Twenty separate patients each underwent SS-MRA using high-resolution 3D ECG-triggered coronal IR-TFE at 1.5T approximately 3-4 minutes following 10 or 15 mL gadofosveset or 20 mL gadobenate. ROIs were placed in the right atrium, left ventricle, left atrium, ascending aorta, descending aorta, and right pulmonary artery to estimate SNR. Vessel ES was estimated as 20-80% rise distances from line intensity profiles in the left pulmonary vein, ascending aorta, and descending aorta. Data were analyzed using nonpaired Student's t-test (threshold for significance set at P < 0.05). There was no significant difference in mean SNR for the gadofosveset or gadobenate groups (P values: 0.14 to 0.85). There was no significant difference in mean vessel ES for gadofosveset and gadobenate groups (P values: 0.17 to 0.78). High quality thoracic SS-MRA can be achieved with gadobenate dimeglumine, similar to that achieved with the blood pool agent gadofosveset trisodium provided that imaging is initiated quickly (3-4 min) after contrast injection.

  15. Anticancer Role of PPARγ Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes

    Directory of Open Access Journals (Sweden)

    P. J. Simpson-Haidaris

    2010-01-01

    Full Text Available The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR-γ agonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARγ agonists in the treatment and prevention of cancer. This paper has two objectives: first to highlight the potential uses for PPARγ agonists in anticancer therapy with special emphasis on their role when used as adjuvant or combined therapy in the treatment of hematological malignancies found in the vasculature, marrow, and eyes, and second, to review the potential role PPARγ and/or its ligands may have in modulating cancer-associated angiogenesis and tumor-stromal microenvironment crosstalk in bone marrow.

  16. Joint volumetric extraction and enhancement of vasculature from low-SNR 3-D fluorescence microscopy images.

    Science.gov (United States)

    Almasi, Sepideh; Ben-Zvi, Ayal; Lacoste, Baptiste; Gu, Chenghua; Miller, Eric L; Xu, Xiaoyin

    2017-03-01

    To simultaneously overcome the challenges imposed by the nature of optical imaging characterized by a range of artifacts including space-varying signal to noise ratio (SNR), scattered light, and non-uniform illumination, we developed a novel method that segments the 3-D vasculature directly from original fluorescence microscopy images eliminating the need for employing pre- and post-processing steps such as noise removal and segmentation refinement as used with the majority of segmentation techniques. Our method comprises two initialization and constrained recovery and enhancement stages. The initialization approach is fully automated using features derived from bi-scale statistical measures and produces seed points robust to non-uniform illumination, low SNR, and local structural variations. This algorithm achieves the goal of segmentation via design of an iterative approach that extracts the structure through voting of feature vectors formed by distance, local intensity gradient, and median measures. Qualitative and quantitative analysis of the experimental results obtained from synthetic and real data prove the effcacy of this method in comparison to the state-of-the-art enhancing-segmenting methods. The algorithmic simplicity, freedom from having a priori probabilistic information about the noise, and structural definition gives this algorithm a wide potential range of applications where i.e. structural complexity significantly complicates the segmentation problem.

  17. The primary cilium of telocytes in the vasculature: electron microscope imaging.

    Science.gov (United States)

    Cantarero, I; Luesma, M J; Junquera, C

    2011-12-01

    Blood vessels are highly organized and complex structure, which are far more than simple tubes conducting the blood to almost any tissue of the body. The fine structure of the wall of blood vessels has been studied previously using the electron microscope, but the presence the telocytes associated with vasculature, a specific new cellular entity, has not been studied in depth. Interestingly, telocytes have been recently found in the epicardium, myocardium, endocardium, human term placenta, duodenal lamina propria and pleura. We show the presence of telocytes located on the extracellular matrix of blood vessels (arterioles, venules and capillaries) by immunohistochemistry and transmission electron microscopy. Also, we demonstrated the first evidence of a primary cilium in telocytes. Several functions have been proposed for these cells. Here, the telocyte-blood vessels cell proximity, the relationship between telocytes, exosomes and nervous trunks may have a special significance. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  18. SEX STEROIDS MODULATE UTERINE-PLACENTAL VASCULATURE: IMPLICATIONS FOR OBSTETRICS AND NEONATAL OUTCOMES

    Directory of Open Access Journals (Sweden)

    Manuel eMaliqueo

    2016-04-01

    Full Text Available Adequate blood supply to the uterine-placental region is crucial to ensure the transport of oxygen and nutrients to the growing fetus. Multiple factors intervene to achieve appropriate uterine blood flow and the structuring of the placental vasculature during the early stages of pregnancy. Among these factors, oxygen concentrations, growth factors, cytokines and steroid hormones are the most important. Sex steroids are present in extremely high concentrations in the maternal circulation and are important paracrine and autocrine regulators of a wide range of maternal and placental functions. In this regard, progesterone and estrogens act as modulators of uterine vessels and decrease the resistance of the spiral uterine arteries. On the other hand, androgens have the opposite effect, increasing the vascular resistance of the uterus. Moreover, progesterone and estrogens modulate the synthesis and release of angiogenic factors by placental cells, which regulates trophoblastic invasion and uterine artery remodeling. In this scenario, it is not surprising that women with pregnancy-related pathologies, such as early miscarriages, preterm delivery, preeclampsia and fetal growth restriction, exhibit altered sex steroid concentrations.

  19. Using Non-Invasive Multi-Spectral Imaging to Quantitatively Assess Tissue Vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, A; Chernomordik, V; Riley, J; Hassan, M; Amyot, F; Dasgeb, B; Demos, S G; Pursley, R; Little, R; Yarchoan, R; Tao, Y; Gandjbakhche, A H

    2007-10-04

    This research describes a non-invasive, non-contact method used to quantitatively analyze the functional characteristics of tissue. Multi-spectral images collected at several near-infrared wavelengths are input into a mathematical optical skin model that considers the contributions from different analytes in the epidermis and dermis skin layers. Through a reconstruction algorithm, we can quantify the percent of blood in a given area of tissue and the fraction of that blood that is oxygenated. Imaging normal tissue confirms previously reported values for the percent of blood in tissue and the percent of blood that is oxygenated in tissue and surrounding vasculature, for the normal state and when ischemia is induced. This methodology has been applied to assess vascular Kaposi's sarcoma lesions and the surrounding tissue before and during experimental therapies. The multi-spectral imaging technique has been combined with laser Doppler imaging to gain additional information. Results indicate that these techniques are able to provide quantitative and functional information about tissue changes during experimental drug therapy and investigate progression of disease before changes are visibly apparent, suggesting a potential for them to be used as complementary imaging techniques to clinical assessment.

  20. Multiple variations of the coeliac axis, hepatic and renal vasculature as incidental findings illustrated by MDCTA.

    Science.gov (United States)

    Rafailidis, Vasileios; Papadopoulos, Georgios; Kouskouras, Konstantinos; Chryssogonidis, Ioannis; Velnidou, Anastasia; Kalogera-Fountzila, Anna

    2016-08-01

    Vascular anatomical variations are not uncommon and may affect any organ's arterial or venous vasculature. The coexistence of variations in different organic systems is less commonly found, but of great clinical significance in a series of clinical conditions like organ transplantation and surgical preoperative planning. Multidetector computed tomography angiography (MDCTA) has emerged as a valuable alternative to the conventional angiography for accurate evaluation of vascular anatomy and pathology. Radiologists should be familiar with each organ's vascular variations and always report them to the clinician, even if they represent an incidental finding. This case report presents a 52-year-old female patient undergoing abdominal MDCTA for characterization of a renal lesion. This examination revealed the presence of three hilar arteries on the left kidney, a main renal vein in combination with an additional renal vein in both sides along with a replaced right hepatic artery originating from the superior mesenteric artery. Moreover, both inferior phrenic arteries were found originating from the coeliac axis. 3D volume rendering technique images were used in the evaluation of vascular anatomy as illustrated in this case report.

  1. A machine learning approach for automated assessment of retinal vasculature in the oxygen induced retinopathy model.

    Science.gov (United States)

    Mazzaferri, Javier; Larrivée, Bruno; Cakir, Bertan; Sapieha, Przemyslaw; Costantino, Santiago

    2018-03-02

    Preclinical studies of vascular retinal diseases rely on the assessment of developmental dystrophies in the oxygen induced retinopathy rodent model. The quantification of vessel tufts and avascular regions is typically computed manually from flat mounted retinas imaged using fluorescent probes that highlight the vascular network. Such manual measurements are time-consuming and hampered by user variability and bias, thus a rapid and objective method is needed. Here, we introduce a machine learning approach to segment and characterize vascular tufts, delineate the whole vasculature network, and identify and analyze avascular regions. Our quantitative retinal vascular assessment (QuRVA) technique uses a simple machine learning method and morphological analysis to provide reliable computations of vascular density and pathological vascular tuft regions, devoid of user intervention within seconds. We demonstrate the high degree of error and variability of manual segmentations, and designed, coded, and implemented a set of algorithms to perform this task in a fully automated manner. We benchmark and validate the results of our analysis pipeline using the consensus of several manually curated segmentations using commonly used computer tools. The source code of our implementation is released under version 3 of the GNU General Public License ( https://www.mathworks.com/matlabcentral/fileexchange/65699-javimazzaf-qurva ).

  2. Trypsin digest protocol to analyze the retinal vasculature of a mouse model.

    Science.gov (United States)

    Chou, Jonathan C; Rollins, Stuart D; Fawzi, Amani A

    2013-06-13

    Trypsin digest is the gold standard method to analyze the retinal vasculature (1-5). It allows visualization of the entire network of complex three-dimensional retinal blood vessels and capillaries by creating a two-dimensional flat-mount of the interconnected vascular channels after digestion of the non-vascular components of the retina. This allows one to study various pathologic vascular changes, such as microaneurysms, capillary degeneration, and abnormal endothelial to pericyte ratios. However, the method is technically challenging, especially in mice, which have become the most widely available animal model to study the retina because of the ease of genetic manipulations (6,7). In the mouse eye, it is particularly difficult to completely remove the non-vascular components while maintaining the overall architecture of the retinal blood vessels. To date, there is a dearth of literature that describes the trypsin digest technique in detail in the mouse. This manuscript provides a detailed step-by-step methodology of the trypsin digest in mouse retina, while also providing tips on troubleshooting difficult steps.

  3. Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy

    International Nuclear Information System (INIS)

    Ran, Sophia; Thorpe, Philip E.

    2002-01-01

    Purpose: (1) To determine whether exposure of phosphatidylserine (PS) occurs on vascular endothelium in solid tumors in mice. (2) To determine whether PS exposure can be induced on viable endothelial cells in tissue culture by conditions present in the tumor microenvironment. Methods and Materials: Externalized PS in vivo was detected by injecting mice with a monoclonal anti-PS antibody and examining frozen sections of tumors and normal tissues for anti-PS antibody bound to vascular endothelium. Apoptotic cells were identified by anti-active caspase-3 antibody or by TUNEL assay. PS exposure on cultured endothelial cells was determined by 125 I-annexin V binding. Results: Anti-PS antibody bound specifically to vascular endothelium in six tumor models. The percentage of PS-positive vessels ranged from 4% to 40% in different tumor types. Vascular endothelium in normal organs was unstained. Very few tumor vessels expressed apoptotic markers. Hypoxia/reoxygenation, acidity, inflammatory cytokines, thrombin, or hydrogen peroxide induced PS exposure on cultured endothelial cells without causing loss of viability. Conclusions: Vascular endothelial cells in tumors, but not in normal tissues, externalize PS. PS exposure might be induced by tumor-associated oxidative stress and activating cytokines. PS is an abundant and accessible marker of tumor vasculature and could be used for tumor imaging and therapy

  4. SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY REVEALS INTERNAL LIMITING MEMBRANE PEELING ALTERS DEEP RETINAL VASCULATURE.

    Science.gov (United States)

    Michalewska, Zofia; Nawrocki, Jerzy

    2018-04-30

    To describe morphology of retinal and choroidal vessels in swept-source optical coherence tomography angiography before and after vitrectomy with the temporal inverted internal limiting membrane (ILM) flap technique for full-thickness macular holes. Prospective, observational study of 36 eyes of 33 patients with full-thickness macular holes swept-source optical coherence tomography angiography was performed in patients before and 1 month after vitrectomy. Vitrectomy with the temporal inverted ILM flap technique was performed. In this method, ILM is peeled only at one side of the fovea. An ILM flap is created to cover the macular hole. Comparison of retina vasculature in the areas of ILM peeling vs. no ILM peeling at 1 and 3 months after successful vitrectomy was performed. The study demonstrated lower density of vessels in the deep retinal plexus in the area where ILM was peeled as compared to the rest of the fovea. Visual acuity and central retinal thickness 1 month after surgery correlates with fovea avascular zone diameter in deep retinal layers at the same time point (P = 0.001). This study confirmed that ILM peeling might alter blood flow in deep retinal vessels below the peeling area in the early postoperative period. The area of the fovea avascular zone corresponds to functional results at the same time point.

  5. The lymphoscintigraphic manifestation of (99m)Tc-dextran lymphatic imaging in primary intestinal lymphangiectasia.

    Science.gov (United States)

    Wen, Zhe; Tong, Guansheng; Liu, Yong; Meeks, Jacqui K; Ma, Daqing; Yang, Jigang

    2014-05-01

    The aim of this study was to analyze the imaging characteristics of (99m)Tc-dextran ((99m)Tc-DX) lymphatic imaging in the diagnosis of primary intestinal lymphangiectasia (PIL). Forty-one PIL patients were diagnosed as having PIL with the diagnosis being subsequently confirmed by laparotomy, endoscopy, biopsy, or capsule colonoscopy. Nineteen patients were male and 22 were female. A whole-body (99m)Tc-DX scan was performed at 10 min, 1 h, 3 h, and 6 h intervals after injection. The 10 min and 1 h postinjection intervals were considered the early phase, the 3 h postinjection interval was considered the middle phase, and the 6 h postinjection interval was considered the delayed phase. The imaging characteristics of (99m)Tc-DX lymphatic imaging in PIL were of five different types: (i) presence of dynamic radioactivity in the intestine, associated with radioactivity moving from the small intestine to the ascending and transverse colon; (ii) presence of delayed dynamic radioactivity in the intestine, no radioactivity or little radioactivity distributing in the intestine in the early phase, or significant radioactivity distributing in the intestine in the delayed phase; (iii) radioactivity distributing in the intestine and abdominal cavity; (iv) radioactivity distributing only in the abdominal cavity with no radioactivity in the intestines; and (v) no radioactivity distributing in the intestine and abdominal activity. (99m)Tc-DX lymphatic imaging in PIL showed different imaging characteristics. Caution should be exercised in the diagnosis of PIL using lymphoscintigraphy. Lymphoscintigraphy is a safe and accurate examination method and is a significant diagnostic tool in the diagnosis of PIL.

  6. Global abnormalities in lymphatic function following systemic therapy in patients with breast cancer.

    Science.gov (United States)

    Bains, S K; Peters, A M; Zammit, C; Ryan, N; Ballinger, J; Glass, D M; Allen, S; Stanton, A W B; Mortimer, P S; Purushotham, A D

    2015-04-01

    Breast cancer-related lymphoedema (BCRL) is a result of interaction between several pathophysiological processes, and is not simply a 'stopcock' effect resulting from removal of axillary lymph nodes. The aim of this study was to test the hypothesis that there is a constitutional 'global' lymphatic dysfunction in patients who develop BCRL. Lower-limb lymphoscintigraphy was performed in 30 women who had undergone axillary lymph node dissection at least 3 years previously, of whom 15 had BCRL and 15 did not. No patient had any clinical abnormality of the lower limb. The control group comprised 24 women with no history of cancer or lower-limb lymphoedema. (99m) Tc-Nanocoll was injected subcutaneously into the first webspace of each foot, followed by whole-body imaging. Scans were reported as abnormal if there was delay in lymph transport or rerouting through skin or deep system. Quantification was expressed as the percentage injected activity accumulating in ilioinguinal nodes. Mean(s.d.) ilioinguinal nodal accumulation at 150 min was significantly lower in women with BCRL than in those without (2·7(2·5) versus 5·9(4·8) per cent respectively; P = 0·006). Abnormal findings on lower-limb lymphoscintigraphy were observed in 17 of the 30 patients: ten of the 15 women who had BCRL and seven of the 15 who did not. None of the 24 control subjects had abnormal scan findings. Women with BCRL had reduced lower-limb lymph drainage, supporting the hypothesis of a predisposition to BCRL. A surprisingly high proportion of patients with breast cancer also demonstrated lymphatic dysfunction, despite clinically normal lower limbs. Possible explanations could be a systemic effect of breast cancer or its treatment, or an unidentified association between breast cancer and lymphatic dysfunction. ISRCTN84866416 ( http://www.isrctn.com). © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

  7. Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node Metastasis

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    Aula Ammar

    2011-01-01

    Full Text Available Background: Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1 in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process. Methods: 148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC, CD209 (immature DC, iDC and CD68 (macrophage, M&phis;. in vitro expression of CLEVER-1 on lymphatic (LEC and blood endothelial cells (BEC was examined by flow cytometry. Results: in vitro results showed that although both endothelial cell types express CLEVER-1, surface expression was only evident on LEC. In tumour sections CLEVER-1 was expressed in blood vessels (BV, 61.4% of samples, lymphatic vessels (LV, 18.2% of samples and in M&phis;/DCs (82.4% of samples. However, only CLEVER-1 expression in LV was associated with LN metastasis (p = 0.027 and with M&phis; indices (p = 0.021. Although LV CLEVER-1 was associated with LN positivity there was no significant correlation with recurrence or overall survival, BV CLEVER-1 expression was, however, associated with increased risk of recurrence (p = 0.049. The density of inflammatory infiltrate correlated with CLEVER-1 expression in BV (p < 0.001 and LV (p = 0.004. Conclusions: The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. Its upregulation on LV, related surface expression, and association with LN metastasis suggest that it may be an important mediator of tumor cell metastasis to LN.

  8. Will mass drug administration eliminate lymphatic filariasis? Evidence from northern coastal Tanzania.

    Science.gov (United States)

    Parker, Melissa; Allen, Tim

    2013-07-01

    This article documents understandings and responses to mass drug administration (MDA) for the treatment and prevention of lymphatic filariasis among adults and children in northern coastal Tanzania from 2004 to 2011. Assessment of village-level distribution registers, combined with self-reported drug uptake surveys of adults, participant observation and interviews, revealed that at study sites in Pangani and Muheza districts the uptake of drugs was persistently low. The majority of people living at these highly endemic locations either did not receive or actively rejected free treatment. A combination of social, economic and political reasons explain the low uptake of drugs. These include a fear of treatment (attributable, in part, to a lack of trust in international aid and a questioning of the motives behind the distribution); divergence between biomedical and local understandings of lymphatic filariasis; and limited and ineffective communication about the rationale for mass treatment. Other contributory factors are the reliance upon volunteers for distribution within villages and, in some locations, strained relationships between different groups of people within villages as well as between local leaders and government officials. The article also highlights a disjuncture between self-reported uptake of drugs by adults at a village level and the higher uptake of drugs recorded in official reports. The latter informs claims that elimination will be a possibility by 2020. This gives voice to a broader problem: there is considerable pressure for those implementing MDA to report positive results. The very real challenges of making MDA work are pushed to one side - adding to a rhetoric of success at the expense of engaging with local realities. It is vital to address the kind of issues raised in this article if current attempts to eliminate lymphatic filariasis in mainland coastal Tanzania are to achieve their goal.

  9. DEGRO practical guidelines: radiotherapy of breast cancer III - radiotherapy of the lymphatic pathways

    International Nuclear Information System (INIS)

    Sautter-Bihl, M.L.; Sedlmayer, F.; Fussl, C.; Budach, W.; Dunst, J.; Feyer, P.; Fietkau, R.; Sauer, R.; Harms, W.; Piroth, M.D.; Souchon, R.; Wenz, F.; Haase, W.

    2014-01-01

    The purpose of this work is to update the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO). A comprehensive survey of the literature concerning regional nodal irradiation (RNI) was performed using the following search terms: ''breast cancer'', ''radiotherapy'', ''regional node irradiation''. Recent randomized trials were analyzed for outcome as well as for differences in target definition. Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas. Moreover, data from recently published meta-analyses and guidelines of international breast cancer societies, yielding new aspects compared to 2008, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the German interdisciplinary S3 guidelines updated in 2012, this paper addresses indications, targeting, and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer. International guidelines reveal substantial differences regarding indications for RNI. Patients with 1-3 positive nodes seem to profit from RNI compared to whole breast (WBI) or chest wall irradiation alone, both with regard to locoregional control and disease-free survival. Irradiation of the regional lymphatics including axillary, supraclavicular, and internal mammary nodes provided a small but significant survival benefit in recent randomized trials and one meta-analysis. Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection (ALND), while reducing the rate of lymph edema. Data concerning the impact of 1-2 macroscopically affected sentinel node (SN) or microscopic metastases on prognosis are conflicting. Recent data suggest that the current restrictive use of RNI should be

  10. Manual lymphatic drainage and therapeutic ultrasound in liposuction and lipoabdominoplasty post-operative period

    Directory of Open Access Journals (Sweden)

    Igor F. B. Masson

    2014-01-01

    Full Text Available Background: Physiotherapy in the plastic surgery post-operative (PO is essential to provide means for an adequate and fast recovery as it restores function through the use of physiotherapeutic procedures. Aim: The aim of the following study is to verify the effects of the association between the manual lymphatic drainage and the therapeutic ultrasound on pain, oedema and the tissue fibrosis in liposuction and lipoabdominoplasty PO. Design: This is a clinical trial prospective. Materials and Methods: Eighteen women aged between 18 and 60 years participated in this study, in the late PO period following lipoabdominoplasty or liposuction in the abdomen, flanks and lower trunk, which showed tissue fibrosis of the flanks and abdomen regions. They were divided into two groups: Liposuction group and lipoabdominoplasty group. A total of twelve sessions of therapeutic ultrasound followed by the manual lymphatic drainage were performed. The patients were assessed with regard to pain, oedema and tissue fibrosis in different moments: Initial assessment, during assessment and final assessment through the application of the protocol of evaluation of cysts fibrosis levels. Statistical Analysis: The test of equality for two proportions and the confidence interval test for mean to evaluate the distribution of variables. The significance level adopted for statistical tests was 5% (P < 0.05. Results: There was a statistically significant reduction of pain, swelling and tissue fibrosis in both groups. Conclusion: the association between manual lymphatic drainage and the therapeutic ultrasound reduced the swelling and the tissue fibrosis and made pain disappear in liposuction and lipoabdominoplasty PO period.

  11. Sentinel lymph node biopsy in endometrial cancer-Feasibility, safety and lymphatic complications.

    Science.gov (United States)

    Geppert, Barbara; Lönnerfors, Céline; Bollino, Michele; Persson, Jan

    2018-03-01

    To compare the rate of lymphatic complications in women with endometrial cancer undergoing sentinel lymph node biopsy versus a full pelvic and infrarenal paraaortic lymphadenectomy, and to examine the overall feasibility and safety of the former. A prospective study of 188 patients with endometrial cancer planned for robotic surgery. Indocyanine green was used to identify the sentinel lymph nodes. In low-risk patients the lymphadenectomy was restricted to removal of sentinel lymph nodes whereas in high-risk patients also a full lymphadenectomy was performed. The impact of the extent of the lymphadenectomy on the rate of complications was evaluated. The bilateral detection rate of sentinel lymph nodes was 96% after cervical tracer injection. No intraoperative complication was associated with the sentinel lymph node biopsy per se. Compared with hysterectomy alone, the additional average operative time for removal of sentinel lymph nodes was 33min whereas 91min were saved compared with a full pelvic and paraaortic lymphadenectomy. Sentinel lymph node biopsy alone resulted in a lower incidence of leg lymphedema than infrarenal paraaortic and pelvic lymphadenectomy (1.3% vs 18.1%, p=0.0003). The high feasibility, the absence of intraoperative complications and the low risk of lymphatic complications supports implementing detection of sentinel lymph nodes in low-risk endometrial cancer patients. Given that available preliminary data on sensitivity and false negative rates in high-risk patients are confirmed in further studies, we also believe that the reduction in lymphatic complications and operative time strongly motivates the sentinel lymph node concept in high-risk endometrial cancer. Copyright © 2017. Published by Elsevier Inc.

  12. Cryotherapy for massive vulvar lymphatic leakage complicated with lymphangiomas following gynecological cancer treatment.

    Science.gov (United States)

    Yanazume, Shintaro; Douzono, Haruhiko; Kubo, Hidemichi; Nagata, Tomomi; Douchi, Tsutomu; Kobayashi, Hiroaki

    2014-11-01

    Vulvar lymphatic leakage is a severe complication associated with gynecological cancer treatments. However, standard treatment strategies have not yet been determined. We encountered a rare case of a 76-year-old multiparous woman suffering from massive lymphatic fluid leakage from the entire vulva, and papules developed and were identified as lymphangiomas. A large amount of straw-colored discharge continued from all vulvar papules, which extended over the mons pubis. Nine years ago, the patient had undergone a radical hysterectomy with concurrent chemoradiation for uterine cervical cancer treatment. Her serum albumin level was 1.9 mg/dl, which was attributed to the loss of a large amount of lymph fluid due to leakage from the vulva. Her quality of life gradually decreased because of general fatigue and the need for frequent diaper exchanges every 2 h. The patient received a less-invasive treatment with cryotherapy using liquid nitrogen. She also received a multimodality treatment consisting of the intravenous administration of albumin, massage of the lower limbs and intensive rehabilitation. Cryotherapy was administered once a week for 3 months. Her discharge almost stopped and vulvar lymphangiomas decreased without any major complications. To the best of our knowledge, this is the first case report of massive lymphatic leakage complicated with vulvar lymphangiomas. Additionally, this case may represent the first successful treatment of vulva lymph leakage by cryotherapy without recurrence. Cryotherapy may have the potential to improve the quality of life as a less-invasive treatment for gynecological cancer survivors without serious complications. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Distribution of lymphatic tissues and autonomic nerves in supporting ligaments around the cervix uteri.

    Science.gov (United States)

    Zhang, Jianping; Feng, Lanlan; Lu, Yi; Guo, Dongxia; Xi, Tengteng; Wang, Xiaochun

    2013-05-01

    To investigate the distribution of lymphatic tissues and nerves in the supporting ligaments around the cervix uteri for their tomographical relationship, 9 adult female cadavers were used in this study. Following the incision of all supporting ligaments around the cervix, hematoxylin and esosin (H&E) and immunohistochemical staining of various sections of these ligaments was performed to enable the distribution of lymph tissues and autonomic nerves to be observed. Four lymph nodes were identified in three cadaver specimens. Three lymph nodes were present at a distance of 2.0 cm from the cervix in the cranial side of the cardinal ligaments (CLs), and one lymph node was located at a distance of 4.0 cm from the cervix in the cranial side of the uterosacral ligament (USL). The lymphatic vessels were dispersed in the CLs, scattered in the cervical side of the USLs, and occasionally distributed in the vesicouterine ligaments (VULs). In the CLs, parasympathetic nerves were located at the pelvic lateral wall and went downwards and medially into the cervix, while sympathetic fibers were located in the middle and lower parts of the ligaments. In the USLs, the autonomic nerves, which consisted primarily of sympathetic fibers, went downwards and laterally from the pelvic wall to the cervix. In the VULs, parasympathetic and sympathetic nerves were located in the inner sides of the vesical veins in the deep layers of the ligaments. It is concluded that there are few lymphatic tissues in the supporting ligaments around the cervix uteri, and that nerve‑sparing radical hysterectomy (NSRH) may be a safe method for the treatment of early‑stage cervical cancer.

  14. hESC Differentiation toward an Autonomic Neuronal Cell Fate Depends on Distinct Cues from the Co-Patterning Vasculature

    Directory of Open Access Journals (Sweden)

    Lisette M. Acevedo

    2015-06-01

    Full Text Available To gain insight into the cellular and molecular cues that promote neurovascular co-patterning at the earliest stages of human embryogenesis, we developed a human embryonic stem cell model to mimic the developing epiblast. Contact of ectoderm-derived neural cells with mesoderm-derived vasculature is initiated via the neural crest (NC, not the neural tube (NT. Neurovascular co-patterning then ensues with specification of NC toward an autonomic fate requiring vascular endothelial cell (EC-secreted nitric oxide (NO and direct contact with vascular smooth muscle cells (VSMCs via T-cadherin-mediated homotypic interactions. Once a neurovascular template has been established, NT-derived central neurons then align themselves with the vasculature. Our findings reveal that, in early human development, the autonomic nervous system forms in response to distinct molecular cues from VSMCs and ECs, providing a model for how other developing lineages might coordinate their co-patterning.

  15. Study of intrarenal vasculature in cases of primary and secondary hypertension (by metallic impregnation technique on whole kidney section

    Directory of Open Access Journals (Sweden)

    Mittal B

    1992-10-01

    Full Text Available Study of intrarenal vasculature was carried out by using the metallic impregnation technique on whole kidney sections in 31 [corrected] cases of (primary and secondary hypertension and 10 normal controls. Distinct patterns of intrarenal vasculature were noted in controls and in cases of hypertension. Gradual tapering of vessels, absence of tortuosity and good peripheral vascularisation were noted in controls. Abrupt tapering, tortuosity of vessels and poor peripheral vascularisation were noted in hypertensive cases. In essential hypertension moderate to severe changes of dilatation of the segmental and/or arcuate arteries was noted. The degree of dilatation was related to the level of systolic BP rather than diastolic in cases of essential hypertension. Secondary hypertension even if severe, rarely showed significant dilatation lesions. Avascular zones and conglomeration of vessels at poles was seen only in cases of pyelonephritis. This helped in distinguishing these, from cases of glomerulonephritis.

  16. Lymphatic Fatty Acid Absorption Profile During 24 Hours After Administration of Triglycerides to Rats

    DEFF Research Database (Denmark)

    Porsgaard, Trine Charlotte; Straarup, Ellen Marie; Høy, Carl-Erik

    1999-01-01

    In this study we determined in rats the complete 24-h lymphatic fatty acid profile after administration of either rapeseedoil (RO) or rapeseed oil interesterified with 10:0 (RO/C10) with special emphasis on the transition from absorptive topostabsorptive phase. Rats were subjected to cannulation......:0), and linoleic acid (18:2n-6) together witholeic acid (18:1 n-9) after RO had not returned to the transport at baseline. In contrast, the transport of decanoic acid(10:0) and alpha-linolenic acid (18:3n-3) returned to baseline values between 12 and 15 h. This indicated that theabsorption of purely exogenous...

  17. Spontaneous and α-adrenoceptor-induced contractility in human collecting lymphatic vessels require chloride

    DEFF Research Database (Denmark)

    Mohanakumar, Sheyanth; Majgaard, Jens; Telinius, Niklas

    2018-01-01

    - with the impermeant anion aspartate and inhibition of Cl- transport and channels with the clinical diuretics furosemide and bendroflumethiazide, as well as DIDS and NPPB. The molecular expression of calcium-activated chloride channels was investigated by RT-PCR and proteins localized using immunoreactivity....... Spontaneous and norepinephrine-induced contractility in human lymphatic vessels was highly abrogated after Cl- substitution with aspartate. 100‒300µM DIDS or NPPB inhibited spontaneous contractile behavior. Norepinephrine-stimulated tone was furthermore markedly abrogated by 200µM DIDS. Furosemide lowered...

  18. Vasculatures in Tumors Growing From Preirradiated Tissues: Formed by Vasculogenesis and Resistant to Radiation and Antiangiogenic Therapy

    International Nuclear Information System (INIS)

    Chen, Fang-Hsin; Chiang, Chi-Shiun; Wang, Chun-Chieh; Fu, Sheng-Yung; Tsai, Chien-Sheng; Jung, Shih-Ming; Wen, Chih-Jen; Lee, Chung-Chi; Hong, Ji-Hong

    2011-01-01

    Purpose: To investigate vasculatures and microenvironment in tumors growing from preirradiated tissues (pre-IR tumors) and study the vascular responses of pre-IR tumors to radiation and antiangiogenic therapy. Methods and Materials: Transgenic adenocarcinoma of the mouse prostate C1 tumors were implanted into unirradiated or preirradiated tissues and examined for vascularity, hypoxia, and tumor-associated macrophage (TAM) infiltrates by immunohistochemistry. The origin of tumor endothelial cells was studied by green fluorescent protein-tagged bone marrow (GFP-BM) transplantation. The response of tumor endothelial cells to radiation and antiangiogenic agent was evaluated by apoptotic assay. Results: The pre-IR tumors had obvious tumor bed effects (TBE), with slower growth rate, lower microvascular density (MVD), and more necrotic and hypoxic fraction compared with control tumors. The vessels were dilated, tightly adhered with pericytes, and incorporated with transplanted GFP-BM cells. In addition, hypoxic regions became aggregated with TAM. As pre-IR tumors developed, the TBE was overcome at the tumor edge where the MVD increased, TAM did not aggregate, and the GFP-BM cells did not incorporate into the vessels. The vessels at tumor edge were more sensitive to the following ionizing radiation and antiangiogenic agent than those in the central low MVD regions. Conclusions: This study demonstrates that vasculatures in regions with TBE are mainly formed by vasculogenesis and resistant to radiation and antiangiogenic therapy. Tumor bed effects could be overcome at the edge of larger tumors, but where vasculatures are formed by angiogenesis and sensitive to both treatments. Vasculatures formed by vasculogenesis should be the crucial target for the treatment of recurrent tumors after radiotherapy.

  19. Functional Response of Tumor Vasculature to PaCO2: Determination of Total and Microvascular Blood Volume by MRI

    Directory of Open Access Journals (Sweden)

    Scott D. Packard

    2003-07-01

    Full Text Available In order to identify differences in functional activity, we compared the reactivity of glioma vasculature and the native cerebral vasculature to both dilate and constrict in response to altered PaCO2. Gliomas were generated by unilateral implantation of U87MGdEGFR human glioma tumor cells into the striatum of adult female athymic rats. Relative changes in total and microvascular cerebral blood volume were determined by steady state contrast agent-enhanced magnetic resonance imaging for transitions from normocarbia to hypercarbia and hypocarbia. Although hypercarbia induced a significant increase in both total and microvascular blood volume in normal brain and glioma, reactivity of glioma vasculature was significantly blunted in comparison to normal striatum; glioma total CBV increased by 0.6±0.1%/mm Hg CO2 whereas normal striatum increased by 1.5±0.2%/mm Hg CO2, (P < .0001, group t-test. Reactivity of microvascular blood volume was also significantly blunted. In contrast, hypocarbia decreased both total and microvascular blood volumes more in glioma than in normal striatum. These results indicate that cerebral blood vessels derived by tumor-directed angiogenesis do retain reactivity to CO2. Furthermore, reduced reactivity of tumor vessels to a single physiological perturbation, such as hypercarbia, should not be construed as a generalized reduction of functional activity of the tumor vascular bed.

  20. Evaluating changes in brain vasculature of murine embryos in utero due to maternal alcohol consumption using optical coherence tomography

    Science.gov (United States)

    Raghunathan, Raksha; Wu, Chen; Singh, Manmohan; Liu, Chih-Hao; Miranda, Rajesh C.; Larin, Kirill V.

    2017-04-01

    Fetal Alcohol Syndrome (FAS) refers to the broad spectrum of developmental and behavioral effects caused due to prenatal alcohol exposure (PAE). Wide range of abnormalities vary depending on the amount of alcohol consumed and the period of consumption during gestation. PAE during early stages of pregnancy is very common. However a large number of women continue to consume alcohol even during the second trimester, a critical period for fetal neurogenesis and angiogenesis. Optical coherence tomography (OCT) has shown to be extremely useful in embryonic imaging. Our previous work showed that OCT is capable of quantitative assessment of ventriculomegaly caused by maternal alcohol consumption. Although structural changes and changes in blood flow in the fetal brain after maternal alcohol consumption have been studied, acute vasculature changes are not well documented. Speckle variance OCT (SVOCT), is a functional extension of OCT that has been used to study vasculature development in embryos. We use SVOCT, to detect vasculature changes in the embryonic brain in utero, minutes after maternal alcohol consumption.

  1. Use of computed tomography and automated software for quantitative analysis of the vasculature of patients with pulmonary hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Wada, Danilo Tadao; Pádua, Adriana Ignácio de; Lima Filho, Moyses Oliveira; Marin Neto, José Antonio; Elias Júnior, Jorge; Baddini-Martinez, José; Santos, Marcel Koenigkam, E-mail: danilowada@yahoo.com.br [Universidade de São Paulo (HCFMRP/USP), Ribeirão Preto, SP (Brazil). Faculdade de Medicina. Hospital das Clínicas

    2017-11-15

    Objective: To perform a quantitative analysis of the lung parenchyma and pulmonary vasculature of patients with pulmonary hypertension (PH) on computed tomography angiography (CTA) images, using automated software. Materials And Methods: We retrospectively analyzed the CTA findings and clinical records of 45 patients with PH (17 males and 28 females), in comparison with a control group of 20 healthy individuals (7 males and 13 females); the mean age differed significantly between the two groups (53 ± 14.7 vs. 35 ± 9.6 years; p = 0.0001). Results: The automated analysis showed that, in comparison with the controls, the patients with PH showed lower 10{sup th} percentile values for lung density, higher vascular volumes in the right upper lung lobe, and higher vascular volume ratios between the upper and lower lobes. In our quantitative analysis, we found no differences among the various PH subgroups. We inferred that a difference in the 10{sup th} percentile values indicates areas of hypovolaemia in patients with PH and that a difference in pulmonary vascular volumes indicates redistribution of the pulmonary vasculature and an increase in pulmonary vasculature resistance. Conclusion: Automated analysis of pulmonary vessels on CTA images revealed alterations and could represent an objective diagnostic tool for the evaluation of patients with PH. (author)

  2. High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Jani, Ashish; Shaikh, Fauzia; Barton, Sunjay [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Willis, Callen [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Banerjee, Debarshi [Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); Mitchell, Jason [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Hernandez, Sonia L. [Department of Surgery, University of Chicago, Chicago, Illinois (United States); Hei, Tom [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Kadenhe-Chiweshe, Angela [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Yamashiro, Darrell J. [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York (United States); Connolly, Eileen P., E-mail: epc2116@cumc.columbia.edu [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States)

    2016-04-01

    Purpose: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.

  3. iNKT Cell Emigration out of the Lung Vasculature Requires Neutrophils and Monocyte-Derived Dendritic Cells in Inflammation

    Directory of Open Access Journals (Sweden)

    Ajitha Thanabalasuriar

    2016-09-01

    Full Text Available iNKT cells are a subset of innate T cells that recognize glycolipids presented on CD1d molecules and protect against bacterial infections, including S. pneumoniae. Using lung intravital imaging, we examined the behavior and mechanism of pulmonary iNKT cell activation in response to the specific iNKT cell ligand α-galactosylceramide or S. pneumoniae infection. In untreated mice, the major fraction of iNKT cells resided in the vasculature, but a small critical population resided in the extravascular space in proximity to monocyte-derived DCs. Administration of either α-GalCer or S. pneumoniae induced CD1d-dependent rapid recruitment of neutrophils out of the vasculature. The neutrophils guided iNKT cells from the lung vasculature via CCL17. Depletion of monocyte-derived DCs abrogated both the neutrophil and subsequent iNKT cell extravasation. Moreover, impairing iNKT cell recruitment by blocking CCL17 increased susceptibility to S. pneumoniae infection, suggesting a critical role for the influx of iNKT cells in host defense.

  4. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle.

    Science.gov (United States)

    Lee, Yang; Fluckey, James D; Chakraborty, Sanjukta; Muthuchamy, Mariappan

    2017-07-01

    Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility. LMCs were treated with different concentrations of insulin or glucose or both at various time points to determine insulin resistance. Onset of insulin resistance significantly impaired glucose uptake, mitochondrial function, oxygen consumption rates, glycolysis, lactic acid, and ATP production in LMCs. Hyperglycemia and hyperinsulinemia also impaired the PI3K/Akt while enhancing the ERK/p38MAPK/JNK pathways in LMCs. Increased NF-κB nuclear translocation and macrophage chemoattractant protein-1 and VCAM-1 levels in insulin-resistant LMCs indicated activation of inflammatory mechanisms. In addition, increased phosphorylation of myosin light chain-20, a key regulator of lymphatic muscle contraction, was observed in insulin-resistant LMCs. Therefore, our data elucidate the mechanisms of insulin resistance in LMCs and provide the first evidence that hyperglycemia and hyperinsulinemia promote insulin resistance and impair lymphatic contractile status by reducing glucose uptake, altering cellular metabolic pathways, and activating inflammatory signaling cascades.-Lee, Y., Fluckey, J. D., Chakraborty, S., Muthuchamy, M. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle. © FASEB.

  5. The muscle contraction mode determines lymphangiogenesis differentially in rat skeletal and cardiac muscles by modifying local lymphatic extracellular matrix microenvironments.

    Science.gov (United States)

    Greiwe, L; Vinck, M; Suhr, F

    2016-05-01

    Lymphatic vessels are of special importance for tissue homeostasis, and increases of their density may foster tissue regeneration. Exercise could be a relevant tool to increase lymphatic vessel density (LVD); however, a significant lack of knowledge remains to understand lymphangiogenesis in skeletal muscles upon training. Interestingly, training-induced lymphangiogenesis has never been studied in the heart. We studied lymphangiogenesis and LVD upon chronic concentric and chronic eccentric muscle contractions in both rat skeletal (Mm. Edl and Sol) and cardiac muscles. We found that LVD decreased in both skeletal muscles specifically upon eccentric training, while this contraction increased LVD in cardiac tissue. These observations were supported by opposing local remodelling of lymphatic vessel-specific extracellular matrix components in skeletal and cardiac muscles and protein levels of lymphatic markers (Lyve-1, Pdpn, Vegf-C/D). Confocal microscopy further revealed transformations of lymphatic vessels into vessels expressing both blood (Cav-1) and lymphatic (Vegfr-3) markers upon eccentric training specifically in skeletal muscles. In addition and phenotype supportive, we found increased inflammation (NF-κB/p65, Il-1β, Ifn-γ, Tnf-α and MPO(+) cells) in eccentrically stressed skeletal, but decreased levels in cardiac muscles. Our data provide novel mechanistic insights into lymphangiogenic processes in skeletal and cardiac muscles upon chronic muscle contraction modes and demonstrate that both tissues adapt in opposing manners specifically to eccentric training. These data are highly relevant for clinical applications, because eccentric training serves as a sufficient strategy to increase LVD and to decrease inflammation in cardiac tissue, for example in order to reduce tissue abortion in transplantation settings. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  6. Correlation between theoretical anatomical patterns of lymphatic drainage and lymphoscintigraphy findings during sentinel node detection in head and neck melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, Monica; Ruiz, Diana Milena [Hospital Clinic de Barcelona, Nuclear Medicine Department, Barcelona (Spain); Vidal-Sicart, Sergi; Paredes, Pilar; Pons, Francesca [Hospital Clinic de Barcelona, Nuclear Medicine Department, Barcelona (Spain); Institut d' Investigacions Biomediques Agusti Pi i Sunyer (IDIBAPS), Barcelona (Spain); Torres, Ferran [Hospital Clinic Barcelona, Statistical of Biostatistics and Data Management Core Facility, IDIBAPS, Barcelona (Spain); Universitat Autonoma de Barcelona, Biostatistics Unit, Faculty of Medicine, Barcelona (Spain)

    2016-04-15

    In the diagnosis of head and neck melanoma, lymphatic drainage is complex and highly variable. As regional lymph node metastasis is one of the most important prognostic factors, lymphoscintigraphy can help map individual drainage patterns. The aim of this study was to compare the results of lymphoscintigraphy and sentinel lymph node (SLN) detection with theoretical anatomical patterns of lymphatic drainage based on the location of the primary tumour lesion in patients with head and neck melanoma. We also determined the percentage of discrepancies between our lymphoscintigraphy and the theoretical location of nodal drainage predicted by a large lymphoscintigraphic database, in order to explain recurrence and false-negative SLN biopsies. In this retrospective study of 152 patients with head and neck melanoma, the locations of the SLNs on lymphoscintigraphy and detected intraoperatively were compared with the lymphatic drainage predicted by on-line software based on a large melanoma database. All patients showed lymphatic drainage and in all patients at least one SLN was identified by lymphoscintigraphy. Of the 152 patients, 4 had a primary lesion in areas that were not described in the Sydney Melanoma Unit database, so agreement could only be evaluated in 148 patients. Agreement between lymphoscintigraphic findings and the theoretical lymphatic drainage predicted by the software was completely concordant in 119 of the 148 patients (80.4 %, 95 % CI 73.3 - 86 %). However, this concordance was partial (some concordant nodes and others not) in 18 patients (12.2 %, 95 % CI 7.8 - 18.4 %). Discordance was complete in 11 patients (7.4 %, 95 % CI 4.2 - 12.8 %). In melanoma of the head and neck there is a high correlation between lymphatic drainage found by lymphoscintigraphy and the predicted drainage pattern and basins provided by a large reference database. Due to unpredictable drainage, preoperative lymphoscintigraphy is essential to accurately detect the SLNs in head and

  7. Lymphoscintigraphy for sentinel lymph node mapping in Japanese patients with malignant skin neoplasms of the lower extremities. Comparison with previously investigated Japanese lymphatic anatomy

    International Nuclear Information System (INIS)

    Miura, Hiroyuki; Ono, Shuichi; Nagahata, Morio

    2010-01-01

    Lymph nodes (LN) and lymphatic drainage were identified by lymphoscintigraphy using 99m Tc-phytate in order to map the sentinel lymph nodes (SLNs) in patients with malignant skin neoplasms of the lower extremities, and to compare the results with an atlas of Japanese lymphatic anatomy. Sentinel lymphoscintigraphs of 18 patients with malignant skin neoplasms of the lower extremities (9 men, 9 women; age range 45-84 years, mean age 66 years) were analyzed retrospectively, and the LNs detected were identified as SLNs or secondary nodes. The patterns of lymphatic drainage were divided into three different categories: initial drainage into inguinal LN without visualization of popliteal LNs (inguinal type), initial drainage into popliteal LNs and then into intrapelvic LNs (popliteal type), and initial drainage into both popliteal and inguinal LNs (inguinal and popliteal type). More than half of the cases were the inguinal and popliteal type, as both inguinal and popliteal LNs were identified as SLNs. In the cases in which the hallux and its surrounding area were injected, all were the inguinal type and popliteal LNs were not visualized. In one case, only dynamic images detected lymphatic drainage without visualization of popliteal LNs. In contrast to the previously published literature on Japanese lymphatic anatomy, SLN lymphatic drainage from the skin of the lower extremities was wide and overlapping in many areas. However, in agreement with currently accepted anatomy, only the great saphenous lymphatic vessel drained the skin of the hallux and its surrounding area. The present results suggest that it is important to confirm lymphatic drainage in order to identify SLNs in the lower extremities. The patterns of lymphatic drainage from the skin of the foot were divided into three different categories. In contrast to previously published Japanese lymphatic anatomy, lymphatic drainage from the skin of the lower extremities was wide and overlapping in many areas. However

  8. Increased extravasation and lymphatic return rate of albumin during diuretic treatment of ascites in patients with liver cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Schlichting, P

    1981-01-01

    During steady state the overall lymphatic return rate of albumin equals the transvascular escape rate of albumin [TERalb, i.e. the fraction of intravascular mass of albumin (IVMalb) passing to the extravascular space per unit time] provided local back-transport is negligible, as previously substa......), indicating a net transport of albumin from the peritoneal cavity to the plasma during diuretic treatment. The results suggest an increased lymphatic drainage of albumin during diuretic treatment, which may play a role in amelioration of cirrhotic ascites....

  9. Factors influencing drug uptake during mass drug administration for control of lymphatic filariasis in rural and urban Tanzania

    DEFF Research Database (Denmark)

    Kisoka, William J.; Simonsen, Paul Erik; Malecela, Mwelecele N.

    2014-01-01

    BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interrupt......BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission...

  10. Computational Study of Thrombus Formation and Clotting Factor Effects under Venous Flow Conditions

    Science.gov (United States)

    2016-04-26

    domain used in our thrombus formation simulations. Fig. 2 B shows the 3D geometry of the flow-chamber section consisting of two channels measuring 250 60...ArticleComputational Study of Thrombus Formation and Clotting Factor Effects under Venous Flow ConditionsVijay Govindarajan,1 Vineet Rakesh,1 Jaques...understanding of thrombus formation as a physicochemical process that has evolved to protect the integrity of the human vasculature is critical to our ability to

  11. Aspects of gorgonopsian paleobiology and evolution: insights from the basicranium, occiput, osseous labyrinth, vasculature, and neuroanatomy

    Directory of Open Access Journals (Sweden)

    Ricardo Araújo

    2017-04-01

    Full Text Available Synapsida, the clade including therapsids and thus also mammals, is one of the two major branches of amniotes. Organismal design, with modularity as a concept, offers insights into the evolution of therapsids, a group that experienced profound anatomical transformations throughout the past 270 Ma, eventually leading to the evolution of the mammalian bauplan. However, the anatomy of some therapsid groups remains obscure. Gorgonopsian braincase anatomy is poorly known and many anatomical aspects of the brain, cranial nerves, vasculature, and osseous labyrinth, remain unclear. We analyzed two gorgonopsian specimens, GPIT/RE/7124 and GPIT/RE/7119, using propagation phase contrast synchrotron micro-computed tomography. The lack of fusion between many basicranial and occipital bones in GPIT/RE/7124, which is an immature specimen, allowed us to reconstruct its anatomy and ontogenetic sequence, in comparison with the mature GPIT/RE/7119, in great detail. We explored the braincase and rendered various skull cavities. Notably, we found that there is a separate ossification between what was previously referred to as the “parasphenoid” and the basioccipital. We reinterpreted this element as a posterior ossification of the basisphenoid: the basipostsphenoid. Moreover, we show that the previously called “parasphenoid” is in fact the co-ossification of the dermal parasphenoid and the endochondral basipresphenoid. In line with previous descriptions, the anatomy of the osseous labyrinth is rendered in detail, revealing a unique discoid morphology of the horizontal semicircular canal, rather than toroidal, probably due to architectural constraints of the ossification of the opisthotic and supraoccipital. In addition, the orientation of the horizontal semicircular canal suggests that gorgonopsians had an anteriorly tilted alert head posture. The morphology of the brain endocast is in accordance with the more reptilian endocast shape of other non

  12. Early vitrectomy effective for bilateral combined anterior and posterior persistent fetal vasculature syndrome.

    Science.gov (United States)

    Walsh, Mark K; Drenser, Kimberly A; Capone, Antonio; Trese, Michael T

    2010-04-01

    The purpose of this study was to review our surgical experience with patients with bilateral combined anterior and posterior persistent fetal vasculature syndrome (PFVS). We retrospectively reviewed the charts of all patients seen in our tertiary care pediatric retinal practice from 1988 to 2008 with a potential diagnosis of bilateral PFVS with posterior involvement. Clinical diagnosis required the presence of either bilateral persistent hyaloidal stalk tissue with retinal involvement or bilateral dense retrolental fibrovascular plaques (usually with no posterior view preoperatively) without a family history or genetic testing consistent with Norrie disease or familial exudative vitreoretinopathy. Chart review showed 22 vitrectomized patients with clinical findings consistent with bilateral PFVS with posterior involvement who did not have a family history or genetic testing consistent with Norrie disease or familial exudative vitreoretinopathy. All 22 of these patients with posterior retinal involvement also had anterior findings and thus can be classified as combined anterior and posterior PFVS. Of the 13 patients with visual acuity follow-up data, 9 patients (69%) maintained at least light perception vision in at least 1 eye at last follow-up. Of the 28 operated eyes in 16 patients with follow-up data, 3 eyes (11%) were phthisical at last follow-up. Children with bilateral PFVS with posterior retinal involvement have a dismal visual prognosis if left unoperated. In this relatively large series of a rare condition, we find that vitrectomy with or without lensectomy is beneficial in bilateral combined anterior and posterior PFVS in two regards: maintenance or restoration of vision and avoidance of phthisis bulbi.

  13. Overactivation of Hedgehog Signaling Alters Development of the Ovarian Vasculature in Mice1

    Science.gov (United States)

    Ren, Yi; Cowan, Robert G.; Migone, Fernando F.; Quirk, Susan M.

    2012-01-01

    ABSTRACT The hedgehog (HH) signaling pathway is critical for ovarian function in Drosophila, but its role in the mammalian ovary has not been defined. Previously, expression of a dominant active allele of the HH signal transducer protein smoothened (SMO) in Amhr2cre/+SmoM2 mice caused anovulation in association with a lack of smooth muscle in the theca of developing follicles. The current study examined events during the first 2 wk of life in Amhr2cre/+SmoM2 mice to gain insight into the cause of anovulation. Expression of transcriptional targets of HH signaling, Gli1, Ptch1, and Hhip, which are used as measures of pathway activity, were elevated during the first several days of life in Amhr2cre/+SmoM2 mice compared to controls but were similar to controls in older mice. Microarray analysis showed that genes with increased expression in 2-day-old mutants compared to controls were enriched for the processes of vascular and tube development and steroidogenesis. The density of platelet endothelial cell adhesion molecule (PECAM)-labeled endothelial tubes was increased in the cortex of newborn ovaries of mutant mice. Costaining of preovulatory follicles for PECAM and smooth muscle actin showed that muscle-type vascular support cells are deficient in theca of mutant mice. Expression of genes for steroidogenic enzymes that are normally expressed in the fetal adrenal gland were elevated in newborn ovaries of mutant mice. In summary, overactivation of HH signaling during early life alters gene expression and vascular development and this is associated with the lifelong development of anovulatory follicles in which the thecal vasculature fails to mature appropriately. PMID:22402963

  14. Choroidal vasculature characteristics based choroid segmentation for enhanced depth imaging optical coherence tomography images

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qiang; Niu, Sijie [School of Computer Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094 (China); Yuan, Songtao; Fan, Wen, E-mail: fanwen1029@163.com; Liu, Qinghuai [Department of Ophthalmology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029 (China)

    2016-04-15

    Purpose: In clinical research, it is important to measure choroidal thickness when eyes are affected by various diseases. The main purpose is to automatically segment choroid for enhanced depth imaging optical coherence tomography (EDI-OCT) images with five B-scans averaging. Methods: The authors present an automated choroid segmentation method based on choroidal vasculature characteristics for EDI-OCT images with five B-scans averaging. By considering the large vascular of the Haller’s layer neighbor with the choroid-sclera junction (CSJ), the authors measured the intensity ascending distance and a maximum intensity image in the axial direction from a smoothed and normalized EDI-OCT image. Then, based on generated choroidal vessel image, the authors constructed the CSJ cost and constrain the CSJ search neighborhood. Finally, graph search with smooth constraints was utilized to obtain the CSJ boundary. Results: Experimental results with 49 images from 10 eyes in 8 normal persons and 270 images from 57 eyes in 44 patients with several stages of diabetic retinopathy and age-related macular degeneration demonstrate that the proposed method can accurately segment the choroid of EDI-OCT images with five B-scans averaging. The mean choroid thickness difference and overlap ratio between the authors’ proposed method and manual segmentation drawn by experts were −11.43 μm and 86.29%, respectively. Conclusions: Good performance was achieved for normal and pathologic eyes, which proves that the authors’ method is effective for the automated choroid segmentation of the EDI-OCT images with five B-scans averaging.

  15. Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia

    Directory of Open Access Journals (Sweden)

    Püntener Ursula

    2012-06-01

    Full Text Available Abstract Background Systemic infection leads to generation of inflammatory mediators that result in metabolic and behavioural changes. Repeated or chronic systemic inflammation leads to a state of innate immune tolerance: a protective mechanism against overactivity of the immune system. In this study, we investigated the immune adaptation of microglia and brain vascular endothelial cells in response to systemic inflammation or bacterial infection. Methods Mice were given repeated doses of lipopolysaccharide (LPS or a single injection of live Salmonella typhimurium. Inflammatory cytokines were measured in serum, spleen and brain, and microglial phenotype studied by immunohistochemistry. To assess priming of the innate immune response in the brain, mice were infected with Salmonella typhimurium and subsequently challenged with a focal unilateral intracerebral injection of LPS. Results Repeated systemic LPS challenges resulted in increased brain IL-1β, TNF-α and IL-12 levels, despite attenuated systemic cytokine production. Each LPS challenge induced significant changes in burrowing behaviour. In contrast, brain IL-1β and IL-12 levels in Salmonella typhimurium-infected mice increased over three weeks, with high interferon-γ levels in the circulation. Behavioural changes were only observed during the acute phase of the infection. Microglia and cerebral vasculature display an activated phenotype, and focal intracerebral injection of LPS four weeks after infection results in an exaggerated local inflammatory response when compared to non-infected mice. Conclusions These studies reveal that the innate immune cells in the brain do not become tolerant to systemic infection, but are primed instead. This may lead to prolonged and damaging cytokine production that may have a profound effect on the onset and/or progression of pre-existing neurodegenerative disease.

  16. Choroidal vasculature characteristics based choroid segmentation for enhanced depth imaging optical coherence tomography images

    International Nuclear Information System (INIS)

    Chen, Qiang; Niu, Sijie; Yuan, Songtao; Fan, Wen; Liu, Qinghuai

    2016-01-01

    Purpose: In clinical research, it is important to measure choroidal thickness when eyes are affected by various diseases. The main purpose is to automatically segment choroid for enhanced depth imaging optical coherence tomography (EDI-OCT) images with five B-scans averaging. Methods: The authors present an automated choroid segmentation method based on choroidal vasculature characteristics for EDI-OCT images with five B-scans averaging. By considering the large vascular of the Haller’s layer neighbor with the choroid-sclera junction (CSJ), the authors measured the intensity ascending distance and a maximum intensity image in the axial direction from a smoothed and normalized EDI-OCT image. Then, based on generated choroidal vessel image, the authors constructed the CSJ cost and constrain the CSJ search neighborhood. Finally, graph search with smooth constraints was utilized to obtain the CSJ boundary. Results: Experimental results with 49 images from 10 eyes in 8 normal persons and 270 images from 57 eyes in 44 patients with several stages of diabetic retinopathy and age-related macular degeneration demonstrate that the proposed method can accurately segment the choroid of EDI-OCT images with five B-scans averaging. The mean choroid thickness difference and overlap ratio between the authors’ proposed method and manual segmentation drawn by experts were −11.43 μm and 86.29%, respectively. Conclusions: Good performance was achieved for normal and pathologic eyes, which proves that the authors’ method is effective for the automated choroid segmentation of the EDI-OCT images with five B-scans averaging.

  17. Brief Communication: Tissue-engineered Microenvironment Systems for Modeling Human Vasculature

    Science.gov (United States)

    Tourovskaia, Anna; Fauver, Mark; Kramer, Gregory; Simonson, Sara; Neumann, Thomas

    2015-01-01

    The high attrition rate of drug candidates late in the development process has led to an increasing demand for test assays that predict clinical outcome better than conventional 2D cell culture systems and animal models. Government agencies, the military, and the pharmaceutical industry have started initiatives for the development of novel in-vitro systems that recapitulate functional units of human tissues and organs. There is growing evidence that 3D cell arrangement, co-culture of different cell types, and physico-chemical cues lead to improved predictive power. A key element of all tissue microenvironments is the vasculature. Beyond transporting blood the microvasculature assumes important organ-specific functions. It is also involved in pathologic conditions, such as inflammation, tumor growth, metastasis, and degenerative diseases. To provide a tool for modeling this important feature of human tissue microenvironments, we developed a microfluidic chip for creating tissue-engineered microenvironment systems (TEMS) composed of tubular cell structures. Our chip design encompasses a small chamber that is filled with an extracellular matrix (ECM) surrounding one or more tubular channels. Endothelial cells seeded into the channels adhere to the ECM walls and grow into perfusable tubular tissue structures that are fluidically connected to upstream and downstream fluid channels in the chip. Using these chips we created models of angiogenesis, the blood-brain-barrier (BBB), and tumor-cell extravasation. Our angiogenesis model recapitulates true angiogenesis, in which sprouting occurs from a “parent” vessel in response to a gradient of growth factors. Our BBB model is composed of a microvessel generated from brain-specific endothelial cells (ECs) within an ECM populated with astrocytes and pericytes. Our tumor-cell extravasation model can be utilized to visualize and measure tumor-cell migration through vessel walls into the surrounding matrix. The described

  18. Functional response of tumor vasculature in rats' glioma to hypercarbia evaluated by MR perfusion weighted imaging

    International Nuclear Information System (INIS)

    Zhang Qingbo; Feng Xiaoyuan; Liang Zonghui; Chen Shuan

    2008-01-01

    Objective: To evaluate the feasibility of MR PWI in judging maturity and variability of tumor vasculature in gliomas in rats. Methods: Twenty male SD rats were randomly assigned to tumor group and control group. Four weeks after implantation of C6 glioma cells in the brains of tumor group and injection of saline in the brains of control group, all rats were examined using MR PWI before and after inhalation of a mixture of 10% CO2 and 90% air. PaCO 2 and blood pH values of rats were monitored. Relative cerebral blood volume (rCBV) and relative cerebral blood flow(rCBF) values of tumors and normal brain tissue were measured. Brain sample were examined histologically using HE and immunohistochemical staining for smooth muscle actin(SMA). The histological features of gliomas were observed and SMA positively stained vessels of each tumor were counted manually using a light microscope. Perfusion data and pathological findings were analyzed statistically with SPSS for Windows. Results: PaCO 2 increased significantly [from(4.69±0.62)kPa to (7.62±0.81) kPa in tumor group and from (4.67±0.51) kPa to (7.63±0.78) kPa in control group, P 0.05), while changing rate of rCBV, rCBF in normal brain tissue correlated well with number of positive SMA labeled vessels (r=0.721 and 0.525, P 2 increase in the normal brain and in the tumor. It may be a useful technique to measure maturity of tumor vessels. (authors)

  19. Differential Gene Expression of Primary Cultured Lymphatic and Blood Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Gregory M. Nelson

    2007-12-01

    Full Text Available Blood vascular endothelial cells (BECs and the developmentally related lymphatic endothelial cells (LECs create complementary, yet distinct vascular networks. Each endothelial cell type interacts with flowing fluid and circulating cells, yet each vascular system has evolved specialized gene expression programs and thus both cell types display different phenotypes. BECs and LECs express distinct genes that are unique to their specific vascular microenvironment. Tumors also take advantage of the molecules that are expressed in these vascular systems to enhance their metastatic potential. We completed transcriptome analyses on primary cultured LECs and BECs, where each comparative set was isolated from the same individual. Differences were resolved in the expression of several major categories, such as cell adhesion molecules (CAMs, cytokines, cytokine receptors. We have identified new molecules that are associated with BECs (e.g., claudin-9, CXCL11, neurexin-1, neurexin-2, the neuronal growth factor regulator-1 and LECs (e.g., claudin-7, CD58, hyaluronan and proteoglycan link protein 1 (HAPLN1, the poliovirus receptor-related 3 molecule that may lead to novel therapeutic treatments for diseases of lymphatic or blood vessels, including metastasis of cancer to lymph nodes or distant organs.

  20. Lymphatic filarial species differentiation using evolutionarily modified tandem repeats: generation of new genetic markers.

    Science.gov (United States)

    Sakthidevi, Moorthy; Murugan, Vadivel; Hoti, Sugeerappa Laxmanappa; Kaliraj, Perumal

    2010-05-01

    Polymerase chain reaction based methods are promising tools for the monitoring and evaluation of the Global Program for the Elimination of Lymphatic Filariasis. The currently available PCR methods do not differentiate the DNA of Wuchereria bancrofti or Brugia malayi by a single PCR and hence are cumbersome. Therefore, we designed a single step PCR strategy for differentiating Bancroftian infection from Brugian infection based on a newly identified gene from the W. bancrofti genome, abundant larval transcript-2 (alt-2), which is abundantly expressed. The difference in PCR product sizes generated from the presence or absence of evolutionarily altered tandem repeats in alt-2 intron-3 differentiated W. bancrofti from B. malayi. The analysis was performed on the genomic DNA of microfilariae from a number of patient blood samples or microfilariae positive slides from different Indian geographical regions. The assay gave consistent results, differentiating the two filarial parasite species accurately. This alt-2 intron-3 based PCR assay can be a potential tool for the diagnosis and differentiation of co-infections by lymphatic filarial parasites. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  1. Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.

    Directory of Open Access Journals (Sweden)

    R Anuradha

    Full Text Available Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+ or without (CP Ag- active infection; with clinically asymptomatic infections (INF; and in those without infection (endemic normal [EN]. Comparisons between the two actively infected groups (CP Ag+ compared to INF and those without active infection (CP Ag- compared to EN were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein, acute phase proteins (haptoglobin and serum amyloid protein-A, and inflammatory cytokines (IL-1β, IL-12, and TNF-α are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.

  2. A pilot study on the status of lymphatic filariasis in a rural community of Bihar.

    Science.gov (United States)

    Das, V N R; Siddiqui, N A; Kumar, N; Verma, N; Verma, R B; Dinesh, D S; Kar, S K; Das, P

    2006-03-01

    A pilot study of lymphatic filariasis was conducted in two contiguous villages of Patna district in Bihar situated at the side of the river Ganges, known to be endemic for lymphatic filariasis, to study present status of transmission parameters of filariasis. Of the 1872 persons examined, 8.4% were found asymptomatic but microfilaraemic. Morbidity pattern due to filarial infection showed an increase with advancement of age and significantly high in males as compared to female (p < 0.001). Acute and chronic filarial disease was observed as 0.5% and 9% respectively. Microfilaria was found in 10% of acute and 11.2% of chronic filarial cases. The Mf rate was found to be 9.9% in males and 9.0% in females respectively. The parasite species was identified as W. bancrofti. The vector fauna surveyed show highest prevalence of vector species of Cx. quinquefasciatus (43%) in both domestic as well as predomestic area in the community. Other species like Cx. vishnui and Ma. uniformis were also seen. Each household and predomestic area was searched for mosquito fauna at night. The infection rate in vectors was found to be 14% and infectivity rate (L3) was 8%. The filariasis cases detected in the study were treated with 12 days course of DEC 6 mg/kg body weight.

  3. Lymphatic vessel density in vocal cord carcinomas assessed with LYVE-1 receptor expression

    International Nuclear Information System (INIS)

    Koskinen, Walter J.; Bono, Petri; Leivo, Ilmo; Vaheri, Antti; Aaltonen, Leena-Maija; Joensuu, Heikki

    2005-01-01

    Background and purpose: Early stage vocal cord carcinomas are usually cured by radiation therapy despite the use of portals that exclude the cervical lymph nodes. We investigated whether the lymphatic vessel density (LVD) of vocal cord carcinomas differs from that of other head and neck carcinomas. Patients and methods: Deparaffinized tissue from tumors of 60 patients diagnosed with head and neck squamous cell carcinoma (HNSCC) were immunostained for LYVE-1, a novel lymphatic vessel marker. Twenty-two had vocal cord carcinoma. Tumor blood vessel density (BVD) was assessed using immunostaining for CD31. Results: Tumor overall LVD, including both intra- and peritumoral lymph vessels, was 10-fold lower than the BVD (5 counts/mm 2 vs. 52 mm -2 , respectively). A high LVD was associated with a high BVD (P=.002), but neither was associated with the tumor size. Both tumor LVD and BVD were lower in vocal cord carcinomas than in HNSCCs arising at other sites (median, 0 vs. 7 mm -2 , P=.016; and median, 36 vs. 52 mm -2 , P=.006, respectively). Only one vocal cord carcinoma was associated with a regional metastasis at the time of the diagnosis. Among the rest of the cases tumor size was a better predictor for the presence of regional metastases than tumor BVD or LVD in a logistic regression model (odds ratio 2.2, 95% CI 1.1-4.5). Conclusion: Vocal cord carcinomas have a low lymph vessel density as compared with HNSCCs arising at other sites

  4. Malignant Pleural Mesothelioma with Marked Lymphatic Involvement: A Report of Two Autopsy Cases

    Directory of Open Access Journals (Sweden)

    Reiko Ideguchi

    2017-01-01

    Full Text Available We herein report two cases of malignant pleural mesothelioma with marked lymphangiosis. The patients included a 68-year-old man and a 67-year-old man who both had a history of exposure to asbestos. Computed tomography (CT on admission showed pleural effusion with pleural thickening. In both cases, a histopathological examination of the pleura confirmed the diagnosis of epithelioid malignant mesothelioma. They received chemotherapy, but the treatment was only palliative. The chest CT assessments during admission revealed marked pleural effusion and mediastinal lymphadenopathy. CT also showed a consolidative mass with bronchovascular bundle and septal thickening in the lungs suggesting pulmonary parenchymal involvement and the lymphangitic spread of the tumor. These CT findings mimicked lung cancer with pleuritis and lymphangitic carcinomatosis. Autopsy was performed in both cases. Macroscopically, the tumor cells infiltrated the lung with the marked lymphatic spread of the tumor. Microscopy also revealed that the tumor had invaded the pulmonary parenchyma with the marked lymphatic spread of the tumor. Although this growth pattern is unusual, malignant pleural mesothelioma should be considered as the differential diagnosis, especially in patients with pleural lesions.

  5. Facial nerve conduction after sclerotherapy in children with facial lymphatic malformations: report of two cases.

    Science.gov (United States)

    Lin, Pei-Jung; Guo, Yuh-Cherng; Lin, Jan-You; Chang, Yu-Tang

    2007-04-01

    Surgical excision is thought to be the standard treatment of choice for lymphatic malformations. However, when the lesions are limited to the face only, surgical scar and facial nerve injury may impair cosmetics and facial expression. Sclerotherapy, an injection of a sclerosing agent directly through the skin into a lesion, is an alternative method. By evaluating facial nerve conduction, we observed the long-term effect of facial lymphatic malformations after intralesional injection of OK-432 and correlated the findings with anatomic outcomes. One 12-year-old boy with a lesion over the right-side preauricular area adjacent to the main trunk of facial nerve and the other 5-year-old boy with a lesion in the left-sided cheek involving the buccinator muscle were enrolled. The follow-up data of more than one year, including clinical appearance, computed tomography (CT) scan and facial nerve evaluation were collected. The facial nerve conduction study was normal in both cases. Blink reflex in both children revealed normal results as well. Complete resolution was noted on outward appearance and CT scan. The neurophysiologic data were compatible with good anatomic and functional outcomes. Our report suggests that the inflammatory reaction of OK-432 did not interfere with adjacent facial nerve conduction.

  6. Lymphatic Filariasis

    Science.gov (United States)

    ... Evaluation and Treatment Care of Patients with Lymphedema, Elephantiasis or Hydrocele Publications Additional Resources Get Email Updates ... with the disease can suffer from lymphedema and elephantiasis and in men, swelling of the scrotum, called ...

  7. Lymphatic Disorders

    Science.gov (United States)

    ... Generic and Brand Natural Products, Search Drug Interactions Pill Identifier Commonly searched drugs Aspirin Metformin Warfarin Tramadol Lactulose Ranitidine News & Commentary Recent News Strict Gun Laws Spare Young Lives: Study 'Smart Dresser' Might Help Alzheimer's Patients Clothe Themselves AHA: ...

  8. Mechanisms of lumen formation during sprouting angiogenesis in vivo

    OpenAIRE

    Gebala, V. M.

    2016-01-01

    During development, vascular networks expand following a process known as sprouting angiogenesis. New vascular branches arise from pre-existing vessels through the coordinated migration and proliferation of endothelial cells, and eventually connect to form new vascular loops. The functionality of these new vessel segments is dependent on the opening of a central lumen to allow perfusion. While mechanisms of lumen formation during the establishment of the primary vasculature by vasculogenesis ...

  9. National Characteristics of Lymphatic Malformations in Children: Inpatient Estimates and Trends in the United States, 2000 to 2009.

    Science.gov (United States)

    Cheng, Jeffrey; Liu, Beiyu; Farjat, Alfredo E; Routh, Jonathan

    2018-04-01

    With ever increasing demands to manage finite resources for health care utilization, we performed an investigation to identify inpatient clinical characteristics and trends in children with lymphatic malformations using the Kids' Inpatient Database, years 2000 to 2009, to help identify populations best suited for resource deployment. Subjects included children 18 years and below with International Classification of Diseases (ICD), ninth revision code: 228.1-lymphangioma, any site. In the United States, between 2000 and 2009, inpatient pediatric patients with lymphatic malformations most commonly affected children aged 3 years and younger, urban hospital locations, and the South and West regions. There was no significant change in age of children with lymphatic malformations or the distribution of their age from year to year, P=0.948 and 0.4223, respectively. No significant evidence for seasonal variation or effect on inpatient admission was identified, P=0.7071. A great majority of admissions (>96%) were in urban locations across each year. There was also no significant change in breakdown of admissions by geographic location, P=0.7133. Further investigation may help to elucidate how to improve access to multidisciplinary vascular anomalies teams to optimize care for these children with unique and complex lymphatic malformations.

  10. Structured triglyceride vehicles for oral delivery of halofantrine: examination of intestinal lymphatic transport and bioavailability in conscious rats.

    Science.gov (United States)

    Holm, René; Porter, Christopher J H; Müllertz, Anette; Kristensen, Henning G; Charman, William N

    2002-09-01

    To compare the influence of triglyceride vehicle intramolecular structure on the intestinal lymphatic transport and systemic absorption of halofantrine in conscious rats. Conscious, lymph cannulated and nonlymph cannulated rats were dosed orally with three structurally different triglycerides; sunflower oil, and two structured triglycerides containing different proportion and position of medium-(M) and long-chain (L) fatty acids on the glycerol backbone. The two structured triglycerides were abbreviated MLM and LML to reflect the structural position on the glycerol. The concentration of halofantrine in blood and lymph samples was analyzed by HPLC. Both the lymphatic transport and the total absorption of halofantrine were enhanced by the use the MLM triglyceride. The estimated total absorption of halofantrine in the lymph cannulated animals was higher than in the nonlymph cannulated animals, and this was most pronounced for the animals dosed with the structured triglycerides. Using MLM as vehicle increases the portal absorption of halofantrine and results in similar lymphatic transport levels when compared to sunflower oil. Total absorption when assessed as absorption in the blood plus lymphatic transport for halofantrine after administration in the MLM triglyceride was higher than after administration in sunflower oil.

  11. Community members' perceptions of mass drug administration for control of lymphatic filariasis in rural rural and urban Tanzania

    DEFF Research Database (Denmark)

    Kisoka, William J.; Tersbøl, Britt Pinkowski; Meyrowitsch, Dan Wolf

    2016-01-01

    Lymphatic filariasis is one of several neglected tropical diseases with severely disabling and stigmatizing manifestations that are referred to as 'neglected diseases of poverty'. It is a mosquito-borne disease found endemically and exclusively in low-income contexts where, concomitantly, general...

  12. Cerebrofacial venous metameric syndrome (CVMS) 3: Sturge-Weber syndrome with bilateral lymphatic/venous malformations of the mandible

    International Nuclear Information System (INIS)

    Ramli, N.; Sachet, M.; Bao, C.; Lasjaunias, P.

    2003-01-01

    We present a case of Sturge-Weber syndrome with a bilateral lymphatic/venous malformation of the mandible. Modern biology suggests an explanation for such a case. The classification of cerebrofacial venous metameric syndromes (CVMS) enables us to recognise this lesion as involving the most caudal of the cranial metamere (CVMS 3). (orig.)

  13. Pleural epithelioid angiosarcoma with lymphatic differentiation arisen after radiometabolic therapy for thyroid carcinoma: immunohistochemical findings and review of the literature.

    Science.gov (United States)

    Cabibi, Daniela; Pipitone, Giulia; Porcasi, Rossana; Ingrao, Sabrina; Benza, Ignazio; Porrello, Calogero; Cajozzo, Massimo; Giannone, Antonino Giulio

    2017-08-15

    Pleural angiosarcoma is a rare tumor that causes diffuse pleural thickening and effusion, mimicking mesothelioma. Immunohistochemistry is needed to highlight endothelial differentiation. We describe the first case of pleural angiosarcoma with lymphatic differentiation following radiometabolic therapy for thyroid carcinoma. A 50-year-old man showed diffuse pleural thickening and effusion. Nine years earlier, he underwent thyroidectomy and radiometabolic therapy for thyroid carcinoma with lymph node metastases. Histologically, the tumor consisted of a solid proliferation of atypical epithelioid cells and anastomosed vascular spaces, lacking of red blood cells and containing Alcian blue positive material. The tumor showed positive immunostaining for Vimentin, CD31, CK7, D2-40, c-MYC, Ki67, focal positivity for PanCK, and negative immunostaining for Factor VIII, CD34, WT1, CK5/6, Calretinin, EMA, HBME-1, CEA, p63, EpCAM, Bcl-2, TTF1 and Thyroglobulin. CD99 showed a granular/paranuclear pattern of positivity. The histological and immunohistochemical features were consistent with "pleural angiosarcoma with lymphatic differentiation, epithelioid variant". Epithelioid angiosarcoma with lymphatic differentiation is very rare and aggressive. Moreover, the positivity for c-MYC suggests the relationship with radiometabolic therapy. To our knowledge, this is the first case of pleural c-MYC-positive angiosarcoma with lymphatic differentiation reported in the literature and the first one arisen after radiometabolic therapy for thyroid carcinoma.

  14. Percutaneous sclerotherapy of massive macrocystic lymphatic malformations of the face and neck using fibrin glue with OK-432 and bleomycin.

    Science.gov (United States)

    Chen, W-l; Huang, Z-q; Chai, Q; Zhang, D-m; Wang, Y-y; Wang, H-j; Wang, L; Fan, S

    2011-06-01

    Picibanil (OK-432) and bleomycin have been used as alternative sclerosing agents for lymphatic malformations. This study evaluated the clinical curative effect of sclerotherapy using fibrin glue combined with OK-432 and bleomycin for the treatment of macrocystic lymphatic malformations of the face and neck. Fifteen paediatric patients (6 males; 9 females, aged 13 months to 14 years) who had received percutaneous sclerotherapy for massive macrocystic lymphatic malformations of the face and neck were retrospectively reviewed. Affected regions included the neck, parotid region and parapharynx, mouth floor, face and cheek, and orbital regions. All patients showed preoperative symptoms of space-occupying lesions between 4 cm × 5 cm and 12 cm × 16 cm in size. Fibrin glue with OK-432 and bleomycin was injected under general anaesthesia. All patients received preoperative and follow-up CT scans. Outcomes were assessed by three surgeons. All patients exhibited mid-facial swelling for 3-4 weeks after surgery, but no major complications. Follow-up periods ranged from 8 to 16 months. Eight lesions were completely involuted, five were mostly involuted, and two were partially involuted. Percutaneous sclerotherapy using fibrin glue with OK-432 and bleomycin provided a simple, safe, and reliable alternative treatment for massive macrocystic lymphatic malformations of the face and neck. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  15. Debulking surgery for elephantiasis nostras with large ectatic podoplanin-negative lymphatic vessels in patients with lipo-lymphedema.

    Science.gov (United States)

    Wollina, Uwe; Heinig, Birgit; Schönlebe, Jaqueline; Nowak, Andreas

    2014-01-01

    Elephantiasis nostras is a rare complication in advanced lipo-lymphedema. While lipedema can be treated by liposuction and lymphedema by decongestive lymphatic therapy, elephantiasis nostras may need debulking surgery. We present 2 cases of advanced lipo-lymphedema complicated by elephantiasis nostras. After tumescent microcannular laser-assisted liposuction both patients underwent a debulking surgery with a modification of Auchincloss-Kim's technique. Histologic examination of the tissue specimen was performed. The surgical treatment was well tolerated and primary healing was uneventful. After primary wound healing and ambulation of the patients, a delayed ulceration with lymphorrhea developed. It was treated by surgical necrectomy and vacuum-assisted closure leading to complete healing. Mobility of the leg was much improved. Histologic examination revealed massive ectatic lymphatic vessels nonreactive for podoplanin. Debulking surgery can be an adjuvant technique for elephantiasis nostras in advanced lipo-lymphedema. Although delayed postoperative wound healing problems were observed, necrectomy and vacuum-assisted closure achieved a complete healing. Histologic data suggest that the ectatic lymphatic vessels in these patients resemble finding in podoplanin knockout mice. The findings would explain the limitations of decongestive lymphatic therapy and tumescent liposuction in such patients and their predisposition to relapsing erysipelas.

  16. Three-dimensional computer-assisted dissection of pancreatic lymphatic anatomy on human fetuses: a step toward automatic image alignment.

    Science.gov (United States)

    Bardol, T; Subsol, G; Perez, M-J; Genevieve, D; Lamouroux, A; Antoine, B; Captier, G; Prudhomme, M; Bertrand, M M

    2018-05-01

    Pancreatic cancer is the fourth cause of death by cancer worldwide. Lymph node (LN) involvement is known to be the main prognostic factor. However, lymphatic anatomy is complex and only partially characterized. The aim of the study was to study the pancreatic lymphatic system using computer-assisted anatomic dissection (CAAD) technique and also to update CAAD technique by automatizing slice alignment. We dissected three human fetuses aged from 18 to 34 WA. 5-µm serial sections of duodeno-pancreas and spleen blocks were stained (hematoxylin-eosin, hematoxylin of Mayer and Masson trichrome), scanned, aligned and modeled in three dimensions. We observed a rich, diffuse but not systematized lymphatic network in the peri-pancreatic region. There was an equal distribution of LNs between the cephalic and body-tail portions. The lymphatic vascularization appeared in continuity from the celiac trunk to the distal ends of its hepatic and splenic arterial branches parallel to the nerve ramifications of the celiac plexus. We also observed a continuity between the drainage of the pancreatic head and the para-aortic region posteriorly. In view of the wealth of peri-pancreatic LNs, the number of LNs to harvest could be increased to improve nodal staging and prognostic evaluation. Pancreatic anatomy as described does not seem to be compatible with the sentinel LN procedure in pancreatic surgery. Finally, we are now able to offer an alternative to manual alignment with a semi-automated alignment.

  17. Anatomy of the transverse colon revisited with respect to complete mesocolic excision and possible pathways of aberrant lymphatic tumor spread.

    Science.gov (United States)

    Stelzner, Sigmar; Hohenberger, Werner; Weber, Klaus; West, Nicholas P; Witzigmann, Helmut; Wedel, Thilo

    2016-02-01

    Although lymph node metastases to pancreatic and gastroepiploic lymph node stations in transverse colon cancer have been described, the mode of lymphatic spread in this area remains unclear. This study was undertaken to describe possible pathways of aberrant lymphatic spread in the complex anatomic area of the proximal superior mesenteric artery and vein, the greater omentum, and the lower pancreatic border. Abdominal specimens obtained from four cadaveric donors were dissected according to the principles of complete mesocolic excision. The vascular architecture of the transverse colon was scrutinized in search of possible pathways of lymphatic spread to the pancreatic and gastroepiploic lymph nodes. Vascular connections between the transverse colon and the greater omentum at the level of both the hepatic and the splenic flexures could be identified. In addition, small vessels running from the transverse mesocolon to the lower pancreatic border in the area between the middle colic artery and the inferior mesenteric vein were demonstrated. Moreover, venous tributaries to the gastrocolic trunk could be exposed to highlight its surgical importance as a guiding structure for complete mesocolic excision. The technical feasibility to clearly separate embryologic compartments by predefined tissue planes in complete mesocolic excision was confirmed. However, the vicinity of all three endodermal intestinal segments (foregut, midgut, and hindgut) obviously gives way to vascular connections that might serve as potential pathways for lymphatic metastatic spread of transverse colon cancer.

  18. Study Regarding the Effectiveness of Manual Lymphatic Drainage in the Case of Patients with Breast Cancer that Present Lymphedema

    Directory of Open Access Journals (Sweden)

    Alexandru MIOC

    2013-06-01

    Full Text Available Lymphedema is defined as a persistent increase of tissue volume caused by the blocked or absent lymphatic drainage. The purpose of this study is to analyse the effectiveness of lymphatic drainage in the treatment of lymphedema after a mastectomy, with the aim of reducing the volume of the lymphedema and improving overall symptomatology, as well as providing information regarding the impact of this treatment on quality-of-life and the physical limitations of these patients. With these objectives in mind, a series of articles evaluating the effectiveness of manual lymphatic drainage in the case of patients with breast cancer and lymphedema have been studied. The parameters under observation were: duration of lymphedema reduction and improved symptomatology (pain, a feeling of swelling of the upper limb, functional limitation, and patient dissatisfaction towards their body image. Following this analysis, one can conclude that the association of manual lymphatic drainage to physical exercise and physiotherapy has produced changes in the volume of the limb affected by the lymphedema; however, its isolated use has not resulted in significant changes.

  19. Lymphatic-targeted therapy following neoadjuvant chemotherapy: a promising strategy for lymph node-positive breast cancer treatment.

    Science.gov (United States)

    Chen, Jianghao; Yao, Qing; Wang, Hui; Wang, Bo; Zhang, Juliang; Wang, Ting; Lv, Yonggang; Han, Zenghui; Wang, Ling

    2015-07-01

    Neoadjuvant chemotherapy has been increasingly used to downstage breast cancer prior to surgery recently. However, in some cases, it was observed that despite sufficient regression of primary tumors, the metastatic lymph nodes remained nonresponsive. In this study, we applied lymphatic-targeted strategy to evaluate its efficacy and safety for patients presenting refractory nodes following systemic chemotherapy. A total of 318 breast cancer patients were demonstrated with lymph node metastasis by needle biopsy and given neoadjuvant chemotherapy. Two cycles later, 72 patients were observed with responsive tumors but stable nodes, 42 of which received a subcutaneous injection of lymphatic-targeted pegylated liposomal doxorubicin during the third cycle, while the remaining 30 patients were continued with former neoadjuvant therapeutic pattern and regarded as the control. Lymphatic-targeted treatment substantially increased both clinical and pathological node response rate [62 % (26/42) vs. 13 % (4/30) and 12 % (5/42) vs. 0 (0/30), respectively], and induced a higher apoptosis level of metastatic cells (median, 41 vs. 6 %), compared with the control. Moreover, a higher disease-free survival was observed after a median follow-up of 4 years (69 vs. 56 %). Inflammatory reaction surrounding injection sites was the most common side effect. Lymphatic chemotherapy has reliable efficacy and well-tolerated toxicity for breast cancer patients presenting refractory lymph nodes following neoadjuvant chemotherapy.

  20. Comparative evaluation of 64-slice CT angiography and digital subtraction angiography in assessing the cervicocranial vasculature

    Directory of Open Access Journals (Sweden)

    Randolf Klingebiel

    2008-08-01

    Full Text Available Randolf Klingebiel1, Max Kentenich3, Hans-Christian Bauknecht3, Florian Masuhr2, Eberhard Siebert1, Markus Busch2, Georg Bohner11Department of Neuroradiology, 2Department of Neurology, 3Department of Radiology, Charité Universitary Medicine Berlin, GermanyBackground: Noninvasive 64-slice computed tomography angiography (64-MSCTA closely approximates conventional catheter angiography (DSA in terms of detail resolution. Objective: Retrospective evaluation of cervicocranial (cc 64-MSCTA in comparison with DSA in patients with presumptive cc vascular disorders.Material and methods: Twenty-four 64-MSCTA studies (32 mm detector width, slice thickness 0.5 mm, 120 kv, 150 mAs, pitch 0.75 of patients with presumptive cc vascular pathology (13 men, 11 women, mean age 38.3 ± 11.3 yrs, range 19–54 yrs were assessed in comparison with DSA studies without abnormal findings in age-matched patients (11 men, 13 women, mean age 39.7 ± 11.9 yrs, range 18–54 yrs. Study readings were performed in a blinded manner by two neuroradiologists with respect to image quality and assessibility of various cc vascular segments by using a five-point scale. Radiation exposure was calculated for 64-MSCTA.Results: Each reader assessed 384/528 different vessel segments (64-MSCTA/DSA. Superior image quality was attributed to DSA with respect to the C1 ICA–C6 ICA, A3 ACA, and P3 PCA segments as well the AICA and SCA. 64-MSCTA was scored superior for C7 ICA and V4 VA segments. A significantly increased number of nonassessable V2- and V3 VA segments in DSA studies was noted. The effective dose for 64-MSCTA amounted to 2.2 mSv.Conclusions: 64-MSCTA provides near-equivalent diagnostic information of the cc vasculature as compared with DSA. According to our results, DSA should be considered primarily when peripheral vessels (A3/P3 or ICA segments close to the skull base (C2-5 are of interest, such as in primary angiitis or stenoocclusive ICA disease, respectively.Keywords: CT

  1. Mathematical models for lymphatic filariasis transmission and control: Challenges and prospects

    Directory of Open Access Journals (Sweden)

    Kaliannagounder Krishnamoorthy

    2008-02-01

    Full Text Available Abstract Background Mathematical models developed for describing the dynamics of transmission, infection, disease and control of lymphatic filariasis (LF gained momentum following the 1997 World Health Assembly resolution and the launching of the Global Programme to Eliminate Lymphatic Filariasis (GPELF in 2000. Model applications could provide valuable inputs for making decisions while implementing large scale programmes. However these models need to be evaluated at different epidemiological settings for optimization and fine-tuning with new knowledge and understanding on infection/disease dynamics. Discussion EPIFIL and LYMFASIM are the two mathematical simulation models currently available for lymphatic filariasis transmission and control. Both models have been used for prediction and evaluation of control programmes under research settings. Their widespread application in evaluating large-scale elimination programmes warrants validation of assumptions governing the dynamics of infection and disease in different epidemiological settings. Furthermore, the predictive power of the models for decision support can be enhanced by generating knowledge on some important issues that pose challenges and incorporating such knowledge into the models. We highlight factors related to the efficacy of the drugs of choice, their mode of action, and the possibility that drug resistance may develop; the role of vector-parasite combinations; the magnitude of transmission thresholds; host-parasite interactions and their effects on the dynamics of infection and immunity; parasite biology, and progression to LF-associated disease. Summary The two mathematical models developed offer potential decision making tools for transmission and control of LF. In view of the goals of the GPELF, the predictive power of these models needs to be enhanced for their wide-spread application in large scale programmes. Assimilation and translation of new information into the models is

  2. Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species

    Directory of Open Access Journals (Sweden)

    Armstrong Dianna

    2004-12-01

    Full Text Available Abstract Background The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to humans has never been clarified. The purpose of this study was to compare the CSF and nasal lymph associations in human and non-human primates with those observed in other mammalian species. Methods Studies were performed in sheep, pigs, rabbits, rats, mice, monkeys and humans. Immediately after sacrifice (or up to 7 hours after death in humans, yellow Microfil was injected into the CSF compartment. The heads were cut in a sagittal plane. Results In the seven species examined, Microfil was observed primarily in the subarachnoid space around the olfactory bulbs and cribriform plate. The contrast agent followed the olfactory nerves and entered extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. This is the first direct evidence of the association between the CSF and nasal lymph compartments in humans. Conclusions The fact that the pattern of Microfil distribution was similar in all species tested, suggested that CSF absorption into nasal lymphatics is a characteristic feature of all mammals including humans. It is tempting to speculate that some disorders of the CSF system (hydrocephalus and idiopathic intracranial hypertension for example may relate either directly or indirectly to a lymphatic CSF absorption deficit.

  3. Validation of ALFIA: a platform for quantifying near-infrared fluorescent images of lymphatic propulsion in humans

    Science.gov (United States)

    Rasmussen, John C.; Bautista, Merrick; Tan, I.-Chih; Adams, Kristen E.; Aldrich, Melissa; Marshall, Milton V.; Fife, Caroline E.; Maus, Erik A.; Smith, Latisha A.; Zhang, Jingdan; Xiang, Xiaoyan; Zhou, Shaohua Kevin; Sevick-Muraca, Eva M.

    2011-02-01

    Recently, we demonstrated near-infrared (NIR) fluorescence imaging for quantifying real-time lymphatic propulsion in humans following intradermal injections of microdose amounts of indocyanine green. However computational methods for image analysis are underdeveloped, hindering the translation and clinical adaptation of NIR fluorescent lymphatic imaging. In our initial work we used ImageJ and custom MatLab programs to manually identify lymphatic vessels and individual propulsion events using the temporal transit of the fluorescent dye. In addition, we extracted the apparent velocities of contractile propagation and time periods between propulsion events. Extensive time and effort were required to analyze the 6-8 gigabytes of NIR fluorescent images obtained for each subject. To alleviate this bottleneck, we commenced development of ALFIA, an integrated software platform which will permit automated, near real-time analysis of lymphatic function using NIR fluorescent imaging. However, prior to automation, the base algorithms calculating the apparent velocity and period must be validated to verify that they produce results consistent with the proof-of-concept programs. To do this, both methods were used to analyze NIR fluorescent images of two subjects and the number of propulsive events identified, the average apparent velocities, and the average periods for each subject were compared. Paired Student's t-tests indicate that the differences between their average results are not significant. With the base algorithms validated, further development and automation of ALFIA can be realized, significantly reducing the amount of user interaction required, and potentially enabling the near real-time, clinical evaluation of NIR fluorescent lymphatic imaging.

  4. Basic Description of the Lymphatic System from the Perspective of SLN Uptake of Radioactive Tracers. Chapter 2

    International Nuclear Information System (INIS)

    Pasqualini, R.; Janevik-Ivanovska, E.

    2015-01-01

    The lymphatic system is part of the circulatory system. It is closely associated with the cardiovascular system because it includes a network of vessels that contributes to liquid transportation throughout the body. This circulatory system is essential for the maintenance of interstitial fluid balance, uptake of dietary fat and for body defence against invasion by disease causing agents. Lymph nodes, which contain large numbers of B and T lymphocytes and macrophages, are located along lymphatic pathways. They have two primary functions: filtering and digesting potentially harmful particles from lymph before returning it to the bloodstream and contributing to the immune surveillance provided by lymphocytes and macrophages. In their function of filtering particles or cell debris, lymph nodes may collect cancer cells that are breaking and travelling away from the primary tumour. The spread of some forms of cancer usually follows an orderly progression, spreading first to regional lymph nodes, then the next rank of lymph nodes and so on. Therefore, the first lymph node (the SLN) is more likely than other lymph nodes to contain cancer cells. If a suitable radioactive tracer, generally a nanocolloid or a dye, is administrated in the proximity of the tumour site, it will travel through the lymphatic system and be trapped in the SLN, allowing its localization using an appropriate probe or by visual determination. The size and the charge of the radioactive tracer will mainly influence the extent of radioactivity remaining at the site of injection, the rate of diffusion into the lymphatic vessels and the uptake in the SLN. Knowledge of the physiology of the lymphatic system will help to identify factors influencing the diffusion and uptake mechanism of radioactive tracers in the lymph nodes and will assist in the design of more efficient and selective SLN seeking drugs. (author)

  5. Anterior Segment Optical Coherence Tomography Angiography for Identification of Iris Vasculature and Staging of Iris Neovascularization: A Pilot Study.

    Science.gov (United States)

    Roberts, Philipp K; Goldstein, Debra A; Fawzi, Amani A

    2017-08-01

    Purpose/Aim of the study: To assess the ability of optical coherence tomographic angiography (OCTA) to visualize the normal iris vasculature as well as neovascularization of the iris (NVI). Study participants with healthy eyes, patients at risk of NVI development and patients with active or regressed NVI were consecutively included in this cross-sectional observational study. Imaging was performed using a commercially available OCTA system (RTVue- XR Avanti, Optovue Inc., Fremont, CA, USA). Abnormal iris vessels were graded on OCTA according to a modified clinical staging system and compared to slitlamp and gonioscopic findings. Fifty eyes of 26 study participants (16 healthy eyes, 19 eyes at risk, 15 eyes with different stages of NVI) were imaged using OCTA. In 11 out of 16 healthy eyes (69%) with light or moderately dark iris pigmentation, we observed physiological, radially aligned iris vasculature on OCTA imaging, which could not be visualized in five eyes (31%) with darkly pigmented irides. One eye in the "eyes at risk" group was diagnosed with NVI based on OCTA, which was not observed clinically. Fifteen eyes with clinically active or regressed NVI were imaged. Different stages of NVI could be differentiated by OCTA, corresponding well to an established clinical grading system. Four eyes showed regressed NVI by OCTA, not seen clinically, and were graded as a newly defined stage 4. This pilot clinical study showed that OCTA for imaging of the iris vasculature in health and disease is highly dependent on iris pigmentation. Fine, clinically invisible iris vessels can be visualized by OCTA in the very early stages as well as in the regressed stage of NVI.

  6. Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature

    DEFF Research Database (Denmark)

    Hansen, Pernille B; Poulsen, Christian B; Walter, Steen

    2011-01-01

    Calcium channel blockers are widely used for treatment of hypertension, because they decrease peripheral vascular resistance through inhibition of voltage-gated calcium channels. Animal studies of renal vasculature have shown expression of several types of calcium channels that are involved......-type subtype (Ca(v) 3.1 and Ca(v) 3.2) voltage-gated calcium channels (Ca(v)s), and quantitative PCR showed highest expression of L-type channels in renal arteries and variable expression between patients of subtypes of calcium channels in intrarenal vessels. Immunohistochemical labeling of kidney sections...

  7. Hematopoietic and lymphatic cancers in relatives of patients with infectious mononucleosis

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Rostgaard, Klaus; Askling, Johan

    2002-01-01

    BACKGROUND: Young adults with a history of Epstein-Barr virus (EBV)-related infectious mononucleosis have an increased risk for Hodgkin's lymphoma. EBV is detected in Hodgkin's lymphoma Reed-Sternberg cells from some patients, but in young adult patients, it is detected at a relatively low...... frequency in these cells. Hodgkin's lymphoma and infectious mononucleosis are both associated with high social class, and unknown confounding factors that are also associated with socioeconomic status might explain or contribute to the apparent association between these diseases. To indirectly assess...... the importance of socioeconomic status on the association between these diseases, we determined the risk for hematopoietic and lymphatic cancers in first-degree relatives of patients with confirmed EBV-related infectious mononucleosis. METHODS: We identified parents, siblings, and offspring of 17,045 persons...

  8. Venous anastomosis procedure for treatment of lymphatic malformation in Klippel-Trenaunay syndrome

    Directory of Open Access Journals (Sweden)

    Motoi Kato, M.D.

    2017-05-01

    We previously reported that lymphatic venous anastomosis (LVA may be a safe and effective procedure for reducing the size of micro cystic type LM by decreasing the intra cystic lymph [3]. We treated a case of KTS in a 9-year-old boy who had improvement of lower abdominal swelling and penile pain after a single LVA. The method involved is to make a bypass, from the afferent lymph-collecting vessel to subcutaneous veins. However, to apply LVA to LM, it is sometimes problematic to detect the afferent flow in combined vascular malformations, such as KTS. Therefore, we performed VA making a bypass directly from LM, instead. We classify two types of LVA methods for LM: afferent lymph vessel LMVA (A-LMVA, and sidewall LMVA (S-LMVA. S-LMVA has more merits than the previously reported A-LMVA.

  9. SPECIFIC ROLE OF LYMPHATIC MARKER PODOPLANIN IN RETINAL PIGMENT EPITHELIAL CELLS

    Science.gov (United States)

    Grimaldo, S.; Garcia, M.; Zhang, H.; Chen, L.

    2015-01-01

    Podoplanin is a small transmembrane glycoprotein widely known to be a marker for lymphatic endothelial cells. In this study, we identify a novel localization of podoplanin in the retinal pigment epithelium (RPE), a cellular monolayer critically involved in the visual process. Using a small interfering RNA (siRNA)-mediated gene silencing approach, we have also demonstrated, for the first time, that podoplanin depletion in human RPE cells leads to a marked reduction of cell aggregates and tight junctions. Additionally, the podoplanin-depleted cells also exhibit a significantly lower rate of proliferation. These data together indicate that podoplanin plays a crucial role in RPE cell functions. Further investigation on this factor may reveal novel mechanisms and therapeutic strategies for RPE-related eye diseases, such as proliferative retinopathy and age-related macular degeneration. PMID:21226415

  10. Radiologic appearance of primary anomalies of lung lymphatics. Review and experience

    International Nuclear Information System (INIS)

    Kirchner, J.; Jacobi, V.; Stein, A.; Berkefeld, J.; Thalhammer. A.; Kollath, J.

    1997-01-01

    Congenital disorders of the lymphatics of the lung are rare. On the basis of a literature review and our own experiences the disorders are divided into four groups and their radiographic findings are described. Pulmonary lymphangiectasia shows not typical signs. As an expression of the underlying pathophysiologic processes CT shows thickening of interlobular septs, interstitial edema and pleural effusions. Neither architectural distraction nor thickening of intralobular septs was seen. Lymphangioleiomyomatosis shows rather typical findings with multiple thin-walled bullae. In contrast to the opinion that architectural distraction is not seen in LAM we sometimes found signs of fibrosis. Disseminated pulmonary lymphangioma is characterised by proliferation of lymph vessels. CT-findings of this disorder have not been described before. CT shows multiple disseminated nodules of up to 2.5 cm accompanied by multiple bullae of similar distribution and size. (orig.) [de

  11. Data base management system for lymphatic filariasis--a neglected tropical disease.

    Science.gov (United States)

    Upadhyayula, Suryanaryana Murty; Mutheneni, Srinivasa Rao; Kadiri, Madhusudhan Rao; Kumaraswamy, Sriram; Nelaturu, Sarat Chandra Babu

    2012-01-01

    Researchers working in the area of Public Health are being confronted with large volumes of data on various aspects of entomology and epidemiology. To obtain the relevant information out of these data requires particular database management system. In this paper, we have described about the usages of our developed database on lymphatic filariasis. This database application is developed using Model View Controller (MVC) architecture, with MySQL as database and a web based interface. We have collected and incorporated the data on filariasis in the database from Karimnagar, Chittoor, East and West Godavari districts of Andhra Pradesh, India. The importance of this database is to store the collected data, retrieve the information and produce various combinational reports on filarial aspects which in turn will help the public health officials to understand the burden of disease in a particular locality. This information is likely to have an imperative role on decision making for effective control of filarial disease and integrated vector management operations.

  12. Investing in justice: ethics, evidence, and the eradication investment cases for lymphatic filariasis and onchocerciasis.

    Science.gov (United States)

    Bailey, Theodore C; Merritt, Maria W; Tediosi, Fabrizio

    2015-04-01

    It has been suggested that initiatives to eradicate specific communicable diseases need to be informed by eradication investment cases to assess the feasibility, costs, and consequences of eradication compared with elimination or control. A methodological challenge of eradication investment cases is how to account for the ethical importance of the benefits, burdens, and distributions thereof that are salient in people's experiences of the diseases and related interventions but are not assessed in traditional approaches to health and economic evaluation. We have offered a method of ethical analysis grounded in theories of social justice. We have described the method and its philosophical rationale and illustrated its use in application to eradication investment cases for lymphatic filariasis and onchocerciasis, 2 neglected tropical diseases that are candidates for eradication.

  13. Albumin uptake by renal lymphatics with and without obstruction of the renal vein

    International Nuclear Information System (INIS)

    Threefoot, S.A.; Pearson, J.E. Jr.; Georgiardis, A.

    1989-01-01

    Experiments involving injection of radio-iodinated albumin into the left renal arteries or left ureters of dogs indicate that the renal lymphatics are capable of a major contribution in returning to the circulation albumin (or other large molecules) escaping from renal capillaries. I-131-albumin was injected into the jugular vein of controls or into the left renal artery or in retrograde manner into the left ureter of female dogs. Experimental groups included those with no obstruction, occlusion of left renal veins or left renal lymphatics, or both. Collections were made from the right femoral artery, both renal veins, thoracic duct and both ureters at frequent intervals for 2 to 4 hours. Data analysis included I-131 concentration, specific activity, rate of recovery and selected ratios. After renal arterial injection, the percentage of I131 recovered in thoracic duct lymph of dogs without renal venous obstruction was 5 to 10 times that recovered in those that received injections into the jugular vein. In dogs with renal venous obstruction, recovery from the thoracic duct was 10 to 1,000 times that in control dogs. Most of the differences occurred during the first hour, after which time as recirculation and redistribution occurred the rates of appearance in thoracic duct lymph in each group were similar. The differences in the ratios of concentration in thoracic duct lymph to concentration in femoral arterial blood were also much greater when the renal vein was obstructed than in dogs with no obstruction. The greater return of albumin through the thoracic duct in those with impeded renal venous outflow was probably related to both sequestered concentration and increased intrarenal pressure

  14. Using kernel density estimates to investigate lymphatic filariasis in northeast Brazil

    Science.gov (United States)

    Medeiros, Zulma; Bonfim, Cristine; Brandão, Eduardo; Netto, Maria José Evangelista; Vasconcellos, Lucia; Ribeiro, Liany; Portugal, José Luiz

    2012-01-01

    After more than 10 years of the Global Program to Eliminate Lymphatic Filariasis (GPELF) in Brazil, advances have been seen, but the endemic disease persists as a public health problem. The aim of this study was to describe the spatial distribution of lymphatic filariasis in the municipality of Jaboatão dos Guararapes, Pernambuco, Brazil. An epidemiological survey was conducted in the municipality, and positive filariasis cases identified in this survey were georeferenced in point form, using the GPS. A kernel intensity estimator was applied to identify clusters with greater intensity of cases. We examined 23 673 individuals and 323 individuals with microfilaremia were identified, representing a mean prevalence rate of 1.4%. Around 88% of the districts surveyed presented cases of filarial infection, with prevalences of 0–5.6%. The male population was more affected by the infection, with 63.8% of the cases (P<0.005). Positive cases were found in all age groups examined. The kernel intensity estimator identified the areas of greatest intensity and least intensity of filarial infection cases. The case distribution was heterogeneous across the municipality. The kernel estimator identified spatial clusters of cases, thus indicating locations with greater intensity of transmission. The main advantage of this type of analysis lies in its ability to rapidly and easily show areas with the highest concentration of cases, thereby contributing towards planning, monitoring, and surveillance of filariasis elimination actions. Incorporation of geoprocessing and spatial analysis techniques constitutes an important tool for use within the GPELF. PMID:22943547

  15. Percutaneous sclerotherapy of pediatric lymphatic malformations: experience and outcomes according to the agent used.

    Science.gov (United States)

    Gallego Herrero, C; Navarro Cutillas, V

    Analyze statistically the success, number of sessions required and complete duration of treatment of agents used in pediatric percutaneous sclerotherapy of lymphatic malformations, to determine the most suitable. Retrospective study based on outcomes from percutaneous sclerotherapy performed on lymphatic malformations of 56 patients conducted by pediatric interventional radiologist for 14 years. As first approach, the procedure consists of ultrasound-guided introduction of sclerosing agent. Sessions were repeated until clinical resolution. Success, number of sessions and the duration of treatment were recorded and statistical treatment of the data was performed to obtain further conclusions. Lost patients in follow up and other minority agents used were excluded from the data. Eventually, 52 patients treated with OK432 (n=29), Ethibloc (n=5) and combination therapy (n=18) were included. The average number of sessions and duration in months of treatment was respectively 2.38 and 8.6 for OK432, 1.4 and 5.6 for Ethibloc, and 1.83 and 2.30 for dual therapy. The results were statistically significant for the difference in duration between OK432 and dual therapy. Also, 60-80% of patients reached proper results related to success, but the difference was no significant among the agents. Other demographic and anatomical variables were analyzed, not showing any difference, which supports the homogeneity of the sample. Despite of no significant difference in success and number of sessions among agents, longer duration of treatment with OK432 than dual therapy could mean greater health costs and probably greater disturb for patient and family. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Sampling versus systematic full lymphatic dissection in surgical treatment of non-small cell lung cancer.

    Science.gov (United States)

    Koulaxouzidis, Georgios; Karagkiouzis, Grigorios; Konstantinou, Marios; Gkiozos, Ioannis; Syrigos, Konstantinos

    2013-04-22

    The extent of mediastinal lymph node assessment during surgery for non-small cell cancer remains controversial. Different techniques are used, ranging from simple visual inspection of the unopened mediastinum to an extended bilateral lymph node dissection. Furthermore, different terms are used to define these techniques. Sampling is the removal of one or more lymph nodes under the guidance of pre-operative findings. Systematic (full) nodal dissection is the removal of all mediastinal tissue containing the lymph nodes systematically within anatomical landmarks. A Medline search was conducted to identify articles in the English language that addressed the role of mediastinal lymph node resection in the treatment of non-small cell lung cancer. Opinions as to the reasons for favoring full lymphatic dissection include complete resection, improved nodal staging and better local control due to resection of undetected micrometastasis. Arguments against routine full lymphatic dissection are increased morbidity, increase in operative time, and lack of evidence of improved survival. For complete resection of non-small cell lung cancer, many authors recommend a systematic nodal dissection as the standard approach during surgery, and suggest that this provides both adequate nodal staging and guarantees complete resection. Whether extending the lymph node dissection influences survival or recurrence rate is still not known. There are valid arguments in favor in terms not only of an improved local control but also of an improved long-term survival. However, the impact of lymph node dissection on long-term survival should be further assessed by large-scale multicenter randomized trials.

  17. Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Barleon Bernhard

    2010-07-01

    Full Text Available Abstract Background Postnatal endothelial progenitor cells (EPCs have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated. Results In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels. Mouse lung microvascular endothelial cells (MLMVECs were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony. These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels. Conclusion The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.

  18. Radionuclide studies of the lymphatic systems and their particular role in the assessment of the lymphoedema

    International Nuclear Information System (INIS)

    Zakkou, E.

    1984-01-01

    Dynamic radionuclide studies of the lymphatic system are used to measure the length of time required for the tracer to transit the upper and lower extremities as well as to determine, for any given point of time, the transportation and storage capacities of lymph vessels and nodes, respectively. Secondary lymphoedemas of more substantial proportions can reliably be diagnosed and classified on the basis of degrees of severity. The presence of those lymphoedemas is typically indicated by dermal back flow at circulatory bottlenecks, delays or marked delays (by more than 15 min) in transit and durations of transit beyond the measurable range. Further characteristic signs are passive dilatation of the prefacial bundle of lymph vessels (which is likely to be a first degree dilatation, if seen in late scintigrams and a second or third degree dilatation in cases escaping scintigraphic detection) and wide-spread inhibitions of activity over the entire extremity examined. Combined oedematous changes of lymph vessels and veins can only be predicted from lymph circulation disorders. This method permits an immediate diagnosis of any conditions precluding the use of endolymphatic therapy in malignant melanomas, thus sparing the patient the discomforts of treatment and helping to avoid unnecessary expenditure. Dynamic scintigraphy offers advantages over lymphography in that it has a greater discriminating power in diagnostic evaluations of active or passive dilatation of the bundle of lymph vessels, dermal back flow as well as the functional performance of damaged lymph vessels and also in that it permits a more precise visualisation of the superfacial and deep vessels of the lymphatic systems. (TRV) [de

  19. Lymphatic mapping and sentinel lymph node detection in patients with breast cancer

    International Nuclear Information System (INIS)

    Chen, S.L.; Du, Q.Q.; Shi, H.C.; Chen, J.X.; Wang, H.

    2002-01-01

    Objectives: To localize sentinel lymph node (SLN) and to test the hypothesis that the histologic characteristics of the SLN can predict the histologic characteristic of the remaining lymph nodes along the lymphatic chain. To calculate the absorbed dose of patients, doctors and nurses. Methods: Seventy-one patients with early-stage breast cancer underwent SLN localization using filtered technetium-99m labeled sulfur colloid, blue dye, or combination of them. SLN was identified as a blue lymph node and/or a 'hot lymph node' detected by ex vivo gamma probe. A 'hot lymph node' is the lymph node the radioactivity of which was 10 times higher than that of background. Pathological examination was performed with all resected lymph nodes. The approximate absorbed dose of the patients, doctors and nurses was calculated by using MIRD techniques. Results: For patients who were injected with only blue dye, the sensitivity, accuracy and false negative rate was 80.0%, 90.7% and 20.0% respectively. For patients who were injected with only radioactive colloids, the sensitivity, accuracy and false negative rate was 100%, 100% and 0% respectively. For patients who were injected with both blue dye and radioactive colloids, the sensitivity, accuracy and false negative rate was 100%, 100% and 100% respectively. The absorbed dose of breast tissue was 26.52 rad. The absorbed dose of nuclear medicine doctors, surgeons, nurses and pathologists was 1.9x10 -2 rad, 9.6x10 -3 rad, 3.8x10 -4 rad and 9.6x10 -3 rad respectively. Conclusions: Lymphatic mapping and SLN biopsy were the most effective when a combination of blue dye and radio-labeled sulfur colloid was used. Radio-labeled sulfur colloid was safe to patients and the medical staff. SLN biopsy had the potential value for avoiding unnecessary axillary lymph nodes resection for patients with early-stage breast cancer

  20. Lymphatic absorption of hypolipidemic compound, 1-O-[p-(myristyloxy)-alpha-methylcinnamoyl] glycerol (LK-903).

    Science.gov (United States)

    Sugihara, J; Furuuchi, S

    1988-02-01

    The intestinal absorption process of 1-O-[p-(myristyloxy)-alpha-methylcinnamoyl] glycerol (LK-903), a new hypolipidemic compound, was studied in rats. When 3H-LK-903 or 3H-LKA [3H-p- (myristyloxy)-alpha-methyl cinnamic acid], labeled at the cinnamic acid moiety, or 14C-LK-903, labeled at the glycerol moiety, were administered orally to thoracic duct-cannulated rats at a dose of 0.233 mmol/kg, 31.1, 6.7 and 18.1% of the dose, respectively, appeared in the lymph within 24 h. In this case, radioactive compounds in the lymph lipids consisted of LKA (radioactivity was not detected in the fraction of LKA with 14C-LK-903), LK-903, diglyceride analogues and triglyceride analogues. The percentages of the triglyceride analogues were the highest, followed by the diglyceride analogues. On the other hand, when doubly labeled LK-903 (3H/14C = 1, corrected ratio) was administered orally, the values of 3H/14C for the monoglyceride, diglyceride and triglyceride analogues in the lymph were 1.2-1.5, 1.7-1.9 and 1.9-2.7, respectively. The lymphatic absorption of LK-903 was stimulated by the presence of lecithin but inhibited by a high dose of triolein. The results indicated that (1) LK-903 formed micelles in the intestine, (2) a large part of LK-903 was absorbed as such, (3) a part of LK-903 was hydrolyzed in the intestinal mucosa, and (4) a part of LKA formed by hydrolysis was again utilized to synthesize the higher glycerides and absorbed via the lymphatic absorption route for lipids.

  1. Morbidity management and disability prevention for lymphatic filariasis in Sri Lanka: Current status and future prospects.

    Science.gov (United States)

    Chandrasena, Nilmini; Premaratna, Ranjan; Gunaratna, Indeewarie E; de Silva, Nilanthi R

    2018-05-01

    Sri Lanka was acknowledged to have eliminated lymphatic filariasis (LF) as a public health problem in 2016, largely due to its success in Mass Drug Administration (MDA) to interrupt disease transmission. Analysis of the Strengths, Weaknesses, Opportunities and Threats (SWOT) of the national Morbidity Management and Disability Prevention (MMDP) program, the other pillar of the LF control program, was carried out with the objective of evaluating it and providing recommendations to optimize the use of available resources. A situation analysis of the MMDP activities provided by the state health sector was carried out using published records, in-depth interviews with key informants of the Anti Filariasis Campaign, site-visits to filariasis clinics with informal discussions with clinic workforce and personal communications to identify strengths and weaknesses; and opportunities to overcome weaknesses and perceived threats to the program were explored. The principal strength of the MMDP program was the filariasis clinics operational in most endemic districts of Sri Lanka, providing free health care and health education to clinic attendees. The weaknesses identified were the low accessibility of clinics, incomplete coverage of the endemic region and lack of facilities for rehabilitation. The perceived threats were diversion of staff and resources for control of other vector-borne infections, under-utilization of clinics and non-compliance with recommended treatment. Enhanced high level commitment for MMDP, wider publicity and referral systems, integration of MMDP with other disease management services and collaboration with welfare organizations and research groups were identified as opportunities to overcome weaknesses and challenges. The recommended basic package of MMDP was functional in most of the LF-endemic region. The highlighted weaknesses and challenges, unless addressed, may threaten program sustainability. The identified opportunities for improvement of the

  2. Lymphatic fiariasis: Surveillance action among immigrants from endemic areas, Acre State, Brazilian Amazon

    Directory of Open Access Journals (Sweden)

    Lucineide Valentin Nunes

    2016-07-01

    Full Text Available Objective: To investigate the positivity of Wuchereria bancrofti (W. bancrofti in immigrants who entered the country through Rio Branco, reducing the risk of introduction of parasites into new areas and endemic areas of the past. Methods: It was realized a descriptive study. The AD12-ICT card test was applied on all immigrants living temporarily in the Chacara Alliance shelter, located in the metropolitan area of Rio Branco-AC, Brazil. For the positive patients, 10 mL of venous blood was collected between 11:00 pm and 1:00 am. About 4 mL of venous blood was collected to detect the presence of microfilariae in circulation in the tube using ethylene diamine tetraacetic acid and 6 mL of venous blood was collected to obtain blood serum for the Og4C3-ELISA, antibody Bm-14 and DNA-W. bancrofti tests. Results: The present study evaluated 415 individuals in September 2014 by circulating filarial antigen for W. bancrofti using the AD12-ICT card test. A total of 15/415 (3.61% positive cases were found, all from Haiti. Night blood collection and serum were performed on 1/14 for confirmation the infection of W. bancrofti, which presented 34 microfilariae/mL, antigen, antibodies and PCR positives. Conclusions: This surveillance action reveals, in a pioneering and unequivocal manner, that Brazil is an influx of immigrants carrying lymphatic filariasis and there is an urgent need to step up surveillance at the main entry point for immigrants. Active surveillance may prevent the reintroduction of lymphatic filariasis in areas under control, or prevent its introduction into other states of Brazil.

  3. Assessment of the lymphatic system in patients with diffuse lymphangiomatosis by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lohrmann, Christian, E-mail: christian.lohrmann@uniklinik-freiburg.de [Department of Radiology, University Hospital of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg i. Br. (Germany); Foeldi, Etelka, E-mail: foeldi@foeldiklinik.de [Foeldi Clinic for Lymphology, Hinterzarten, Roesslehofweg 2-6, D-79856 Hinterzarten (Germany); Langer, Mathias, E-mail: mathias.langer@uniklinik-freiburg.de [Department of Radiology, University Hospital of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg i. Br. (Germany)

    2011-11-15

    Objective: To assess the lymphatic system in patients with diffuse lymphangiomatosis by magnetic resonance imaging. Materials and methods: 15 patients with diffuse lymphangiomatosis were examined by magnetic resonance imaging. Three locations were examined: first, the lower leg and foot region; second, the upper leg and the knee region; and third, the pelvic with retroperitoneal and abdominal region. For magnetic resonance lymphangiography a T1-weighted 3D spoiled gradient-echo and a T2-weighted 3D-TSE sequence was used. Results: The size of the genital lymphangiomas, which were revealed in all patients, varied between 5 and 83 mm. In 47% of the patients lymphangiomas were detected at the level of the lower legs, and in 87% of the patients at the level of the upper leg and retroperitoneum. Furthermore, lymphangiomas were seen in the inguinal and pelvic region in 100% and intraabdominally in 40% of the patients. The lymphangiomas extended into the abdominal wall in 93% of the examined patients. A chylous pleural effusion was revealed in 20% and a chylous ascites in 13% of patients. 93% of patients suffered due to the diffuse lymphangiomatous pathologies from a lymphedema of the lower extremities, while a generalized lymphedema of the trunk was found in 87% of the patients. Conclusion: Magnetic resonance imaging is a safe and accurate minimal-invasive imaging modality for the evaluation of the lymphatic system in patients with diffuse lymphangiomatosis. Since the localization and extension of the lymphangiomas are important prognostic factors, it is crucial to perform a safe radiologic evaluation with a high resolution for the patient's therapeutic planning.

  4. Real-time MRI-guided percutaneous sclerotherapy of low-flow head and neck lymphatic malformations in the pediatric population - a stepwise approach

    Energy Technology Data Exchange (ETDEWEB)

    Partovi, Sasan; Vidal, Lorenna; Lu, Ziang; Nakamoto, Dean A.; Buethe, Ji; Clampitt, Mark; Coffey, Michael; Patel, Indravadan J. [University Hospitals Cleveland Medical Center, Case Western Reserve University, Department of Radiology, Section of Vascular and Interventional Radiology, Cleveland, OH (United States)

    2017-05-15

    Real-time MRI-guided percutaneous sclerotherapy is a novel and evolving treatment for congenital lymphatic malformations in the head and neck. We elaborate on the specific steps necessary to perform an MRI-guided percutaneous sclerotherapy of lymphatic malformations including pre-procedure patient work-up and preparation, stepwise intraprocedural interventional techniques and post-procedure management. Based on our institutional experience, MRI-guided sclerotherapy with a doxycycline-gadolinium-based mixture as a sclerosant for lymphatic malformations of the head and neck region in children is well tolerated and effective. (orig.)

  5. Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment

    Science.gov (United States)

    Martin, Petra; Biniecka, Monika; Ó'Meachair, Shane; Maguire, Aoife; Tosetto, Miriam; Nolan, Blathnaid; Hyland, John; Sheahan, Kieran; O'Donoghue, Diarmuid; Mulcahy, Hugh; Fennelly, David; O'Sullivan, Jacintha

    2018-01-01

    Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC. PMID:29535825

  6. Curcumin elevates sirtuin level but does not postpone in vitro senescence of human cells building the vasculature

    Science.gov (United States)

    Grabowska, Wioleta; Suszek, Małgorzata; Wnuk, Maciej; Lewinska, Anna; Wasiak, Emilia; Sikora, Ewa; Bielak-Zmijewska, Anna

    2016-01-01

    It is believed that curcumin, a component of the turmeric that belongs to hormetins, possesses anti-aging propensity. This property of curcumin can be partially explained by its influence on the level of sirtuins. Previously, we have shown that relatively high (2.5-10 μM) doses of curcumin induce senescence of cancer cells and cells building the vasculature. In the present study we examined whether curcumin at low doses (0.1 and 1 μM) is able to delay cell senescence and upregulate the level of sirtuins in human cells building the vasculature, namely vascular smooth muscle (VSMC) and endothelial (EC) cells. To this end we used cells senescing in a replicative and premature manner. We showed that low doses of curcumin in case of VSMC neither postponed the replicative senescence nor protected from premature senescence induced by doxorubicin. Moreover, curcumin slightly accelerated replicative senescence of EC. Despite some fluctuations, a clear increasing tendency in the level of sirtuins was observed in curcumin-treated young, senescing or already senescent cells. Sirtuin activation could be caused by the activation of AMPK resulting from superoxide elevation and ATP reduction. Our results show that curcumin at low doses can increase the level of sirtuins without delaying senescence of VSMC. PMID:27034011

  7. An immunocytochemical study of the germinal layer vasculature in the developing fetal brain using Ulex europaeus 1 lectin.

    Science.gov (United States)

    Gould, S J; Howard, S

    1988-10-01

    The characteristics of the germinal matrix vasculature were studied in the developing fetal brain using immunocytochemical methods. A preliminary comparative immunocytochemical study was made on six fetal brains to compare endothelial staining by Ulex europaeus I lectin with that of antibody to Factor VIII related antigen. Ulex was found to stain germinal layer vessels better than Factor VIII related antigen. Subsequently, the germinal layers of a further 15 fetal and preterm infant brains ranging from 13 to 35 weeks' gestation were stained with Ulex europaeus I to demonstrate the vasculature. With increasing gestation, there was a gradual increase in vessel density, particularly of capillaries. This was not a uniform process. A plexus of capillaries was prominent immediately beneath the ependyma while the more central parts of the germinal matrix contained fewer, but often larger diameter, vessels. The variation in vessel density which was a feature of the later gestation brains may have implications for local blood flow and may be a factor in haemorrhage at this site.

  8. 3D morphological analysis of the mouse cerebral vasculature: Comparison of in vivo and ex vivo methods.

    Directory of Open Access Journals (Sweden)

    Joe Steinman

    Full Text Available Ex vivo 2-photon fluorescence microscopy (2PFM with optical clearing enables vascular imaging deep into tissue. However, optical clearing may also produce spherical aberrations if the objective lens is not index-matched to the clearing material, while the perfusion, clearing, and fixation procedure may alter vascular morphology. We compared in vivo and ex vivo 2PFM in mice, focusing on apparent differences in microvascular signal and morphology. Following in vivo imaging, the mice (four total were perfused with a fluorescent gel and their brains fructose-cleared. The brain regions imaged in vivo were imaged ex vivo. Vessels were segmented in both images using an automated tracing algorithm that accounts for the spatially varying PSF in the ex vivo images. This spatial variance is induced by spherical aberrations caused by imaging fructose-cleared tissue with a water-immersion objective. Alignment of the ex vivo image to the in vivo image through a non-linear warping algorithm enabled comparison of apparent vessel diameter, as well as differences in signal. Shrinkage varied as a function of diameter, with capillaries rendered smaller ex vivo by 13%, while penetrating vessels shrunk by 34%. The pial vasculature attenuated in vivo microvascular signal by 40% 300 μm below the tissue surface, but this effect was absent ex vivo. On the whole, ex vivo imaging was found to be valuable for studying deep cortical vasculature.

  9. Capability of abdominal 320-detector row CT for small vasculature assessment compared with that of 64-detector row CT

    Energy Technology Data Exchange (ETDEWEB)

    Kitajima, Kazuhiro, E-mail: kitajima@med.kobe-u.ac.jp [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Maeda, Tetsuo; Ohno, Yoshiharu [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Division of Radiology, Kobe University Hospital, Kobe (Japan); Yoshikawa, Takeshi [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Konishi, Minoru [Division of Radiology, Kobe University Hospital, Kobe (Japan); Kanda, Tomonori; Onishi, Yumiko; Matsumoto, Keiko; Koyama, Hisanobu; Takenaka, Daisuke; Sugimura, Kazuro [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan)

    2011-11-15

    Objective: To compare the capability of 320-detector row CT (area-detector CT: ADCT) with step-and-shoot scan protocol for small abdominal vasculature assessment with that of 64-detector row CT with helical scan protocol. Materials and methods: Total of 60 patients underwent contrast-enhanced abdominal CT for preoperative assessment. Of all, 30 suspected to have lung cancer underwent ADCT using step-and-shoot scan protocol. The other 30 suspected to have renal cell carcinoma underwent 64-MDCT using helical scan protocol. Two experienced radiologists independently assessed inferior epigastric, hepatic subsegmental (in the segment 8), mesenteric marginal (Griffith point) and inferior phrenic arteries by using 5-point visual scoring systems. Kappa analysis was used for evaluation of interobserver agreement. To compare the visualization capability of the two systems, the Mann-Whitney U-test was used to compare the scores for each of the arteries. Results: Overall interobserver agreements for both systems were almost perfect ({kappa} > 0.80). Visualization scores for inferior epigastric and mesenteric arteries were significantly higher for ADCT than for 64-detector row CT (p < 0.05). No significant difference was found for hepatic subsegmental and inferior phrenic arteries. Conclusion: Small abdominal vasculature assessment by ADCT with step-and-shoot scan protocol is potentially equal to or better than that by 64-detector row CT with helical scan protocol.

  10. Capability of abdominal 320-detector row CT for small vasculature assessment compared with that of 64-detector row CT

    International Nuclear Information System (INIS)

    Kitajima, Kazuhiro; Maeda, Tetsuo; Ohno, Yoshiharu; Yoshikawa, Takeshi; Konishi, Minoru; Kanda, Tomonori; Onishi, Yumiko; Matsumoto, Keiko; Koyama, Hisanobu; Takenaka, Daisuke; Sugimura, Kazuro

    2011-01-01

    Objective: To compare the capability of 320-detector row CT (area-detector CT: ADCT) with step-and-shoot scan protocol for small abdominal vasculature assessment with that of 64-detector row CT with helical scan protocol. Materials and methods: Total of 60 patients underwent contrast-enhanced abdominal CT for preoperative assessment. Of all, 30 suspected to have lung cancer underwent ADCT using step-and-shoot scan protocol. The other 30 suspected to have renal cell carcinoma underwent 64-MDCT using helical scan protocol. Two experienced radiologists independently assessed inferior epigastric, hepatic subsegmental (in the segment 8), mesenteric marginal (Griffith point) and inferior phrenic arteries by using 5-point visual scoring systems. Kappa analysis was used for evaluation of interobserver agreement. To compare the visualization capability of the two systems, the Mann-Whitney U-test was used to compare the scores for each of the arteries. Results: Overall interobserver agreements for both systems were almost perfect (κ > 0.80). Visualization scores for inferior epigastric and mesenteric arteries were significantly higher for ADCT than for 64-detector row CT (p < 0.05). No significant difference was found for hepatic subsegmental and inferior phrenic arteries. Conclusion: Small abdominal vasculature assessment by ADCT with step-and-shoot scan protocol is potentially equal to or better than that by 64-detector row CT with helical scan protocol.

  11. Deoxypodophyllotoxin suppresses tumor vasculature in HUVECs by promoting cytoskeleton remodeling through LKB1-AMPK dependent Rho A activatio.

    Science.gov (United States)

    Wang, Yurong; Wang, Bin; Guerram, Mounia; Sun, Li; Shi, Wei; Tian, Chongchong; Zhu, Xiong; Jiang, Zhenzhou; Zhang, Luyong

    2015-10-06

    Angiogenesis plays a critical role in the growth and metastasis of tumors, which makes it an attractive target for anti-tumor drug development. Deoxypodophyllotoxin (DPT), a natural product isolated from Anthriscus sylvestris, inhibits cell proliferation and migration in various cancer cell types. Our previous studies indicate that DPT possesses both anti-angiogenic and vascular-disrupting activities. Although the RhoA/ RhoA kinase (ROCK) signaling pathway is implicated in DPT-stimulated cytoskeleton remodeling and tumor vasculature suppressing, the detailed mechanisms by which DPT mediates these effects are poorly understood. In the current study, we found that DPT promotes cytoskeleton remodeling in human umbilical vein endothelial cells (HUVECs) via stimulation of AMP-activated protein kinase (AMPK) and that this effect is abolished by either treatment with a selective AMPK inhibitor or knockdown. Moreover, the cellular levels of LKB1, a kinase upstream of AMPK, were enhanced following DPT exposure. DPT-induced activation of AMPK in tumor vasculature effect was also verified by transgenic zebrafish (VEGFR2:GFP), Matrigel plug assay, and xenograft model in nude mice. The present findings may lay the groundwork for a novel therapeutic approach in treating cancer.

  12. Inhibition of Vascular Endothelial Growth Factor A and Hypoxia-Inducible Factor 1α Maximizes the Effects of Radiation in Sarcoma Mouse Models Through Destruction of Tumor Vasculature

    International Nuclear Information System (INIS)

    Lee, Hae-June; Yoon, Changhwan; Park, Do Joong; Kim, Yeo-Jung; Schmidt, Benjamin; Lee, Yoon-Jin; Tap, William D.; Eisinger-Mathason, T.S. Karin; Choy, Edwin; Kirsch, David G.; Simon, M. Celeste

    2015-01-01

    Purpose: To examine the addition of genetic or pharmacologic inhibition of hypoxia-inducible factor 1α (HIF-1α) to radiation therapy (RT) and vascular endothelial growth factor A (VEGF-A) inhibition (ie trimodality therapy) for soft-tissue sarcoma. Methods and Materials: Hypoxia-inducible factor 1α was inhibited using short hairpin RNA or low metronomic doses of doxorubicin, which blocks HIF-1α binding to DNA. Trimodality therapy was examined in a mouse xenograft model and a genetically engineered mouse model of sarcoma, as well as in vitro in tumor endothelial cells (ECs) and 4 sarcoma cell lines. Results: In both mouse models, any monotherapy or bimodality therapy resulted in tumor growth beyond 250 mm 3 within the 12-day treatment period, but trimodality therapy with RT, VEGF-A inhibition, and HIF-1α inhibition kept tumors at <250 mm 3 for up to 30 days. Trimodality therapy on tumors reduced HIF-1α activity as measured by expression of nuclear HIF-1α by 87% to 95% compared with RT alone, and cytoplasmic carbonic anhydrase 9 by 79% to 82%. Trimodality therapy also increased EC-specific apoptosis 2- to 4-fold more than RT alone and reduced microvessel density by 75% to 82%. When tumor ECs were treated in vitro with trimodality therapy under hypoxia, there were significant decreases in proliferation and colony formation and increases in DNA damage (as measured by Comet assay and γH2AX expression) and apoptosis (as measured by cleaved caspase 3 expression). Trimodality therapy had much less pronounced effects when 4 sarcoma cell lines were examined in these same assays. Conclusions: Inhibition of HIF-1α is highly effective when combined with RT and VEGF-A inhibition in blocking sarcoma growth by maximizing DNA damage and apoptosis in tumor ECs, leading to loss of tumor vasculature

  13. Inhibition of Vascular Endothelial Growth Factor A and Hypoxia-Inducible Factor 1α Maximizes the Effects of Radiation in Sarcoma Mouse Models Through Destruction of Tumor Vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae-June [Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Yoon, Changhwan [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Park, Do Joong [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Surgery, Seoul National University Bundang Hospital, Sungnam (Korea, Republic of); Kim, Yeo-Jung [Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Schmidt, Benjamin [Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Lee, Yoon-Jin [Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Tap, William D. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Eisinger-Mathason, T.S. Karin [Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Choy, Edwin [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Kirsch, David G. [Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina (United States); Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Simon, M. Celeste [Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Howard Hughes Medical Institute (United States); and others

    2015-03-01

    Purpose: To examine the addition of genetic or pharmacologic inhibition of hypoxia-inducible factor 1α (HIF-1α) to radiation therapy (RT) and vascular endothelial growth factor A (VEGF-A) inhibition (ie trimodality therapy) for soft-tissue sarcoma. Methods and Materials: Hypoxia-inducible factor 1α was inhibited using short hairpin RNA or low metronomic doses of doxorubicin, which blocks HIF-1α binding to DNA. Trimodality therapy was examined in a mouse xenograft model and a genetically engineered mouse model of sarcoma, as well as in vitro in tumor endothelial cells (ECs) and 4 sarcoma cell lines. Results: In both mouse models, any monotherapy or bimodality therapy resulted in tumor growth beyond 250 mm{sup 3} within the 12-day treatment period, but trimodality therapy with RT, VEGF-A inhibition, and HIF-1α inhibition kept tumors at <250 mm{sup 3} for up to 30 days. Trimodality therapy on tumors reduced HIF-1α activity as measured by expression of nuclear HIF-1α by 87% to 95% compared with RT alone, and cytoplasmic carbonic anhydrase 9 by 79% to 82%. Trimodality therapy also increased EC-specific apoptosis 2- to 4-fold more than RT alone and reduced microvessel density by 75% to 82%. When tumor ECs were treated in vitro with trimodality therapy under hypoxia, there were significant decreases in proliferation and colony formation and increases in DNA damage (as measured by Comet assay and γH2AX expression) and apoptosis (as measured by cleaved caspase 3 expression). Trimodality therapy had much less pronounced effects when 4 sarcoma cell lines were examined in these same assays. Conclusions: Inhibition of HIF-1α is highly effective when combined with RT and VEGF-A inhibition in blocking sarcoma growth by maximizing DNA damage and apoptosis in tumor ECs, leading to loss of tumor vasculature.

  14. Prediction of occult lymph node metastasis in squamous cell carcinoma of the oral cavity and the oropharynx using peritumoral Prospero homeobox protein 1 lymphatic nuclear quantification.

    Science.gov (United States)

    Mermod, Maxime; Bongiovanni, Massimo; Petrova, Tatiana V; Dubikovskaya, Elena A; Simon, Christian; Tolstonog, Genrich; Monnier, Yan

    2016-09-01

    The use of lymphatic vessel density as a predictor of occult lymph node metastasis (OLNM) in head and neck squamous cell carcinoma (HNSCC) has never been reported. Staining of the specific lymphatic endothelial cells nuclear marker, PROX1, as an indicator of lymphatic vessel density was determined by counting the number of positive cells in squamous cell carcinomas (SCCs) of the oral cavity and the oropharynx with clinically negative necks. Correlation with histopathological data was established. Peritumoral PROX1 lymphatic nuclear count significantly correlated with the detection of OLNM in multivariate analysis (p oral cavity and the oropharynx allows accurate prediction of occult lymph node metastasis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1407-1415, 2016. © 2016 Wiley Periodicals, Inc.

  15. VEGFR-3 signaling is regulated by a G-protein activator, activator of G-protein signaling 8, in lymphatic endothelial cells.

    Science.gov (United States)

    Sakima, Miho; Hayashi, Hisaki; Mamun, Abdullah Al; Sato, Motohiko

    2018-07-01

    Vascular endothelial growth factor C (VEGFC) and its cognate receptor VEGFR-3 play a key role in lymphangiogenesis. We previously reported that an ischemia-inducible Gβγ signal regulator, activator of G-protein signaling 8 (AGS8), regulated the subcellular distribution of vascular endothelial growth factor receptor-2 (VEGFR-2) and influenced VEGFA-induced signaling in vascular endothelial cells. Here, we report that AGS8 regulates VEGFR-3, which is another subtype of the VEGF receptor family, and mediates VEGFC signaling in human dermal lymphatic endothelial cells (HDLECs). VEGFC stimulated the proliferation of HDLECs and tube formation by HDLECs, which were inhibited by knocking down AGS8 by small interfering RNA (siRNA). AGS8 siRNA inhibited VEGFC-mediated phosphorylation of VEGFR-3 and its downstream molecules, including ERK1/2 and AKT. Analysis of fluorescence-activated cell sorting and immunofluorescence staining demonstrated that AGS8 knockdown was associated with a reduction of VEGFR-3 at the cell surface. Endocytosis inhibitors did not rescue the decrease of cell-surface VEGFR-3, suggesting that AGS8 regulated the trafficking of VEGFR-3 to the plasma membrane. An immunoprecipitation assay indicated that VEGFR-3 formed a complex including AGS8 and Gβγ in cells. These data suggest the novel regulation of VEGFC-VEGFR-3 by AGS8 in HDLECs and a potential role for AGS8 in lymphangiogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELM alpha recruits bone marrow-derived cells to the murine pulmonary vasculature.

    Directory of Open Access Journals (Sweden)

    Daniel J Angelini

    2010-06-01

    Full Text Available Pulmonary hypertension (PH is a disease of multiple etiologies with several common pathological features, including inflammation and pulmonary vascular remodeling. Recent evidence has suggested a potential role for the recruitment of bone marrow-derived (BMD progenitor cells to this remodeling process. We recently demonstrated that hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELM alpha is chemotactic to murine bone marrow cells in vitro and involved in pulmonary vascular remodeling in vivo.We used a mouse bone marrow transplant model in which lethally irradiated mice were rescued with bone marrow transplanted from green fluorescent protein (GFP(+ transgenic mice to determine the role of HIMF in recruiting BMD cells to the lung vasculature during PH development. Exposure to chronic hypoxia and pulmonary gene transfer of HIMF were used to induce PH. Both models resulted in markedly increased numbers of BMD cells in and around the pulmonary vasculature; in several neomuscularized small (approximately 20 microm capillary-like vessels, an entirely new medial wall was made up of these cells. We found these GFP(+ BMD cells to be positive for stem cell antigen-1 and c-kit, but negative for CD31 and CD34. Several of the GFP(+ cells that localized to the pulmonary vasculature were alpha-smooth muscle actin(+ and localized to the media layer of the vessels. This finding suggests that these cells are of mesenchymal origin and differentiate toward myofibroblast and vascular smooth muscle. Structural location in the media of small vessels suggests a functional role in the lung vasculature. To examine a potential mechanism for HIMF-dependent recruitment of mesenchymal stem cells to the pulmonary vasculature, we performed a cell migration assay using cultured human mesenchymal stem cells (HMSCs. The addition of recombinant HIMF induced migration of HMSCs in a phosphoinosotide-3-kinase-dependent manner.These results demonstrate HIMF-dependent recruitment of BMD

  17. Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

    Science.gov (United States)

    Chan, Linda J; Ascher, David B; Yadav, Rajbharan; Bulitta, Jürgen B; Williams, Charlotte C; Porter, Christopher J H; Landersdorfer, Cornelia B; Kaminskas, Lisa M

    2016-04-04

    The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs.

  18. Foot skin depots of 18F-fluorodeoxyglucose do not enable PET/CT lymphography of the lower extremity lymphatic system in man

    DEFF Research Database (Denmark)

    Jensen, Mads Radmer; Simonsen, Lene; Lonsdale, Markus

    2013-01-01

    consecutive PET scans of the same region.Blood activity increased faster and to a greater extent in the great saphenous veins compared to the medial cubital vein. PET/CT images showed activity in the superficial and deep veins of the lower extremities. No lymphatic collectors or nodes were visualized....... CONCLUSION: Neither subcutaneous nor intradermal injection of 18F-FDG allows imaging of the lower extremity lymphatic system in man....

  19. Structured triglyceride vehicles for oral delivery of halofantrine: examination of intestinal lymphatic transport and bioavailability in conscious rats

    DEFF Research Database (Denmark)

    Holm, René; Porter, Christopher J H; Müllertz, Anette

    2002-01-01

    PURPOSE: To compare the influence of triglyceride vehicle intramolecular structure on the intestinal lymphatic transport and systemic absorption of halofantrine in conscious rats. METHODS: Conscious, lymph cannulated and nonlymph cannulated rats were dosed orally with three structurally different...... triglycerides; sunflower oil, and two structured triglycerides containing different proportion and position of medium-(M) and long-chain (L) fatty acids on the glycerol backbone. The two structured triglycerides were abbreviated MLM and LML to reflect the structural position on the glycerol. The concentration...... animals, and this was most pronounced for the animals dosed with the structured triglycerides. CONCLUSIONS: Using MLM as vehicle increases the portal absorption of halofantrine and results in similar lymphatic transport levels when compared to sunflower oil. Total absorption when assessed as absorption...

  20. DEGRO practical guidelines: radiotherapy of breast cancer III - radiotherapy of the lymphatic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Sautter-Bihl, M.L. [Staedtisches Klinikum Karlsruhe, Klinik fuer Radioonkologie und Strahlentherapie, Karlsruhe (Germany); Sedlmayer, F.; Fussl, C. [LKH Salzburg, Paracelsus Medical University Hospital, Department of Radiotherapy and Radiation Oncology, Salzburg (Austria); Budach, W. [University Hospital Duesseldorf, Duesseldorf (Germany); Dunst, J. [University Hospital Schleswig-Holstein, Luebeck (Germany); Feyer, P. [Klinikum Neukoelln, Berlin (Germany); Fietkau, R.; Sauer, R. [University Hospital Erlangen, Erlangen (Germany); Harms, W. [St. Clara Hospital, Basel, Basel (Switzerland); Piroth, M.D. [Helios-Klinikum Wuppertal, Klinik fuer Strahlentherapie und Radioonkologie, Wuppertal (Germany); Souchon, R. [University Hospital Tuebingen, Tuebingen (Germany); Wenz, F. [University Hospital Mannheim, Mannheim (Germany); Haase, W.

    2014-04-15

    The purpose of this work is to update the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO). A comprehensive survey of the literature concerning regional nodal irradiation (RNI) was performed using the following search terms: ''breast cancer'', ''radiotherapy'', ''regional node irradiation''. Recent randomized trials were analyzed for outcome as well as for differences in target definition. Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas. Moreover, data from recently published meta-analyses and guidelines of international breast cancer societies, yielding new aspects compared to 2008, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the German interdisciplinary S3 guidelines updated in 2012, this paper addresses indications, targeting, and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer. International guidelines reveal substantial differences regarding indications for RNI. Patients with 1-3 positive nodes seem to profit from RNI compared to whole breast (WBI) or chest wall irradiation alone, both with regard to locoregional control and disease-free survival. Irradiation of the regional lymphatics including axillary, supraclavicular, and internal mammary nodes provided a small but significant survival benefit in recent randomized trials and one meta-analysis. Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection (ALND), while reducing the rate of lymph edema. Data concerning the impact of 1-2 macroscopically affected sentinel node (SN) or microscopic metastases on prognosis are conflicting. Recent data

  1. Microemulsions containing long-chain oil ethyl oleate improve the oral bioavailability of piroxicam by increasing drug solubility and lymphatic transportation simultaneously.

    Science.gov (United States)

    Xing, Qiao; Song, Jia; You, Xiuhua; Xu, Dongling; Wang, Kexin; Song, Jiaqi; Guo, Qin; Li, Pengyu; Wu, Chuanbin; Hu, Haiyan

    2016-09-25

    Drug solubility and lymphatic transport enhancements are two main pathways to improve drug oral bioavailability for microemulsions. However, it is not easy to have both achieved simultaneously because excipients used for improving lymphatic transport were usually insufficient in forming microemulsions and solubilizing drugs. Our research is to explore whether ethyl oleate, an oil effective in developing microemulsions with desired solubilizing capability, could increase bioavailability to a higher extent by enhancing lymphatic transport. As a long-chain oil, ethyl oleate won larger microemulsion area than short-chain tributyrin and medium-chain GTCC. In contrast, long-chain soybean oil failed to prepare microemulsions. The solubility of piroxicam in ethyl oleate microemulsions (ME-C) increased by about 30 times than in water. ME-C also won significantly higher AUC0-t compared with tributyrin microemulsions (ME-A) and GTCC microemulsions (ME-B). Oral bioavailability in ME-C decreased by 38% after lymphatic transport was blocked by cycloheximide, severer than those in ME-A and ME-B (8% and 34%). These results suggest that improving lymphatic transport and solubility simultaneously might be a novel strategy to increase drug oral bioavailability to a higher extent than increasing solubility only. Ethyl oleate is a preferred oil candidate due to its integrated advantages of high solubilizing capability, large microemulsion area and effective lymphatic transport. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood-brain barrier: mechanisms of brain clearing

    Science.gov (United States)

    Semyachkina-Glushkovskaya, Oxana; Abdurashitov, Arkady; Dubrovsky, Alexander; Bragin, Denis; Bragina, Olga; Shushunova, Nataliya; Maslyakova, Galina; Navolokin, Nikita; Bucharskaya, Alla; Tuchin, Valery; Kurths, Juergen; Shirokov, Alexander

    2017-12-01

    The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood-brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB. Here, using the model of sound-induced opening of the BBB, we clearly show how the brain clears dextran after it crosses the BBB via the meningeal lymphatic vessels. We first demonstrate successful application of optical coherence tomography (OCT) for imaging of the lymphatic vessels in the meninges after opening of the BBB, which might be a new useful strategy for noninvasive analysis of lymphatic drainage in daily clinical practice. Also, we give information about the depth and size of the meningeal lymphatic vessels in mice. These new fundamental data with the applied focus on the OCT shed light on the mechanisms of brain clearance and the role of lymphatic drainage in these processes that could serve as an informative platform for a development of therapy and diagnostics of diseases associated with injuries of the BBB such as stroke, brain trauma, glioma, depression, or Alzheimer disease.

  3. Systematic review of efficacy for manual lymphatic drainage techniques in sports medicine and rehabilitation: an evidence-based practice approach.

    Science.gov (United States)

    Vairo, Giampietro L; Miller, Sayers John; McBrier, Nicole M; Buckley, William E

    2009-01-01

    Manual therapists question integrating manual lymphatic drainage techniques (MLDTs) into conventional treatments for athletic injuries due to the scarcity of literature concerning musculoskeletal applications and established orthopaedic clinical practice guidelines. The purpose of this systematic review is to provide manual therapy clinicians with pertinent information regarding progression of MLDTs as well as to critique the evidence for efficacy of this method in sports medicine. We surveyed English-language publications from 1998 to 2008 by searching PubMed, PEDro, CINAHL, the Cochrane Library, and SPORTDiscus databases using the terms lymphatic system, lymph drainage, lymphatic therapy, manual lymph drainage, and lymphatic pump techniques. We selected articles investigating the effects of MLDTs on orthopaedic and athletic injury outcomes. Nine articles met inclusion criteria, of which 3 were randomized controlled trials (RCTs). We evaluated the 3 RCTs using a validity score (PEDro scale). Due to differences in experimental design, data could not be collapsed for meta-analysis. Animal model experiments reinforce theoretical principles for application of MLDTs. When combined with concomitant musculoskeletal therapy, pilot and case studies demonstrate MLDT effectiveness. The best evidence suggests that efficacy of MLDT in sports medicine and rehabilitation is specific to resolution of enzyme serum levels associated with acute skeletal muscle cell damage as well as reduction of edema following acute ankle joint sprain and radial wrist fracture. Currently, there is limited high-ranking evidence available. Well-designed RCTs assessing outcome variables following implementation of MLDTs in treating athletic injuries may provide conclusive evidence for establishing applicable clinical practice guidelines in sports medicine and rehabilitation.

  4. Visualization of tumor blockage and rerouting of lymphatic drainage in penile cancer patients by use of SPECT/CT.

    Science.gov (United States)

    Leijte, Joost A P; van der Ploeg, Iris M C; Valdés Olmos, Renato A; Nieweg, Omgo E; Horenblas, Simon

    2009-03-01

    The reliability of sentinel node biopsy is dependent on the accurate visualization and identification of the sentinel node(s). It has been suggested that extensive metastatic involvement of a sentinel node can lead to blocked inflow and rerouting of lymph fluid to a "neo-sentinel node" that may not yet contain tumor cells, causing a false-negative result. However, there is little evidence to support this hypothesis. Recently introduced hybrid SPECT/CT scanners provide both tomographic lymphoscintigraphy and anatomic detail. Such a scanner enabled the present study of the concept of tumor blockage and rerouting of lymphatic drainage in patients with palpable groin metastases. Seventeen patients with unilateral palpable and cytologically proven metastases in the groin underwent bilateral conventional lymphoscintigraphy and SPECT/CT before sentinel node biopsy of the contralateral groin. The pattern of lymphatic drainage in the 17 palpable groin metastases was evaluated for signs of tumor blockage or rerouting. On the CT images, the palpable node metastases could be identified in all 17 groins. Four of the 17 palpable node metastases (24%) showed uptake of radioactivity on the SPECT/CT images. In 10 groins, rerouting of lymphatic drainage to a neo-sentinel node was seen; one neo-sentinel node was located in the contralateral groin. A complete absence of lymphatic drainage was seen in the remaining 3 groins. The concept of tumor blockage and rerouting was visualized in 76% of the groins with palpable metastases. Precise physical examination and preoperative ultrasound with fine-needle aspiration cytology may identify nodes with considerable tumor invasion at an earlier stage and thereby reduce the incidence of false-negative results.

  5. A comparison of the observed and the expected cancers of the haematopoietic and lymphatic systems among workers at Windscale

    International Nuclear Information System (INIS)

    Dolphin, G.W.

    1976-12-01

    Data are given about the cases of cancers of the haematopoietic and lymphatic systems among workers at Windscale Works, BNFL during the period 1950 to 1974. The number of cancers of these types expected to occur in the working population at Windscale has been estimated for the same period. For none of these types is the observed number of cancers significantly different at the 95% confidence level from that expected. (author)

  6. Data reporting constraints for the lymphatic filariasis mass drug administration activities in two districts in Ghana: A qualitative study

    Directory of Open Access Journals (Sweden)

    Frances Baaba da-Costa Vroom

    2015-07-01

    Full Text Available Objectives: Timely and accurate health data are important for objective decision making and policy formulation. However, little evidence exists to explain why poor quality routine health data persist. This study examined the constraints to data reporting for the lymphatic filariasis mass drug administration programme in two districts in Ghana. This qualitative study focused on timeliness and accuracy of mass drug administration reports submitted by community health volunteers. Methods: The study is nested within a larger study focusing on the feasibility of mobile phone technology for the lymphatic filariasis programme. Using an exploratory study design, data were obtained through in-depth interviews (n = 7 with programme supervisors and focus group discussions (n = 4 with community health volunteers. Results were analysed using thematic content analysis. Results: Reasons for delays in reporting were attributed to poor numeracy skills among community health volunteers, difficult physical access to communities, high supervisor workload, poor adherence reporting deadlines, difficulty in reaching communities within allocated time and untimely release of programme funds. Poor accuracy of data was mainly attributed to inadequate motivation for community health volunteers and difficulty calculating summaries. Conclusion: This study has shown that there are relevant issues that need to be addressed in order to improve the quality of lymphatic filariasis treatment coverage reports. Some of the factors identified are problems within the health system; others are specific to the community health volunteers and the lymphatic filariasis programme. Steps such as training on data reporting should be intensified for community health volunteers, allowances for community health volunteers should be re-evaluated and other non-monetary incentives should be provided for community health volunteers.

  7. Socio-cultural aspects of lymphatic filariasis and the role of communities in its control in Ghana

    OpenAIRE

    Gyapong, Margaret

    2000-01-01

    Lymphatic Filariasis (LF) is one of the worlds most debilitating and disfiguring tropical diseases. The World Health Organization estimates that there are about one billion people at risk in about 80 countries worldwide. It is the world’s second leading cause of permanent long-term disability and its prevalence continues to increase. The World Bank development report indicates that the global burden for the disease was estimated at 850,000 DALY’s lost which represents only 0.23...

  8. How effective is integrated vector management against malaria and lymphatic filariasis where the diseases are transmitted by the same vector?

    OpenAIRE

    Stone, C.; Lindsay, S.W.; Chitnis, N.

    2014-01-01

    Background: The opportunity to integrate vector management across multiple vector-borne diseases is particularly plausible for malaria and lymphatic filariasis (LF) control where both diseases are transmitted by the same vector. To date most examples of integrated control targeting these diseases have been unanticipated consequences of malaria vector control, rather than planned strategies that aim to maximize the efficacy and take the complex ecological and biological interactions between th...

  9. Preliminary clinical application in the cranial internal carotid artery of covered stents specially designed for intracranial vasculature

    International Nuclear Information System (INIS)

    Li Minghua; Luo Qiyi; Fang Chun; Xie Zhiyong; Cheng Yingsheng; Gao Bulang; Li Yu; Zhang Beilei; Xie Jian; Wang Yongli

    2007-01-01

    Objective: To investigate the flexibility of both the covered stents specially designed for use in intracranial vasculature and the delivering system in passing through the bone tube and the physiological curves of the cranial internal carotid artery (CICA) to reach the targeted area, the performance (adherence) of the covered stents in occluding vascular wall diseases and the impact on the vascular branches of the covered segment. Methods: The covered stents specially designed for use in intracranial vasculature were used to treat 13 patients with CICA diseases using endovascular techniques. There were 4 huge pseudoaneurysms, 4 giant aneurysms, 3 small wide-necked aneurysms, 1 giant pseudoaneurysm with concurrent internal carotid cavernous fistula (CCF), and 1 CCF. Prior to the detachment of the covered stents, balloon occlusion test (BOT) of the internal carotid artery on the diseased side and whole-brain digital subtraction angiography (DSA) were performed in all the patients. Three to 16 months following procedure, DSA and clinical follow-ups were performed. Results: Thirteen patients all tolerated the BOT well with the DSA demonstrating well-opened anterior and posterior communicating arteries. The covered stents and the delivering systems all successfully passed CICA to reach the targeted diseased area, with the diseased segments of the internal carotid artery including C3-C4 in 4 cases, C4-C5 in 4 and C6-C7 in 5. Immediately following the detachment of the covered stents, DSA demonstrated that 7 aneurysms were completely occluded, 4 aneurysms had slight endoleak, and 1 CCF had markedly-decreased blood flow through the fistula. In the patient with concurrent pseudoaneurysm and CCF, the pseudoaneurysm disappeared and the blood flow through the fistula was markedly-reduced immediately following the stenting procedure. Apart from one patient with aneurysmal subarachnoid hemorrhage who died due to extensive vascular spasm on the 9th day following the stenting

  10. Oral bioavailability assessment and intestinal lymphatic transport of Org 45697 and Org 46035, two highly lipophilic novel immunomodulator analogues.

    Science.gov (United States)

    Caliph, Suzanne M; Faassen, W A Fried; Vogel, Gerard M; Porter, Christopher J H

    2009-08-01

    Org 45697 (MW 600.7, clogP 7.92, soybean oil solubility 50 mg/g) and Org 46035 (MW 601.6, clog P 8.46, soybean oil solubility 40 mg/g) are two poorly water soluble ( 5 fold) after oral administration in a long chain triglyceride lipid (olive oil) formulation. Subsequent studies have explored the potential for solubilising formulations, including lipid-based formulations, to enhance the oral bioavailability of Org 45697 and Org 46035 and secondly to explore the potential contribution of intestinal lymphatic transport to intestinal absorption. The experimental data show that solubilising formulations may provide for significant increases in oral bioavailability for Org 45697 and Org 46035 and that after co-administration with lipid, 35-50% of the absorbed dose may be transported to the systemic circulation via the intestinal lymph. Interestingly, the lymphatic transport of the less lipid soluble analogue, Org 46035 was approximately 40% lower than that of Org 45697 suggesting that relatively subtle differences in lipid solubility can have significant impact on the extent of lymphatic transport.

  11. Efficacy of complete decongestive therapy and manual lymphatic drainage on treatment-related lymphedema in breast cancer

    International Nuclear Information System (INIS)

    Koul, Rashmi; Dufan, Tarek; Russell, Catherine; Guenther, Wanda; Nugent, Zoan; Sun Xuyan; Cooke, Andrew L.

    2007-01-01

    Objective: To evaluate the results of combined decongestive therapy and manual lymphatic drainage in patients with breast cancer-related lymphedema. Methods and Materials: The data from 250 patients were reviewed. The pre- and posttreatment volumetric measurements were compared, and the correlation with age, body mass index, and type of surgery, chemotherapy, and radiotherapy was determined. The Spearman correlation coefficients and Wilcoxon two-sample test were used for statistical analysis. Results: Of the 250 patients, 138 were included in the final analysis. The mean age at presentation was 54.3 years. Patients were stratified on the basis of the treatment modality used for breast cancer management. Lymphedema was managed with combined decongestive therapy in 55%, manual lymphatic drainage alone in 32%, and the home program in 13%. The mean pretreatment volume of the affected and normal arms was 2929 and 2531 mL. At the end of 1 year, the posttreatment volume of the affected arm was 2741 mL. The absolute volume of the affected arm was reduced by a mean of 188 mL (p < 0.0001). The type of surgery (p = 0.0142), age (p = 0.0354), and body mass index (p < 0.0001) were related to the severity of lymphedema. Conclusion: Combined decongestive therapy and manual lymphatic drainage with exercises were associated with a significant reduction in the lymphedema volume

  12. Heterogeneity of Mesenchymal Markers Expression—Molecular Profiles of Cancer Cells Disseminated by Lymphatic and Hematogenous Routes in Breast Cancer

    International Nuclear Information System (INIS)

    Markiewicz, Aleksandra; Książkiewicz, Magdalena; Seroczyńska, Barbara; Skokowski, Jarosław; Szade, Jolanta; Wełnicka-Jaśkiewicz, Marzena; Zaczek, Anna J.

    2013-01-01

    Breast cancers can metastasize via hematogenous and lymphatic routes, however in some patients only one type of metastases are detected, suggesting a certain proclivity in metastatic patterns. Since epithelial-mesenchymal transition (EMT) plays an important role in cancer dissemination it would be worthwhile to find if a specific profile of EMT gene expression exists that is related to either lymphatic or hematogenous dissemination. Our study aimed at evaluating gene expression profile of EMT-related markers in primary tumors (PT) and correlated them with the pattern of metastatic spread. From 99 early breast cancer patients peripheral blood samples (N = 99), matched PT (N = 47) and lymph node metastases (LNM; N = 22) were collected. Expression of TWIST1, SNAI1, SNAI2 and VIM was analyzed in those samples. Additionally expression of CK19, MGB1 and HER2 was measured in CTCs-enriched blood fractions (CTCs-EBF). Results were correlated with each other and with clinico-pathological data of the patients. Results show that the mesenchymal phenotype of CTCs-EBF correlated with poor clinico-pathological characteristics of the patients. Additionally, PT shared more similarities with LNM than with CTCs-EBF. Nevertheless, LNM showed increased expression of EMT-related markers than PT; and EMT itself in PT did not seem to be necessary for lymphatic dissemination

  13. Oral cancer cells with different potential of lymphatic metastasis displayed distinct biologic behaviors and gene expression profiles.

    Science.gov (United States)

    Zhuang, Zhang; Jian, Pan; Longjiang, Li; Bo, Han; Wenlin, Xiao

    2010-02-01

    Oral squamous cell carcinoma (OSCC) often spreads from the primary tumor to regional lymph nodes in the early stage. Better understanding of the biology of lymphatic spread of oral cancer cells is important for improving the survival rate of cancer patients. We established the cell line LNMTca8113 by repeated injections in foot pads of nude mice, which had a much higher lymphatic metastasis rate than its parental cell line Tca8113. Then, we compared the biologic behaviors of cancer cells between them. Moreover, microarray-based expression profiles between them were also compared, and a panel of differential genes was validated using real-time-PCR. In contrast to Tca8113 cells, LNMTca8113 cells were more proliferative and resistant to apoptosis in the absence of serum, and had enhanced ability of inducing capillary-like structures. Moreover, microarray-based expression profiles between them identified 1341 genes involved in cell cycle, cell adhesion, lymphangiogenesis, regulation of apoptosis, and so on. Some genes dedicating to the metastatic potential, including JAM2, TNC, CTSC, LAMB1, VEGFC, HAPLN1, ACPP, GDF9 and FGF11, were upregulated in LNMTca8113 cells. These results suggested that LNMTca8113 and Tca8113 cells were proper models for lymphatic metastasis study because there were differences in biologic behaviors and metastasis-related genes between them. Additionally, the differentially expressed gene profiles in cancer progression may be helpful in exploring therapeutic targets and provide the foundation for further functional validation of these specific candidate genes for OSCC.

  14. cAMP signalling in the vasculature: the role of Epac (exchange protein directly activated by cAMP).

    Science.gov (United States)

    Roberts, Owain Llŷr; Dart, Caroline

    2014-02-01