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Sample records for anatomical lymphatic mapping

  1. Mapping superficial lymphatic territories in the rabbit.

    PubMed

    Soto-Miranda, Miguel A; Suami, Hiroo; Chang, David W

    2013-06-01

    Little is known about the anatomy of the lymphatic system in the rabbit with regard to relationships between the lymphatic vessel and lymph node. According to our previous studies in human cadavers and canines, the superficial lymphatic system could be divided into lymphatic territories. The aim of this study was to completely map the superficial lymphatic system in the rabbit. We used our microinjection technique and histological analysis for dissecting studies and recently developed indocyanine green (ICG) fluorescent lymphography for demonstrating dynamic lymph flow in living rabbits. Real-time ICG fluorescent lymphography was performed in two living New Zealand White rabbits, and direct dye microinjection of the lymphatic vessels was performed in eight dead rabbits. To assess the relationships between the vascular and lymphatic systems in rabbits, we performed radiocontrast injection into arteries in two dead rabbits prior to the lymphatic injection. The ICG fluorescent lymphography revealed eight lymphatic territories in the preauricular, submandibular, root of the lateral neck, axillary, lumbar, inguinal, root of the tail, and popliteal regions. We injected blue acrylic dye into every lymphatic vessel 0.1 mm in diameter or larger. We then dissected and chased the stained lymphatic vessels proximally until the vessels connected to the first tier lymph node. This procedure was repeated throughout the body until all the relationships between the lymphatic vessels and lymph nodes were defined. The lymphatic system of the rabbit could be defined as eight lymphatic territories, each with its own lymphatic vessels and lymph node.

  2. Lymphosome concept: Anatomical study of the lymphatic system.

    PubMed

    Suami, Hiroo

    2017-01-01

    The gross anatomical study of the lymphatic system in humans and animals has been suspended for almost 100 years. This article introduces the author's technique for investigating the lymphatic system using the concept of the lymphosome. In revisiting the anatomical study of the lymphatic system, our updated knowledge can potentially be utilized either to reassure surgeons about their current procedures in the surgical management of cancers and lymphedema or assist them to refine them. J. Surg. Oncol. 2017;115:13-17. © 2016 Wiley Periodicals, Inc.

  3. Predictive lymphatic mapping: a method for mapping lymphatic channels in patients with advanced unilateral lymphedema using indocyanine green lymphography.

    PubMed

    Mihara, Makoto; Seki, Yukio; Hara, Hisako; Iida, Takuya; Oka, Aiko; Kikuchi, Kazuki; Narushima, Mitsunaga; Haragi, Makiko; Furniss, Dominic; Hin-Lun, Lawrence; Mitsui, Kito; Murai, Noriyuki; Koshima, Isao

    2014-01-01

    In severe lymphedema, indocyanine green lymphography cannot be used to map lymphatic channels before lymphaticovenular anastomosis (LVA) because linear lymphatics cannot be detected in a severely affected leg. Here, we describe a new method, which we refer to as predictive lymphatic mapping, to predict the location of lymphatics for anastomosis in unilateral lymphedema, thereby improving surgical accuracy and efficiency. The approach consists of marking anatomical landmarks and joining selected landmarks with fixed lines. The distance from these fixed lines to lymphatic channels mapped by indocyanine green lymphography in the unaffected leg is then measured, scaled up based on the difference in circumference between the legs, and transposed to the affected leg. To date, we have used this method in 5 cases of unilateral or asymmetric lymphedema of the lower extremities. In no cases have we failed to find a lymphatic channel suitable for LVA within a 2-cm incision. These results suggest that predictive lymphatic mapping is a useful additional tool for surgeons performing LVA under local anesthesia, which will help to improve the accuracy of incisions and the efficiency of surgery.

  4. Cardiac mouse lymphatics: developmental and anatomical update.

    PubMed

    Flaht-Zabost, Aleksandra; Gula, Grzegorz; Ciszek, Bogdan; Czarnowska, Elżbieta; Jankowska-Steifer, Ewa; Madej, Maria; Niderla-Bielińska, Justyna; Radomska-Leśniewska, Dorota; Ratajska, Anna

    2014-06-01

    The adult mouse heart possesses an extensive lymphatic plexus draining predominantly the subepicardium and the outer layer of the myocardial wall. However, the development of this plexus has not been entirely explored, partially because of the lack of suitable methods for its visualization as well as prolonged lymphatic vessel formation that starts prenatally and proceeds during postnatal stages. Also, neither the course nor location of collecting vessels draining lymph from the mouse heart have been precisely characterized. In this article, we report that murine cardiac lymphatic plexus development that is limited prenatally only to the subepicardial area, postnatally proceeds from the subepicardium toward the myocardial wall with the base-to-apex gradient; this plexus eventually reaches the outer half of the myocardium with a predominant location around branches of coronary arteries and veins. Based on multiple marker immunostaining, the molecular marker-phenotype of cardiac lymphatic endothelial cells can be characterized as: Prox-1(+), Lyve-1(+), VEGFR3(+), Podoplanin(+), VEGFR2(+), CD144(+), Tie2(+), CD31(+), vWF(-), CD34(-), CD133(-). There are two major collecting vessels: one draining the right and left ventricles along the left conal vein and running upwards to the left side of the pulmonary trunk and further to the nearest lymph nodes (under the aortic arch and near the trachea), and the other one with its major branch running along the left cardiac vein and further on the surface of the coronary sinus and the left atrium to paratracheal lymph nodes. The extracardiac collectors gain the smooth muscle cell layer during late postnatal stages.

  5. Lymphatic mapping for upper gastrointestinal malignancies.

    PubMed

    Kitagawa, Yuko; Kitajima, Masaki

    2004-06-01

    Recent studies on lymphatic mapping of upper gastrointestinal (GI) malignancies have provided new insights with regard to the sentinel node (SN) concept in solid tumors. At present, the SN concept seems to be valid not only for breast cancer, but also for esophageal and gastric cancers, which have multidirectional and complicated lymphatic flows. In addition to the staging merits, individualized surgical management has been proposed for upper GI cancer based on the SN concept. Gastric cancer is now a suitable target of SN-guided surgery after breast cancer because of its anatomical situation. Laparoscopic local resection is theoretically feasible for curative treatment of SN-negative early gastric cancer. Because SNs in esophageal cancer are multiple and widespread, complete sampling of SNs is not a minimally invasive procedure, as it is in breast cancer. However, selective and modified lymphadenectomy targeting SNs for clinically N0 esophageal cancer instead of three-field lymph node dissection should become not only feasible but also clinically important. When performing chemoradiotherapy as curative treatment for cT1N0 esophageal cancer, lymphoscintigrams revealing the distribution of SNs in each individual case are useful to tailor the field of irradiation to control occult micrometastases. Although there are several issues to be resolved, this novel procedure has the potential to improve quality control in upper GI cancer.

  6. Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance

    PubMed Central

    Zolla, Valerio; Nizamutdinova, Irina Tsoy; Scharf, Brian; Clement, Cristina C; Maejima, Daisuke; Akl, Tony; Nagai, Takashi; Luciani, Paola; Leroux, Jean-Christophe; Halin, Cornelia; Stukes, Sabriya; Tiwari, Sangeeta; Casadevall, Arturo; Jacobs, William R; Entenberg, David; Zawieja, David C; Condeelis, John; Fooksman, David R; Gashev, Anatoliy A; Santambrogio, Laura

    2015-01-01

    The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic’s endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport. PMID:25982749

  7. Anatomic considerations of the penis, lymphatic drainage, and biopsy of the sentinel node.

    PubMed

    Wood, Hadley M; Angermeier, Kenneth W

    2010-08-01

    This article reviews anatomic considerations in penile and urethral surgery, with a particular emphasis on lymphatic anatomy. The historical evolution of techniques to reduce the unnecessary use and operative morbidity of inguinofemoral lymph node dissection are reviewed, with an emphasis on sentinel node (SN) biopsy and dynamic SN biopsy techniques. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Anatomical Mercury: Changing Understandings of Quicksilver, Blood, and the Lymphatic System, 1650-1800.

    PubMed

    Hendriksen, Marieke M A

    2015-10-01

    The use of mercury as an injection mass in anatomical experiments and preparations was common throughout Europe in the long eighteenth century, and refined mercury-injected preparations as well as plates of anatomical mercury remain today. The use and meaning of mercury in related disciplines such as medicine and chemistry in the same period have been studied, but our knowledge of anatomical mercury is sparse and tends to focus on technicalities. This article argues that mercury had a distinct meaning in anatomy, which was initially influenced by alchemical and classical understandings of mercury. Moreover, it demonstrates that the choice of mercury as an anatomical injection mass was deliberate and informed by an intricate cultural understanding of its materiality, and that its use in anatomical preparations and its perception as an anatomical material evolved with the understanding of the circulatory and lymphatic systems. By using the material culture of anatomical mercury as a starting point, I seek to provide a new, object-driven interpretation of complex and strongly interrelated historiographical categories such as mechanism, vitalism, chemistry, anatomy, and physiology, which are difficult to understand through a historiography that focuses exclusively on ideas.

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

    PubMed

    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

  10. Mapping the Geographical Distribution of Lymphatic Filariasis in Zambia

    PubMed Central

    Mwase, Enala T.; Stensgaard, Anna-Sofie; Nsakashalo-Senkwe, Mutale; Mubila, Likezo; Mwansa, James; Songolo, Peter; Shawa, Sheila T.; Simonsen, Paul E.

    2014-01-01

    Background Past case reports have indicated that lymphatic filariasis (LF) occurs in Zambia, but knowledge about its geographical distribution and prevalence pattern, and the underlying potential environmental drivers, has been limited. As a background for planning and implementation of control, a country-wide mapping survey was undertaken between 2003 and 2011. Here the mapping activities are outlined, the findings across the numerous survey sites are presented, and the ecological requirements of the LF distribution are explored. Methodology/Principal findings Approximately 10,000 adult 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 presence, and to predict potential suitable habitats over unsurveyed areas. Of note, areas associated with human modification of the landscape appeared to play an important role for the general presence of LF, whereas temperature (measured as averaged seasonal land surface temperature) seemed 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 and start-up of geographically targeted and cost-effective LF control in Zambia. PMID:24587466

  11. Mapping the geographical distribution of lymphatic filariasis in Zambia.

    PubMed

    Mwase, Enala T; Stensgaard, Anna-Sofie; Nsakashalo-Senkwe, Mutale; Mubila, Likezo; Mwansa, James; Songolo, Peter; Shawa, Sheila T; Simonsen, Paul E

    2014-02-01

    Past case reports have indicated that lymphatic filariasis (LF) occurs in Zambia, but knowledge about its geographical distribution and prevalence pattern, and the underlying potential environmental drivers, has been limited. As a background for planning and implementation of control, a country-wide mapping survey was undertaken between 2003 and 2011. Here the mapping activities are outlined, the findings across the numerous survey sites are presented, and the ecological requirements of the LF distribution are explored. Approximately 10,000 adult 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 presence, and to predict potential suitable habitats over unsurveyed areas. Of note, areas associated with human modification of the landscape appeared to play an important role for the general presence of LF, whereas temperature (measured as averaged seasonal land surface temperature) seemed to be an important determinant of medium-high prevalence levels. 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 and start-up of geographically targeted and cost-effective LF control in Zambia.

  12. Pattern of lymph node metastases of squamous cell esophageal cancer based on the anatomical lymphatic drainage system: efficacy of lymph node dissection according to tumor location

    PubMed Central

    2017-01-01

    Knowing the anatomical lymphatic drainage of the esophagus is crucial to understanding the dissemination pattern of esophageal tumor. During the embryonal growth, the middle and lower part of the esophagus stretches as the lymphatic networks develop in the submucosal layer. The abundant submucosal lymphatics drain in a longitudinal fashion directly to their proximal and distal ends. The lymphatic route from the proximal esophagus through recurrent nerve nodes to supraclavicular nodes are a component of the mesentery of the proximal esophagus. The lower esophagus mostly drains its lymph into paracardial nodes related to celiac nodes through the mesentery of the distal esophagus. Lymphatic routes to mid and lower paraesophageal nodes usually originate from the intermuscular area of the muscularis propria. The lymphatic communication between the submucosa and intermuscular area is limited. The anatomical concept was confirmed clinically by a large series of single institution and the nationwide registry in Japan. The clinical data for the incidence of involved nodes verified the anatomical observations that long longitudinal extension of lymphatic drainage in the submucosa connected to the upper mediastinum lymphatics and paracardial lymphatics. The extent of dissection should be not tailored according to the anatomical distance from the tumor but according to the incidences of metastasis of each area, those were differed by tumor location. The areas for node dissection should be modified according to the tumor location. Although in patients with tumor limited to within the submucosal layer, even with tumors located in the mid- and lower esophagus, lymphatic metastasis was frequent in the upper mediastinum and perigastric area via the abundant submucosal lymphatics in a longitudinal fashion. When tumor invades or penetrates the muscle layer, the incidence of paraesophageal lymph node metastasis in the middle and lower mediastinum increases. PMID:28815068

  13. Shrinking the lymphatic filariasis map: update on diagnostic tools for mapping and transmission monitoring.

    PubMed

    Rebollo, Maria P; Bockarie, Moses John

    2014-12-01

    Lymphatic filariasis (LF), which is highly endemic in 73 countries worldwide, is targeted for elimination by 2020. The strategy for achieving this goal is based on 4 sequential programmatic steps: mapping, Mass drug administration (MDA) implementation, post-MDA surveillance and verification of LF elimination. All 4 stages of the implementation process are dependent on the availability of user friendly and highly sensitive rapid diagnostic tools. By the end of 2012, 59 countries had completed mapping for LF and Eritrea was the only country yet to start the process. Rolling out new diagnostic tools to facilitate the mapping process will enable an accelerated shrinking of the LF map to zero endemic countries by 2020. When the Global Programme to Eliminate Lymphatic Filariasis was launched in 2000, diagnostic tools for LF were limited to clinical examination, detection of microfilaria (MF) by microscopy in night blood samples and detection of antibodies to native-antigen preparations. There has been a significant improvement in the traditional LF diagnostic methods in recent years and some new tools are now available. This paper provides an update on the human diagnostic tests available for LF and their current applications as tools in mapping and transmission monitoring. The values of entomological indicators and parasite detection and speciation methods applied to vector populations are also discussed.

  14. Lymphatic mapping and sentinel node location with magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Jung, Chu W.; Rogers, James M.; Groman, Ernest V.

    1999-04-01

    Subcutaneously administered magnetite nanoparticles were used to locate sentinel lymph nodes in normal rats. Nanoparticles sequestered in brachial and axillary lymph nodes produced magnetic susceptibility artifacts in gradient recall echo magnetic resonance images. The artifact sizes enabled the determination of nanoparticle nodal uptake rates and lymphatic drainage patterns. These studies were confirmed by use of 59Fe labeled magnetite nanoparticles.

  15. Lymphatic mapping and intraoperative lymphoscintigraphy for identifying the sentinel node in penile tumors.

    PubMed

    Han, K R; Brogle, B N; Goydos, J; Perrotti, M; Cummings, K B; Weiss, R E

    2000-04-01

    Lymph node mapping has become an integral part of the management of melanoma and breast cancer with regard to both staging and treatment. We report our technique for lymphatic mapping and intraoperative lymphoscintigraphy applied to a patient with penile melanoma. This technique may improve the sensitivity of identifying the sentinel lymph node in patients with malignant penile lesions.

  16. A cautionary tale: anaphylaxis to isosulfan blue dye after 12 years and 3339 cases of lymphatic mapping.

    PubMed

    Kaufman, Gabriel; Guth, Amber A; Pachter, H Leon; Roses, Daniel F

    2008-02-01

    Sentinel node biopsy has become the standard method for lymphatic staging in early-stage breast cancer and melanomas. The most commonly used technique uses both a radioactive tracer as well as blue dye, usually isosulfan blue. In this report, we discuss two episodes of anaphylaxis to isosulfan blue during lymphatic mapping, occurring 12 years and 3339 lymphatic mapping cases after adoption of the technique, and discuss management issues raised by these events.

  17. Lymphatic drainage of the skull base: comparative anatomic and advanced imaging studies in the rabbit and human with implications for spread of nasopharyngeal carcinoma.

    PubMed

    Qiuhang, Z; Zhenlin, W; Yan, Q; Jun, H; Yongfeng, S; Bo, H

    2010-09-01

    This preliminary study investigated the lymphatic drainage and distribution of lymphatic structures in the skull base. Characteristics of the rabbit skull base were analyzed and compared correspondingly with those of the human skull. The lymphatic circulation in the rabbit cranial base was detected by digital subtraction angiography (DSA), and lymph drainage in the human skull base was illustrated by interstitial magnetic resonance lymphography (MRL). Lymphatic structures and their distribution in MRL were identified by comparing with contrast-enhanced MRI and clinical data on basilar metastasis of nasopharyngeal carcinoma (NPC) in the human skull base. Anatomic similarity was found between the rabbit and human basilar regions. Well-visualized lymphatic pathways were found in the rabbit cranial base, and human lymphatic structures showed high signal intensity in enhanced T1-weighted MRL images. Lymphatic tissues in the human basilar region were found mainly distributed in the areas of the jugular foramen, foramen lacerum, and petrosal section of the internal carotid artery (ICA). Their distribution in the human basilar region was similar to the distribution in the rabbit basilar region and consistent with our clinical findings of the predilection sites of NPC metastasis in the skull base. Our studies show that bilateral symmetrical lymphatic structures were distributed along the ICA, internal jugular vein, and dura of cranial base in the central part of the middle and posterior skull base.

  18. Shrinking the Lymphatic Filariasis Map of Ethiopia: Reassessing the Population at Risk through Nationwide Mapping

    PubMed Central

    Assefa, Ashenafi; Cano, Jorge; Deribe, Kebede; Gonzalez-Escalada, Alba; Shafi, Oumer; Davey, Gail; Brooker, Simon J.; Kebede, Amha; Bockarie, Moses J.

    2015-01-01

    Background Mapping of lymphatic filariasis (LF) is essential for the delineation of endemic implementation units and determining the population at risk that will be targeted for mass drug administration (MDA). Prior to the current study, only 116 of the 832 woredas (districts) in Ethiopia had been mapped for LF. The aim of this study was to perform a nationwide mapping exercise to determine the number of people that should be targeted for MDA in 2016 when national coverage was anticipated. Methodology/Principal Finding A two-stage cluster purposive sampling was used to conduct a community-based cross-sectional survey for an integrated mapping of LF and podoconiosis, in seven regional states and two city administrations. Two communities in each woreda were purposely selected using the World Health Organization (WHO) mapping strategy for LF based on sampling 100 individuals per community and two purposely selected communities per woreda. Overall, 130 166 people were examined in 1315 communities in 658 woredas. In total, 140 people were found to be positive for circulating LF antigen by immunochromatographic card test (ICT) in 89 communities. Based on WHO guidelines, 75 of the 658 woredas surveyed in the nine regions were found to be endemic for LF with a 2016 projected population of 9 267 410 residing in areas of active disease transmission. Combining these results with other data it is estimated that 11 580 010 people in 112 woredas will be exposed to infection in 2016. Conclusions We have conducted nationwide mapping of LF in Ethiopia and demonstrated that the number of people living in LF endemic areas is 60% lower than current estimates. We also showed that integrated mapping of multiple NTDs is feasible and cost effective and if properly planned, can be quickly achieved at national scale. PMID:26539700

  19. Lymphatic mapping and lymphedema surgery in the breast cancer patient

    PubMed Central

    Manrique, Oscar; Sosin, Michael; Hashmi, Mahjabeen Aftab; Poysophon, Poysophon; Henderson, Robert

    2015-01-01

    Upper limb lymphedema can be an unfortunate sequela following the oncologic treatment of breast cancer. The surgical treatment of lymphedema has had a recent renewed clinical interest paralleling innovative descriptions of surgical techniques and imaging modalities. In addition, an improved understanding of the physiology and pathophysiology of lymphedema has allowed improved translation to the clinical condition. Various surgical options exist to decrease the symptom-burden of upper limb lymphedema, including vascularized lymph node (VLN) transfer, lymphovenous bypass (LVB), liposuction, lymphatic grafting, and excisional procedures. Modern imaging techniques help to improve the consistency and accuracy of these surgical treatment options. A multi-modal treatment plan utilizing non-operative and surgical therapies has the potential to improve various factors related to overall patient quality of life. This review details all of the current operative treatment strategies and modern imaging modalities used in the treatment of lymphedema. PMID:26161309

  20. Technique of sentinel lymph node biopsy and lymphatic mapping during laparoscopic colon resection for cancer

    PubMed Central

    Bianchi, PP; Andreoni, B; Rottoli, M; Celotti, S; Chiappa, A; Montorsi, M

    2007-01-01

    Background: The utility of lymph node mapping to improve staging in colon cancer is still under evaluation. Laparoscopic colectomy for colon cancer has been validated in multi-centric trials. This study assessed the feasibility and technical aspects of lymph node mapping in laparoscopic colectomy for colon cancer. Methods: A total of 42 patients with histologically proven colon cancer were studied from January 2006 to September 2007. Exclusion criteria were: advanced disease (clinical stage III), rectal cancer, previous colon resection and contraindication to laparoscopy. Lymph-nodal status was assessed preoperatively by computed tomography (CT) scan and intra-operatively with the aid of laparoscopic ultrasound. Before resection, 2–3 ml of Patent Blue V dye was injected sub-serosally around the tumour. Coloured lymph nodes were marked as sentinel (SN) with metal clips or suture and laparoscopic colectomy with lymphadenectomy completed as normal. In case of failure of the intra-operative procedure, an ex vivo SN biopsy was performed on the colectomy specimen after resection. Results: A total number of 904 lymph nodes were examined, with a median number of 22 lymph nodes harvested per patient. The SN detection rate was 100%, an ex vivo lymph node mapping was necessary in four patients. Eleven (26.2%) patients had lymph-nodal metastases and in five (45.5%) of these patients, SN was the only positive lymph node. There were two (18.2%) false-negative SN. In three cases (7.1%) with aberrant lymphatic drainage, lymphadenectomy was extended. The accuracy of SN mapping was 95.2% and negative predictive value was 93.9%. Conclusions: Laparoscopic lymphatic mapping and SN removal is feasible in laparoscopic colectomy for colon cancer. The ex vivo technique is useful as a salvage technique in case of failure of the intra-operative procedure. Prospective studies are justified to determine the real accuracy and false-negative rate of the technique. PMID:22275957

  1. Lymphatic filariasis morbidity mapping: a comprehensive examination of lymphoedema burden in Chikwawa district, Malawi.

    PubMed

    Smith, Emma L; Mkwanda, Square Z; Martindale, Sarah; Kelly-Hope, Louise A; Stanton, Michelle C

    2014-12-01

    Managing lymphatic filariasis (LF) morbidity and reducing disability is one of the two primary goals of the Global Programme to Eliminate Lymphatic Filariasis. However, in order to achieve this, the geographical distribution of LF morbidity needs to be better estimated. All cases of lymphoedema within a single health centre catchment area (pop. 42 000) in the southern region of Malawi were examined. Maps of lymphoedema burden were produced and trends in patient demographics, severity of lymphoedema (Dreyer staging) and health-seeking behaviour were explored. The number of lymphoedema cases was compared with records maintained by the Ministry of Health, Malawi. A total of 69 lymphoedema cases were identified (32 per 10 000 population), of which 48 (70%) were female and 21 (30%) male. The majority of cases (51/69) had Dreyer stage 2-3, and almost all (65/69) had experienced acute attacks as a result of their lymphoedema. This burden was much greater than that estimated by Ministry of Health (33 cases). Current case detection methods underestimate the burden of lymphoedema in Malawi. There is a continued need to develop new LF morbidity identification and surveillance approaches to ensure that future morbidity management strategies are effectively targeted. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Mapping of lymphatic filariasis: "to be (in English) or not to be".

    PubMed

    Carme, B

    2010-12-01

    Despite lack of supporting evidence from epidemiologic studies and/or confirmed case reports over the last 30 years, maps in non-specialist works on tropical medicine as well as in documents from specialized organizations (e.g. WHO) systematically include Congo and Gabon, two French-speaking countries, within the zone of endemic filariasis due to Wuchereria bancrofti. One certainty is that no cases were found in field studies carried out in these countries in the late 1970s and 1980s but unfortunately published only in French. Studies that we carried out in the Congo between 1982 and 1987 as part of the National Project on Onchocerciasis and Other Filarioses confirmed the presence of four types of human filariasis: onchocerciasis, loaiasis filarioses caused by Mansonella perstans and M. streptocerca. However, there were no confirmed cases of lymphatic filariosis (bancroftosis). Hopefully the WHO program aimed at the elimination of lymphatic filariasis as a public health problem will provide up-to-date data on the distribution and endemicity of filariasis in Central Africa. Achievement of this objective will depend not only on carrying out new field studies but also on taking into account past studies published in languages other than Shakespeare's.

  3. Lymphatic Territories (Lymphosomes) in Swine: An Animal Model for Future Lymphatic Research.

    PubMed

    Ito, Ran; Suami, Hiroo

    2015-08-01

    The swine is a common preclinical large-animal model for medical research because of the resemblance of its tissue structures to those of humans. However, the lymphatic system in swine is poorly understood. The authors investigated the lymphatic system and defined territories (lymphosomes) in swine using the microinjection technique. Six swine (two male and four female 17.5- to 50-kg Sus domesticus) were used. Real-time indocyanine green fluorescence lymphography was performed in four live swine. After the animals were killed, the authors injected a radiocontrast mixture consisting of barium sulfate and hydrogen peroxide with red acrylic dye directly into lymphatic vessels in six swine carcasses. Courses of the lymphatic vessel were analyzed radiographically. The lymphatic vessels were dissected meticulously and chased until they connected to the first-tier (sentinel) lymph node. This procedure was repeated throughout the body until all the relationships between the lymphatic vessels and lymph nodes were defined. The authors successfully mapped the superficial lymphatic vessels and their corresponding lymph nodes. Indocyanine green fluorescence lymphography and subsequent radiography revealed that the swine lymphatic system contained seven lymphosomes: parotid, mandibular, dorsal cervical, ventral cervical, subiliac, inguinal, and popliteal territories. Of note, no lymph nodes existed in the superficial axillary region. The swine could be a useful large-animal model for lymphatic research because of the anatomical consistency of the lymphosomes among animals and the sizable lymphatic vessels. However, swine lack the superficial axillary lymph node found in humans, suggesting that swine may not be a good model for breast cancer-related lymphedema.

  4. Adverse drug reactions during lymphatic mapping and sentinel lymph node biopsy for solid neoplasms.

    PubMed

    Amr, Dena; Broderick-Villa, Gregory; Haigh, Philip I; Guenther, J Michael; DiFronzo, L Andrew

    2005-09-01

    Currently, 1 per cent isosulfan blue dye and technetium-99-labeled sulfur colloid (SC) are used in lymphatic mapping (LM). Several reports have suggested that the incidence of adverse drug reactions (ADRs) during LM is high. We report our experience with LM for solid neoplasms in order to determine the incidence and risk factors for development of ADRs. Seven hundred fifty-three patients (90% women, mean age 57) underwent LM with blue dye alone or in combination with SC from 1998 to 2004. The most common malignancy was breast cancer (83%). One hundred ten patients (14%) had injection of both mapping agents. Most patients (87%) underwent intraparenchymal injection of LM agent. Eight patients (1.1%) had an ADR during LM; none had prior exposure to LM. Of these, 7 had limited reactions (mostly blue hives) that quickly resolved. One patient (0.1%) developed anaphylaxis. The ADR incidence in patients with a sulfa allergy was not significantly different than that in patients without a sulfa allergy (3.4 vs 1%, P = 0.12). No risk factors for development of ADR were identified. Overall, the incidence of ADR during LM is low. Patients with sulfa allergies and prior exposure to LM did not demonstrate an increased incidence of ADR. Anaphylaxis, though rare, can occur during LM.

  5. Lymphatic mapping with 99mTc-Evans Blue dye in sheep.

    PubMed

    Tsopelas, Chris; Bellon, Max; Bevington, Elaine; Kollias, James; Shibli, Sabah; Chatterton, Barry E

    2008-11-01

    99mTc-Evans Blue (EB) is an agent that contains both radioactive and color signals in a single dose. Earlier studies in animal models have suggested that this agent when compared with the dual-injection technique of radiocolloid/blue dye can successfully discriminate the sentinel lymph node. The aim of this study was to investigate the potential of 99mTc-EB as an agent to map the lymphatic system in an ovine model. Doses of 99mTc-EB (23 MBq) containing EB dye (4 mg) were administered intradermally to the limbs of four anesthetized sheep, and they were then imaged over 20-30 min using a gamma camera. The study protocol was repeated using 99mTc-antimony trisulfide colloid (ATC) and Patent Blue V dye. The lymph nodes (popliteal, inguinal, and iliac for hind limbs or prescapular for fore limbs) were identified with a gamma probe during the operative exposure, then dissected and counted in a large volume counter. Simple and complex (dual) drainage patterns were visible on the scans, and the sentinel node was more radioactive than higher tier nodes in a chain, for both radiotracers. For 99mTc-EB, maximum radioactive uptake was achieved at 3-6 min for popliteal lymph nodes, 12-14 min for iliac nodes, and 13-14 min for prescapular nodes. 99mTc-ATC resulted in maximum radioactive uptake at 4-6 min for popliteal lymph nodes, 13 min for an inguinal node, 13-20 min for iliac nodes, and 18 min for a prescapular node. Following 99mTc-EB injection, 15/15 lymph nodes harvested were all radioactive and blue. For 99mTc-radiocolloid/Patent Blue V injection, 8/14 nodes were radioactive and blue, and 6/14 nodes were radioactive only. The soluble radiotracer 99mTc-EB appeared to be a useful lymphoscintigraphic agent in sheep, in which radioactive counts from superficial lymphatic channels and lymph nodes were sufficient for planar imaging. In comparison with 99mTc-antimony trisulfide colloid, both tracers discriminated the sentinel lymph node up to 50 min after administration; however

  6. Lymphatic Filariasis Transmission Risk Map of India, Based on a Geo-Environmental Risk Model

    PubMed Central

    Sabesan, Shanmugavelu; Raju, Konuganti Hari Kishan; Srivastava, Pradeep Kumar; Jambulingam, Purushothaman

    2013-01-01

    Abstract The strategy adopted by a global program to interrupt transmission of lymphatic filariasis (LF) is mass drug administration (MDA) using chemotherapy. India also followed this strategy by introducing MDA in the historically known endemic areas. All other areas, which remained unsurveyed, were presumed to be nonendemic and left without any intervention. Therefore, identification of LF transmission risk areas in the entire country has become essential so that they can be targeted for intervention. A geo-environmental risk model (GERM) developed earlier was used to create a filariasis transmission risk map for India. In this model, a Standardized Filariasis Transmission Risk Index (SFTRI, based on geo-environmental risk variables) was used as a predictor of transmission risk. The relationship between SFTRI and endemicity (historically known) of an area was quantified by logistic regression analysis. The quantified relationship was validated by assessing the filarial antigenemia status of children living in the unsurveyed areas through a ground truth study. A significant positive relationship was observed between SFTRI and the endemicity of an area. Overall, the model prediction of filarial endemic status of districts was found to be correct in 92.8% of the total observations. Thus, among the 190 districts hitherto unsurveyed, as many as 113 districts were predicted to be at risk, and the remaining at no risk. The GERM developed on geographic information system (GIS) platform is useful for LF spatial delimitation on a macrogeographic/regional scale. Furthermore, the risk map developed will be useful for the national LF elimination program by identifying areas at risk for intervention and for undertaking surveillance in no-risk areas. PMID:23808973

  7. Lymphatic mapping improves staging and reduces morbidity in women undergoing total mastectomy for breast carcinoma.

    PubMed

    Langer, Samantha; Guenther, J Michael; Haigh, Philip I; Difronzo, L Andrew

    2004-10-01

    Lymphatic mapping (LM) and sentinel lymph node biopsy (SLNB) have become widely accepted in the setting of breast conservation surgery. We hypothesized that LM can be extended to women undergoing total mastectomy, being technically feasible, yielding highly accurate and sensitive results, improving axillary staging, and reducing postoperative morbidity. Between 1995 and 2003, 99 women (mean age 59 years, range 34-87) underwent 100 mastectomies with LM using blue dye alone. Fifty-nine operations (60%) were followed by a completion axillary lymph node dissection (ALND). Ninety per cent of patients had invasive carcinoma; 10 per cent had in situ carcinoma. Mean tumor size was 2.5 cm (range 0.3-8 cm). One hundred fifty-nine sentinel nodes (SNs) (mean 1.65, range 1-5) were successfully identified in 96 (96%) axillae. Twenty-five (25%) sentinel nodes revealed nodal metastases. Five of 25 (20%) SNs had micrometasteses. Three patients had a false-negative SN, yielding a sensitivity of 91 per cent. The accuracy of LM was 97 per cent. No patient who underwent SLNB alone developed lymphedema, axillary seroma formation, infection, or restricted arm movement. This was contrasted with patients undergoing ALND, where 10 (16%) developed lymphedema and 2 (3%) developed an infection. Ten (25%) patients developed axillary paresthesias after SNB compared with 47 (78%) patients after ALND (P < 0.0001). LM in the setting of mastectomy is accurate and sensitive. This technique improves axillary staging and decreases morbidity. Patients who are not candidates for breast conservation should be offered LM and SLNB at the time of mastectomy.

  8. CAVEman: Standardized anatomical context for biomedical data mapping.

    PubMed

    Turinsky, Andrei L; Fanea, Elena; Trinh, Quang; Wat, Stephen; Hallgrímsson, Benedikt; Dong, Xiaoli; Shu, Xueling; Stromer, Julie N; Hill, Jonathan W; Edwards, Carol; Grosenick, Brenda; Yajima, Masumi; Sensen, Christoph W

    2008-01-01

    The authors have created a software system called the CAVEman, for the visual integration and exploration of heterogeneous anatomical and biomedical data. The CAVEman can be applied for both education and research tasks. The main component of the system is a three-dimensional digital atlas of the adult male human anatomy, structured according to the nomenclature of Terminologia Anatomica. The underlying data-indexing mechanism uses standard ontologies to map a range of biomedical data types onto the atlas. The CAVEman system is now used to visualize genetic processes in the context of the human anatomy and to facilitate visual exploration of the data. Through the use of Javatrade mark software, the atlas-based system is portable to virtually any computer environment, including personal computers and workstations. Existing Java tools for biomedical data analysis have been incorporated into the system. The affordability of virtual-reality installations has increased dramatically over the last several years. This creates new opportunities for educational scenarios that model important processes in a patient's body, including gene expression patterns, metabolic activity, the effects of interventions such as drug treatments, and eventually surgical simulations.

  9. Electro-Anatomical Four-Dimensional Mapping of Ventricular Tachycardia

    DTIC Science & Technology

    2007-11-02

    pulmonary vein (PV) region reported ulterior stenosis . Anatomic reconstruction by CT has helped understand the frequency of occurrence and effects of PV... stenosis [1]. Our group presented that the bi-atrial activation sequence became well understood when cardiac activity data and anatomic information...through the Aortic Valve, and of deploying the ICE catheter into the LV transseptally via the IVC, through the Fossa Ovalis and through the Mitral

  10. Lymphatic obstruction

    MedlinePlus

    ... certain directions based on the structure of the lymphatic system. This helps the lymph fluid drain through the ... always appropriate or effective. Alternative Names Lymphedema Images Lymphatic system Yellow nail syndrome References Feldman JL, Jackson KA, ...

  11. Lymphatic Diseases

    MedlinePlus

    The lymphatic system is a network of tissues and organs. It is made up of Lymph - a fluid that contains ... They are part of the system, too. The lymphatic system clears away infection and keeps your body fluids ...

  12. Anatomic mapping of molecular subtypes in diffuse glioma.

    PubMed

    Tang, Qisheng; Lian, Yuxi; Yu, Jinhua; Wang, Yuanyuan; Shi, Zhifeng; Chen, Liang

    2017-09-15

    Tumor location served as an important prognostic factor in glioma patients was considered to postulate molecular features according to cell origin theory. However, anatomic distribution of unique molecular subtypes was not widely investigated. The relationship between molecular phenotype and histological subgroup were also vague based on tumor location. Our group focuses on the study of glioma anatomic location of distinctive molecular subgroups and histology subtypes, and explores the possibility of their consistency based on clinical background. We retrospectively reviewed 143 cases with both molecular information (IDH1/TERT/1p19q) and MRI images diagnosed as cerebral diffuse gliomas. The anatomic distribution was analyzed between distinctive molecular subgroups and its relationship with histological subtypes. The influence of tumor location, molecular stratification and histology diagnosis on survival outcome was investigated as well. Anatomic locations of cerebral diffuse glioma indicate varied clinical outcome. Based on that, it can be stratified into five principal molecular subgroups according to IDH1/TERT/1p19q status. Triple-positive (IDH1 and TERT mutation with 1p19q codeletion) glioma tended to be oligodendroglioma present with much better clinical outcome compared to TERT mutation only group who is glioblastoma inclined (median overall survival 39 months VS 18 months). Five molecular subgroups were demonstrated with distinctive locational distribution. This kind of anatomic feature is consistent with its corresponding histological subtypes. Each molecular subgroup in glioma has unique anatomic location which indicates distinctive clinical outcome. Molecular diagnosis can be served as perfect complementary tool for the precise diagnosis. Integration of histomolecular diagnosis will be much more helpful in routine clinical practice in the future.

  13. CAVEman: Standardized Anatomical Context for Biomedical Data Mapping

    ERIC Educational Resources Information Center

    Turinsky, Andrei L.; Fanea, Elena; Trinh, Quang; Wat, Stephen; Hallgrimsson, Benedikt; Dong, Xiaoli; Shu, Xueling; Stromer, Julie N.; Hill, Jonathan W.; Edwards, Carol; Grosenick, Brenda; Yajima, Masumi; Sensen, Christoph W.

    2008-01-01

    The authors have created a software system called the CAVEman, for the visual integration and exploration of heterogeneous anatomical and biomedical data. The CAVEman can be applied for both education and research tasks. The main component of the system is a three-dimensional digital atlas of the adult male human anatomy, structured according to…

  14. CAVEman: Standardized Anatomical Context for Biomedical Data Mapping

    ERIC Educational Resources Information Center

    Turinsky, Andrei L.; Fanea, Elena; Trinh, Quang; Wat, Stephen; Hallgrimsson, Benedikt; Dong, Xiaoli; Shu, Xueling; Stromer, Julie N.; Hill, Jonathan W.; Edwards, Carol; Grosenick, Brenda; Yajima, Masumi; Sensen, Christoph W.

    2008-01-01

    The authors have created a software system called the CAVEman, for the visual integration and exploration of heterogeneous anatomical and biomedical data. The CAVEman can be applied for both education and research tasks. The main component of the system is a three-dimensional digital atlas of the adult male human anatomy, structured according to…

  15. Linking retinotopic fMRI mapping and anatomical probability maps of human occipital areas V1 and V2.

    PubMed

    Wohlschläger, A M; Specht, K; Lie, C; Mohlberg, H; Wohlschläger, A; Bente, K; Pietrzyk, U; Stöcker, T; Zilles, K; Amunts, K; Fink, G R

    2005-05-15

    Using functional MRI, we characterized field sign maps of the occipital cortex and created three-dimensional maps of these areas. By averaging the individual maps into group maps, probability maps of functionally defined V1 or V2 were determined and compared to anatomical probability maps of Brodmann areas BA17 and BA18 derived from cytoarchitectonic analysis (Amunts, K., Malikovic, A., Mohlberg, H., Schormann, T., Zilles, K., 2000. Brodmann's areas 17 and 18 brought into stereotaxic space-where and how variable? NeuroImage 11, 66-84). Comparison of areas BA17/V1 and BA18/V2 revealed good agreement of the anatomical and functional probability maps. Taking into account that our functional stimulation (due to constraints of the visual angle of stimulation achievable in the MR scanner) only identified parts of V1 and V2, for statistical evaluation of the spatial correlation of V1 and BA17, or V2 and BA18, respectively, the a priori measure kappa was calculated testing the hypothesis that a region can only be part of functionally defined V1 or V2 if it is also in anatomically defined BA17 or BA18, respectively. kappa = 1 means the hypothesis is fully true, kappa = 0 means functionally and anatomically defined visual areas are independent. When applying this measure to the probability maps, kappa was equal to 0.84 for both V1/BA17 and V2/BA18. The data thus show a good correspondence of functionally and anatomically derived segregations of early visual processing areas and serve as a basis for employing anatomical probability maps of V1 and V2 in group analyses to characterize functional activations of early visual processing areas.

  16. Quantifying filariasis and malaria control activities in relation to lymphatic filariasis elimination: a multiple intervention score map (MISM) for Malawi.

    PubMed

    Stanton, Michelle C; Mkwanda, Square; Mzilahowa, Themba; Bockarie, Moses J; Kelly-Hope, Louise A

    2014-02-01

    To quantify the geographical extent of filariasis and malaria control interventions impacting lymphatic filariasis (LF) in Malawi and to produce a multiple intervention score map (MISM) for prioritising surveillance and intervention strategies. Interventions included mass drug administration (MDA) for LF and onchocerciasis, and bed nets and indoor residual spraying (IRS) for malaria. District and subdistrict-level data were obtained from the Ministry of Health in Malawi, the Demographic and Health Survey (DHS) and President's Malaria Initiative reports. Single intervention scores were calculated for each variable based on population coverage thresholds, and these were combined in a weighted sum to form a multiple intervention score, which was then used to produce maps, that is MISMs. Districts were further classified into four groups based on the combination of their baseline LF prevalence and multiple intervention score. The district- and subdistrict-level MISMs highlighted specific areas that have received high and low coverage of LF-impacting interventions. High coverage areas included the LF-onchocerciasis endemic areas in the southern region of the country and areas along the shores of Lake Malawi, where malaria vector control had been prioritised. Three districts with high baseline LF prevalence measures but low coverage of multiple interventions were identified and considered to be most at risk of ongoing transmission or re-emergence. These maps and district classifications will be used by LF programme managers to identify and target high-risk areas that may not have received adequate LF-impacting interventions to interrupt the transmission of the disease.

  17. lyve1 expression reveals novel lymphatic vessels and new mechanisms for lymphatic vessel development in zebrafish.

    PubMed

    Okuda, Kazuhide S; Astin, Jonathan W; Misa, June P; Flores, Maria V; Crosier, Kathryn E; Crosier, Philip S

    2012-07-01

    We have generated novel transgenic lines that brightly mark the lymphatic system of zebrafish using the lyve1 promoter. Facilitated by these new transgenic lines, we generated a map of zebrafish lymphatic development up to 15 days post-fertilisation and discovered three previously uncharacterised lymphatic vessel networks: the facial lymphatics, the lateral lymphatics and the intestinal lymphatics. We show that a facial lymphatic vessel, termed the lateral facial lymphatic, develops through a novel developmental mechanism, which initially involves vessel growth through a single vascular sprout followed by the recruitment of lymphangioblasts to the vascular tip. Unlike the lymphangioblasts that form the thoracic duct, the lymphangioblasts that contribute to the lateral facial lymphatic vessel originate from a number of different blood vessels. Our work highlights the additional complexity of lymphatic vessel development in the zebrafish that may increase its versatility as a model of lymphangiogenesis.

  18. Anatomical mapping for atrial fibrillation ablation: a head-to-head comparison of ultrasound-assisted reconstruction versus fast anatomical mapping.

    PubMed

    Rordorf, Roberto; Chieffo, Enrico; Savastano, Simone; Vicentini, Alessandro; Petracci, Barbara; De Regibus, Valentina; Valentini, Adele; Klersy, Catherine; Dore, Roberto; Landolina, Maurizio

    2015-02-01

    Accuracy in left atrial (LA) anatomical reconstruction is crucial to the safe and effective performance of catheter ablation of atrial fibrillation (AF). The aim of this study was to evaluate the accuracy of LA reconstruction performed with intracardiac echocardiography (ICE) as compared to fast anatomical mapping (FAM) both integrated in the CARTO mapping system (Biosense Webster, Diamond Bar, CA, USA). A multislice computed tomography (MSCT) was preacquired from 29 patients with AF who underwent catheter ablation and 3D-LA geometry was reconstructed using both ICE and FAM separately. The accuracy of the LA anatomical definition was evaluated by comparing LA volumes, LA and pulmonary vein (PV) diameters obtained using ICE and FAM versus MSCT (gold standard). Anterior-posterior and superior-inferior LA diameters were shorter in ICE versus MSCT (32 ± 10 vs 46 ± 9 mm and 48 ± 7 vs 53 ± 7 mm, P < 0.01) but similar in FAM versus MSCT (45 ± 9 vs 46 ± 9 mm and 52 ± 10 vs 53 ± 7 mm). Latero-septal LA diameter was similar in ICE versus MSCT (63 ± 11 vs 63 ± 9 mm) but larger in FAM versus MSCT (69 ± 9 vs 63 ± 9 mm, P < 0.001). LA volume was lower in ICE versus MSCT (73 ± 30 mL vs 116 ± 45 mL, P < 0.0001) and slightly larger in FAM versus MSCT (132 ± 45 vs 116 ± 45 mL, P = 0.06). PV diameters were similar in FAM versus MSCT but significantly underestimated with ICE. Overall accuracy in the LA and PV anatomical reconstruction was found to be superior with FAM compared to ICE-guided approach. ICE resulted in a significant underestimate of both LA and PV dimensions, while FAM slightly overestimated LA geometry. © 2014 Wiley Periodicals, Inc.

  19. Molecular Xenomonitoring Using Mosquitoes to Map Lymphatic Filariasis after Mass Drug Administration in American Samoa

    PubMed Central

    Schmaedick, Mark A.; Koppel, Amanda L.; Pilotte, Nils; Torres, Melissa; Williams, Steven A.; Dobson, Stephen L.; Lammie, Patrick J.; Won, Kimberly Y.

    2014-01-01

    Background Mass drug administration (MDA) programs have dramatically reduced lymphatic filariasis (LF) incidence in many areas around the globe, including American Samoa. As infection rates decline and MDA programs end, efficient and sensitive methods for detecting infections are needed to monitor for recrudescence. Molecular methods, collectively termed ‘molecular xenomonitoring,’ can identify parasite DNA or RNA in human blood-feeding mosquitoes. We tested mosquitoes trapped throughout the inhabited islands of American Samoa to identify areas of possible continuing LF transmission after completion of MDA. Methodology/Principle Findings Mosquitoes were collected using BG Sentinel traps from most of the villages on American Samoa's largest island, Tutuila, and all major villages on the smaller islands of Aunu'u, Ofu, Olosega, and Ta'u. Real-time PCR was used to detect Wuchereria bancrofti DNA in pools of ≤20 mosquitoes, and PoolScreen software was used to infer territory-wide prevalences of W. bancrofti DNA in the mosquitoes. Wuchereria bancrofti DNA was found in mosquitoes from 16 out of the 27 village areas sampled on Tutuila and Aunu'u islands but none of the five villages on the Manu'a islands of Ofu, Olosega, and Ta'u. The overall 95% confidence interval estimate for W. bancrofti DNA prevalence in the LF vector Ae. polynesiensis was 0.20–0.39%, and parasite DNA was also detected in pools of Culex quinquefasciatus, Aedes aegypti, and Aedes (Finlaya) spp. Conclusions/Significance Our results suggest low but widespread prevalence of LF on Tutuila and Aunu'u where 98% of the population resides, but not Ofu, Olosega, and Ta'u islands. Molecular xenomonitoring can help identify areas of possible LF transmission, but its use in the LF elimination program in American Samoa is limited by the need for more efficient mosquito collection methods and a better understanding of the relationship between prevalence of W. bancrofti DNA in mosquitoes and infection and

  20. Pulmonary lymph node charting in normal dogs with blue dye and scintigraphic lymphatic mapping.

    PubMed

    Tuohy, Joanne L; Worley, Deanna R

    2014-08-01

    The prognosis of dogs with primary lung tumors and lymph node metastasis is poorer than of dogs without metastasis. Biopsy of intrathoracic lymph nodes is recommended, but without specific guidelines. This study investigated incorporation of a human lymph node classification in normal dogs with intercostal thoracotomies. Methylene blue and technetium-99m sulfur colloid lobar injections were used for enhanced nodal identification. Descriptive comparisons were made for lymph node resections utilizing both veterinary and human anatomic lymph node charts. Amedian of 2 (range 1–4) lymph nodes were removed per hemithorax in vivo versus a median 6.5 (range 2–8) lymph nodes removed ex vivo from each hemithorax following in vivo dissections. Incorporation of a human thoracic lymph node classification system may be useful for future clinical application in dogs. Future use of either methylene blue or technetium for canine thoracic lymphadenectomy needs to be evaluated further.

  1. Intra-Operative Lymphatic Mapping and Sentinel Node Biopsy in Laryngeal Carcinoma: Preliminary Results

    PubMed Central

    Khadivi, Ehsan; Daghighi, Maryam; Khazaeni, Kamran; Dabbagh Kakhki, Vahid Reza; Zarifmahmoudi, Leili; Sadeghi, Ramin

    2015-01-01

    Introduction: Sentinel node mapping has been used for laryngeal carcinoma in several studies, with excellent results thus far. In the current study, we report our preliminary results on sentinel node mapping in laryngeal carcinoma using intra-operative peri-tumoral injection of a radiotracer. Materials and Methods: Patients with biopsy-proven squamous cell carcinoma of the larynx were included in the study. Two mCi/0.4 cc Tc-99m-phytate in four aliquots was injected on the day of surgery, after induction of anesthesia, in the sub-mucosal peri-tumoral location using a suspension laryngoscopy. After waiting for 10 minutes, a portable gamma probe was used to search for sentinel nodes. All patients underwent laryngectomy and modified radical bilateral neck dissection. All sentinel nodes and removed non-sentinel nodes were examined by hematoxylin and eosin (H&E) staining. Results: Ten patients with laryngeal carcinoma were included. At least one sentinel node could be detected in five patients (bilateral nodes in four patients). One patient had pathologically involved sentinel and non-sentinel nodes (no false-negative cases). Conclusion: Sentinel node mapping in laryngeal carcinoma is technically feasible using an intra-operative radiotracer injection. In order to evaluate the relationship of T-stage and the laterality of the tumor with accuracy, larger studies are needed. PMID:26788477

  2. Mapping, Bayesian Geostatistical Analysis and Spatial Prediction of Lymphatic Filariasis Prevalence in Africa

    PubMed Central

    Slater, Hannah; Michael, Edwin

    2013-01-01

    There is increasing interest to control or eradicate the major neglected tropical diseases. Accurate modelling of the geographic distributions of parasitic infections will be crucial to this endeavour. We used 664 community level infection prevalence data collated from the published literature in conjunction with eight environmental variables, altitude and population density, and a multivariate Bayesian generalized linear spatial model that allows explicit accounting for spatial autocorrelation and incorporation of uncertainty in input data and model parameters, to construct the first spatially-explicit map describing LF prevalence distribution in Africa. We also ran the best-fit model against predictions made by the HADCM3 and CCCMA climate models for 2050 to predict the likely distributions of LF under future climate and population changes. We show that LF prevalence is strongly influenced by spatial autocorrelation between locations but is only weakly associated with environmental covariates. Infection prevalence, however, is found to be related to variations in population density. All associations with key environmental/demographic variables appear to be complex and non-linear. LF prevalence is predicted to be highly heterogenous across Africa, with high prevalences (>20%) estimated to occur primarily along coastal West and East Africa, and lowest prevalences predicted for the central part of the continent. Error maps, however, indicate a need for further surveys to overcome problems with data scarcity in the latter and other regions. Analysis of future changes in prevalence indicates that population growth rather than climate change per se will represent the dominant factor in the predicted increase/decrease and spread of LF on the continent. We indicate that these results could play an important role in aiding the development of strategies that are best able to achieve the goals of parasite elimination locally and globally in a manner that may also account

  3. Mapping, bayesian geostatistical analysis and spatial prediction of lymphatic filariasis prevalence in Africa.

    PubMed

    Slater, Hannah; Michael, Edwin

    2013-01-01

    There is increasing interest to control or eradicate the major neglected tropical diseases. Accurate modelling of the geographic distributions of parasitic infections will be crucial to this endeavour. We used 664 community level infection prevalence data collated from the published literature in conjunction with eight environmental variables, altitude and population density, and a multivariate Bayesian generalized linear spatial model that allows explicit accounting for spatial autocorrelation and incorporation of uncertainty in input data and model parameters, to construct the first spatially-explicit map describing LF prevalence distribution in Africa. We also ran the best-fit model against predictions made by the HADCM3 and CCCMA climate models for 2050 to predict the likely distributions of LF under future climate and population changes. We show that LF prevalence is strongly influenced by spatial autocorrelation between locations but is only weakly associated with environmental covariates. Infection prevalence, however, is found to be related to variations in population density. All associations with key environmental/demographic variables appear to be complex and non-linear. LF prevalence is predicted to be highly heterogenous across Africa, with high prevalences (>20%) estimated to occur primarily along coastal West and East Africa, and lowest prevalences predicted for the central part of the continent. Error maps, however, indicate a need for further surveys to overcome problems with data scarcity in the latter and other regions. Analysis of future changes in prevalence indicates that population growth rather than climate change per se will represent the dominant factor in the predicted increase/decrease and spread of LF on the continent. We indicate that these results could play an important role in aiding the development of strategies that are best able to achieve the goals of parasite elimination locally and globally in a manner that may also account

  4. Secondary Mapping of Lymphatic Filariasis in Haiti-Definition of Transmission Foci in Low-Prevalence Settings

    PubMed Central

    Drexler, Naomi; Washington, Charles H.; Lovegrove, Maribeth; Grady, Caroline; Milord, Marie Denise; Streit, Thomas; Lammie, Patrick

    2012-01-01

    To eliminate Lymphatic filariasis (LF) as a public health problem, the World Health Organization (WHO) recommends that any area with infection prevalence greater than or equal to 1% (denoted by presence of microfilaremia or antigenemia) should receive mass drug administration (MDA) of antifilarial drugs for at least five consecutive rounds. Areas of low-antigen prevalence (<1%) are thought to pose little risk for continued transmission of LF. Five low-antigen prevalence communes in Haiti, characterized as part of a national survey, were further assessed for transmission in this study. An initial evaluation of schoolchildren was performed in each commune to identify antigen-positive children who served as index cases for subsequent community surveys conducted among households neighboring the index cases. Global positioning system (GPS) coordinates and immunochromatographic tests (ICT) for filarial antigenemia were collected on approximately 1,600 persons of all ages in the five communes. The relationship between antigen-positive cases in the community and distance from index cases was evaluated using multivariate regression techniques and analyses of spatial clustering. Community surveys demonstrated higher antigen prevalence in three of the five communes than was observed in the original mapping survey; autochthonous cases were found in the same three communes. Regression techniques identified a significantly increased likelihood of being antigen-positive when living within 20 meters of index cases when controlling for age, gender, and commune. Spatial clustering of antigen-positive cases was observed in some, but not all communes. Our results suggest that localized transmission was present even in low-prevalence settings and suggest that better surveillance methods may be needed to detect microfoci of LF transmission. PMID:23071849

  5. A Channelized Hotelling Observer Study of Lesion Detection in SPECT MAP Reconstruction Using Anatomical Priors

    PubMed Central

    Kulkarni, S.; Khurd, P.; Hsiao, I.; Zhou, L.; Gindi, G.

    2010-01-01

    In emission tomography, anatomical side information, in the form of organ and lesion boundaries, derived from intra-patient coregistered CT or MR scans can be incorporated into the reconstruction. Our interest is in exploring the efficacy of such side information for lesion detectability. To assess detectability we used the SNR of a channelized Hotelling observer and a signal-known exactly/background known exactly detection task. In simulation studies we incorporated anatomical side information into a SPECT MAP (maximum a posteriori) reconstruction by smoothing within but not across organ or lesion boundaries. A non-anatomical prior was applied by uniform smoothing across the entire image. We investigated whether the use of anatomical priors with organ boundaries alone or with perfect lesion boundaries alone would change lesion detectability relative to the case of a prior with no anatomical information. Furthermore, we investigated whether any such detectability changes for the organ-boundary case would be a function of the distance of the lesion to the organ boundary. We also investigated whether any detectability changes for the lesion-boundary case would be a function of the degree of proximity, i.e. a difference in the radius of the true functional lesion and the radius of the anatomical lesion boundary. Our results showed almost no detectability difference with vs without organ boundaries at any lesion-to-organ boundary distance. Our results also showed no difference in lesion detectability with and without lesion boundaries, and no variation of lesion detectability with degree of proximity. PMID:17664562

  6. Anatomical mapping of the nasal muscles and application to cosmetic surgery.

    PubMed

    Konschake, Marko; Fritsch, Helga

    2014-11-01

    We present an anatomical mapping of the most important muscles influencing the nose, incorporating constant anatomical structures, and their spatial correlations. At our disposal were the midfaces of 18 bodies of both sexes, obtained by informed consent from body donors aged between 60 and 80 years. Macroscopically, we dissected the nasal regions of eight corpses, six midfaces were prepared according to plastination histology, four by creating plastinated slices. On their way from their periosteal origin to the edge of the skin, the muscles of the nose cross the subcutaneous adipose tissue, dividing it into superficial and deep layers. The individual muscle fibers insert into the skin directly at the reticular corium. Sometimes, they reach the border of the epidermis which represents a special arrangement of corial muscle attachments. The course of the anatomical fibers of individual nasal muscles presented macroscopically and microscopically in this study offers surgeons a detailed overview of the anatomically important muscular landmarks of the midface. © 2014 Wiley Periodicals, Inc.

  7. Response Properties of Human Amygdala Subregions: Evidence Based on Functional MRI Combined with Probabilistic Anatomical Maps

    PubMed Central

    Rahm, Benjamin; Eickhoff, Simon B.; Schulze-Bonhage, Andreas; Speck, Oliver

    2007-01-01

    The human amygdala is thought to play a pivotal role in the processing of emotionally significant sensory information. The major subdivisions of the human amygdala—the laterobasal group (LB), the superficial group (SF), and the centromedial group (CM)—have been anatomically delineated, but the functional response properties of these amygdala subregions in humans are still unclear. We combined functional MRI with cyto-architectonically defined probabilistic maps to analyze the response characteristics of amygdala subregions in subjects presented with auditory stimuli. We found positive auditory stimulation-related signal changes predominantly in probabilistically defined LB, and negative responses predominantly in SF and CM. In the left amygdala, mean response magnitude in the core area of LB with 90–100% assignment probability was significantly larger than in the core areas of SF and CM. These differences were observed for pleasant and unpleasant stimuli. Our findings reveal that the probabilistically defined anatomical subregions of the human amygdala show distinctive fMRI response patterns. The stronger auditory responses in LB as compared with SF and CM may reflect a predominance of auditory inputs to human LB, similar to many animal species in which the majority of sensory, including auditory, afferents project to this subdivision of the amygdala. Our study indicates that the intrinsic functional differentiation of the human amygdala may be probed using fMRI combined with probabilistic anatomical maps. PMID:17375193

  8. Lymphatic filariasis.

    PubMed

    2008-02-01

    (1) Lymphatic filariasis is a set of parasitic diseases that are endemic in tropical and subtropical regions and can be disabling in the long term. (2) The standard antiparasitic drug for adults is oral diethylcarbamazine. Ivermectin is an alternative, especially for patients with intercurrent onchocercosis or loasis.

  9. Social deprivation index and lymphatic filariasis: a tool for mapping urban areas at risk in northeastern Brazil.

    PubMed

    Bonfim, Cristine; Aguiar-Santos, Ana Maria; Pedroza, Dinilson; Costa, Tadeu Rodrigues; Portugal, José Luiz; Oliveira, Conceição; Medeiros, Zulma

    2009-09-01

    This paper describes the construction and application of a social deprivation index that was created to explore the relationship between lymphatic filariasis and socioenvironmental variables in the municipality of Jaboatão dos Guararapes, Pernambuco, Brazil, thereby contributing towards identifying priority areas for interventions. This indicator was obtained from principal-component factor analysis. Variables available from the national census representing socioenvironmental conditions, household characteristics and urban services were used. Epidemiological data came from a parasitological survey on lymphatic filariasis. 23 673 individuals were examined and 323 were positive (1.4%). Two factors that together explained 80.61% of the total variance were selected. The social deprivation strata were capable of indicating a risk gradient, with 74.9% of the microfilaremia cases situated in the high-risk stratum. Principal-component factor analysis was shown to be sensitive for selecting indicators associated with the risk of lymphatic filariasis transmission and for detecting areas potentially at risk. The capacity of the social deprivation index for picking up social inequalities qualifies it as a new tool for use in planning interventions aimed at controlling lymphatic filariasis in urban spaces.

  10. Lymphatic filariasis mapping by Immunochromatographic Test cards and baseline microfilaria survey prior to mass drug administration in Sierra Leone

    PubMed Central

    2012-01-01

    Background National mapping of lymphatic filariasis (LF) was conducted using Immunochromatographic tests (ICT) in 2005 to determine endemicity and geographic spread of the disease. A baseline microfilaria survey was then conducted to determine LF prevalence and microfilaria intensity. Methods In 2005 1,982 persons of 15 years and over from 14 health districts were selected and fingertip blood samples were tested with ICT cards. In 2007-8 blood samples were taken between 10 p.m. and 2 a.m. and examined for microfilaria (mf) from 9,288 persons from 16 sentinel sites representing each district and 2 additional sites for districts with populations over 500,000 (Bo and Kenema). Results The overall LF prevalence by ICT cards was 21% (males 28%, females 15%). All districts had a prevalence of Wuchereria bancrofti antigen > 1%. Distribution of LF prevalence showed a strong spatial correlation pattern with high prevalence in a large area in the northeast gradually decreasing to a relatively low prevalence in the southwest coast. High prevalence was found in the northeast, Bombali (52%), Koinadugu (46%), Tonkolili (37%) and Kono (30%). Low prevalence was found in the southwest, Bonthe (3%) and Pujehun (4%). The mf prevalence was higher in the northeast: Bombali, 6.7%, Koinadugu 5.7%, Port Loko 4.4% and Kono 2.4%. Overall there was a significant difference in mf prevalence by gender: males 2.9%, females 1.8% (p = 0.0002) and within districts in Kailahun, Kono, Port Loko, Moyamba and Koinadugu (all p < 0.05). The mf prevalence was higher in people > 20 years (2.5%) than in people ≤ 20 years (1.7%) (p = 0.043). The overall arithmetic mean mf density was 50.30 mf/ml among mf-positive individuals and 1.19 mf/ml in the population examined which varied significantly between districts. Conclusions The ICT results showed that LF was endemic nationwide and that preventive chemotherapy (PCT) was justified across the country. Both the ICT and microfilaraemia surveys found that

  11. Lymphatic Imaging: Focus on Imaging Probes

    PubMed Central

    Niu, Gang; Chen, Xiaoyuan

    2015-01-01

    In view of the importance of sentinel lymph nodes (SLNs) in tumor staging and patient management, sensitive and accurate imaging of SLNs has been intensively explored. Along with the advance of the imaging technology, various contrast agents have been developed for lymphatic imaging. In this review, the lymph node imaging agents were summarized into three groups: tumor targeting agents, lymphatic targeting agents and lymphatic mapping agents. Tumor targeting agents are used to detect metastatic tumor tissue within LNs, lymphatic targeting agents aim to visualize lymphatic vessels and lymphangionesis, while lymphatic mapping agents are mainly for SLN detection during surgery after local administration. Coupled with various signal emitters, these imaging agents work with single or multiple imaging modalities to provide a valuable way to evaluate the location and metastatic status of SLNs. PMID:25897334

  12. Preclinical Lymphatic Imaging

    PubMed Central

    Zhang, Fan; Niu, Gang; Lu, Guangming; Chen, Xiaoyuan

    2011-01-01

    Non-invasive in vivo imaging of lymphatic vessels and lymphatic nodes is expected to fulfill the purpose of analyzing lymphatic vessels and their function, understanding molecular mechanisms of lymphangiogenesis and lymphatic spread of tumors, and utilizing lymphatic molecular markers as a prognostic or diagnostic indicator. In this review, we provide a comprehensive summary of in vivo imaging modalities for detecting lymphatic vessels, lymphatic drainage, lymphatic nodes, which include conventional lymphatic imaging techniques such as dyes and radionuclide scintigraphy as well as novel techniques for lymphatic imaging such as optical imaging, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, positron emission tomography (PET) using lymphatic biomarkers, photoacoustic imaging and combinations of multiple modalities. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve the research of lymphatic vascular system in health and disease states as well as to improve the accuracy of diagnosis in the relevant diseases. PMID:20862613

  13. Brain mapping in stereotactic surgery: a brief overview from the probabilistic targeting to the patient-based anatomic mapping.

    PubMed

    Lemaire, Jean-Jacques; Coste, Jérôme; Ouchchane, Lemlih; Caire, François; Nuti, Christophe; Derost, Philippe; Cristini, Vittorio; Gabrillargues, Jean; Hemm, Simone; Durif, Franck; Chazal, Jean

    2007-01-01

    In this article, we briefly review the concept of brain mapping in stereotactic surgery taking into account recent advances in stereotactic imaging. The gold standard continues to rely on probabilistic and indirect targeting, relative to a stereotactic reference, i.e., mostly the anterior (AC) and the posterior (PC) commissures. The theoretical position of a target defined on an atlas is transposed into the stereotactic space of a patient's brain; final positioning depends on electrophysiological analysis. The method is also used to analyze final electrode or lesion position for a patient or group of patients, by projection on an atlas. Limitations are precision of definition of the AC-PC line, probabilistic location and reliability of the electrophysiological guidance. Advances in MR imaging, as from 1.5-T machines, make stereotactic references no longer mandatory and allow an anatomic mapping based on an individual patient's brain. Direct targeting is enabled by high-quality images, an advanced anatomic knowledge and dedicated surgical software. Labeling associated with manual segmentation can help for the position analysis along non-conventional, interpolated planes. Analysis of final electrode or lesion position, for a patient or group of patients, could benefit from the concept of membership, the attribution of a weighted membership degree to a contact or a structure according to its level of involvement. In the future, more powerful MRI machines, diffusion tensor imaging, tractography and computational modeling will further the understanding of anatomy and deep brain stimulation effects.

  14. Lymphatic Education & Research Network

    MedlinePlus

    Lymphatic Education & Research Network Donate Now Become a Supporting Member X Living with LYMPHEDEMA AND Lymphatic Disease FAQs About ... 261 Madison Avenue, New York, NY 10016 | Lymphatic Education & Research Network is a 501(c)(3) under ...

  15. Lymphatic Anomalies Registry

    ClinicalTrials.gov

    2016-07-26

    Lymphatic Malformation; Generalized Lymphatic Anomaly (GLA); Central Conducting Lymphatic Anomaly; CLOVES Syndrome; Gorham-Stout Disease ("Disappearing Bone Disease"); Blue Rubber Bleb Nevus Syndrome; Kaposiform Lymphangiomatosis; Kaposiform Hemangioendothelioma/Tufted Angioma; Klippel-Trenaunay Syndrome; Lymphangiomatosis

  16. “Triple injection” lymphatic mapping technique to determine if parametrial nodes are the true sentinel lymph nodes in women with cervical cancer

    PubMed Central

    Frumovitz, Michael; Euscher, Elizabeth D.; Deavers, Michael T.; Soliman, Pamela T.; Schmeler, Kathleen M.; Ramirez, Pedro T.; Levenback, Charles F.

    2014-01-01

    Objectives Lymphatic mapping studies in women with cervical cancer typically identify sentinel nodes (SLNs) in the pelvis and not the parametrium. We added India ink as a mapping agent to determine whether this would allow us to pathologically identify sentinel parametrial nodes and to test our hypothesis that the parametrial nodes are the true SLNs in women with cervical cancer. Methods We performed lymphatic mapping and SLN biopsy in 20 women with early-stage cervical cancer undergoing radical hysterectomy or trachelectomy using a “triple injection” technique with blue dye, radiocolloid, and India ink. Pathologic processing of parametrium and nodal tissue was then performed to identify India ink in specimens. Results On pathology review, 15 (75%) patients had a parametrial node identified, and 9 patients (45%) had bilateral parametrial nodes identified; the median number of parametrial nodes identified was 2 (range, 0-7). India ink was seen in at least 1 parametrial node in 13 (87%) of the 15 patients with a parametrial node identified pathologically. Of the 9 patients with bilateral parametrial nodes identified pathologically, only 5 (54%) had bilateral parametrial nodes containing India ink. India ink was found in 26 (44%) of 59 SLNs and only 1 (0.3%) of 289 non-SLNs. In 5 patients, India ink was seen in a SLN on the same side of the pelvis where a parametrial node was identified but not microscopically black. Conclusions There appears to be direct drainage of cervical lesions to pelvic nodal basins bypassing small parametrial nodes. Parametrial nodes, therefore, may not always be the SLNs in women with cervical cancer. PMID:22910691

  17. An anatomical basis for visual calibration of the auditory space map in the barn owl's midbrain.

    PubMed

    Feldman, D E; Knudsen, E I

    1997-09-01

    The map of auditory space in the external nucleus of the inferior colliculus (ICX) of the barn owl is calibrated by visual experience during development. ICX neurons are tuned for interaural time difference (ITD), the owl's primary cue for sound source azimuth, and are arranged into a map of ITD. When vision is altered by rearing owls with prismatic spectacles that shift the visual field in azimuth, ITD tuning in the ICX shifts adaptively. In contrast, ITD tuning remains unchanged in the lateral shell of the central nucleus of the inferior colliculus (ICCls), which provides the principal auditory input to the ICX, suggesting that the projection from the ICCls to the ICX is altered by prism-rearing. In this study, the topography of the ICCls-ICX projection was assessed in normal and prism-reared owls by retrograde labeling using biotinylated dextran amine. In juvenile owls at the age before prism attachment, and in normal adults, labeling patterns were consistent with a topographic projection, with each ICX site receiving input from a restricted region of the ICCls with similar ITD tuning. In prism-reared owls, labeling patterns were systematically altered: each ICX site received additional, abnormal input from a region of the ICCls where ITD tuning matched the shifted ITD tuning of the ICX neurons. These results indicate that anatomical reorganization of the ICCls-ICX projection contributes to the visual calibration of the ICX auditory space map.

  18. Phantom-based investigation of nonrigid registration constraints in mapping fMRI to anatomical MRI

    NASA Astrophysics Data System (ADS)

    Studholme, Colin; Constable, R. Todd; Duncan, James S.

    2000-06-01

    In previous work we have introduced an approach to improving the registration of EPI fMRI data with anatomical MRI by accounting for differences in magnetic field induced geometric distortion in the two types of MRI acquisition. In particular we began to explore the use of imaging physics based constraints in a non-rigid multi-modality registration algorithm. In this paper we present phantom based experimental work examining the behavior of different non-rigid registration constraints compared to a field map acquisition of the MRI distortion. This acquisition provides a pixel by pixel 'ground truth' estimate of the displacement field within the EPI data. In our registration based approach we employ a B-spline based estimate of the relative geometric distortion with a multi-grid optimization scheme. We maximize the normalized mutual information between the two types of MRI scans to estimate the B-Spline parameters. Using the field map estimates as a gold standard, registration estimates using no additional geometric constraints are compared to those using the spin echo based signal conservation. We also examine the use of logarithmic EPI values in the criteria to provide additional sensitivity in areas of low signal. Results indicate that registration of EPI to conventional MRI incorporating a spin echo distortion model can provide comparable estimates of geometric distortion to those from field mapping data without the need for significant additional acquisitions during each fMRI sequence.

  19. Lymphatic imaging in unsedated infants and children

    NASA Astrophysics Data System (ADS)

    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.

  20. Anatomical connectivity mapping: a new tool to assess brain disconnection in Alzheimer's disease.

    PubMed

    Bozzali, Marco; Parker, Geoffrey J M; Serra, Laura; Embleton, Karl; Gili, Tommaso; Perri, Roberta; Caltagirone, Carlo; Cercignani, Mara

    2011-02-01

    Previous studies suggest that the clinical manifestations of Alzheimer's disease (AD) are not only associated with regional gray matter damage but also with abnormal functional integration of different brain regions by disconnection mechanisms. A measure of anatomical connectivity (anatomical connectivity mapping or ACM) can be obtained by initiating diffusion tractography streamlines from all parenchymal voxels and then counting the number of streamlines passing through each voxel of the brain. In order to assess the potential of this parameter for the study of disconnection in AD, we computed it in a group of patients with AD (N=9), in 16 patients with amnestic mild cognitive impairment (a-MCI, which is considered the prodromal stage of AD) and in 12 healthy volunteers. All subjects had an MRI scan at 3T, and diffusion MRI data were analyzed to obtain fractional anisotropy (FA) and ACM. Two types of ACM maps, absolute count (ac-ACM) and normalized by brain size count (nc-ACM), were obtained. No between group differences in FA surviving correction for multiple comparison were found, while areas of both decreased (in the supramarginal gyrus) and increased (in the putamen) ACM were found in patients with AD. Similar results were obtained with ac-ACM and nc-ACM. ACM of the supramarginal gyrus was strongly associated with measures of short-term memory in healthy subjects. This study shows that ACM provides information that is complementary to that offered by FA and appears to be more sensitive than FA to brain changes in patients with AD. The increased ACM in the putamen was unexpected. Given the nature of ACM, an increase of this parameter may reflect a change in any of the areas connected to it. One intriguing possibility is that this increase of ACM in AD patients might reflect processes of brain plasticity driven by cholinesterase inhibitors.

  1. Towards optical spectroscopic anatomical mapping (OSAM) for lesion validation in cardiac tissue (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Singh-Moon, Rajinder P.; Zaryab, Mohammad; Hendon, Christine P.

    2017-02-01

    Electroanatomical mapping (EAM) is an invaluable tool for guiding cardiac radiofrequency ablation (RFA) therapy. The principle roles of EAM is the identification of candidate ablation sites by detecting regions of abnormal electrogram activity and lesion validation subsequent to RF energy delivery. However, incomplete lesions may present interim electrical inactivity similar to effective treatment in the acute setting, despite efforts to reveal them with pacing or drugs, such as adenosine. Studies report that the misidentification and recovery of such lesions is a leading cause of arrhythmia recurrence and repeat procedures. In previous work, we demonstrated spectroscopic characterization of cardiac tissues using a fiber optic-integrated RF ablation catheter. In this work, we introduce OSAM (optical spectroscopic anatomical mapping), the application of this spectroscopic technique to obtain 2-dimensional biodistribution maps. We demonstrate its diagnostic potential as an auxiliary method for lesion validation in treated swine preparations. Endocardial lesion sets were created on fresh swine cardiac samples using a commercial RFA system. An optically-integrated catheter console fabricated in-house was used for measurement of tissue optical spectra between 600-1000nm. Three dimensional, Spatio-spectral datasets were generated by raster scanning of the optical catheter across the treated sample surface in the presence of whole blood. Tissue optical parameters were recovered at each spatial position using an inverse Monte Carlo method. OSAM biodistribution maps showed stark correspondence with gross examination of tetrazolium chloride stained tissue specimens. Specifically, we demonstrate the ability of OSAM to readily distinguish between shallow and deeper lesions, a limitation faced by current EAM techniques. These results showcase the OSAMs potential for lesion validation strategies for the treatment of cardiac arrhythmias.

  2. Sentinel lymph node biopsy for melanoma: is there a correlation of preoperative lymphatic mapping with sentinel lymph nodes harvested?

    PubMed

    Hudak, Kristen Ann; Hudak, Kevin E; Dzwierzynski, William W

    2015-04-01

    Nodal status is the most significant prognostic factor in melanoma. No study has examined the relationship between lymphoscintigraphy, γ probe counts, harvested nodes, and nodal status. Two-hundred sixty two patients were identified who underwent sentinel lymph node biopsy for melanoma between 2001 and 2010. Clinicopathologic and treatment information was collected. The number of lymph nodes and basins demonstrated on lymphoscintigraphy was compared to those at surgery. γ Probe counts were compared. Median age was 54.5 years (range, 18-90 years) with 52.3% male. Average Breslow depth was 2.0 (1.9) mm; 99.6% of lymphoscintigraphy studies identified at least 1 basin, 80% showed only 1 (range, 0-4). Lymphoscintigraphy identified on average 1.5 (0.9) sentinel nodes and 31% with secondary node. Surgery excised on average 2.6 (1.4) nodes involving 1.2 (0.5) basins; 17.6% had a positive sentinel lymph node. There was no difference in the sum or average of γ counts between positive and negative sentinel lymph node groups (P = 0.2, P = 0.5). When comparing lymphoscintigraphy and surgical excision, the correlation of lymphatic basins was r = 0.67 and of lymph node numbers was r = 0.33. Lymphoscintigraphy should be used to identify the proper lymphatic basins for a sentinel node procedure, however, the removal of nodes must continue until the background count is less than 10%. The correlation of lymph node number identified on lymphoscintigraphy to surgical excision is weak. γ Probe counts cannot be used to differentiate positive from negative nodes and the positive lymph node is not always the hottest node.

  3. Combining Anatomical Manifold Information via Diffeomorphic Metric Mappings for Studying Cortical Thinning of the Cingulate Gyrus in Schizophrenia

    PubMed Central

    Qiu, Anqi; Younes, Laurent; Wang, Lei; Ratnanather, J. Tilak; Gillepsie, Sarah K.; Kaplan, Gillian; Csernansky, John; Miller, Michael I.

    2015-01-01

    Spatial normalization is a crucial step in assessing patterns of neuroanatomical structure and function associated with health and disease. Errors that occur during spatial normalization can influence hypothesis testing due to the dimensionalities of mapping algorithms and anatomical manifolds (landmarks, curves, surfaces, volumes) used to drive the mapping algorithms. The primary aim of this paper is to improve statistical inference using multiple anatomical manifolds and Large Deformation Diffeomorphic Metric Mapping (LDDMM) algorithms. We propose that combining information generated by the various manifolds and algorithms improves the reliability of hypothesis testing. We used this unified approach to assess variation in the thickness of the cingulate gyrus in subjects with schizophrenia and healthy comparison subjects. Three different LDDMM algorithms for mapping landmarks, curves and triangulated meshes were used to transform thickness maps of the cingulate surfaces into an atlas coordinate system. We then tested for group differences by combining the information from the three types of anatomical manifolds and LDDMM mapping algorithms. The unified approach provided reliable statistical results and eliminated ambiguous results due to surface mismatches. Subjects with schizophrenia had non-uniform cortical thinning over the left and right cingulate gyri, especially in the anterior portion, as compared to healthy comparison subjects. PMID:17613251

  4. Chemokine signaling directs trunk lymphatic network formation along the preexisting blood vasculature.

    PubMed

    Cha, Young Ryun; Fujita, Misato; Butler, Matthew; Isogai, Sumio; Kochhan, Eva; Siekmann, Arndt F; Weinstein, Brant M

    2012-04-17

    The lymphatic system is crucial for fluid homeostasis, immune responses, and numerous pathological processes. However, the molecular mechanisms responsible for establishing the anatomical form of the lymphatic vascular network remain largely unknown. Here, we show that chemokine signaling provides critical guidance cues directing early trunk lymphatic network assembly and patterning. The chemokine receptors Cxcr4a and Cxcr4b are expressed in lymphatic endothelium, whereas chemokine ligands Cxcl12a and Cxcl12b are expressed in adjacent tissues along which the developing lymphatics align. Loss- and gain-of-function studies in zebrafish demonstrate that chemokine signaling orchestrates the stepwise assembly of the trunk lymphatic network. In addition to providing evidence for a lymphatic vascular guidance mechanism, these results also suggest a molecular basis for the anatomical coalignment of lymphatic and blood vessels.

  5. The Emergence of Somatotopic Maps of the Body in S1 in Rats: The Correspondence Between Functional and Anatomical Organization

    PubMed Central

    Seelke, Adele M. H.; Dooley, James C.; Krubitzer, Leah A.

    2012-01-01

    Most of what we know about cortical map development and plasticity comes from studies in mice and rats, and for the somatosensory cortex, almost exclusively from the whisker-dominated posteromedial barrel fields. Whiskers are the main effector organs of mice and rats, and their representation in cortex and subcortical pathways is a highly derived feature of murine rodents. This specialized anatomical organization may therefore not be representative of somatosensory cortex in general, especially for species that utilize other body parts as their main effector organs, like the hands of primates. For these reasons, we examined the emergence of whole body maps in developing rats using electrophysiological recording techniques. In P5, P10, P15, P20 and adult rats, multiple recordings were made in the medial portion of S1 in each animal. Subsequently, these functional maps were related to anatomical parcellations of S1 based on a variety of histological stains. We found that at early postnatal ages (P5) medial S1 was composed almost exclusively of the representation of the vibrissae. At P10, other body part representations including the hindlimb and forelimb were present, although these were not topographically organized. By P15, a clear topographic organization began to emerge coincident with a reduction in receptive field size. By P20, body maps were adult-like. This study is the first to describe how topography of the body develops in S1 in any mammal. It indicates that anatomical parcellations and functional maps are initially incongruent but become tightly coupled by P15. Finally, because anatomical and functional specificity of developing barrel cortex appears much earlier in postnatal life than the rest of the body, the entire primary somatosensory cortex should be considered when studying general topographic map formation in development. PMID:22393398

  6. Anatomically-standardized maps reveal distinct patterns of cartilage thickness with increasing severity of medial compartment knee osteoarthritis.

    PubMed

    Favre, Julien; Erhart-Hledik, Jennifer C; Blazek, Katerina; Fasel, Benedikt; Gold, Garry E; Andriacchi, Thomas P

    2017-02-24

    While cartilage thickness alterations are a central element of knee osteoarthritis (OA), differences among disease stages are still incompletely understood. This study aimed to quantify the spatial-variations in cartilage thickness using anatomically-standardized thickness maps and test if there are characteristic patterns in patients with different stages of medial compartment knee OA. Magnetic resonance images were acquired for 75 non-OA and 100 OA knees of varying severities (Kellgren and Lawrence (KL) scores 1-4). Three-dimensional cartilage models were reconstructed and a shape matching technique was applied to convert the models into two-dimensional anatomically-standardized thickness maps. Difference thickness maps and statistical parametric mapping were used to compare the four OA and the non-OA subgroups. This analysis showed distinct thickness patterns for each clinical stage that formed a coherent succession from the non-OA to the KL 4 subgroups. Interestingly, the only significant difference for early stage (KL 1) was thicker femoral cartilage. With increase in disease severity, typical patterns developed, including thinner cartilage in the anterior area of the medial condyle (significant for KL 3 and 4) and thicker cartilage in the posterior area of the medial and lateral condyles (significant for all OA subgroups). The tibial patterns mainly consisted of thinner cartilage for both medial and lateral compartments (significant for KL 2-4). Comparing anatomically-standardized maps allowed identifying patterns of thickening and thinning over the entire cartilage surface, consequently improving the characterization of thickness differences associated with OA. The results also highlighted the value of anatomically-standardized maps to analyze spatial variations in cartilage thickness. This article is protected by copyright. All rights reserved.

  7. Geographic information system (GIS) mapping of lymphatic filariasis endemic areas of Gampaha District, Sri Lanka based on epidemiological and entomological screening.

    PubMed

    Wijegunawardana, N D A D; Gunawardene, Y I N Silva; Manamperi, Aresha; Senarathne, H; Abeyewickreme, W

    2012-05-01

    The objective of this study was to develop a site directed geographic information system (GIS) map of lymphatic filariasis (LF) in Gampaha District, Sri Lanka as a guide for targeted control activities. Epidemiological and entomological screening of LF was carried out in nine pre-identified endemic areas in Gampaha District, using night blood screening and pool-screening PCR-ELISA. In total, 1,073 subjects (286 children, 787 adults) from 9 sites were examined. Positive cases were detected at 2 sites, with prevalence rates of 0.5% (Hekiththa) and 3.4% (Peliyagoda); the prevalence of microfilaria (mf) among adult Culex quinquefasciatus mosquitoes surveyed was 30%. The overall prevalence of mosquitoes with L1-L2 larvae of W. bancrofti ranged from 0% to 8.31% using dissection and point estimates of infection prevalence, and ranged from 0 to 32.4% using PCR-ELISA. The largest number of human cases was found at altitudes of 2.5-3.5 min highly populated areas, where transmission appears to have taken place. Questionnaires indicated that limited community awareness of LF may be a reason for the fairly static infection prevalent among the local population. The GIS mapping of LF cases shows a considerable prevalence of LF and marked variability by geographic site in Gampaha.

  8. Lymphatic filariasis in the Democratic Republic of Congo; micro-stratification overlap mapping (MOM) as a prerequisite for control and surveillance.

    PubMed

    Kelly-Hope, Louise A; Thomas, Brent C; Bockarie, Moses J; Molyneux, David H

    2011-09-18

    The Democratic Republic of Congo (DRC) has a significant burden of lymphatic filariasis (LF) caused by the parasite Wuchereria bancrofti. A major impediment to the expansion of the LF elimination programme is the risk of serious adverse events (SAEs) associated with the use of ivermectin in areas co-endemic for onchocerciasis and loiasis. It is important to analyse these and other factors, such as soil transmitted helminths (STH) and malaria co-endemicity, which will impact on LF elimination. We analysed maps of onchocerciasis community-directed treatment with ivermectin (CDTi) from the African Programme for Onchocerciasis Control (APOC); maps of predicted prevalence of Loa loa; planned STH control maps of albendazole (and mebendazole) from the Global Atlas of Helminth Infections (GAHI); and bed nets and insecticide treated nets (ITNs) distribution from Demographic and Health Surveys (DHS) as well as published historic data which were incorporated into overlay maps. We developed an approach we designate as micro-stratification overlap mapping (MOM) to identify areas that will assist the implementation of LF elimination in the DRC. The historic data on LF was found through an extensive review of the literature as no recently published information was available. This paper identifies an approach that takes account of the various factors that will influence not only country strategies, but suggests that country plans will require a finer resolution mapping than usual, before implementation of LF activities can be efficiently deployed. This is because 1) distribution of ivermectin through APOC projects will already have had an impact of LF intensity and prevalence 2) DRC has been up scaling bed net distribution which will impact over time on transmission of W. bancrofti and 3) recently available predictive maps of L. loa allow higher risk areas to be identified, which allow LF implementation to be initiated with reduced risk where L. loa is considered non-endemic. We

  9. Lymphatic filariasis in the Democratic Republic of Congo; micro-stratification overlap mapping (MOM) as a prerequisite for control and surveillance

    PubMed Central

    2011-01-01

    Background The Democratic Republic of Congo (DRC) has a significant burden of lymphatic filariasis (LF) caused by the parasite Wuchereria bancrofti. A major impediment to the expansion of the LF elimination programme is the risk of serious adverse events (SAEs) associated with the use of ivermectin in areas co-endemic for onchocerciasis and loiasis. It is important to analyse these and other factors, such as soil transmitted helminths (STH) and malaria co-endemicity, which will impact on LF elimination. Results We analysed maps of onchocerciasis community-directed treatment with ivermectin (CDTi) from the African Programme for Onchocerciasis Control (APOC); maps of predicted prevalence of Loa loa; planned STH control maps of albendazole (and mebendazole) from the Global Atlas of Helminth Infections (GAHI); and bed nets and insecticide treated nets (ITNs) distribution from Demographic and Health Surveys (DHS) as well as published historic data which were incorporated into overlay maps. We developed an approach we designate as micro-stratification overlap mapping (MOM) to identify areas that will assist the implementation of LF elimination in the DRC. The historic data on LF was found through an extensive review of the literature as no recently published information was available. Conclusions This paper identifies an approach that takes account of the various factors that will influence not only country strategies, but suggests that country plans will require a finer resolution mapping than usual, before implementation of LF activities can be efficiently deployed. This is because 1) distribution of ivermectin through APOC projects will already have had an impact of LF intensity and prevalence 2) DRC has been up scaling bed net distribution which will impact over time on transmission of W. bancrofti and 3) recently available predictive maps of L. loa allow higher risk areas to be identified, which allow LF implementation to be initiated with reduced risk where L. loa

  10. Spleen and Lymphatic System

    MedlinePlus

    ... A Week of Healthy Breakfasts Shyness Spleen and Lymphatic System KidsHealth > For Teens > Spleen and Lymphatic System A A A What's in this article? Why ... español El bazo y el sistema linfático The lymphatic system is an extensive drainage network that helps keep ...

  11. Estimation of Purkinje trees from electro-anatomical mapping of the left ventricle using minimal cost geodesics.

    PubMed

    Cárdenes, Rubén; Sebastian, Rafael; Soto-Iglesias, David; Berruezo, Antonio; Camara, Oscar

    2015-08-01

    The electrical activation of the heart is a complex physiological process that is essential for the understanding of several cardiac dysfunctions, such as ventricular tachycardia (VT). Nowadays, patient-specific activation times on ventricular chambers can be estimated from electro-anatomical maps, providing crucial information to clinicians for guiding cardiac radio-frequency ablation treatment. However, some relevant electrical pathways such as those of the Purkinje system are very difficult to interpret from these maps due to sparsity of data and the limited spatial resolution of the system. We present here a novel method to estimate these fast electrical pathways from the local activations maps (LATs) obtained from electro-anatomical maps. The location of Purkinje-myocardial junctions (PMJs) is estimated considering them as critical points of a distance map defined by the activation maps, and then minimal cost geodesic paths are computed on the ventricular surface between the detected junctions. Experiments to validate the proposed method have been carried out in simplified and realistic simulated data, showing good performance on recovering the main characteristics of simulated Purkinje networks (e.g. PMJs). A feasibility study with real cases of fascicular VT was also performed, showing promising results.

  12. Lymphatic Filariasis in Nigeria; Micro-stratification Overlap Mapping (MOM) as a Prerequisite for Cost-Effective Resource Utilization in Control and Surveillance

    PubMed Central

    Okorie, Patricia N.; Ademowo, George O.; Saka, Yisa; Davies, Emmanuel; Okoronkwo, Chukwu; Bockarie, Moses J.; Molyneux, David H.; Kelly-Hope, Louise A.

    2013-01-01

    Background Nigeria has a significant burden of lymphatic filariasis (LF) caused by the parasite Wuchereria bancrofti. A major concern to the expansion of the LF elimination programme is the risk of serious adverse events (SAEs) associated with the use of ivermectin in areas co-endemic with Loa filariasis. To better understand this, as well as other factors that may impact on LF elimination, we used Micro-stratification Overlap Mapping (MOM) to highlight the distribution and potential impact of multiple disease interventions that geographically coincide in LF endemic areas and which will impact on LF and vice versa. Methodology/Principal findings LF data from the literature and Federal Ministry of Health (FMoH) were collated into a database. LF prevalence distributions; predicted prevalence of loiasis; ongoing onchocerciasis community-directed treatment with ivermectin (CDTi); and long-lasting insecticidal mosquito net (LLIN) distributions for malaria were incorporated into overlay maps using geographical information system (GIS) software. LF was prevalent across most regions of the country. The mean prevalence determined by circulating filarial antigen (CFA) was 14.0% (n = 134 locations), and by microfilaria (Mf) was 8.2% (n = 162 locations). Overall, LF endemic areas geographically coincided with CDTi priority areas, however, LLIN coverage was generally low (<50%) in areas where LF prevalence was high or co-endemic with L. loa. Conclusions/Significance The extensive database and series of maps produced in this study provide an important overview for the LF Programme and will assist to maximize existing interventions, ensuring cost effective use of resources as the programme scales up. Such information is a prerequisite for the LF programme, and will allow for other factors to be included into planning, as well as monitoring and evaluation activities given the broad spectrum impact of the drugs used. PMID:24040432

  13. Lymphatic filariasis in Nigeria; micro-stratification overlap mapping (MOM) as a prerequisite for cost-effective resource utilization in control and surveillance.

    PubMed

    Okorie, Patricia N; Ademowo, George O; Saka, Yisa; Davies, Emmanuel; Okoronkwo, Chukwu; Bockarie, Moses J; Molyneux, David H; Kelly-Hope, Louise A

    2013-01-01

    Nigeria has a significant burden of lymphatic filariasis (LF) caused by the parasite Wuchereria bancrofti. A major concern to the expansion of the LF elimination programme is the risk of serious adverse events (SAEs) associated with the use of ivermectin in areas co-endemic with Loa filariasis. To better understand this, as well as other factors that may impact on LF elimination, we used Micro-stratification Overlap Mapping (MOM) to highlight the distribution and potential impact of multiple disease interventions that geographically coincide in LF endemic areas and which will impact on LF and vice versa. LF data from the literature and Federal Ministry of Health (FMoH) were collated into a database. LF prevalence distributions; predicted prevalence of loiasis; ongoing onchocerciasis community-directed treatment with ivermectin (CDTi); and long-lasting insecticidal mosquito net (LLIN) distributions for malaria were incorporated into overlay maps using geographical information system (GIS) software. LF was prevalent across most regions of the country. The mean prevalence determined by circulating filarial antigen (CFA) was 14.0% (n = 134 locations), and by microfilaria (Mf) was 8.2% (n = 162 locations). Overall, LF endemic areas geographically coincided with CDTi priority areas, however, LLIN coverage was generally low (<50%) in areas where LF prevalence was high or co-endemic with L. loa. The extensive database and series of maps produced in this study provide an important overview for the LF Programme and will assist to maximize existing interventions, ensuring cost effective use of resources as the programme scales up. Such information is a prerequisite for the LF programme, and will allow for other factors to be included into planning, as well as monitoring and evaluation activities given the broad spectrum impact of the drugs used.

  14. Improving anatomical mapping of complexly deformed anatomy for external beam radiotherapy and brachytherapy dose accumulation in cervical cancer

    SciTech Connect

    Vásquez Osorio, Eliana M. Kolkman-Deurloo, Inger-Karine K.; Schuring-Pereira, Monica; Zolnay, András; Heijmen, Ben J. M.; Hoogeman, Mischa S.

    2015-01-15

    Purpose: In the treatment of cervical cancer, large anatomical deformations, caused by, e.g., tumor shrinkage, bladder and rectum filling changes, organ sliding, and the presence of the brachytherapy (BT) applicator, prohibit the accumulation of external beam radiotherapy (EBRT) and BT dose distributions. This work proposes a structure-wise registration with vector field integration (SW+VF) to map the largely deformed anatomies between EBRT and BT, paving the way for 3D dose accumulation between EBRT and BT. Methods: T2w-MRIs acquired before EBRT and as a part of the MRI-guided BT procedure for 12 cervical cancer patients, along with the manual delineations of the bladder, cervix-uterus, and rectum-sigmoid, were used for this study. A rigid transformation was used to align the bony anatomy in the MRIs. The proposed SW+VF method starts by automatically segmenting features in the area surrounding the delineated organs. Then, each organ and feature pair is registered independently using a feature-based nonrigid registration algorithm developed in-house. Additionally, a background transformation is calculated to account for areas far from all organs and features. In order to obtain one transformation that can be used for dose accumulation, the organ-based, feature-based, and the background transformations are combined into one vector field using a weighted sum, where the contribution of each transformation can be directly controlled by its extent of influence (scope size). The optimal scope sizes for organ-based and feature-based transformations were found by an exhaustive analysis. The anatomical correctness of the mapping was independently validated by measuring the residual distances after transformation for delineated structures inside the cervix-uterus (inner anatomical correctness), and for anatomical landmarks outside the organs in the surrounding region (outer anatomical correctness). The results of the proposed method were compared with the results of the

  15. Imaging the lymphatic system.

    PubMed

    Munn, Lance L; Padera, Timothy P

    2014-11-01

    Visualization of the lymphatic system is clinically necessary during diagnosis or treatment of many conditions and diseases; it is used for identifying and monitoring lymphedema, for detecting metastatic lesions during cancer staging and for locating lymphatic structures so they can be spared during surgical procedures. Imaging lymphatic anatomy and function also plays an important role in experimental studies of lymphatic development and function, where spatial resolution and accessibility are better. Here, we review technologies for visualizing and imaging the lymphatic system for clinical applications. We then describe the use of lymphatic imaging in experimental systems as well as some of the emerging technologies for improving these methodologies. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. MRI-based anatomical model of the human head for specific absorption rate mapping

    PubMed Central

    Makris, Nikos; Angelone, Leonardo; Tulloch, Seann; Sorg, Scott; Kaiser, Jonathan; Kennedy, David

    2009-01-01

    In this study, we present a magnetic resonance imaging (MRI)-based, high-resolution, numerical model of the head of a healthy human subject. In order to formulate the model, we performed quantitative volumetric segmentation on the human head, using T1-weighted MRI. The high spatial resolution used (1 × 1 × 1 mm3), allowed for the precise computation and visualization of a higher number of anatomical structures than provided by previous models. Furthermore, the high spatial resolution allowed us to study individual thin anatomical structures of clinical relevance not visible by the standard model currently adopted in computational bioelectromagnetics. When we computed the electromagnetic field and specific absorption rate (SAR) at 7 Tesla MRI using this high-resolution model, we were able to obtain a detailed visualization of such fine anatomical structures as the epidermis/dermis, bone structures, bone-marrow, white matter and nasal and eye structures. PMID:18985401

  17. Clinical feasibility study of combined optoacoustic and ultrasonic imaging modality providing coregistered functional and anatomical maps of breast tumors

    NASA Astrophysics Data System (ADS)

    Zalev, Jason; Herzog, Don; Clingman, Bryan; Miller, Tom; Kist, Kenneth; Dornbluth, N. Carol; McCorvey, B. Michelle; Otto, Pamela; Ermilov, Sergey; Nadvoretsky, Vyacheslav; Conjusteau, Andre; Su, Richard; Tsyboulski, Dmitri; Oraevsky, Alexander

    2012-02-01

    Two-dimensional optoacoustic imaging with a hand-held probe operated in backward mode is being developed for diagnostic imaging of breast cancer to evaluate the feasibility of a dual-modality optoacoustic plus ultrasonic system that maps functional information of anatomical tissue structures with ultrasonic resolution. Tissue is illuminated at 757nm and 1064nm for optical contrast between hypoxic blood of breast carcinomas and normally oxygenated blood in benign masses. The system is optimized and calibrated in phantoms for a pilot clinical study of patients with breast masses suspected for malignancy. Capability of the non-invasive system to improve detection and diagnosis of breast tumors is discussed.

  18. Lymphatic drainage of skin to a sentinel lymph node in a feline model.

    PubMed Central

    Wong, J H; Cagle, L A; Morton, D L

    1991-01-01

    To determine the feasibility of selective lymphadenectomy, the authors developed a feline model to identify and determine the utility of mapping dyes for this purpose. Adult cats were injected intradermally with a variety of mapping substances to determine whether the anatomic site of injection had a predictable pattern of drainage to a particular lymph node. Isosulfan blue provided the optimal mapping material. Injection of isosulfan blue intradermally into the skin of the medial thigh consistently led to coloration of the central lymph node, whereas intradermal abdominal wall injections and intradermal lateral thigh injections resulted in coloration of the lateral lymph node. Intradermal injections into skin about the perineum resulted in coloration of the most medial lymph node only. The feline model proved to a useful model to examine the utility of mapping dyes and to demonstrate dermal lymphatics. The predictable pattern of drainage of the skin in this feline model supports the feasibility of selective lymphadenectomy. Images Fig. 1. Fig. 2. PMID:1953118

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

    PubMed

    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.

  20. Assessing lymphatic response to treatments in head and neck cancer using near-infrared fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Tan, I.-Chih; Karni, Ron J.; Rasmussen, John C.; Sevick-Muraca, Eva M.

    2014-05-01

    Care for head and neck (HN) cancer could be improved with better mapping of lymphatic drainage pathways in HN region as well as understanding the effect of the cancer treatments on lymphatics. In this study, near-infrared fluorescence imaging is being used to visualize the lymphatics in human subjects diagnosed with HN cancer before and after treatments. Imaging results show the lymphatic architecture and contractile function in HN. Reformation of lymphatics during the course of cancer care was also seen in the longitudinal imaging. This allows us to better understand the lymphatics in HN cancer patients.

  1. Spleen and Lymphatic System

    MedlinePlus

    ... Get Weight Loss Surgery? A Week of Healthy Breakfasts Shyness Spleen and Lymphatic System KidsHealth > For Teens > Spleen and Lymphatic System Print A A A What's in this article? Why They're Important Basic Anatomy How It Works Things That Can ...

  2. QTL mapping and phenotypic variation of root anatomical traits in maize (Zea mays L.).

    PubMed

    Burton, Amy L; Johnson, James; Foerster, Jillian; Hanlon, Meredith T; Kaeppler, Shawn M; Lynch, Jonathan P; Brown, Kathleen M

    2015-01-01

    Root anatomical trait variation is described for three maize RIL populations. Six quantitative trait loci (QTL) are presented for anatomical traits: root cross-sectional area, % living cortical area, aerenchyma area, and stele area. Root anatomy is directly related to plant performance, influencing resource acquisition and transport, the metabolic cost of growth, and the mechanical strength of the root system. Ten root anatomical traits were measured in greenhouse-grown plants from three recombinant inbred populations of maize [intermated B73 × Mo17 (IBM), Oh43 × W64a (OhW), and Ny821 × H99 (NyH)]. Traits included areas of cross section, stele, cortex, aerenchyma, and cortical cells, percentages of the cortex occupied by aerenchyma, and cortical cell file number. Significant phenotypic variation was observed for each of the traits, with maximum values typically seven to ten times greater than minimum values. Means and ranges were similar for the OhW and NyH populations for all traits, while the IBM population had lower mean values for the majority of traits, but a 50% greater range of variation for aerenchyma area. A principal component analysis showed a similar trait structure for the three families, with clustering of area and count traits. Strong correlations were observed among area traits in the cortex, stele, and cross-section. The aerenchyma and percent living cortical area traits were independent of other traits. Six QTL were identified for four of the traits. The phenotypic variation explained by the QTL ranged from 4.7% (root cross-sectional area, OhW population) to 12.0% (percent living cortical area, IBM population). Genetic variation for root anatomical traits can be harnessed to increase abiotic stress tolerance and provide insights into mechanisms controlling phenotypic variation for root anatomy.

  3. Mechanobiology of lymphatic contractions.

    PubMed

    Munn, Lance L

    2015-02-01

    The lymphatic system is responsible for controlling tissue fluid pressure by facilitating flow of lymph (i.e. the plasma and cells that enter the lymphatic system). Because lymph contains cells of the immune system, its transport is not only important for fluid homeostasis, but also immune function. Lymph drainage can occur via passive flow or active pumping, and much research has identified the key biochemical and mechanical factors that affect output. Although many studies and reviews have addressed how tissue properties and fluid mechanics (i.e. pressure gradients) affect lymph transport [1-3] there is less known about lymphatic mechanobiology. As opposed to passive mechanical properties, mechanobiology describes the active coupling of mechanical signals and biochemical pathways. Lymphatic vasomotion is the result of a fascinating system affected by mechanical forces exerted by the flowing lymph, including pressure-induced vessel stretch and flow-induced shear stresses. These forces can trigger or modulate biochemical pathways important for controlling the lymphatic contractions. Here, I review the current understanding of lymphatic vessel function, focusing on vessel mechanobiology, and summarize the prospects for a comprehensive understanding that integrates the mechanical and biomechanical control mechanisms in the lymphatic system.

  4. Genetics of lymphatic anomalies

    PubMed Central

    Brouillard, Pascal; Boon, Laurence; Vikkula, Miikka

    2014-01-01

    Lymphatic anomalies include a variety of developmental and/or functional defects affecting the lymphatic vessels: sporadic and familial forms of primary lymphedema, secondary lymphedema, chylothorax and chylous ascites, lymphatic malformations, and overgrowth syndromes with a lymphatic component. Germline mutations have been identified in at least 20 genes that encode proteins acting around VEGFR-3 signaling but also downstream of other tyrosine kinase receptors. These mutations exert their effects via the RAS/MAPK and the PI3K/AKT pathways and explain more than a quarter of the incidence of primary lymphedema, mostly of inherited forms. More common forms may also result from multigenic effects or post-zygotic mutations. Most of the corresponding murine knockouts are homozygous lethal, while heterozygotes are healthy, which suggests differences in human and murine physiology and the influence of other factors. PMID:24590274

  5. Cortex mapping of ipsilateral somatosensory area following anatomical hemispherectomy: a MEG study.

    PubMed

    Yao, Ning; Qiao, Hui; Shu, Ning; Wang, Zide; Chen, Daxing; Wu, Liang; Deng, Xiaofeng; Xu, Yulun

    2013-04-01

    A remarkable preservation of sensorimotor function is observed in patients with refractory epilepsy who were treated by hemispherectomy. Cortical regions in the remaining hemisphere or contralateral subcortical region contribute to the residual sensorimotor function. Somatosensory evoked field (SEF) is used to investigate the residual sensory function in hemispherectomized patients. The SEFs are usually recorded with magnetoencephalography (MEG). The objective is to investigate the ipsilateral cortical regions associated with residual sensory function in hemispherectomized patients using somatosensory evoked field techniques. Six patients with anatomical hemispherectomy were included. Ipsilateral and contralateral sensory functions were assessed by physical examination. Somatosensory evoked fields to electrical stimulation of the bilateral median nerves were recorded by MEG in the hemispherectomized patients and six control subjects. The stimulus intensity was adjusted to the minimum threshold that elicited a thumb twitch. The presumed neuronal source was identified as the equivalent current dipole. Six patients demonstrated different degrees of residual sensory function. Three patients had somatosensory evoked field activation in the ipsilateral cortex upon electrical stimulation of the hemiplegic hand. In these patients the locations of the ipsilateral sensorimotor cortex activation were in the primary somatosensory cortex (SI). The latency of the reliable somatosensory evoked field after stimulation of the median nerve was significantly longer for responses from the hemiplegic side compared with responses to stimulation of the median nerve from the normal side. In conclusion, ipsilateral sensory function has a time-locked relation to the cortical electromagnetic activation in the SI area of hemispherectomized patients.

  6. Vegfc acts through ERK to induce sprouting and differentiation of trunk lymphatic progenitors.

    PubMed

    Shin, Masahiro; Male, Ira; Beane, Timothy J; Villefranc, Jacques A; Kok, Fatma O; Zhu, Lihua J; Lawson, Nathan D

    2016-10-15

    Vascular endothelial growth factor C (Vegfc) activates its receptor, Flt4, to induce lymphatic development. However, the signals that act downstream of Flt4 in this context in vivo remain unclear. To understand Flt4 signaling better, we generated zebrafish bearing a deletion in the Flt4 cytoplasmic domain that eliminates tyrosines Y1226 and 1227. Embryos bearing this deletion failed to initiate sprouting or differentiation of trunk lymphatic vessels and did not form a thoracic duct. Deletion of Y1226/7 prevented ERK phosphorylation in lymphatic progenitors, and ERK inhibition blocked trunk lymphatic sprouting and differentiation. Conversely, endothelial autonomous ERK activation rescued lymphatic sprouting and differentiation in flt4 mutants. Interestingly, embryos bearing the Y1226/7 deletion formed a functional facial lymphatic network enabling them to develop normally to adulthood. By contrast, flt4 null larvae displayed hypoplastic facial lymphatics and severe lymphedema. Thus, facial lymphatic vessels appear to be the first functional lymphatic network in the zebrafish, whereas the thoracic duct is initially dispensable for lymphatic function. Moreover, distinct signaling pathways downstream of Flt4 govern lymphatic morphogenesis and differentiation in different anatomical locations. © 2016. Published by The Company of Biologists Ltd.

  7. Adaptive algorithms to map how brain trauma affects anatomical connectivity in children

    NASA Astrophysics Data System (ADS)

    Dennis, Emily L.; Prasad, Gautam; Babikian, Talin; Kernan, Claudia; Mink, Richard; Babbitt, Christopher; Johnson, Jeffrey; Giza, Christopher C.; Asarnow, Robert F.; Thompson, Paul M.

    2015-12-01

    Deficits in white matter (WM) integrity occur following traumatic brain injury (TBI), and often persist long after the visible scars have healed. Heterogeneity in injury types and locations can complicate analyses, making it harder to discover common biomarkers for tracking recovery. Here we apply a newly developed adaptive connectivity method, EPIC (evolving partitions to improve connectomics) to identify differences in structural connectivity that persist longitudinally. This data comes from a longitudinal study, in which we scanned participants (aged 8-19 years) with anatomical and diffusion MRI in both the post-acute and chronic phases (1-6 months and 13-19 months post-injury). To identify patterns of abnormal connectivity, we trained a model on data from 32 TBI patients in the post-acute phase and 45 well-matched healthy controls, reducing an initial 68x68 connectivity matrix to a 14x14 matrix. We then applied this reduced parcellation to the chronic data in participants who had returned for their chronic assessment (21 TBI and 26 healthy controls) and tested for group differences. We found significant differences in two connections, comprising callosal fibers and long anterior-posterior fibers, with the TBI group showing increased fiber density relative to controls. Longitudinal analysis revealed that these were connections that were decreasing over time in the healthy controls, as is a common developmental phenomenon, but they were increasing in the TBI group. While we cannot definitively tell why this may occur with our current data, this study provides targets for longitudinal tracking, and poses questions for future investigation.

  8. [Lymphatic system of the tongue and its role in glositis of odontogenic origin].

    PubMed

    Chkhikvishvili, M Dzh

    2005-02-01

    In aged persons reduction of diameter of tongue lymphatic capillaries precedes thinning of the Kaarl net. In the process of tongue inflammation, lymphogenic way of inclusion in 6|6 and 8|8 teeth lower area should be stuck out with existence of alleged "Integration Centers". Lymphatic knots and lymphatic ducts are in prevailed placed in corresponding tissues of lower-chin and lower teeth. Lymphatic-muscular system and its anatomical links and age-related changeability raise the special interest during odontogenic infections with tongue inflammation.

  9. Spleen and Lymphatic System (For Parents)

    MedlinePlus

    ... Your 1- to 2-Year-Old Spleen and Lymphatic System KidsHealth > For Parents > Spleen and Lymphatic System A ... help fight off infection. About the Spleen and Lymphatic System One of the lymphatic system's major jobs is ...

  10. Spleen and Lymphatic System (For Parents)

    MedlinePlus

    ... TV, Video Games, and the Internet Spleen and Lymphatic System KidsHealth > For Parents > Spleen and Lymphatic System Print ... help fight off infection. About the Spleen and Lymphatic System One of the lymphatic system's major jobs is ...

  11. Cortical connectivity maps reveal anatomically distinct areas in the parietal cortex of the rat.

    PubMed

    Wilber, Aaron A; Clark, Benjamin J; Demecha, Alexis J; Mesina, Lilia; Vos, Jessica M; McNaughton, Bruce L

    2014-01-01

    A central feature of theories of spatial navigation involves the representation of spatial relationships between objects in complex environments. The parietal cortex has long been linked to the processing of spatial visual information and recent evidence from single unit recording in rodents suggests a role for this region in encoding egocentric and world-centered frames. The rat parietal cortex can be subdivided into four distinct rostral-caudal and medial-lateral regions, which includes a zone previously characterized as secondary visual cortex. At present, very little is known regarding the relative connectivity of these parietal subdivisions. Thus, we set out to map the connectivity of the entire anterior-posterior and medial-lateral span of this region. To do this we used anterograde and retrograde tracers in conjunction with open source neuronal segmentation and tracer detection tools to generate whole brain connectivity maps of parietal inputs and outputs. Our present results show that inputs to the parietal cortex varied significantly along the medial-lateral, but not the rostral-caudal axis. Specifically, retrosplenial connectivity is greater medially, but connectivity with visual cortex, though generally sparse, is more significant laterally. Finally, based on connection density, the connectivity between parietal cortex and hippocampus is indirect and likely achieved largely via dysgranular retrosplenial cortex. Thus, similar to primates, the parietal cortex of rats exhibits a difference in connectivity along the medial-lateral axis, which may represent functionally distinct areas.

  12. Anatomically-adapted graph wavelets for improved group-level fMRI activation mapping.

    PubMed

    Behjat, Hamid; Leonardi, Nora; Sörnmo, Leif; Van De Ville, Dimitri

    2015-12-01

    A graph based framework for fMRI brain activation mapping is presented. The approach exploits the spectral graph wavelet transform (SGWT) for the purpose of defining an advanced multi-resolutional spatial transformation for fMRI data. The framework extends wavelet based SPM (WSPM), which is an alternative to the conventional approach of statistical parametric mapping (SPM), and is developed specifically for group-level analysis. We present a novel procedure for constructing brain graphs, with subgraphs that separately encode the structural connectivity of the cerebral and cerebellar gray matter (GM), and address the inter-subject GM variability by the use of template GM representations. Graph wavelets tailored to the convoluted boundaries of GM are then constructed as a means to implement a GM-based spatial transformation on fMRI data. The proposed approach is evaluated using real as well as semi-synthetic multi-subject data. Compared to SPM and WSPM using classical wavelets, the proposed approach shows superior type-I error control. The results on real data suggest a higher detection sensitivity as well as the capability to capture subtle, connected patterns of brain activity.

  13. Mechanical Forces and Lymphatic Transport

    PubMed Central

    Breslin, Jerome W.

    2014-01-01

    This review examines current understanding of how the lymphatic vessel network can optimize lymph flow in response to various mechanical forces. Lymphatics are organized as a vascular tree, with blind-ended initial lymphatics, precollectors, prenodal collecting lymphatics, lymph nodes, postnodal collecting lymphatics and the larger trunks (thoracic duct and right lymph duct) that connect to the subclavian veins. The formation of lymph from interstitial fluid depends heavily on oscillating pressure gradients to drive fluid into initial lymphatics. Collecting lymphatics are segmented vessels with unidirectional valves, with each segment, called a lymphangion, possessing an intrinsic pumping mechanism. The lymphangions propel lymph forward against a hydrostatic pressure gradient. Fluid is returned to the central circulation both at lymph nodes and via the larger lymphatic trunks. Several recent developments are discussed, including: evidence for the active role of endothelial cells in lymph formation; recent developments on how inflow pressure, outflow pressure, and shear stress affect pump function of the lymphangion; lymphatic valve gating mechanisms; collecting lymphatic permeability; and current interpretations of the molecular mechanisms within lymphatic endothelial cells and smooth muscle. Improved understanding of the physiological mechanisms by lymphatic vessels sense mechanical stimuli, integrate the information, and generate the appropriate response is key for determining the pathogenesis of lymphatic insufficiency and developing treatments for lymphedema. PMID:25107458

  14. Semi-automated registration-based anatomical labelling, voxel based morphometry and cortical thickness mapping of the mouse brain.

    PubMed

    Pagani, Marco; Damiano, Mario; Galbusera, Alberto; Tsaftaris, Sotirios A; Gozzi, Alessandro

    2016-07-15

    Morphoanatomical MRI methods have recently begun to be applied in the mouse. However, substantial differences in the anatomical organisation of human and rodent brain prevent a straightforward extension of clinical neuroimaging tools to mouse brain imaging. As a result, the vast majority of the published approaches rely on tailored routines that address single morphoanatomical readouts and typically lack a sufficiently-detailed description of the complex workflow required to process images and quantify structural alterations. Here we provide a detailed description of semi-automated registration-based procedures for voxel based morphometry, cortical thickness estimation and automated anatomical labelling of the mouse brain. The approach relies on the sequential use of advanced image processing tools offered by ANTs, a flexible open source toolkit freely available to the scientific community. To illustrate our procedures, we described their application to quantify morphological alterations in socially-impaired BTBR mice with respect to normosocial C57BL/6J controls, a comparison recently described by us and other research groups. We show that the approach can reliably detect both focal and large-scale grey matter alterations using complementary readouts. No detailed operational workflows for mouse imaging are available for direct comparison with our methods. However, empirical assessment of the mapped inter-strain differences is in good agreement with the findings of other groups using analogous approaches. The detailed operational workflows described here are expected to help the implementation of rodent morphoanatomical methods by non-expert users, and ultimately promote the use of these tools across the preclinical neuroimaging community. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. What Is the Lymphatic System?

    MedlinePlus

    ... 9) 2017 NLN International Conference What is the Lymphatic System? To better understand lymphedema , we first must understand the normal lymphatic system (see diagram) . This system functions parallel to the ...

  16. What Is the Lymphatic System?

    MedlinePlus

    ... information and to apply now! What is the Lymphatic System? To better understand lymphedema , we first must understand the normal lymphatic system (see diagram) . This system functions parallel to the ...

  17. Near-Infrared Fluorescence Lymphatic Imaging of a Toddler With Congenital Lymphedema.

    PubMed

    Greives, Matthew R; Aldrich, Melissa B; Sevick-Muraca, Eva M; Rasmussen, John C

    2017-03-29

    Primary lymphedema in the pediatric population remains poorly diagnosed and misunderstood due to a lack of information on the causation and underlying anatomy of the lymphatic system. Consequently, therapeutic protocols for pediatric patients remain sparse and with little evidence to support them. In an effort to better understand the causation of primary pediatric lymphedema and to better inform clinical care, we report the use of near-infrared fluorescence lymphatic imaging on the extremities of an alert, 21-month-old boy who presented with unilateral right arm and hand lymphedema at birth. The imaging results indicated an intact, apparently normal lymphatic anatomy with no obvious malformation, but with decreased lymphatic contractile function of the affected upper extremity relative to the contralateral and lower extremities. We hypothesized that the lack of contraction of the lymphatic vessels rather than an anatomic malformation was the source of the unilateral extremity swelling, and that compression and manual lymphatic drainage could be effective treatments.

  18. Endothelial Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 Is Critical for Lymphatic Vascular Development and Function

    PubMed Central

    Guo, Chang-An; Danai, Laura V.; Yawe, Joseph C.; Gujja, Sharvari; Edwards, Yvonne J. K.

    2016-01-01

    The molecular mechanisms underlying lymphatic vascular development and function are not well understood. Recent studies have suggested a role for endothelial cell (EC) mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) in developmental angiogenesis and atherosclerosis. Here, we show that constitutive loss of EC Map4k4 in mice causes postnatal lethality due to chylothorax, suggesting that Map4k4 is required for normal lymphatic vascular function. Mice constitutively lacking EC Map4k4 displayed dilated lymphatic capillaries, insufficient lymphatic valves, and impaired lymphatic flow; furthermore, primary ECs derived from these animals displayed enhanced proliferation compared with controls. Yeast 2-hybrid analyses identified the Ras GTPase-activating protein Rasa1, a known regulator of lymphatic development and lymphatic endothelial cell fate, as a direct interacting partner for Map4k4. Map4k4 silencing in ECs enhanced basal Ras and extracellular signal-regulated kinase (Erk) activities, and primary ECs lacking Map4k4 displayed enhanced lymphatic EC marker expression. Taken together, these results reveal that EC Map4k4 is critical for lymphatic vascular development by regulating EC quiescence and lymphatic EC fate. PMID:27044870

  19. Mapping grey matter reductions in schizophrenia: an anatomical likelihood estimation analysis of voxel-based morphometry studies.

    PubMed

    Fornito, A; Yücel, M; Patti, J; Wood, S J; Pantelis, C

    2009-03-01

    Voxel-based morphometry (VBM) is a popular tool for mapping neuroanatomical changes in schizophrenia patients. Several recent meta-analyses have identified the brain regions in which patients most consistently show grey matter reductions, although they have not examined whether such changes reflect differences in grey matter concentration (GMC) or grey matter volume (GMV). These measures assess different aspects of grey matter integrity, and may therefore reflect different pathological processes. In this study, we used the Anatomical Likelihood Estimation procedure to analyse significant differences reported in 37 VBM studies of schizophrenia patients, incorporating data from 1646 patients and 1690 controls, and compared the findings of studies using either GMC or GMV to index grey matter differences. Analysis of all studies combined indicated that grey matter reductions in a network of frontal, temporal, thalamic and striatal regions are among the most frequently reported in literature. GMC reductions were generally larger and more consistent than GMV reductions, and were more frequent in the insula, medial prefrontal, medial temporal and striatal regions. GMV reductions were more frequent in dorso-medial frontal cortex, and lateral and orbital frontal areas. These findings support the primacy of frontal, limbic, and subcortical dysfunction in the pathophysiology of schizophrenia, and suggest that the grey matter changes observed with MRI may not necessarily result from a unitary pathological process.

  20. Lymphatics and the breast

    MedlinePlus Videos and Cool Tools

    ... a very worrisome role in the spread of breast cancer. Components of the lymphatic system called lymph nodes ... may result in the formation of a secondary cancer mass in a different location of the body. Regular breast self examinations can help to detect tumors earlier ...

  1. [Pleural lymphatics and effusions].

    PubMed

    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.

  2. The passive biomechanics of human pelvic collecting lymphatic vessels

    PubMed Central

    Athanasiou, Dimitrios; Jafarnejad, Mohammad; Nixon, Katherine; Duarte, Delfim; Hawkins, Edwin D.; Jamalian, Samira; Cunnea, Paula; Lo Celso, Cristina; Kobayashi, Shunichi; Fotopoulou, Christina; Moore, James E.

    2017-01-01

    The lymphatic system has a major significance in the metastatic pathways in women’s cancers. Lymphatic pumping depends on both extrinsic and intrinsic mechanisms, and the mechanical behavior of lymphatic vessels regulates the function of the system. However, data on the mechanical properties and function of human lymphatics are lacking. Our aim is to characterize, for the first time, the passive biomechanical behavior of human collecting lymphatic vessels removed at pelvic lymph node dissection during primary debulking surgeries for epithelial ovarian cancer. Isolated vessels were cannulated and then pressurized at varying levels of applied axial stretch in a calcium-free Krebs buffer. Pressurized vessels were then imaged using multi-photon microscopy for collagen-elastin structural composition and fiber orientation. Both pressure-diameter and force-elongation responses were highly nonlinear, and axial stretching of the vessel served to decrease diameter at constant pressure. Pressure-diameter behavior for the human vessels is very similar to data from rat mesenteric vessels, though the human vessels were approximately 10× larger than those from rats. Multiphoton microscopy revealed the vessels to be composed of an inner layer of elastin with an outer layer of aligned collagen fibers. This is the first study that successfully described the passive biomechanical response and composition of human lymphatic vessels in patients with ovarian cancer. Future work should expand on this knowledge base with investigations of vessels from other anatomical locations, contractile behavior, and the implications on metastatic cell transport. PMID:28827843

  3. The passive biomechanics of human pelvic collecting lymphatic vessels.

    PubMed

    Athanasiou, Dimitrios; Edgar, Lowell T; Jafarnejad, Mohammad; Nixon, Katherine; Duarte, Delfim; Hawkins, Edwin D; Jamalian, Samira; Cunnea, Paula; Lo Celso, Cristina; Kobayashi, Shunichi; Fotopoulou, Christina; Moore, James E

    2017-01-01

    The lymphatic system has a major significance in the metastatic pathways in women's cancers. Lymphatic pumping depends on both extrinsic and intrinsic mechanisms, and the mechanical behavior of lymphatic vessels regulates the function of the system. However, data on the mechanical properties and function of human lymphatics are lacking. Our aim is to characterize, for the first time, the passive biomechanical behavior of human collecting lymphatic vessels removed at pelvic lymph node dissection during primary debulking surgeries for epithelial ovarian cancer. Isolated vessels were cannulated and then pressurized at varying levels of applied axial stretch in a calcium-free Krebs buffer. Pressurized vessels were then imaged using multi-photon microscopy for collagen-elastin structural composition and fiber orientation. Both pressure-diameter and force-elongation responses were highly nonlinear, and axial stretching of the vessel served to decrease diameter at constant pressure. Pressure-diameter behavior for the human vessels is very similar to data from rat mesenteric vessels, though the human vessels were approximately 10× larger than those from rats. Multiphoton microscopy revealed the vessels to be composed of an inner layer of elastin with an outer layer of aligned collagen fibers. This is the first study that successfully described the passive biomechanical response and composition of human lymphatic vessels in patients with ovarian cancer. Future work should expand on this knowledge base with investigations of vessels from other anatomical locations, contractile behavior, and the implications on metastatic cell transport.

  4. Edge density imaging: mapping the anatomic embedding of the structural connectome within the white matter of the human brain.

    PubMed

    Owen, Julia P; Chang, Yi Shin; Mukherjee, Pratik

    2015-04-01

    The structural connectome has emerged as a powerful tool to characterize the network architecture of the human brain and shows great potential for generating important new biomarkers for neurologic and psychiatric disorders. The edges of the cerebral graph traverse white matter to interconnect cortical and subcortical nodes, although the anatomic embedding of these edges is generally overlooked in the literature. Mapping the paths of the connectome edges could elucidate the relative importance of individual white matter tracts to the overall network topology of the brain and also lead to a better understanding of the effect of regionally-specific white matter pathology on cognition and behavior. In this work, we introduce edge density imaging (EDI), which maps the number of network edges that pass through every white matter voxel. Test-retest analysis shows good to excellent reliability for edge density (ED) measurements, with consistent results using different cortical and subcortical parcellation schemes and different diffusion MR imaging acquisition parameters. We also demonstrate that ED yields complementary information to both traditional and emerging voxel-wise metrics of white matter microstructure and connectivity, including fractional anisotropy, track density, fiber orientation dispersion and neurite density. Our results demonstrate spatially ordered variations of ED throughout the white matter, notably including greater ED in posterior than anterior cerebral white matter. The EDI framework is employed to map the white matter regions that are enriched with pathways connecting rich club nodes and also those with high densities of intra-modular and inter-modular edges. We show that periventricular white matter has particularly high ED and high densities of rich club edges, which is significant for diseases in which these areas are selectively affected, ranging from white matter injury of prematurity in infants to leukoaraiosis in the elderly. Using edge

  5. Edge Density Imaging: Mapping the Anatomic Embedding of the Structural Connectome Within the White Matter of the Human Brain

    PubMed Central

    Owen, Julia P.; Chang, Yi-Shin; Mukherjee, Pratik

    2015-01-01

    The structural connectome has emerged as a powerful tool to characterize the network architecture of the human brain and shows great potential for generating important new biomarkers for neurologic and psychiatric disorders. The edges of the cerebral graph traverse white matter to interconnect cortical and subcortical nodes, although the anatomic embedding of these edges is generally overlooked in the literature. Mapping the paths of the connectome edges could elucidate the relative importance of individual white matter tracts to the overall network topology of the brain and also lead to a better understanding of the effect of regionally-specific white matter pathology on cognition and behavior. In this work, we introduce edge density imaging (EDI), which maps the number of network edges that pass through every white matter voxel. Test-retest analysis shows good to excellent reliability for edge density (ED) measurements, with consistent results using different cortical and subcortical parcellation schemes and different diffusion MR imaging acquisition parameters. We also demonstrate that ED yields complementary information to both traditional and emerging voxel-wise metrics of white matter microstructure and connectivity, including fractional anisotropy, track density, fiber orientation dispersion and neurite density. Our results demonstrate spatially ordered variations of ED throughout the white matter, notably including greater ED in posterior than anterior cerebral white matter. The EDI framework is employed to map the white matter regions that are enriched with pathways connecting rich club nodes and also those with high densities of intra-modular and inter-modular edges. We show that periventricular white matter has particularly high ED and high densities of rich club edges, which is significant for diseases in which these areas are selectively affected, ranging from white matter injury of prematurity in infants to leukoaraiosis in the elderly. Using edge

  6. A stereotaxic MRI template set for the rat brain with tissue class distribution maps and co-registered anatomical atlas: application to pharmacological MRI.

    PubMed

    Schwarz, Adam J; Danckaert, Anne; Reese, Torsten; Gozzi, Alessandro; Paxinos, George; Watson, Charles; Merlo-Pich, Emilio V; Bifone, Angelo

    2006-08-15

    We describe a stereotaxic rat brain MRI template set with a co-registered digital anatomical atlas and illustrate its application to the analysis of a pharmacological MRI (phMRI) study of apomorphine. The template set includes anatomical images and tissue class probability maps for brain parenchyma and cerebrospinal fluid (CSF). These facilitate the use of standard fMRI software for spatial normalisation and tissue segmentation of rat brain data. A volumetric reconstruction of the Paxinos and Watson rat brain atlas is also co-localised with the template, enabling the atlas structure and stereotaxic coordinates corresponding to a feature within a statistical map to be interactively reported, facilitating the localisation of functional effects. Moreover, voxels falling within selected brain structures can be combined to define anatomically based 3D volumes of interest (VOIs), free of operator bias. As many atlas structures are small relative to the typical resolution of phMRI studies, a mechanism for defining composite structures as agglomerations of individual atlas structures is also described. This provides a simple and robust means of interrogating structures that are otherwise difficult to delineate and an objective framework for comparing and classifying compounds based on an anatomical profile of their activity. These developments allow a closer alignment of pre-clinical and clinical analysis techniques.

  7. Technique of right lymphatic duct cannulation for pulmonary lymph collection in an acute porcine model.

    PubMed

    Chuang, G J; Gao, C X; Mulder, D S; Chiu, R C

    1986-12-01

    The pig is an increasingly preferred model for biomedical research, including studies for pulmonary pathophysiology. However, in piglets, the technique for cannulating the right lymphatic duct, which is subject to more anatomical variations and technically more demanding than that in dogs, has not been described. Our technique evolved to enable this collection of porcine lung lymph in acute experiments. The lymphatic ampulla is cannulated via one of the cervical lymphatics. The right lymphatic duct is invariably dorsal to the cranial vena cava and classically leads to the lymphatic ampulla. Yet in 18% of our pigs, cannulation was difficult or not feasible because the lymphatic duct either drained directly into the cranial vena cava at a distance from the lymphatic ampulla, or into the axillary lymph node of the first rib or the caudal deep cervical lymph nodes. Gently squeezing back regurgitated blood in the lymphatic ampulla before tying the suture and frequently withdrawing lymph with a syringe when the flow is small enabled us to collect clear lymph, usually immediately after completing the cannulation. The rate of lymph flow varied widely (1.7 +/- 0.6 ml/hr) and increased when the left atrial pressure was raised. The lymph protein was 2.8 +/- 0.2 g% with lymph/plasma protein ratio at 0.55 +/- 0.04. The anatomical variations encountered in our 34 dissections, as well as the technical maneuvers found to be useful in the successful cannulation and collection of the porcine lung lymph, are described in detail.

  8. Lymphedema: A General Outline of Its Anatomical Base.

    PubMed

    Amore, M; Tapia, L; Mercado, D; Pattarone, G; Ciucci, J

    2016-01-01

    The anatomic research of the lymphatic system has been a very controversial subject throughout due to the complexity of the methods for its visualization. More than 30 years ago, together with Prof. Caplan, we began the vascular anatomy research, focusing on the lymphatic anatomy, developing and adapting different techniques of injection. On the third Normal Anatomy Chair of Buenos Aires University, we summarized the lymphatic drainage of the breast and the limbs to interpret the anatomic bases of lymphedema. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. PAVA: physiological and anatomical visual analytics for mapping of tissue-specific concentration and time-course data.

    PubMed

    Goldsmith, Michael-Rock; Transue, Thomas R; Chang, Daniel T; Tornero-Velez, Rogelio; Breen, Michael S; Dary, Curtis C

    2010-06-01

    We describe the development and implementation of a Physiological and Anatomical Visual Analytics tool (PAVA), a web browser-based application, used to visualize experimental/simulated chemical time-course data (dosimetry), epidemiological data and Physiologically-Annotated Data (PAD). Using continuous color mapping scheme both spatial (organ shape and location) and temporal (time-course/kinetics) data was cast onto an abstract, layered, 2D visual representation of the human anatomy and physiology. This approach is aligned with the compartment-level of detail afforded by Physiologically-Based Pharmacokinetic (PBPK) modeling of chemical disposition. In this tutorial we provide several illustrative examples of how PAVA may be applied: (1) visualization of multiple organ/tissue simulated dosimetry of a previously published oral exposure route ethanol PBPK model, (2) visualization of PAD such as organ-specific disease time-lines or (3) tissue-specific mRNA expression-level profiles (e.g. phase I/II metabolic enzymes and nuclear receptors) to draw much needed molecular biological conclusions at organ-level resolution conducive to model development. Furthermore, discussion is raised on how graphical representations of PBPK models, and the use of PAVA more generally to visualize PAD, can be of benefit. We believe this novel platform-independent tool for visualizing PAD on physiologically-relevant representations of human anatomy will become a valuable visual analytic addition to the tool-kits of modern exposure scientists, computational biologists, toxicologists, biochemists, molecular biologists, epidemiologists and pathologists alike in visually translating, representing and mining complex PAD relationships required to understand systems biology or manage chemical risk.

  10. Real-time Intraoperative Fluorescent Lymphography: A New Technique for Lymphatic Sparing Surgery.

    PubMed

    Ietto, G; Amico, F; Soldini, G; Chiappa, C; Franchin, M; Iovino, D; Romanzi, A; Saredi, G; Cassinotti, E; Boni, L; Tozzi, M; Carcano, G

    2016-11-01

    Many surgical procedures can produce persistent lymphorrhea, lymphoceles, and lymphedema after lymph node and lymph vessel damage. Appropriate visualization of the lymphatic system is challenging. Indocyanine green (ICG) is a well-known nontoxic dye for lymphatic flow evaluation. ICG fluorescence-guided lymphography has emerged as a promising technique for intraoperative lymphatic mapping. Our goal was to develop a high spatial resolution, real-time intraoperative imaging technique to avoid or recognize early deep lymphatic vessel damage. We intraoperatively performed ICG fluorescence-guided lymphography during a kidney transplant. ICG was injected in the subcutaneous tissue of the patient's groin in the Scarpa's triangle. A dedicated laparoscopic high-definition camera system was used. Soon after ICG injection, the lymphatic vessels were identified in the abdominal retroperitoneal compartment as fluorescent linear structures running side by side to the iliac vessels. Surgical dissection was therefore performed, avoiding iatrogenic damage to major lymphatic structures. Another ICG injection at the end of the procedure confirmed that the lymphatic vessels were intact without lymph spread. Intraoperative lymphatic mapping with an ICG fluorescence-sensitive camera system is a safe and feasible procedure. ICG real-time fluorescence lymphography can be used to avoid or recognize early deep lymphatic vessel damage and reduce postoperative complications related to the lymphatic system. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Lymphatic filariasis and onchocerciasis.

    PubMed

    Taylor, Mark J; Hoerauf, Achim; Bockarie, Moses

    2010-10-02

    Lymphatic filariasis and onchocerciasis are parasitic helminth diseases that constitute a serious public health issue in tropical regions. The filarial nematodes that cause these diseases are transmitted by blood-feeding insects and produce chronic and long-term infection through suppression of host immunity. Disease pathogenesis is linked to host inflammation invoked by the death of the parasite, causing hydrocoele, lymphoedema, and elephantiasis in lymphatic filariasis, and skin disease and blindness in onchocerciasis. Most filarial species that infect people co-exist in mutualistic symbiosis with Wolbachia bacteria, which are essential for growth, development, and survival of their nematode hosts. These endosymbionts contribute to inflammatory disease pathogenesis and are a target for doxycycline therapy, which delivers macrofilaricidal activity, improves pathological outcomes, and is effective as monotherapy. Drugs to treat filariasis include diethylcarbamazine, ivermectin, and albendazole, which are used mostly in combination to reduce microfilariae in blood (lymphatic filariasis) and skin (onchocerciasis). Global programmes for control and elimination have been developed to provide sustained delivery of drugs to affected communities to interrupt transmission of disease and ultimately eliminate this burden on public health. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. The lymphatic vasculature in disease.

    PubMed

    Alitalo, Kari

    2011-11-07

    Blood vessels form a closed circulatory system, whereas lymphatic vessels form a one-way conduit for tissue fluid and leukocytes. In most vertebrates, the main function of lymphatic vessels is to collect excess protein-rich fluid that has extravasated from blood vessels and transport it back into the blood circulation. Lymphatic vessels have an important immune surveillance function, as they import various antigens and activated antigen-presenting cells into the lymph nodes and export immune effector cells and humoral response factors into the blood circulation. Defects in lymphatic function can lead to lymph accumulation in tissues, dampened immune responses, connective tissue and fat accumulation, and tissue swelling known as lymphedema. This review highlights the most recent developments in lymphatic biology and how the lymphatic system contributes to the pathogenesis of various diseases involving immune and inflammatory responses and its role in disseminating tumor cells.

  13. PAVA: Physiological and Anatomical Visual Analytics for Mapping of Tissue-Specific Concentration and Time-Course Data

    EPA Science Inventory

    We describe the development and implementation of a Physiological and Anatomical Visual Analytics tool (PAVA), a web browser-based application, used to visualize experimental/simulated chemical time-course data (dosimetry), epidemiological data and Physiologically-Annotated Data ...

  14. PAVA: Physiological and Anatomical Visual Analytics for Mapping of Tissue-Specific Concentration and Time-Course Data

    EPA Science Inventory

    We describe the development and implementation of a Physiological and Anatomical Visual Analytics tool (PAVA), a web browser-based application, used to visualize experimental/simulated chemical time-course data (dosimetry), epidemiological data and Physiologically-Annotated Data ...

  15. Mechanosensing in developing lymphatic vessels.

    PubMed

    Planas-Paz, Lara; Lammert, Eckhard

    2014-01-01

    The lymphatic vasculature is responsible for fluid homeostasis, transport of immune cells, inflammatory molecules, and dietary lipids. It is composed of a network of lymphatic capillaries that drain into collecting lymphatic vessels and ultimately bring fluid back to the blood circulation. Lymphatic endothelial cells (LECs) that line lymphatic capillaries present loose overlapping intercellular junctions and anchoring filaments that support fluid drainage. When interstitial fluid accumulates within tissues, the extracellular matrix (ECM) swells and pulls the anchoring filaments. This results in opening of the LEC junctions and permits interstitial fluid uptake. The absorbed fluid is then transported within collecting lymphatic vessels, which exhibit intraluminal valves that prevent lymph backflow and smooth muscle cells that sequentially contract to propel lymph.Mechanotransduction involves translation of mechanical stimuli into biological responses. LECs have been shown to sense and respond to changes in ECM stiffness, fluid pressure-induced cell stretch, and fluid flow-induced shear stress. How these signals influence LEC function and lymphatic vessel growth can be investigated by using different mechanotransduction assays in vitro and to some extent in vivo.In this chapter, we will focus on the mechanical forces that regulate lymphatic vessel expansion during embryonic development and possibly secondary lymphedema. In mouse embryos, it has been recently shown that the amount of interstitial fluid determines the extent of lymphatic vessel expansion via a mechanosensory complex formed by β1 integrin and vascular endothelial growth factor receptor-3 (VEGFR3). This model might as well apply to secondary lymphedema.

  16. Infrared fluorescence imaging of lymphatic regeneration in nonhuman primate facial vascularized composite allografts.

    PubMed

    Mundinger, Gerhard S; Narushima, Mitsunaga; Hui-Chou, Helen G; Jones, Luke S; Ha, Jinny S; Shipley, Steven T; Drachenberg, Cinthia B; Dorafshar, Amir H; Koshima, Isao; Bartlett, Stephen T; Barth, Rolf N; Rodriguez, Eduardo D

    2012-03-01

    Clinical vascularized composite allografts (VCA), although performed with good success, have been characterized by rejection episodes and postoperative graft edema. We investigated lymphatic donor-recipient reconstitution and lymphatic regeneration in a nonhuman primate facial VCA model. Heterotopic partial face (n = 9) VCAs were performed in cynomolgus macaques. Grafts were monitored for rejection episodes and response to immunosuppressive therapies as previously described. Donor and recipient lymphatic channels were evaluated using a near-infrared handheld dual-channel light-emitting diode camera system capable of detecting fluorescence from indocyanine green injections. Graft lymphatic channels were serially evaluated from postoperative day 0 to 364. Preoperative imaging demonstrated superficial lymphatic anatomy similar to human anatomy. Initial resolution of facial allograft swelling coincided with superficial donor-recipient lymphatic channel reconstitution. Reconstitution occurred despite early acute rejection episodes in 2 animals. However, lymphatic channels demonstrated persistent functional and anatomic pathology, and graft edema never fully resolved. No differences in lymphatic channels were noted between grafts that developed transplant vasculopathy (n = 3) and those that did not (n = 6). Dynamic changes in patterns of lymphatic drainage were noted in 4 animals following withdrawal of immunosuppression. Donor-recipient lymphatic channel regeneration following VCA did not result in resolution of edema. Technical causes of graft edema may be overcome with alternative surgical techniques, allowing for direct investigation of the immunologic relationship between VCA graft edema and rejection responses. Mechanisms and timing of dynamic donor-recipient lymphatic channel relationships can be evaluated using fluorescent imaging systems to better define the immunologic role of lymphatic channels in VCA engraftment and rejection responses, which may have direct

  17. Is tuberculosis a lymphatic disease with a pulmonary portal?

    PubMed

    Behr, Marcel A; Waters, W Ray

    2014-03-01

    Tuberculosis most commonly presents as a pulmonary disease, in which infection, persistence, and induction of transmissible pathology all occur in the lungs. If viewed as a pulmonary disease, enlarged lymph nodes represent reactive adenitis, and extrapulmonary forms of tuberculosis (including lymphatic tuberculosis) are not transmissible, hence representing an evolutionary dead-end for the pathogen. In an alternative theory, Mycobacterium tuberculosis passes asymptomatically through the lungs and rapidly establishes a chronic lymphatic infection. After a period of weeks to decades secondary lung pathology develops, ultimately allowing transmission to occur. Evidence that supports this lymphatic model includes historical descriptions of human tuberculosis from the preantibiotic era, analogy with other mycobacterial infections, observations of tuberculosis in non-human hosts, and experimental models of tuberculosis disease. At a fundamental level, a lymphocentric model proposes that spread of organisms outside the lung parenchyma is essential to induce adaptive immunity, which is crucial for the generation of transmissible pathology. Furthermore, a lymphatic model could explain why the lesion associated with primary infection (Ghon focus) is anatomically separated from the most common site of reactivation disease (the apex). More practically, an alternative perspective that classes tuberculosis as a lymphatic disease might affect strategies for preclinical and clinical assessment of novel diagnostics, drugs, and vaccines.

  18. First report of image integration of cine-angiography with 3D electro-anatomical mapping of the right ventricle in postoperative tetralogy of Fallot.

    PubMed

    Russo, Mario Salvatore; Righi, Daniela; Di Mambro, Corrado; Ruoppolo, Valentina; Silvetti, Massimo Stefano; Drago, Fabrizio

    2015-01-01

    Ventricular tachycardia and, more rarely, sudden cardiac death are potential complications affecting the long-term outcome after Tetralogy of Fallot (ToF) repair. Intraventricular septal scar, fibro-fatty substitution around infundibular resection and patchy myocardial fibrosis may provide anatomical substrates of abnormal depolarization and repolarization causing reentrant ventricular arrhythmias. Recently, three-dimensional electro-anatomical mapping (3D EAM) has allowed to investigate the electro-anatomical status of the right ventricle. Radiation exposure during cardiac electrophysiological procedures is still a major concern. We report the first case of 3D mapping of the right ventricle in a postoperative ToF patient performed with a new module of the CARTO® 3 System-the CARTOUnivu™ Module-that combines, simultaneously, fluoroscopic images or cine-angiographic sequences with 3D cardiac mapping to allow real-time visualization of the electrocatheter during the 3D EAM reconstruction. The same volume, previously evaluated with cardiac MRI, was mapped. A perfect match of the diastolic edges of the RV obtained either by cine-loop acquisition during contrast fluoroscopy and by the 3D EAM, was observed. The fluoroscopy time for 3D EAM was 10 s. In conclusion, CARTOUnivu™ Module can integrate, in real time, fluoroscopic images/cine-angiography in virtual biplane view and the 3D EAM allowing a contextual visualization of position and movement of all electrocatheters. This can further increase the accuracy of the 3D EAM in very complex-operated congenital heart diseases, even decreasing radiation exposure.

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

    PubMed

    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.

  20. Invasion of lymphatic vessels into the eye after open globe injuries.

    PubMed

    Wessel, Julia M; Hofmann-Rummelt, Carmen; Kruse, Friedrich E; Cursiefen, Claus; Heindl, Ludwig M

    2012-06-20

    We analyzed whether lymphatic vessels can be detected in eyes enucleated after an open globe injury. The presence of lymphatic vessels was analyzed immunohistochemically using podoplanin as a specific lymphatic endothelial marker in 21 globes that had been enucleated after open globe injury. The localization of pathologic lymphatic vessels (within the eye wall or inside the eye) was correlated with the mechanism of trauma, anatomic site of perforation or rupture, and time interval between trauma and enucleation. Pathologic lymphatic vessels were detected in 15 of 21 eyes (71%) enucleated after an open globe injury. In 5 globes (24%) they were found within the eye, located in retrocorneal membranes, underneath the sclera, and adjacent to uveal tissue (ciliary body, iris). No significant association was observed between the presence of pathologic lymphatic vessels and the mechanism of trauma (P = 0.598), anatomic site of perforation or rupture (P = 0.303), and time interval between trauma and enucleation (P = 0.145). The human eye can be invaded secondarily by lymphatic vessels if the eye wall is opened by trauma. This mechanism could be important for wound healing, immunologic defense against intruding microorganisms, and autoimmune reactions against intraocular antigens.

  1. Investigation of the lymphatic stream of the stomach in gastric cancer with solitary lymph node metastasis.

    PubMed

    Tokunaga, Masanori; Ohyama, Shigekazu; Hiki, Naoki; Fukunaga, Tetsu; Yamada, Kazuhiko; Sano, Takeshi; Yamaguchi, Toshiharu

    2009-06-01

    Understanding the lymphatic drainage route in gastric cancer is crucial for complete lymph node retrieval from sites susceptible to metastasis. However, the lymphatic stream of the stomach is complex and remains incompletely characterized. Patients with small (<4 cm) serosa-negative gastric cancer with solitary lymph node metastasis treated at the Cancer Institute Hospital were included in this study. A total of 135 patients were classified according to the location of the solitary lymph node metastasis into the left gastric artery (LGA) group, the right gastroepiploic artery (RGEA) group, the right gastric artery (RGA) group, or the splenic artery (SA) group. The location of the primary tumors was investigated to aid the mapping of the lymphatic stream of the stomach. Lymphatic flow in LGA (65 patients) and in RGEA (57 patients) are main lymphatic drainage routes of the stomach. The lymphatic area overlapped in the lower third of the stomach in LGA and RGEA, and the lymphatic flow associated with gastric cancer located within this overlapped area can be multidirectional. Skip metastases were observed in 13 patients (10%), and all skip metastases were observed in the suprapancreatic area (station 7, 8a, 9, or 11p). The lymphatic stream of the stomach is complicated and multidirectional. Understanding and mapping the complex lymphatic streams of the stomach will allow surgeons to perform more effective lymph node dissection during gastric cancer surgery.

  2. West Nile Virus Spreads Transsynaptically within the Pathways of Motor Control: Anatomical and Ultrastructural Mapping of Neuronal Virus Infection in the Primate Central Nervous System

    PubMed Central

    Maximova, Olga A.; Bernbaum, John G.; Pletnev, Alexander G.

    2016-01-01

    Background During recent West Nile virus (WNV) outbreaks in the US, half of the reported cases were classified as neuroinvasive disease. WNV neuroinvasion is proposed to follow two major routes: hematogenous and/or axonal transport along the peripheral nerves. How virus spreads once within the central nervous system (CNS) remains unknown. Methodology/Principal Findings Using immunohistochemistry, we examined the expression of viral antigens in the CNS of rhesus monkeys that were intrathalamically inoculated with a wild-type WNV. The localization of WNV within the CNS was mapped to specific neuronal groups and anatomical structures. The neurological functions related to structures containing WNV-labeled neurons were reviewed and summarized. Intraneuronal localization of WNV was investigated by electron microscopy. The known anatomical connectivity of WNV-labeled neurons was used to reconstruct the directionality of WNV spread within the CNS using a connectogram design. Anatomical mapping revealed that all structures identified as containing WNV-labeled neurons belonged to the pathways of motor control. Ultrastructurally, virions were found predominantly within vesicular structures (including autophagosomes) in close vicinity to the axodendritic synapses, either at pre- or post-synaptic positions (axonal terminals and dendritic spines, respectively), strongly indicating transsynaptic spread of the virus between connected neurons. Neuronal connectivity-based reconstruction of the directionality of transsynaptic virus spread suggests that, within the CNS, WNV can utilize both anterograde and retrograde axonal transport to infect connected neurons. Conclusions/Significance This study offers a new insight into the neuropathogenesis of WNV infection in a primate model that closely mimics WNV encephalomyelitis in humans. We show that within the primate CNS, WNV primarily infects the anatomical structures and pathways responsible for the control of movement. Our findings

  3. Lymphatic System in Cardiovascular Medicine.

    PubMed

    Aspelund, Aleksanteri; Robciuc, Marius R; Karaman, Sinem; Makinen, Taija; Alitalo, Kari

    2016-02-05

    The mammalian circulatory system comprises both the cardiovascular system and the lymphatic system. In contrast to the blood vascular circulation, the lymphatic system forms a unidirectional transit pathway from the extracellular space to the venous system. It actively regulates tissue fluid homeostasis, absorption of gastrointestinal lipids, and trafficking of antigen-presenting cells and lymphocytes to lymphoid organs and on to the systemic circulation. The cardinal manifestation of lymphatic malfunction is lymphedema. Recent research has implicated the lymphatic system in the pathogenesis of cardiovascular diseases including obesity and metabolic disease, dyslipidemia, inflammation, atherosclerosis, hypertension, and myocardial infarction. Here, we review the most recent advances in the field of lymphatic vascular biology, with a focus on cardiovascular disease. © 2016 American Heart Association, Inc.

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

    PubMed

    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.

  5. In vivo albumin labeling and lymphatic imaging

    PubMed Central

    Wang, Yu; Lang, Lixin; Huang, Peng; Wang, Zhe; Jacobson, Orit; Kiesewetter, Dale O.; Ali, Iqbal U.; Teng, Gaojun; Niu, Gang; Chen, Xiaoyuan

    2015-01-01

    The ability to accurately and easily locate sentinel lymph nodes (LNs) with noninvasive imaging methods would assist in tumor staging and patient management. For this purpose, we developed a lymphatic imaging agent by mixing fluorine-18 aluminum fluoride-labeled NOTA (1,4,7-triazacyclononane-N,N',N''-triacetic acid)-conjugated truncated Evans blue (18F-AlF-NEB) and Evans blue (EB) dye. After local injection, both 18F-AlF-NEB and EB form complexes with endogenous albumin in the interstitial fluid and allow for visualizing the lymphatic system. Positron emission tomography (PET) and/or optical imaging of LNs was performed in three different animal models including a hind limb inflammation model, an orthotropic breast cancer model, and a metastatic breast cancer model. In all three models, the LNs can be distinguished clearly by the apparent blue color and strong fluorescence signal from EB as well as a high-intensity PET signal from 18F-AlF-NEB. The lymphatic vessels between the LNs can also be optically visualized. The easy preparation, excellent PET and optical imaging quality, and biosafety suggest that this combination of 18F-AlF-NEB and EB has great potential for clinical application to map sentinel LNs and provide intraoperative guidance. PMID:25535368

  6. Shared and distinct anatomical correlates of semantic and phonemic fluency revealed by lesion-symptom mapping in patients with ischemic stroke.

    PubMed

    Biesbroek, J Matthijs; van Zandvoort, Martine J E; Kappelle, L Jaap; Velthuis, Birgitta K; Biessels, Geert Jan; Postma, Albert

    2016-05-01

    Semantic and phonemic fluency tasks are frequently used to test executive functioning, speed and attention, and access to the mental lexicon. In semantic fluency tasks, subjects are required to generate words belonging to a category (e.g., animals) within a limited time window, whereas in phonemic fluency tasks subjects have to generate words starting with a given letter. Anatomical correlates of semantic and phonemic fluency are currently assumed to overlap in left frontal structures, reflecting shared executive processes, and to be distinct in left temporal and right frontal structures, reflecting involvement of distinct memory processes and search strategies. Definite evidence for this assumption is lacking. To further establish the anatomical correlates of semantic and phonemic fluency, we applied assumption-free voxel-based and region-of-interest-based lesion-symptom mapping in 93 patients with ischemic stroke. Fluency was assessed by asking patients to name animals (semantic), and words starting with the letter N and A (phonemic). Our findings indicate that anatomical correlates of semantic and phonemic fluency overlap in the left inferior frontal gyrus and insula, reflecting shared underlying cognitive processes. Phonemic fluency additionally draws on the left rolandic operculum, which might reflect a search through phonological memory, and the middle frontal gyrus. Semantic fluency additionally draws on left medial temporal regions, probably reflecting a search through semantic memory, and the right inferior frontal gyrus, which might reflect the application of a visuospatial mental imagery strategy in semantic fluency. These findings establish shared and distinct anatomical correlates of semantic and phonemic fluency.

  7. Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD

    PubMed Central

    2013-01-01

    Background De novo lymphatic vessel formation has recently been observed in lungs of patients with moderate chronic obstructive pulmonary disease (COPD). However, the distribution of lymphatic vessel changes among the anatomical compartments of diseased lungs is unknown. Furthermore, information regarding the nature of lymphatic vessel alterations across different stages of COPD is missing. This study performs a detailed morphometric characterization of lymphatic vessels in major peripheral lung compartments of patients with different severities of COPD and investigates the lymphatic expression of molecules involved in immune cell trafficking. Methods Peripheral lung resection samples obtained from patients with mild (GOLD stage I), moderate-severe (GOLD stage II-III), and very severe (GOLD stage IV) COPD were investigated for podoplanin-immunopositive lymphatic vessels in distinct peripheral lung compartments: bronchioles, pulmonary blood vessels and alveolar walls. Control subjects with normal lung function were divided into never smokers and smokers. Lymphatics were analysed by multiple morphological parameters, as well as for their expression of CCL21 and the chemokine scavenger receptor D6. Results The number of lymphatics increased by 133% in the alveolar parenchyma in patients with advanced COPD compared with never-smoking controls (p < 0.05). In patchy fibrotic lesions the number of alveolar lymphatics increased 20-fold from non-fibrotic parenchyma in the same COPD patients. The absolute number of lymphatics per bronchiole and artery was increased in advanced COPD, but numbers were not different after normalization to tissue area. Increased numbers of CCL21- and D6-positive lymphatics were observed in the alveolar parenchyma in advanced COPD compared with controls (p < 0.01). Lymphatic vessels also displayed increased mean levels of immunoreactivity for CCL21 in the wall of bronchioles (p < 0.01) and bronchiole-associated arteries (p < 0

  8. Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD.

    PubMed

    Mori, Michiko; Andersson, Cecilia K; Graham, Gerard J; Löfdahl, Claes-Göran; Erjefält, Jonas S

    2013-06-11

    De novo lymphatic vessel formation has recently been observed in lungs of patients with moderate chronic obstructive pulmonary disease (COPD). However, the distribution of lymphatic vessel changes among the anatomical compartments of diseased lungs is unknown. Furthermore, information regarding the nature of lymphatic vessel alterations across different stages of COPD is missing. This study performs a detailed morphometric characterization of lymphatic vessels in major peripheral lung compartments of patients with different severities of COPD and investigates the lymphatic expression of molecules involved in immune cell trafficking. Peripheral lung resection samples obtained from patients with mild (GOLD stage I), moderate-severe (GOLD stage II-III), and very severe (GOLD stage IV) COPD were investigated for podoplanin-immunopositive lymphatic vessels in distinct peripheral lung compartments: bronchioles, pulmonary blood vessels and alveolar walls. Control subjects with normal lung function were divided into never smokers and smokers. Lymphatics were analysed by multiple morphological parameters, as well as for their expression of CCL21 and the chemokine scavenger receptor D6. The number of lymphatics increased by 133% in the alveolar parenchyma in patients with advanced COPD compared with never-smoking controls (p < 0.05). In patchy fibrotic lesions the number of alveolar lymphatics increased 20-fold from non-fibrotic parenchyma in the same COPD patients. The absolute number of lymphatics per bronchiole and artery was increased in advanced COPD, but numbers were not different after normalization to tissue area. Increased numbers of CCL21- and D6-positive lymphatics were observed in the alveolar parenchyma in advanced COPD compared with controls (p < 0.01). Lymphatic vessels also displayed increased mean levels of immunoreactivity for CCL21 in the wall of bronchioles (p < 0.01) and bronchiole-associated arteries (p < 0.05), as well as the alveolar

  9. LYMPHATIC VESSELS IN HEALTH AND DISEASE

    PubMed Central

    Kesler, Cristina T.; Liao, Shan; Munn, Lance L.; Padera, Timothy P.

    2012-01-01

    The lymphatic vasculature plays vital roles in tissue fluid balance, immune defense, metabolism and cancer metastasis. In adults, lymphatic vessel formation and remodeling occurs primarily during inflammation, development of the corpus luteum, wound healing, and tumor growth. Unlike the blood circulation, where unidirectional flow is sustained by the pumping actions of the heart, pumping actions intrinsic to the lymphatic vessels themselves are important drivers of lymphatic flow. This review summarizes critical components that control lymphatic physiology. PMID:23209022

  10. Lymphatic Biodistribution of Polylactide Nanoparticles

    PubMed Central

    Chaney, Eric J.; Tang, Li; Tong, Rong; Cheng, Jianjun; Boppart, Stephen A.

    2013-01-01

    Tumor metastases occur through both the cardiovascular and lymphatic circulations. However, the majority of nanoparticle biodistribution studies have been focused on the cardiovascular circulation. In this study, we report the formulation of Cy5-labeled polylactide (Cy5-PLA) nanoparticles with controlled size and surface features and the subsequent evaluation of their lymphatic biodistribution. Cy5-PLA nanoparticles were formulated through Cy5/(BDI)ZnN(TMS)2-mediated [(BDI) = 2-((2,6-diisopropylphenyl) amido)-4-((2,6-diisopropylphenyl)-imino)-2-pentene] ring-opening polymerization of lactide followed by nanoprecipitation. Their lymphatic biodistribution was evaluated by using whole-body fluorescence imaging of nude mice and ex vivo fluorescence imaging of the resected organs. This technique has the potential for providing optical contrast and drug delivery through the lymphatic circulation for the treatment of metastatic cancer. PMID:20487681

  11. Olfactory route for cerebrospinal fluid drainage into the cervical lymphatic system in a rabbit experimental model☆

    PubMed Central

    Liu, Haisheng; Ni, Zhili; Chen, Yetao; Wang, Dong; Qi, Yan; Zhang, Qiuhang; Wang, Shijie

    2012-01-01

    The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil® (Microfil compounds fill and opacify microvascular and other spaces of non-surviving animals and post-mortem tissue under physiological injection pressure) were injected into the cisterna magna of the rabbit, and perineural routes of cerebrospinal fluid outflow into the lymphatic system were visualized. Under a surgical operating microscope, Microfil was found within the subarachnoid space and along the olfactory nerves. At the nasal mucosa, a lymphatic network was identified near the olfactory nerves, which crossed the nasopharyngeal region and finally emptied into the superficial and deep cervical lymph nodes. Under a light microscope, Microfil was visible around the olfactory nerves and within lymphatic vessels. These results suggested that cerebrospinal fluid drained from the subarachnoid space along the olfactory nerves to nasal lymphatic vessels, which in turn, emptied into the cervical lymph nodes. This anatomical route, therefore, allowed connection between the central nervous system and the lymphatic system. PMID:25737700

  12. Lymphatic Regulation of Cellular Trafficking

    PubMed Central

    Jackson, David G.

    2016-01-01

    Lymphatic vessels play vital roles in immune surveillance and immune regulation by conveying antigen loaded dendritic cells, memory T cells, macrophages and neutrophils from the peripheral tissues to draining lymph nodes where they initiate as well as modify immune responses. Until relatively recently however, there was little understanding of how entry and migration through lymphatic vessels is organized or the specific molecular mechanisms that might be involved. Within the last decade, the situation has been transformed by an explosion of knowledge generated largely through the application of microscopic imaging, transgenic animals, specific markers and function blocking mAbs that is beginning to provide a rational conceptual framework. This article provides a critical review of the recent literature, highlighting seminal discoveries that have revealed the fascinating ultrastructure of leucocyte entry sites in lymphatic vessels, as well as generating controversies over the involvement of integrin adhesion, chemotactic and haptotactic mechanisms in DC entry under normal and inflamed conditions. It also discusses the major changes in lymphatic architecture that occur during inflammation and the different modes of leucocyte entry and trafficking within inflamed lymphatic vessels, as well as presenting a timely update on the likely role of hyaluronan and the major lymphatic endothelial hyaluronan receptor LYVE-1 in leucocyte transit. PMID:27808282

  13. Catheter ablation of atypical atrial flutter: a novel 3D anatomic mapping approach to quickly localize and terminate atypical atrial flutter.

    PubMed

    Sundaram, Sri; Choe, William; Ryan Jordan, J; Mullins, Nate; Boorman, Charles; Kessler, Eric J; Nath, Sunil

    2017-09-01

    This study aims to describe a novel method of High Density Activation Sequence Mapping combined with Voltage Gradient Mapping Overlay (HD-VGM) to quickly localize and terminate atypical atrial flutter. Twenty-one patients presenting with 26 different atypical atrial flutter circuits after a previous catheter or surgical AF ablation were studied. HD-VGM was performed with a commercially available impedance-based mapping system to locate and successfully ablate the critical isthmus of each tachycardia circuit. The results were compared to 21 consecutive historical control patients who had undergone an atypical flutter ablation without HD-VGM. Twenty-six different atypical flutter circuits were evaluated. An average 3D anatomic mapping time of 12.39 ± 4.71 min was needed to collect 2996 ± 690 total points and 1016 ± 172 used mapping points. A mean of 195 ± 75 s of radiofrequency (RF) energy was needed to terminate the arrhythmias. The mean procedure time was 135 ± 46 min. With a mean follow-up 16 ± 9 months, 90% are in normal rhythm. In comparison to the control cohort, the study cohort had a shorter procedure time (135 ± 46 vs. 210 ± 41 min, p = 0.0009), fluoroscopy time (8.5 ± 3.7 vs. 17.7 ± 7.7 min, p = 0.0021), and success in termination of the arrhythmia during the procedure (100 vs. 68.2%, p = 0.0230). Ablation of atypical atrial flutter is challenging and time consuming. This case series shows that HD-VGM mapping can quickly localize and terminate an atypical flutter circuit.

  14. Absence of lymphatic vessels in the dog dental pulp: an immunohistochemical study.

    PubMed

    Martin, Anna; Gasse, Hagen; Staszyk, Carsten

    2010-11-01

    In spite of numerous investigations it has not been precisely determined whether lymphatic vessels are present in the dental pulp of dogs. Therefore, this study attempted a specific immunohistochemical detection of lymphatic endothelium. The canine teeth of 19 healthy beagle dogs were dissected into three segments (apical, intermediate and occlusal). After decalcification, specimens were embedded in paraffin wax and histologic cross-sections were stained immunohistochemically using a reliable antibody (anti-Prox-1) against the homeobox transcription factor Prox-1, which is located within the nucleus of lymphatic endothelium. Anti-Prox-1 reacted positively with canine control tissues (lymph nodes, gingiva, nasal mucosa), but showed no staining in tissue sections of the dental pulp. The dog dental pulp contained no vascular structures lined with lymphatic endothelium. This suggests that drainage of interstitial fluid makes use of other routes, i.e. extravascular pathways. © 2010 The Authors. Journal of Anatomy © 2010 Anatomical Society of Great Britain and Ireland.

  15. [Comparative characteristics of the lymphatic bed of organ of vision in animals].

    PubMed

    Paninskiĭ, S M

    2005-01-01

    This investigation was aimed at the study of peculiarities of of lymphatic bed of organ of vision in herbivorous (cattle) and predatory (dog) animals, which have some anatomical differences in the eye structure. The methods of preparation, morphometry, light and electron microscopy were used. It was found that in the cattle, lymphatic capillaries of the sclera have lower density of distribution than those in dogs. In the cattle, extraorgan lymphatic vessels of lower and upper eyelids could be subdivided into a lateral and medial groups. The former group drains into parotid lymph node, while the latter group is connected to a mandibular one. In dogs an additional pathway of lymph transport was found that carried the lymph through the extraorgan lymphatic vessels into the facial lymph node.

  16. General surgery, translational lymphology and lymphatic surgery.

    PubMed

    Campisi, C; Witte, M H; Fulcheri, E; Campisi, C; Bellini, C; Villa, G; Campisi, C; Santi, P L; Parodi, A; Murdaca, G; Puppo, F; Boccardo, F

    2011-12-01

    A wide clinical experience in General Surgery has brought about a remarkable knowledge about lymphatic disorders both primary and secondary ones. Diagnostic and histopathological studies of lymphatic diseases allowed to better understand etiological aspects and pathophysiological mechanisms responsible of complex clinical features correlated to lymphatic dysfunctions. Translational lymphologic basic and clinical researches permitted to improve therapeutical approaches both from the medical and surgical point of view. Thus, strategies of treatment were proposed to prevent lymphatic injuries, to avoid lymphatic complications and to treat lymphatic diseases early in order to be able even to cure these pathologies.

  17. Clinical applications of the superior epigastric artery perforator (SEAP) flap: anatomical studies and preoperative perforator mapping with multidetector CT.

    PubMed

    Hamdi, Moustapha; Van Landuyt, Koenraad; Ulens, Sara; Van Hedent, Eddy; Roche, Nathalie; Monstrey, Stan

    2009-09-01

    Pedicled superior epigastric artery perforator (SEAP) flaps can be raised to cover challenging thoracic defects. We present an anatomical study based on multidetector computerized tomography (MDCT) scan findings of the SEA perforators in addition to the first reported clinical series of SEAP flaps in anterior chest wall reconstruction. (a) In the CT scan study, images of a group of 20 patients who underwent MDCT scan analysis were used to visualise bilaterally the location of musculocutaneous SEAP. X- and Y-axes were used as landmarks to localise the perforators. The X-axis is a horizontal line at the junction of sternum and xyphoid (JCX) and the Y-axis is at the midline. (b) In the clinical study, seven pedicled SEAP flaps were performed in another group of patients. MDCT images revealed totally 157 perforators with a mean of 7.85 perforators per patient. The dominant perforators (137 perforators) were mainly localised in an area between 1.5 and 6.5 cm from the X-axis on both sides and between 3 and 16 cm below the Y-axis. The calibre of these dominant perforators was judged as 'good' to 'very good' in 82.5% of the cases. The average dimension of the flap was 21.7x6.7 cm. All flaps were based on one perforator. Mean harvesting time was 110 min. There were no flap losses. Minor tip necrosis occurred in two flaps. One of them was treated with excision and primary closure. Our clinical experience indicates that the SEAP flap provides a novel and useful approach for reconstruction of anterior chest wall defects. CT-based imaging allows for anatomical assessment of the perforators of the superior epigastric artery (SEA).

  18. Lymphatic regulation in nonmammalian vertebrates.

    PubMed

    Hedrick, Michael S; Hillman, Stanley S; Drewes, Robert C; Withers, Philip C

    2013-08-01

    All vertebrate animals share in common the production of lymph through net capillary filtration from their closed circulatory system into their tissues. The balance of forces responsible for net capillary filtration and lymph formation is described by the Starling equation, but additional factors such as vascular and interstitial compliance, which vary markedly among vertebrates, also have a significant impact on rates of lymph formation. Why vertebrates show extreme variability in rates of lymph formation and how nonmammalian vertebrates maintain plasma volume homeostasis is unclear. This gap hampers our understanding of the evolution of the lymphatic system and its interaction with the cardiovascular system. The evolutionary origin of the vertebrate lymphatic system is not clear, but recent advances suggest common developmental factors for lymphangiogenesis in teleost fishes, amphibians, and mammals with some significant changes in the water-land transition. The lymphatic system of anuran amphibians is characterized by large lymphatic sacs and two pairs of lymph hearts that return lymph into the venous circulation but no lymph vessels per se. The lymphatic systems of reptiles and some birds have lymph hearts, and both groups have extensive lymph vessels, but their functional role in both lymph movement and plasma volume homeostasis is almost completely unknown. The purpose of this review is to present an evolutionary perspective in how different vertebrates have solved the common problem of the inevitable formation of lymph from their closed circulatory systems and to point out the many gaps in our knowledge of this evolutionary progression.

  19. Neuroanatomical substrates of action perception and understanding: an anatomic likelihood estimation meta-analysis of lesion-symptom mapping studies in brain injured patients.

    PubMed

    Urgesi, Cosimo; Candidi, Matteo; Avenanti, Alessio

    2014-01-01

    Several neurophysiologic and neuroimaging studies suggested that motor and perceptual systems are tightly linked along a continuum rather than providing segregated mechanisms supporting different functions. Using correlational approaches, these studies demonstrated that action observation activates not only visual but also motor brain regions. On the other hand, brain stimulation and brain lesion evidence allows tackling the critical question of whether our action representations are necessary to perceive and understand others' actions. In particular, recent neuropsychological studies have shown that patients with temporal, parietal, and frontal lesions exhibit a number of possible deficits in the visual perception and the understanding of others' actions. The specific anatomical substrates of such neuropsychological deficits however, are still a matter of debate. Here we review the existing literature on this issue and perform an anatomic likelihood estimation meta-analysis of studies using lesion-symptom mapping methods on the causal relation between brain lesions and non-linguistic action perception and understanding deficits. The meta-analysis encompassed data from 361 patients tested in 11 studies and identified regions in the inferior frontal cortex, the inferior parietal cortex and the middle/superior temporal cortex, whose damage is consistently associated with poor performance in action perception and understanding tasks across studies. Interestingly, these areas correspond to the three nodes of the action observation network that are strongly activated in response to visual action perception in neuroimaging research and that have been targeted in previous brain stimulation studies. Thus, brain lesion mapping research provides converging causal evidence that premotor, parietal and temporal regions play a crucial role in action recognition and understanding.

  20. Neuroanatomical substrates of action perception and understanding: an anatomic likelihood estimation meta-analysis of lesion-symptom mapping studies in brain injured patients

    PubMed Central

    Urgesi, Cosimo; Candidi, Matteo; Avenanti, Alessio

    2014-01-01

    Several neurophysiologic and neuroimaging studies suggested that motor and perceptual systems are tightly linked along a continuum rather than providing segregated mechanisms supporting different functions. Using correlational approaches, these studies demonstrated that action observation activates not only visual but also motor brain regions. On the other hand, brain stimulation and brain lesion evidence allows tackling the critical question of whether our action representations are necessary to perceive and understand others’ actions. In particular, recent neuropsychological studies have shown that patients with temporal, parietal, and frontal lesions exhibit a number of possible deficits in the visual perception and the understanding of others’ actions. The specific anatomical substrates of such neuropsychological deficits however, are still a matter of debate. Here we review the existing literature on this issue and perform an anatomic likelihood estimation meta-analysis of studies using lesion-symptom mapping methods on the causal relation between brain lesions and non-linguistic action perception and understanding deficits. The meta-analysis encompassed data from 361 patients tested in 11 studies and identified regions in the inferior frontal cortex, the inferior parietal cortex and the middle/superior temporal cortex, whose damage is consistently associated with poor performance in action perception and understanding tasks across studies. Interestingly, these areas correspond to the three nodes of the action observation network that are strongly activated in response to visual action perception in neuroimaging research and that have been targeted in previous brain stimulation studies. Thus, brain lesion mapping research provides converging causal evidence that premotor, parietal and temporal regions play a crucial role in action recognition and understanding. PMID:24910603

  1. Successful treatment of plastic bronchitis by selective lymphatic embolization in a Fontan patient.

    PubMed

    Dori, Yoav; Keller, Marc S; Rychik, Jack; Itkin, Maxim

    2014-08-01

    Plastic bronchitis is a rare and often fatal complication of single-ventricle surgical palliation after total cavopulmonary connection. Although lymphatic abnormalities have been postulated to play a role in the disease process, the etiology and pathophysiology of this complication remain incompletely understood. Here we report on the etiology of plastic bronchitis in a child with total cavopulmonary connection as demonstrated by magnetic resonance (MR) lymphangiography. We also report on a new treatment of this disease. The patient underwent noncontrast T2-weighted MR lymphatic mapping and dynamic contrast MR lymphangiography with bi-inguinal intranodal contrast injection to determine the anatomy and flow pattern of lymph in his central lymphatic system. The MRI scan demonstrated the presence of a dilated right-sided peribronchial lymphatic network supplied by retrograde lymphatic flow through a large collateral lymphatic vessel originating from the thoracic duct. After careful analysis of the MRI scans we performed selective lymphatic embolization of the pathologic lymphatic network and supplying vessel. This provided resolution of plastic bronchitis for this patient. Five months after the procedure, the patient remains asymptomatic off respiratory medications.

  2. Cross-Reactivity of Filariais ICT Cards in Areas of Contrasting Endemicity of Loa loa and Mansonella perstans in Cameroon: Implications for Shrinking of the Lymphatic Filariasis Map in the Central African Region

    PubMed Central

    Wanji, Samuel; Koudou, Benjamin; Chounna Ndongmo, Patrick W.; Kengne-Ouafo, Jonas A.; Datchoua-Poutcheu, Fabrice R.; Fovennso, Bridget Adzemye; Tayong, Dizzle Bita; Fombad, Fanny Fri; Fischer, Peter U.; Enyong, Peter I.; Bockarie, Moses

    2015-01-01

    Background Immunochromatographic card test (ICT) is a tool to map the distribution of Wuchereria bancrofti. In areas highly endemic for loaisis in DRC and Cameroon, a relationship has been envisaged between high L. loa microfilaria (Mf) loads and ICT positivity. However, similar associations have not been demonstrated from other areas with contrasting levels of L. loa endemicity. This study investigated the cross-reactivity of ICT when mapping lymphatic filariasis (LF) in areas with contrasting endemicity levels of loiasis and mansonellosis in Cameroon. Methodology/Principal Findings A cross-sectional study to assess the prevalence and intensity of W. bancrofti, L. loa and M. perstans was carried out in 42 villages across three regions (East, North-west and South-west) of the Cameroon rainforest domain. Diurnal blood was collected from participants for the detection of circulating filarial antigen (CFA) by ICT and assessment of Mf using a thick blood smear. Clinical manifestations of LF were also assessed. ICT positives and patients clinically diagnosed with lymphoedema were further subjected to night blood collection for the detection of W. bancrofti Mf. Overall, 2190 individuals took part in the study. Overall, 24 individuals residing in 14 communities were tested positive by ICT, with prevalence rates ranging from 0% in the South-west to 2.1% in the North-west. Lymphoedema were diagnosed in 20 individuals with the majority of cases found in the North-west (11/20), and none of them were tested positive by ICT. No Mf of W. bancrofti were found in the night blood of any individual with a positive ICT result or clinical lymphoedema. Positive ICT results were strongly associated with high L. loa Mf intensity with 21 subjects having more than 8,000 L. loa Mf ml/blood (Odds ratio = 15.4; 95%CI: 6.1–39.0; p < 0.001). Similarly, a strong positive association (Spearman’s rho = 0.900; p = 0.037) was observed between the prevalence of L. loa and ICT positivity by area

  3. Cross-Reactivity of Filariais ICT Cards in Areas of Contrasting Endemicity of Loa loa and Mansonella perstans in Cameroon: Implications for Shrinking of the Lymphatic Filariasis Map in the Central African Region.

    PubMed

    Wanji, Samuel; Amvongo-Adjia, Nathalie; Koudou, Benjamin; Njouendou, Abdel Jelil; Chounna Ndongmo, Patrick W; Kengne-Ouafo, Jonas A; Datchoua-Poutcheu, Fabrice R; Fovennso, Bridget Adzemye; Tayong, Dizzle Bita; Fombad, Fanny Fri; Fischer, Peter U; Enyong, Peter I; Bockarie, Moses

    2015-11-01

    Immunochromatographic card test (ICT) is a tool to map the distribution of Wuchereria bancrofti. In areas highly endemic for loaisis in DRC and Cameroon, a relationship has been envisaged between high L. loa microfilaria (Mf) loads and ICT positivity. However, similar associations have not been demonstrated from other areas with contrasting levels of L. loa endemicity. This study investigated the cross-reactivity of ICT when mapping lymphatic filariasis (LF) in areas with contrasting endemicity levels of loiasis and mansonellosis in Cameroon. A cross-sectional study to assess the prevalence and intensity of W. bancrofti, L. loa and M. perstans was carried out in 42 villages across three regions (East, North-west and South-west) of the Cameroon rainforest domain. Diurnal blood was collected from participants for the detection of circulating filarial antigen (CFA) by ICT and assessment of Mf using a thick blood smear. Clinical manifestations of LF were also assessed. ICT positives and patients clinically diagnosed with lymphoedema were further subjected to night blood collection for the detection of W. bancrofti Mf. Overall, 2190 individuals took part in the study. Overall, 24 individuals residing in 14 communities were tested positive by ICT, with prevalence rates ranging from 0% in the South-west to 2.1% in the North-west. Lymphoedema were diagnosed in 20 individuals with the majority of cases found in the North-west (11/20), and none of them were tested positive by ICT. No Mf of W. bancrofti were found in the night blood of any individual with a positive ICT result or clinical lymphoedema. Positive ICT results were strongly associated with high L. loa Mf intensity with 21 subjects having more than 8,000 L. loa Mf ml/blood (Odds ratio = 15.4; 95%CI: 6.1-39.0; p < 0.001). Similarly, a strong positive association (Spearman's rho = 0.900; p = 0.037) was observed between the prevalence of L. loa and ICT positivity by area: a rate of 1% or more of positive ICT results

  4. Fluid-solid modeling of lymphatic valves

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

    The lymphatic system performs important physiological functions such as the return of interstitial fluid to the bloodstream to maintain tissue fluid balance, as well as the transport of immune cells in the body. It utilizes contractile lymphatic vessels, which contain valves that open and close to allow flow in only one direction, to directionally pump lymph against a pressure gradient. We develop a fluid-solid model of geometrically representative lymphatic valves. Our model uses a hybrid lattice-Boltzmann lattice spring method to capture fluid-solid interactions with two-way coupling between a viscous fluid and lymphatic valves in a lymphatic vessel. We use this model to investigate the opening and closing of lymphatic valves, and its effect on lymphatic pumping. This helps to broaden our understanding of the fluid dynamics of the lymphatic system.

  5. Acute and long-term results of PVI at antrum using a novel high-density mapping catheter without help of 3D electro-anatomic mapping in patients with paroxysmal and chronic atrial fibrillation.

    PubMed

    Neumann, Thomas; Kuniss, Malte; Erkapic, Damir; Zaltsberg, Sergey; Berkowitsch, Alexander; Pajitnev, Dimitri; Wojcik, Maciej; Janin, Sebastien; Hamm, Christian W; Pitschner, Heinz F

    2010-03-01

    Multi-electrode circumferential mapping catheters have been developed by several manufacturers to facilitate catheter ablation procedures for atrial fibrillation (AF). We tested the effectiveness and safety of a conventional, fully endocardial electrogram-guided circumferential antrum isolation (PVI) with a novel mapping device. The study enrolled 250 consecutive patients with paroxysmal or chronic AF. High-density (HD) mapping of the pulmonary veins was performed with the HD Mesh Mapper (HDMM; Bard Electrophysiology, Lowell, MA, USA). The device was not constructed for radiofrequency energy delivery. Antral PVI was performed by irrigated radiofrequency application around the HDMM. Entry and exit conduction block, as well as decreased local electrode amplitude, were endpoints for acute successful ablation. Primary endpoint of the study was the AF free event probability during follow-up. As secondary endpoints, the acute results and related complications were determined. In 984 of 1,002 pulmonary vein (PV, 98.2%), signals were characterized as PV potentials by mapping the proximal part of the PV and the antrum. We achieved a complete antrum ablation in front of the 25-mm ring of the MESH Mapper in 95% of the PV in all patients. In difficult anatomic relationships, the repositioning of the mapping catheter could be necessary. The median follow-up time was 20.8 and 15.6 months in patients with paroxysmal and chronic AF, respectively. Log Rang test revealed a probability to be free from AF episodes of 71.2% and 49.4% after one ablation procedure and improved in chronic AF after a second procedure (71.1%). Our study demonstrates satisfactory success rate regarding the safety and long-term results in patients both with paroxysmal and persistent AF when a 3D mapping system is not being implemented. The study underlines the importance of a continuous signal analysis during the ablation procedure even with a conventional mapping system.

  6. In-vivo MRI and in-vivo electro-anatomical voltage map characteristics of infarct heterogeneity in a swine model.

    PubMed

    Shokrollahi, E; Pop, M; Safri, M; Yang, Y; Radau, P E; Barry, J; Detsky, J; Griffin, G H; Crystal, E; Wright, G A

    2011-01-01

    The arrhythmogenic substrate in patients with prior myocardial infarct (MI) is located at the border zone, BZ. In this study we correlated the BZ identified by two methods: electro-anatomical voltage mapping (EAVM) and a novel MRI method, multi-contrast late enhancement (MCLE). A pre-clinical porcine model with chronic MI was used to characterize BZ via MRI and EAVM. Results focus on the comparison between scar percentage and BZ percentage identified by each method. The correlation coefficient for BZ percentage between the two methods was 0.74 with a p-value of less the 0.0001. Bland-Altman plots were also used to compare between the two methods (slope of 0.83 ± 0.045). For a case of subtle infarct, there was only 1.3% infarct identified on EAVM compared to 22.2% on the corresponding slice on MCLE. The percentage of infarct on MCLE in subtle infarct does not relate to percentage of infarct in EAVM. Future registration between T(1) maps and EAVM will permit a quantitative comparison of MRI and EAVM measures.

  7. Pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis in tumor lymphangiogenesis and lymphatic metastasis.

    PubMed

    Wang, Jingwen; Huang, Yuhong; Zhang, Jun; Wei, Yuanyi; Mahoud, Salma; Bakheet, Ahmed Musa Hago; Wang, Li; Zhou, Shuting; Tang, Jianwu

    2016-10-01

    Precondition for tumor lymphatic metastasis is that tumor cells induce formation of original and newborn lymphatic vessels and invade surrounding lymphatic vessels in tumor stroma, while some pathway-related molecules play an important role in mechanisms associated with proliferation and migration of lymphatic endothelial cells (LECs) and tumor cells. In lymphangiogenesis and lymphatic metastasis, the pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, such as Furin-like enzyme, CNTN1, Prox1, LYVE-1, Podoplanin, SOX18, SDF1 and CXCR4, are direct constitutors as a portion of VEGFC/D-VEGFR3/NRP2 axis, and their biological activities rely on this ligand-receptor system. These axis-related signal molecules could gradually produce waterfall-like cascading effects, mediate differentiation and maturation of LECs, remodel original and neonatal lymphatic vessels, as well as ultimately promote tumor cell chemotaxis, migration, invasion and metastasis to lymphoid tracts. This review summarizes the structure and function features of pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, the expression changes of these molecules in different anatomic organs or histopathologic types or development stages of various tumors, the characteristics of transduction, implementation, integration of signal networks, the interactive effects on biological behaviors between tumor cells and lymphatic endothelial cells, and their molecular mechanisms and significances in tumor lymphangiogenesis and lymphatic metastasis.

  8. Interaction between vascularized lymph node transfer and recipient lymphatics after lymph node dissection- a pilot study in a canine model

    PubMed Central

    Suami, Hiroo; Scaglioni, Mario F.; Dixon, Katherine A.; Tailor, Ramesh C.

    2016-01-01

    Background Vascularized lymph node transfer (VLNT) has become more wide-spread for surgical treatment of lymphedema. However, interaction between a transferred lymph node and the recipient lymphatic system in relieving lymphedema has not been identified. The aims of this study were to investigate anatomical changes in the lymphatic system in the forelimb of a canine after lymph node dissection and irradiation and to clarify the interaction between the transferred lymph node and recipient lymphatics. Materials and Methods Two adult female mongrel canines were used for this exploratory study. The unilateral axillary and lower neck node dissections were performed, and 15-Gy irradiation was applied on postoperative day three. After one year, a VLNT flap was harvested from the lower abdominal region and inset in the axilla with vascular anastomoses. The girth of each forelimb was determined with a tape measure at different time points. Indocyanine green fluorescence lymphography and lymphangiography were performed before and after each surgery to evaluate morphological changes in the lymphatics. Results Both canines revealed identical changes in the lymphatic system but only one canine developed lymphedema. After lymph node dissection, a collateral lymphatic pathway formed a connection to the contralateral cervical node. After VLNT, an additional collateral pathway formed a connection to the internal mammary node via the transferred node in the axilla. Conclusions The findings suggest that the lymphatic system has a homing mechanism, which allows the severed lymphatic vessels to detect and connect to adjacent lymph nodes. VLNT may create new collateral pathways to relieve lymphedema. PMID:27565078

  9. Mapping the Internal Anatomy of the Lateral Brainstem: Anatomical Study with Application to Far Lateral Approaches to Intrinsic Brainstem Tumors

    PubMed Central

    Granger, Andre; Vahedi, Payman; Loukas, Marios; Oskouian, Rod J; Fries, Fabian N; Lotfinia, Iraj; Mortazavi, Martin M; Oakes, W. Jerry; Tubbs, R. Shane

    2017-01-01

    Introduction Intramedullary brainstem tumors present a special challenge to the neurosurgeon. Unfortunately, there is no ideal part of the brainstem to incise for approaches to such pathology. Therefore, the present study was performed to identify what incisions on the lateral brainstem would result in the least amount of damage to eloquent tracts and nuclei. Case illustrations are also discussed. Materials and methods Eight human brainstems were evaluated. Based on dissections and the use of standard atlases of brainstem anatomy, the most important deeper brainstem structures were mapped to the surface of the lateral brainstem. Results With these data, we defined superior acute and inferior obtuse corridors for surgical entrance into the lateral brainstem that would minimize injury to deeper tracts and nuclei, the damage to which would result in significant morbidity. Conclusions To our knowledge, a superficial map of the lateral brainstem for identifying deeper lying and clinically significant nuclei and tracts has not previously been available. Such data might decrease patient morbidity following biopsy or tumor removal or aspiration of brainstem hemorrhage. Additionally, this information can be coupled with the previous literature on approaches into the fourth ventricular floor for more complex, multidimensional lesions. PMID:28357160

  10. [Urological pathology of lymphatic origin].

    PubMed

    Domènech, A; Serrano, A; Forner-Cordero, I; Gómez, F; Maldonado, D; Domínguez, C

    2016-01-25

    Lymphatic disease is a rarely cause of some very unspecific genitourinary manifestations, assuming a diagnostic challenge in most cases. The aim of this paper is to warn about the possible etiology of these urological lymphatic presentations and discuss its management. Retrospective review of clinical data in pediatric patients with urological pathology of lymphatic origin between 2008-2014. Three patients, two boys and a girl, were included. The complaints were: redundant prepuce, inguinal scrotal tumor and urinary incontinence. Clinical, diagnosis and treatment protocol is described. The first case is a male with genital lymphedema presented at birth as a redundant prepuce and the subsequent emergence of lower limb lymphedema, treated with compression bandages. The second case, a groin lymphangioma which debuted as a sudden painless inguinal tumor simulating a cord cyst, it was sclerosed and treated with OK- 432. Finally, a preteen who consulted for involuntary leakage of urine, genital lymphedema likely primary cause (lymphodisplasia) or malformation was diagnosed, which improved with two Lipiodol® embolization. Genitourinary manifestations can be the debut of more complex lymphatic pathology, so it is necessary to consider this cause, uncommon and nonspecific. Its management must be conservative initially by compression bandages, OK-432 or embolization with Lipiodol®.

  11. Immunopathogenesis of lymphatic filarial disease.

    PubMed

    Babu, Subash; Nutman, Thomas B

    2012-11-01

    Although two thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ~40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and thickening of the lymphatic vessel walls. Progressive lymphatic damage and pathology results from the summation of the effect of tissue alterations induced by both living and nonliving adult parasites, the host inflammatory response to the parasites and their secreted antigens, the host inflammatory response to the endosymbiont Wolbachia, and those seen as a consequence of secondary bacterial or fungal infections. Inflammatory damage induced by filarial parasites appears to be multifactorial, with endogenous parasite products, Wolbachia, and host immunity all playing important roles. This review will initially examine the prototypical immune responses engendered by the parasite and delineate the regulatory mechanisms elicited to prevent immune-mediated pathology. This will be followed by a discussion of the proposed mechanisms underlying pathogenesis, with the central theme being that pathogenesis is a two-step process-the first initiated by the parasite and host innate immune system and the second propagated mainly by the host's adaptive immune system and by other factors (including secondary infections).

  12. Blood and Lymphatic Vessel Formation

    PubMed Central

    Bautch, Victoria L.; Caron, Kathleen M.

    2015-01-01

    Blood and lymphatic vessels deliver oxygen and nutrients, remove waste and CO2, and regulate interstitial pressure in tissues and organs. These vessels begin life early in embryogenesis using transcription factors and signaling pathways that regulate differentiation, morphogenesis, and proliferation. Here we describe how these vessels develop in the mouse embryo, and the signals that are important to their development. PMID:25731762

  13. Endpoints for lymphatic filariasis programs.

    PubMed

    Grady, Caroline A; de Rochars, Madsen Beau; Direny, Abdel N; Orelus, Jean Nicolas; Wendt, Joyanna; Radday, Jeanne; Mathieu, Els; Roberts, Jacquelin M; Streit, Thomas G; Addiss, David G; Lammie, Patrick J

    2007-04-01

    In 2000, annual mass administration of diethlycarbamazine and albendazole began in Leogane Commune, Haiti, to interrupt transmission of lymphatic filariasis (LF). After 5 years of treatment, microfilaremia, antigenemia, and mosquito infection rates were significantly reduced, but LF transmission was not interrupted. These finding have implications for other LF elimination programs.

  14. New Horizons for Imaging Lymphatic Function

    PubMed Central

    Sharma, Ruchi; Wendt, Juliet A.; Rasmussen, John C.; Adams, Kristen E.; Marshall, Milton V.; Sevick-Muraca, Eva M.

    2011-01-01

    In this review, we provide a comprehensive summary of noninvasive imaging modalities used clinically for the diagnosis of lymphatic diseases, new imaging agents for assessing lymphatic architecture and cancer status of lymph nodes, and emerging near-infrared (NIR) fluorescent optical imaging technologies and agents for functional lymphatic imaging. Given the promise of NIR optical imaging, we provide example results of functional lymphatic imaging in mice, swine, and humans, showing the ability of this technology to quantify lymph velocity and frequencies of propulsion resulting from the contractility of lymphatic structures. PMID:18519956

  15. Cytoarchitecture of the lamina muscularis mucosae and distribution of the lymphatic vessels in the human stomach.

    PubMed

    Akashi, Yuichi; Noguchi, Tsuyoshi; Nagai, Kaoruko; Kawahara, Katsunobu; Shimada, Tatsuo

    2011-03-01

    The aim of the present study was to clarify the anatomical structure of the lamina muscularis mucosae (LMM) in the human stomach and to correlate it with the lymphatic spread of gastric cancer cells. Human stomachs taken at operation or autopsy were used. The specimens derived from these stomachs were examined by light microscopy immunohistochemistry and scanning electron microscopy (SEM). In the cardia and pyloric wall, bundles of smooth muscle cells of the LMM were relatively loose and thin and formed a reticular configuration. Small lymphatic capillaries (approximately 10-30 μm in diameter) were present directly above the LMM, and relatively large lymphatics (approximately 80-100 μm in diameter) were observed in the submucosal layer and within the LMM. In contrast, the LMM in the fundus, body, and antral wall was composed of tight, thick bundles of smooth muscle cells that ran straight. Large lymphatics were found directly beneath the LMM, but they were few in the lamina propria mucosae. In addition, lymphatics adjacent to veins were also found in the submucosa of the fundus. Structural differences in the LMM of the stomach wall might depend on physiological function. In this study, the relationship between the cytoarchitecture of the LMM or the distribution of lymphatic vessels and cancer invasion is discussed.

  16. Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease.

    PubMed

    Randolph, Gwendalyn J; Bala, Shashi; Rahier, Jean-François; Johnson, Michael W; Wang, Peter L; Nalbantoglu, ILKe; Dubuquoy, Laurent; Chau, Amélie; Pariente, Benjamin; Kartheuser, Alex; Zinselmeyer, Bernd H; Colombel, Jean-Frederic

    2016-12-01

    Early pathological descriptions of Crohn disease (CD) argued for a potential defect in lymph transport; however, this concept has not been thoroughly investigated. In mice, poor healing in response to infection-induced tissue damage can cause hyperpermeable lymphatic collecting vessels in mesenteric adipose tissue that impair antigen and immune cell access to mesenteric lymph nodes (LNs), which normally sustain appropriate immunity. To investigate whether analogous changes might occur in human intestinal disease, we established a three-dimensional imaging approach to characterize the lymphatic vasculature in mesenteric tissue from controls or patients with CD. In CD specimens, B-cell-rich aggregates resembling tertiary lymphoid organs (TLOs) impinged on lymphatic collecting vessels that enter and exit LNs. In areas of creeping fat, which characterizes inflammation-affected areas of the bowel in CD, we observed B cells and apparent innate lymphoid cells that had invaded the lymphatic vessel wall, suggesting these cells may be mediators of lymphatic remodeling. Although TLOs have been described in many chronic inflammatory states, their anatomical relationship to preestablished LNs has never been revealed. Our data indicate that, at least in the CD-affected mesentery, TLOs are positioned along collecting lymphatic vessels in a manner expected to affect delivery of lymph to LNs. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. The lymphatic system of the major head and neck glands in rats.

    PubMed

    Dünne, Anja A; Steinke, Lars; Teymoortash, Afshin; Kuropkat, Christiane; Folz, Benedikt J; Werner, Jochen A

    2004-01-01

    Many studies concerning therapy and also investigations on lymphogenic metastatic spread of head and neck malignancies require animal models. This article completes the existing findings with regard to the lymphatic system of the head and neck region of the rat. Investigations (light microscopy, immuno-histochemistry, enzyme histochemistry, lympho-graphy) on architecture, distribution and density of the intraglandular lymphatic flow of the major head and neck glands (infraorbital lacrimal gland, extraorbital lacrimal gland, Harderian gland, parotid gland, major sublingual gland, mandibular gland and thyroid gland) in rats were performed. Architecture of the seven major head and neck glands in rats do not differ from other regions of the upper aerodigestive tract. While the Harderian gland shows the highest density of lymphatics, within the major sublingual gland only scare lymph vessels could be identified. Distribution and density of initial lymphatics influence directly the transmission of inflammatory and malignant diseases. The presented results are the morphologically and anatomically basis to initiate further investigations in the rat animal model emphasizing special questions concerning the lymphatic system of the major head and neck glands e.g. lymphatic drainage and new treatment concepts in cases of lymphogenic metastatic spread.

  18. Not one extrastriate body area: Using anatomical landmarks, hMT+, and visual field maps to parcellate limb-selective activations in human lateral occipitotemporal cortex

    PubMed Central

    Weiner, Kevin S.; Grill-Spector, Kalanit

    2011-01-01

    The prevailing view of human lateral occipitotemporal cortex (LOTC) organization suggests a single area selective for images of the human body (extrastriate body area, EBA) that highly overlaps with the human motion-selective complex (hMT+). Using functional magnetic resonance imaging with higher resolution (1.5mm voxels) than past studies (3–4mm voxels), we examined the fine-scale spatial organization of these activations relative to each other, as well as to visual field maps in LOTC. Rather than one contiguous EBA highly overlapping hMT+, results indicate three limb-selective activations organized in a crescent surrounding hMT+: (1) an activation posterior to hMT+ on the lateral occipital sulcus/middle occipital gyrus (LOS/MOG) overlapping the lower vertical meridian shared between visual field maps LO-2 and TO-1, (2) an activation anterior to hMT+ on the middle temporal gyrus (MTG) consistently overlapping the lower vertical meridian of TO-2 and extending outside presently defined visual field maps, and (3) an activation inferior to hMT+ on the inferotemporal gyrus (ITG) overlapping the parafoveal representation of the TO cluster. This crescent organization of limb-selective activations surrounding hMT+ is reproducible over a span of three years and is consistent across different image types used for localization. Further, these regions exhibit differential position properties: preference for contralateral image presentation decreases and preference for foveal presentation increases from the limb-selective LOS to the MTG. Finally, the relationship between limb-selective activations and visual field maps extends to the dorsal stream where a posterior IPS activation overlaps V7. Overall, our measurements demonstrate a series of LOTC limb-selective activations that 1) have separate anatomical and functional boundaries, 2) overlap distinct visual field maps, and 3) illustrate differential position properties. These findings indicate that category selectivity

  19. Lymphatic malformations: current cellular and clinical investigations.

    PubMed

    Perkins, Jonathan A; Manning, Scott C; Tempero, Richard M; Cunningham, Michael J; Edmonds, Joseph L; Hoffer, Fredric A; Egbert, Mark A

    2010-06-01

    Summarize current knowledge of lymphatic malformation development, biology, and clinical outcome measures. Panel presentation of lymphatic malformation biology and measurement of head and neck malformation treatment outcomes. Characterization of lymphatic malformation endothelial and stromal cells may lead to biologically based treatment. Traditionally, lymphatic malformation treatment outcomes have been measured according to reduction of malformation size. Currently, methods to measure functional outcomes following lymphatic malformation treatment are lacking. This is particularly apparent when the malformation directly involves the upper aerodigestive tract. The etiology and pathogenesis of head and neck lymphatic malformations are poorly understood, but understanding is improving through ongoing investigation. Reduction of lymphatic malformation size is generally possible, but further work is necessary to optimize methods for measuring therapeutic outcomes in problematic areas. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

  20. Functional imaging in tumor-associated lymphatics

    NASA Astrophysics Data System (ADS)

    Kwon, Sunkuk; Sevick-Muraca, Eva M.

    2011-03-01

    The lymphatic system plays an important role in cancer cell dissemination; however whether lymphatic drainage pathways and function change during tumor progression and metastasis remains to be elucidated. In this report, we employed a non-invasive, dynamic near-infrared (NIR) fluorescence imaging technique for functional lymphatic imaging. Indocyanine green (ICG) was intradermally injected into tumor-free mice and mice bearing C6/LacZ rat glioma tumors in the tail or hindlimb. Our imaging data showed abnormal lymphatic drainage pathways and reduction/loss of lymphatic contractile function in mice with lymph node (LN) metastasis, indicating that cancer metastasis to the draining LNs is accompanied by transient changes of the lymphatic architectural network and its function. Therefore, functional lymphatic imaging may provide a role in the clinical staging of cancer.

  1. Integrated morbidity management for lymphatic filariasis and podoconiosis, Ethiopia.

    PubMed

    Deribe, Kebede; Kebede, Biruck; Tamiru, Mossie; Mengistu, Belete; Kebede, Fikreab; Martindale, Sarah; Sime, Heven; Mulugeta, Abate; Kebede, Biruk; Sileshi, Mesfin; Mengiste, Asrat; McPherson, Scott; Fentaye, Amha

    2017-09-01

    Lymphatic filariasis and podoconiosis are the major causes of tropical lymphoedema in Ethiopia. The diseases require a similar provision of care, but until recently the Ethiopian health system did not integrate the morbidity management. To establish health-care services for integrated lymphoedema morbidity management, the health ministry and partners used existing governmental structures. Integrated disease mapping was done in 659 out of the 817 districts, to identify endemic districts. To inform resource allocation, trained health extension workers carried out integrated disease burden assessments in 56 districts with a high clinical burden. To ensure standard provision of care, the health ministry developed an integrated lymphatic filariasis and podoconiosis morbidity management guideline, containing a treatment algorithm and a defined package of care. Experienced professionals on lymphoedema management trained government-employed health workers on integrated morbidity management. To monitor the integration, an indicator on the number of lymphoedema-treated patients was included in the national health management information system. In 2014, only 24% (87) of the 363 health facilities surveyed provided lymphatic filariasis services, while 12% (44) provided podoconiosis services. To date, 542 health workers from 53 health centres in 24 districts have been trained on integrated morbidity management. Between July 2013 and June 2016, the national health management information system has recorded 46 487 treated patients from 189 districts. In Ethiopia, an integrated approach for lymphatic filariasis and podoconiosis morbidity management was feasible. The processes used could be applicable in other settings where these diseases are co-endemic.

  2. Posttraumatic edema of the lower extremities: evaluation of the lymphatic vessels with magnetic resonance lymphangiography.

    PubMed

    Lohrmann, Christian; Pache, Gregor; Felmerer, Gunter; Foeldi, Etelka; Schaefer, Oliver; Langer, Mathias

    2009-02-01

    To assess for the first time the morphology of the lymphatic system in patients with posttraumatic edema of the lower extremities by magnetic resonance (MR) imaging using the interstitial lymphangiography technique Six patients with posttraumatic edema in eight of their 12 lower extremities were examined by MR lymphangiography. Eighteen mL of gadoteridol and one mL of mepivacainhydrochloride 1% were subdivided into 10 portions and injected intracutaneously. MR imaging was performed with a 1.5-T system equipped with high-performance gradients. For MR lymphangiography, a 3D-spoiled gradient-echo sequence was used. In five of the eight (63%) traumatized lower extremities, enlarged lymphatic vessels were detected, with the largest diameter measuring 5 mm. Additionally, a fast lymphatic outflow was observed in seven of the eight (88%) traumatized legs with enhancement of the inguinal lymph nodes already in the first image acquisition 15 minutes after contrast material injection. In two of the eight (25%) traumatized lower extremities, an extensive network of collateral lymphatic vessels was detected at the level of the calf. In both extremities, lymphatic collateralization involved not only the epifascial but also the subfascial lymphatic system. In one patient, who sustained a trauma of the left lower leg with tibial fracture, a small aneurysmatic widening of 7 mm could be detected at the middle level of the calf. MR lymphangiography is a safe and accurate minimal-invasive imaging modality for the evaluation of the lymphatic circulation in patients with posttraumatic edema of the lower extremities. If the extent of lymphatic damage is unclear at the initial clinical examination or requires a better definition for optimal therapeutic planning, MR lymphangiography is able to identify the anatomic and physiological derangements and to establish an objective baseline.

  3. FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1

    PubMed Central

    Norrmén, Camilla; Ivanov, Konstantin I.; Cheng, Jianpin; Zangger, Nadine; Delorenzi, Mauro; Jaquet, Muriel; Miura, Naoyuki; Puolakkainen, Pauli; Horsley, Valerie; Hu, Junhao; Augustin, Hellmut G.; Ylä-Herttuala, Seppo; Alitalo, Kari

    2009-01-01

    The mechanisms of blood vessel maturation into distinct parts of the blood vasculature such as arteries, veins, and capillaries have been the subject of intense investigation over recent years. In contrast, our knowledge of lymphatic vessel maturation is still fragmentary. In this study, we provide a molecular and morphological characterization of the major steps in the maturation of the primary lymphatic capillary plexus into collecting lymphatic vessels during development and show that forkhead transcription factor Foxc2 controls this process. We further identify transcription factor NFATc1 as a novel regulator of lymphatic development and describe a previously unsuspected link between NFATc1 and Foxc2 in the regulation of lymphatic maturation. We also provide a genome-wide map of FOXC2-binding sites in lymphatic endothelial cells, identify a novel consensus FOXC2 sequence, and show that NFATc1 physically interacts with FOXC2-binding enhancers. As damage to collecting vessels is a major cause of lymphatic dysfunction in humans, our results suggest that FOXC2 and NFATc1 are potential targets for therapeutic intervention. PMID:19398761

  4. Prospective randomized comparison of rotational angiography with three-dimensional reconstruction and computed tomography merged with electro-anatomical mapping: a two center atrial fibrillation ablation study.

    PubMed

    Anand, Rishi; Gorev, Maxim V; Poghosyan, Hermine; Pothier, Lindsay; Matkins, John; Kotler, Gregory; Moroz, Sarah; Armstrong, James; Nemtsov, Sergei V; Orlov, Michael V

    2016-08-01

    To compare the efficacy and accuracy of rotational angiography with three-dimensional reconstruction (3DATG) image merged with electro-anatomical mapping (EAM) vs. CT-EAM. A prospective, randomized, parallel, two-center study conducted in 36 patients (25 men, age 65 ± 10 years) undergoing AF ablation (33 % paroxysmal, 67 % persistent) guided by 3DATG (group 1) vs. CT (group 2) image fusion with EAM. 3DATG was performed on the Philips Allura Xper FD 10 system. Procedural characteristics including time, radiation exposure, outcome, and navigation accuracy were compared between two groups. There was no significant difference between the groups in total procedure duration or time spent for various procedural steps. Minor differences in procedural characteristics were present between two centers. Segmentation and fusion time for 3DATG or CT-EAM was short and similar between both centers. Accuracy of navigation guided by either method was high and did not depend on left atrial size. Maintenance of sinus rhythm between the two groups was no different up to 24 months of follow-up. This study did not find superiority of 3DATG-EAM image merge to guide AF ablation when compared to CT-EAM fusion. Both merging techniques result in similar navigation accuracy.

  5. Gastrointestinal Lymphatics in Health and Disease

    PubMed Central

    Alexander, J.S.; Ganta, Vijay C.; Jordan, P.A.; Witte, Marlys H.

    2010-01-01

    Lymphatics perform essential transport and immune cell regulatory functions to maintain homeostasis in the gastrointestinal (GI) system. Although blood and lymphatic vessels function as parallel and integrated systems, our understanding of lymphatic structure, regulation and functioning lags far behind that of the blood vascular system. This chapter reviews lymphatic flow, differences in lymphangiogenic and hemangiogenic factors, lymphatic fate determinants and structural features, and examines how altered molecular signaling influences lymphatic function in organs of the GI system. Innate errors in lymphatic development frequently disturb GI functioning and physiology. Expansion of lymphatics, a prominent feature of GI inflammation, may also play an important role in tissue restitution following injury. Destruction or dysregulation of lymphatics, following injury, surgery or chronic inflammation also appears to exacerbate GI disease activity and morbidity. Understanding the physiological roles played by GI lymphatics is essential to elucidating their underlying contributions to forms of congenital and acquired forms of GI pathology, and will provide novel approaches for treatment of these conditions. PMID:20022228

  6. Lymphatic Vascular Response to Acute Inflammation

    PubMed Central

    Lachance, Pier-Anne; Hazen, Amy; Sevick-Muraca, Eva M.

    2013-01-01

    During acute inflammation, functioning lymphatics are believed to reduce edema and to provide a transiting route for immune cells, but the extent at which the dermal lymphatic remodeling impacts lymphatic transport or the factors regulating these changes remains unclear. Herein we quantify the increase in lymphatic endothelial cells (LECs) and examine the expression of pro-angiogenenic and lymphangiogenic factors during acute cutaneous hypersensitivity (CHS). We found that LECs actively proliferate during CHS but that this proliferation does not affect the lymphatic vessel density. Instead, lymphatic remodeling is accompanied by lymphatic vessel leakiness and lower ejection of lymph fluid, which is observed only in the proximal lymphatic vessel draining the inflamed area. LECs and the immune cells release growth factors and cytokines during inflammation, which impact the lymphatic microenvironment and function. We identified that FGF-2, PLGF-2, HGF, EGF, and KC/CXCL17 are differentially expressed within tissues during acute CHS, but both VEGF-C and VEGF-D levels do not significantly change. Our results indicate that VEGF-C and VEGF-D are not the only players and other factors may be responsible for the LECs proliferation and altered lymphatic function in acute CHS. PMID:24086691

  7. HA-ving lymphatics improves lung transplantation

    PubMed Central

    Maltzman, Jonathan S.; Reed, Hasina Outtz; Kahn, Mark L.

    2015-01-01

    Lung allografts are prone to rejection, even though recipients undergo aggressive immunosuppressive therapy. Lymphatic vessels serve as conduits for immune cell trafficking and have been implicated in the mediation of allograft rejection. In this issue of the JCI, Cui et al. provide compelling evidence that lymphatic vessel formation improves lung allograft survival in a murine transplant model. Moreover, their data suggest a potential mechanism for the beneficial effects of lymphatics that does not involve immune cell or antigen transport. Together, the results of this study provide new insight into the role of lymphatic vessels in transplant tolerance. PMID:26524589

  8. Lymphatic vessels in osteoarthritic human knees.

    PubMed

    Walsh, D A; Verghese, P; Cook, G J; McWilliams, D F; Mapp, P I; Ashraf, S; Wilson, D

    2012-05-01

    The distribution and function of lymphatic vessels in normal and diseased human knees are understood incompletely. This study aimed to investigate whether lymphatic density is associated with clinical, histological or radiographic parameters in osteoarthritis (OA). Sections of synovium from 60 knees from patients with OA were compared with 60 post mortem control knees (from 37 individuals). Lymphatic vessels were identified using immunohistochemistry for podoplanin, and quantified as lymphatic vessel density (LVD) and lymphatic endothelial cell (LEC) fractional area. Effusion status was determined by clinical examination, radiographs were scored for OA changes, and inflammation grading used haematoxylin and eosin stained sections of synovium. Lymphatic vessels were present in synovia from both disease groups, but were not identified in subchondral bone. Synovial lymphatic densities were independent of radiological severity and age. Synovia from patients with OA displayed lower LVD (z=-3.4, P=0.001) and lower LEC fractional areas (z=-4.5, P<0.0005) than non-arthritic controls. In patients with OA, low LVD was associated with clinically detectable effusion (z=-2.2, P=0.027), but not with histological evidence of synovitis. The negative associations between lymphatics and OA/effusion appeared to be independent of other measured confounders. Lymphatic vessels are present in lower densities in OA synovia. Abnormalities of synovial fluid drainage may confound the value of effusion as a clinical sign of synovitis in OA. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  9. The discovery of the synovial lymphatic stomata and lymphatic reabsorption in knee effusion.

    PubMed

    Ping, Zepeng; Jiang, Tingting; Wang, Chong; Chen, Zhongyi; Chen, Zhongliang; Wang, Jiaxiong; Wang, Li; Wang, Beibei; Xu, Dandan; Liu, Changming; Li, Zhongjie; Li, Ji-Cheng

    2015-06-01

    To illustrate the mechanism of lymphatic reabsorption in knee joint effusion. The current investigation employed transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques to reveal the ultrastructure of the knee synovial membrane in New Zealand rabbits and human. Ultrastructural changes of the synovial lymphatic stomata were observed by using trypan blue absorption and sodium hydroxide (NaOH) digestion methods, and the animal models of synovitis. New Zealand rabbits and human synovial membranes were composed of two types of synovial cells: type A and type B. No lymphatic stomata were found among type A synovial cells, whereas lymphatic stomata with the diameters ranging 0.74-3.26 µm were found in type B synovial cells, and some stomata were closed. After the NaOH digestion, a number of sieve pores, similar to lymphatic stomata in size and shape, were observed in the dense fibrous connective tissue underneath the type B synovial cells. After injecting trypan blue into the rabbit knee joint cavity, absorption of trypan blue through the lymphatic stomata was observed, suggesting the absorption function of the synovial lymphatic stomata. In the rabbit knee joint synovitis models, the synovial lymphatic stomata diameter enlarged. Some macrophages migrated from the lymphatic stomata, indicating that the synovial lymphatic stomata were involved in the joint effusion absorption and inflammatory response. Our study is the first to report the existence of synovial lymphatic stomata in the New Zealand rabbits and human knee joints. Lymphatic stomata may have an important role in the reabsorption of joint effusion.

  10. Lymphangiogenesis and Lymphatic Metastasis in Breast Cancer

    PubMed Central

    Ran, Sophia; Volk, Lisa; Hall, Kelly; Flister, Michael J.

    2009-01-01

    Lymphatic metastasis is the main prognostic factor for survival of patients with breast cancer and other epithelial malignancies. Mounting clinical and experimental data suggest that migration of tumor cells into the lymph nodes is greatly facilitated by lymphangiogenesis, a process that generates new lymphatic vessels from pre-existing lymphatics with the aid of circulating lymphatic endothelial progenitor cells. The key protein that induces lymphangiogenesis is vascular endothelial growth factor receptor-3 (VEGFR-3), which is activated by vascular endothelial growth factor-C and -D (VEGF-C and VEGF-D). These lymphangiogenic factors are commonly expressed in malignant, tumor-infiltrating and stromal cells, creating a favorable environment for generation of new lymphatic vessels. Clinical evidence demonstrates that increased lymphatic vessel density in and around tumors is associated with lymphatic metastasis and reduced patient survival. Recent evidence shows that breast cancers induce remodeling of the local lymphatic vessels and the regional lymphatic network in the sentinel and distal lymph nodes. These changes include an increase in number and diameter of tumor-draining lymphatic vessels. Consequently, lymph flow away from the tumor is increased, which significantly increases tumor cell metastasis to draining lymph nodes and may contribute to systemic spread. Collectively, recent advances in the biology of tumor-induced lymphangiogenesis suggest that chemical inhibitors of this process may be an attractive target for inhibiting tumor metastasis and cancer-related death. Nevertheless, this is a relatively new field of study and much remains to be established before the concept of tumor-induced lymphangiogenesis is accepted as a viable anti-metastatic target. This review summarizes the current concepts related to breast cancer lymphangiogenesis and lymphatic metastasis while highlighting controversies and unanswered questions. PMID:20036110

  11. LYMPHATIC INJURY AND REGENERATION IN CARDIAC ALLOGRAFTS

    PubMed Central

    Soong, Thing Rinda; Pathak, Arvind; Asano, Hiroshi; Fox-Talbot, Karen; Baldwin, William M

    2009-01-01

    Background: Severed donor heart lymphatics are not anastomosed to recipient lymphatics in cardiac transplantation. We evaluated the effects of cellular infiltrates of T cells and macrophages on the morphology of lymphatics in heart grafts. Methods: Dark Agouti (DA) hearts were transplanted to Lewis or control DA rats on sub-therapeutic doses of cyclosporin. Transplants were examined by immunohistology and quantitative immunofluorescence microscopy using LYVE-1 as a lymphatic marker and CD8 and CD68 as markers for cellular infiltration at selected intervals from 1 to 8 weeks post-transplantation. Results: Allograft inner myocardial lymphatic density decreased by more than 30-fold at 1 week, and recovered to only 15% of the native level at 8 weeks post-transplantation. In contrast, allograft lymphatics in and near the epicardium showed no significant density decline, but increased in size by more than 5-fold at 2 weeks, and sustained about a 3-fold increase at 8 weeks post-transplantation. Lymphatic changes correlated temporally with the extent of T cell and macrophage infiltration in allografts, which peaked at 2-3 weeks post-transplantation. When grafts were retransplanted from allogeneic to isogeneic recipients at 3 weeks post-transplantation, inner lymphatic density returned close to native level within 2 weeks after retransplantation. Conclusions: This is the first characterization of regional and morphological effects of immunological responses on heart lymphatics after transplantation. Elimination of alloimmune responses produces rapid restoration of inner lymphatic vessels, suggesting that lymphatics injured during rejection can recover when rejection is reversed during the post-transplantation course. PMID:20118845

  12. The Lymphatic Response to Injury with Soft-Tissue Reconstruction in High-Energy Open Tibial Fractures of the Lower Extremity.

    PubMed

    van Zanten, Malou C; Mistry, Raakhi M; Suami, Hiroo; Campbell-Lloyd, Andrew; Finkemeyer, James P; Piller, Neil B; Caplash, Yugesh

    2017-02-01

    Severe compound tibial fractures are associated with extensive soft-tissue damage, resulting in disruption of lymphatic pathways that leave the patient at risk of developing chronic lymphedema. There are limited data on lymphatic response following lower limb trauma. Indocyanine green fluorescence lymphography is a novel, real-time imaging technique for superficial lymphatic mapping. The authors used this technique to image the superficial lymphatic vessels of the lower limbs in patients with severe compound tibial fracture. Baseline demographics and clinical and operative details were recorded in a prospective cohort of 17 patients who had undergone bone and soft-tissue reconstruction after severe compound tibial fracture between 2009 and 2014. Normal lymphatic images were obtained from the patients' noninjured limbs as a control. In this way, the authors investigated any changes to the normal anatomy of the lymphatic system in the affected limbs. Of the 17 patients, eight had free muscle flaps with split-thickness skin grafting, one had a free fasciocutaneous flap, one had a full-thickness skin graft, six had local fasciocutaneous flaps, and one had a pedicled gastrocnemius flap. None of the free flaps demonstrated any functional lymphatic vessels; the fasciocutaneous flaps and the skin graft demonstrated impaired lymphatic vessel function and dermal backflow pattern similar to that in lymphedema. Local flaps demonstrated lymphatic blockage at the scar edge. Severe compound fractures and the associated soft-tissue injury can result in significant lymphatic disruption and an increased risk for the development of chronic lymphedema.

  13. Lymphatic filariasis in the Philippines.

    PubMed

    Kron, M; Walker, E; Hernandez, L; Torres, E; Libranda-Ramirez, B

    2000-08-01

    Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is endemic throughout most of the southern half of the Philippine archipelago. Economic and manpower shortages prior to 1996 made it difficult to acquire new prevalence data and vector control data concurrently from all provinces. Nevertheless, analysis of cumulative prevalence data on filariasis indicates the persistence of filariasis in each of the three major island groups - Luzon, Visayas and Mindanao - including 45 out of 77 provinces. Here, Michael Kron and colleagues summarize the prevalence data, and review host, parasite and vector characteristics relevant to the design and implementation of disease control initiatives in the Philippines planned for the year 2000.

  14. Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis

    PubMed Central

    Glasgow, Connie G.; El-Chemaly, Souheil; Moss, Joel

    2013-01-01

    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. PMID:22941884

  15. Lymphatic pumping: mechanics, mechanisms and malfunction.

    PubMed

    Scallan, Joshua P; Zawieja, Scott D; Castorena-Gonzalez, Jorge A; Davis, Michael J

    2016-10-15

    A combination of extrinsic (passive) and intrinsic (active) forces move lymph against a hydrostatic pressure gradient in most regions of the body. The effectiveness of the lymph pump system impacts not only interstitial fluid balance but other aspects of overall homeostasis. This review focuses on the mechanisms that regulate the intrinsic, active contractions of collecting lymphatic vessels in relation to their ability to actively transport lymph. Lymph propulsion requires not only robust contractions of lymphatic muscle cells, but contraction waves that are synchronized over the length of a lymphangion as well as properly functioning intraluminal valves. Normal lymphatic pump function is determined by the intrinsic properties of lymphatic muscle and the regulation of pumping by lymphatic preload, afterload, spontaneous contraction rate, contractility and neural influences. Lymphatic contractile dysfunction, barrier dysfunction and valve defects are common themes among pathologies that directly involve the lymphatic system, such as inherited and acquired forms of lymphoedema, and pathologies that indirectly involve the lymphatic system, such as inflammation, obesity and metabolic syndrome, and inflammatory bowel disease.

  16. Organization and developmental aspects of lymphatic vessels.

    PubMed

    Ohtani, Osamu; Ohtani, Yuko

    2008-05-01

    The lymphatic system plays important roles in maintaining tissue fluid homeostasis, immune surveillance of the body, and the taking up dietary fat and fat-soluble vitamins A, D, E and K. The lymphatic system is involved in many pathological conditions, including lymphedema, inflammatory diseases, and tumor dissemination. A clear understanding of the organization of the lymphatic vessels in normal conditions would be critically important to develop new treatments for diseases involving the lymphatic vascular system. Therefore, the present paper reviews the organization of the lymphatic vascular system of a variety of organs, including the thyroid gland, lung and pleura, small intestine, cecum and colon in the rat, the diaphragm in the rat, monkey, and human, Peyer's patches and the appendix in the rabbit, and human tonsils. Methods employed include scanning electron microscopy of lymphatic corrosion casts and tissues with or without treatment of alkali maceration technique, transmission electron microscopy of intact tissues, confocal microscopy in conjunction with immunohistochemistry to some lymphatic-specific markers (i.e., LYVE-1 and VEGFR-3), and light microscopy in conjunction with enzyme-histochemistry to 5'-nucleotidase. Some developmental aspects of the lymphatic vessels and lymphedema are also discussed.

  17. Dendritic Cell Interactions with Lymphatic Endothelium

    PubMed Central

    Russo, Erica; Nitschké, Maximilian

    2013-01-01

    Abstract Afferent lymphatic vessels fulfill essential immune functions by transporting leukocytes and lymph-borne antigen to draining lymph nodes (dLNs). An important cell type migrating through lymphatic vessels are dendritic cells (DCs). DCs reside in peripheral tissues like the skin, where they take up antigen and transport it via the lymphatic vascular network to dLNs for subsequent presentation to T cells. As such, DCs play a key role in the induction of adaptive immune responses during infection and vaccination, but also for the maintenance of tolerance. Although the migratory pattern of DCs has been known for long time, interactions between DCs and lymphatic vessels are only now starting to be unraveled at the cellular level. In particular, new tools for visualizing lymphatic vessels in combination with time-lapse microscopy have recently generated valuable insights into the process of DC migration to dLNs. In this review we summarize and discuss current approaches for visualizing DCs and lymphatic vessels in tissues for imaging applications. Furthermore, we review the current state of knowledge about DC migration towards, into and within lymphatic vessels, particularly focusing on the cellular interactions that take place between DCs and the lymphatic endothelium. PMID:24044757

  18. Lymphatic endothelial lineage assemblage during corneal lymphangiogenesis

    PubMed Central

    Connor, Alicia L.; Kelley, Philip M.; Tempero, Richard M.

    2015-01-01

    Post natal inflammatory lymphangiogenesis presumably requires precise regulatory processes to properly assemble proliferating lymphatic endothelial cells (LECs). The specific mechanisms that regulate the assembly of LECs during new lymphatic vessel synthesis are unclear. Dynamic endothelial shuffling and rearrangement has been proposed as a mechanism of blood vessel growth. We developed genetic lineage tracing strategies using an inductive transgenic technology to track the fate of entire tandem dimer tomato positive (tdT) lymphatic vessels or small, in some cases clonal, populations of LECs. We coupled this platform with a suture induced mouse model of corneal lymphangiogenesis and used different analytic microscopy techniques including serial live imaging to study the spatial properties of proliferating tdT+ LEC progenies. LEC precursors and their progeny expanded from the corneal limbal lymphatic vessel and were assembled contiguously to comprise a subunit within a new lymphatic vessel. VE-cadherin blockade induced morphologic abnormalities in newly synthesized lymphatic vessels, but did not disrupt the tdT+ lymphatic endothelial lineage assembly. Analysis of this static and dynamic data based largely on direct in vivo observations supports a model of lymphatic endothelial lineage assemblage during corneal inflammatory lymphangiogenesis. PMID:26658452

  19. Emerging Roles of Lymphatic Vasculature in Immunity

    PubMed Central

    2017-01-01

    The lymphatic vasculature has been regarded as a passive conduit for interstitial fluid and responsible for the absorption of macromolecules such as proteins or lipids and transport of nutrients from food. However, emerging data show that the lymphatic vasculature system plays an important role in immune modulation. One of its major roles is to coordinate antigen transport and immune-cell trafficking from peripheral tissues to secondary lymphoid organs, lymph nodes. This perspective was recently updated with the notion that the interaction between lymphatic endothelial cells and leukocytes controls the immune-cell migration and immune responses by regulating lymphatic flow and various secreted molecules such as chemokines and cytokines. In this review, we introduce the lymphatic vasculature networks and genetic transgenic models for research on the lymphatic vasculature system. Next, we discuss the contribution of lymphatic endothelial cells to the control of immune-cell trafficking and to maintenance of peripheral tolerance. Finally, the physiological roles and features of the lymphatic vasculature system are further discussed regarding inflammation-induced lymphangiogenesis in a pathological condition, especially in mucosal tissues such as the gastrointestinal tract and respiratory tract. PMID:28261022

  20. Increased nitric oxide production in lymphatic endothelial cells causes impairment of lymphatic drainage in cirrhotic rats.

    PubMed

    Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Tugues, Sònia; Fernández-Varo, Guillermo; Held, Kara F; Soria, Guadalupe; Tudela, Raúl; Planas, Anna M; Fernández-Hernando, Carlos; Arroyo, Vicente; Jiménez, Wladimiro; Morales-Ruiz, Manuel

    2013-01-01

    The lymphatic network plays a major role in maintaining tissue fluid homoeostasis. Therefore several pathological conditions associated with oedema formation result in deficient lymphatic function. However, the role of the lymphatic system in the pathogenesis of ascites and oedema formation in cirrhosis has not been fully clarified. The aim of this study was to investigate whether the inability of the lymphatic system to drain tissue exudate contributes to the oedema observed in cirrhosis. Cirrhosis was induced in rats by CCl(4) inhalation. Lymphatic drainage was evaluated using fluorescent lymphangiography. Expression of endothelial nitric oxide synthase (eNOS) was measured in primary lymphatic endothelial cells (LyECs). Inhibition of eNOS activity in cirrhotic rats with ascites (CH) was carried out by L-N(G)-methyl-L-arginine (L-NMMA) treatment (0.5 mg/kg/day). The (CH) rats had impaired lymphatic drainage in the splanchnic and peripheral regions compared with the control (CT) rats. LyECs isolated from the CH rats showed a significant increase in eNOS and nitric oxide (NO) production. In addition, the lymphatic vessels of the CH rats showed a significant reduction in smooth muscle cell (SMC) coverage compared with the CT rats. CH rats treated with L-NMMA for 7 days showed a significant improvement in lymphatic drainage and a significant reduction in ascites volume, which were associated with increased plasma volume. This beneficial effect of L-NMMA inhibition was also associated with a significant increase in lymphatic SMC coverage. The upregulation of eNOS in the LyECs of CH rats causes long-term lymphatic remodelling, which is characterised by a loss of SMC lymphatic coverage. The amelioration of this lymphatic abnormality by chronic eNOS inhibition results in improved lymphatic drainage and reduced ascites.

  1. Lymphatic Lipid Transport: Sewer or Subway?

    PubMed Central

    Dixon, J. Brandon

    2010-01-01

    The lymphatics began receiving attention in the scientific community as early as 1622, when Gasparo Aselli noted the appearance of milky white vessels in the mesentery of a well-fed dog. Since this time, the lymphatic system has been historically regarded as the sewer of the vasculature, passively draining fluid and proteins from the interstitial spaces (along with lipid from the gut) into the blood. Recent reports, however, suggest that the lymphatic role in lipid transport is an active and intricate process and when lymphatic function is compromised, there are systemic consequences to lipid metabolism and transport. This review highlights these recent findings and suggests future directions for understanding the interplay between lymphatic and lipid biology in health and disease. PMID:20541951

  2. The Lymphatic System: Integral Roles in Immunity

    PubMed Central

    Randolph, Gwendalyn J.; Ivanov, Stoyan; Zinselmeyer, Bernd H.; Scallan, Joshua P.

    2017-01-01

    The lymphatic vasculature is not considered a formal part of the immune system, but it is critical to immunity. One of its major roles is in the coordination of the trafficking of antigen and immune cells. However, other roles in immunity are emerging. Lymphatic endothelial cells, for example, directly present antigen or express factors that greatly influence the local environment. We cover these topics herein and discuss how other properties of the lymphatic vasculature, such as mechanisms of lymphatic contraction (which immunologists traditionally do not take into account), are nonetheless integral in the immune system. Much is yet unknown, and this nascent subject is ripe for exploration. We argue that to consider the impact of lymphatic biology in any given immunological interaction is a key step toward integrating immunology with organ physiology and ultimately many complex pathologies. PMID:27860528

  3. [Lymphatic system and water homeostasis].

    PubMed

    Borodin, Iu I; Golubeva, I A; Mashak, A N

    2005-01-01

    Using the methods of light and electron microscopy as well as histochemistry, the complex study of structural-cellular state of the wall of small intestine and its grouped lymphoid nodules, mesenterial and iliac lymph nodes and thymus was performed in rats subjected to the changes of a type of drinking water. Tap, distilled and radon waters were used. The organism was found to respond to the changes in the type of drinking water by both non-specific (increase in sectional area of lymphatic vessels and the number of eosinophilic granulocytes in the wall of small intestine, in lymphoid nodule number containing germinal centers in lymph nodes, in proportion of thymus connective tissue component, increased lymphocyte dehydrogenase activity) and specific reactions, which were characteristic only to a given type of water. The latter, for example, included the activation of the function of protein synthesis in endothelial cells of lymphatic capillaries of the small intestine and increased numbers of plasma cells and dividing cells in lymphoid organs in rats consuming distilled water; increased proportion of blood capillaries in the wall of the small intestine, accompanied by the ultrastructural signs of reduction of plastic processes in them in animals drinking radon water. The response of the wall of the small intestine and lymphoid organs of an animal to the effect of drinking waters, different in their mineral content and radon concentrations, was subjected to general biological regularities and took place in two phases of an adaptation process, functional stress and resistivity.

  4. The geographical distribution of lymphatic filariasis infection in Malawi

    PubMed Central

    Ngwira, Bagrey MM; Tambala, Phillimon; Perez, A Maria; Bowie, Cameron; Molyneux, David H

    2007-01-01

    Mapping distribution of lymphatic filariasis (LF) is a prerequisite for planning national elimination programmes. Results from a nation wide mapping survey for lymphatic filariasis (LF) in Malawi are presented. Thirty-five villages were sampled from 23 districts excluding three districts (Karonga, Chikwawa and Nsanje) that had already been mapped and Likoma, an Island, where access was not possible in the time frame of the survey. Antigenaemia prevalence [based on immunochromatographic card tests (ICT)] ranged from 0% to 35.9%. Villages from the western side of the country and distant from the lake tended to be of lower prevalence. The exception was a village in Mchinji district on the Malawi-Zambia border where a prevalence of 18.2% was found. In contrast villages from lake shore districts [Salima, Mangochi, Balaka and Ntcheu (Bwanje valley)] and Phalombe had prevalences of over 20%. A national map is developed which incorporates data from surveys in Karonga, Chikwawa and Nsanje districts, carried out in 2000. There is a marked decline in prevalence with increasing altitude. Further analysis revealed a strong negative correlation (R2 = 0.7 p < 0.001) between altitude and prevalence. These results suggest that the lake shore, Phalombe plain and the lower Shire valley will be priority areas for the Malawi LF elimination programme. Implications of these findings as regards implementing a national LF elimination programme in Malawi are discussed. PMID:18047646

  5. [Morphogenesis, structure and properties of lymphatic vessels].

    PubMed

    Ratajska, Anna; Jankowska-Steifer, Ewa; Czarnowska, Elżbieta; Flaht, Aleksandra; Radomska-Leśniewska, Dorota

    2012-11-19

    In this paper, we present literature results related to structure and various manners of lymphatic vessel formation during embryonic development and in pathological events, such as tumorigenesis, wound healing, and other diseases. The functions of the lymphatic system include the collection of fluids that enter tissues from the circulation, absorption of lipids and lipid-soluble vitamins from the intestine and their subsequent transport, participation in antigen, dendritic cell, and lymphocyte migration. The lymphatic system is also a route for tumor cell and inflammatory cell transport. Native lymphatic capillaries differ from blood capillaries by having an irregular lumen, a discontinuous basement membrane, absence of pericytes, and a strong anchorage of their endothelial cells to the extracellular matrix via microfibrils built of emilin and fibrillin. Lymphatic endothelial cells express surface antigens such as Lyve-1, podoplanin, VEGFR3 (Flk4) and transcription factor Prox-1, as well as molecules which are common for blood endothelial cells and lymphatic endothelial cells (CD31, CD34, Flk-1, Tie-1, Tie-2, neuropilin 2). Lymphatic vessel formation during embryonic development starts with the occurrence of lymphatic sacs sprouting from systemic jugular veins and/or by co-option of lymphangioblasts or hematopoietic-derived cells. It can also proceed by dedifferentiation of venous endothelial cells after their detachment from the venous system, migration to the target places within the body and assembly in the lymphatic lumen. Mechanisms of lymphatic vessel formation during embryonic development and in pathological conditions, such as tumorigenesis, wound healing, and metastasis, is regulated by a plethora of growth factors and molecules, among which the most important are VEGF-C, VEGF-D, HGF, FGF, retinoic acid, IL-3, and IL-7. Macrophages and cells bearing CD45 phenotype seem to take part in the formation of lymphatics. Macrophages might act as a source of growth

  6. T Cell Trafficking through Lymphatic Vessels

    PubMed Central

    Hunter, Morgan C.; Teijeira, Alvaro; Halin, Cornelia

    2016-01-01

    T cell migration within and between peripheral tissues and secondary lymphoid organs is essential for proper functioning of adaptive immunity. While active T cell migration within a tissue is fairly slow, blood vessels and lymphatic vessels (LVs) serve as speedy highways that enable T cells to travel rapidly over long distances. The molecular and cellular mechanisms of T cell migration out of blood vessels have been intensively studied over the past 30 years. By contrast, less is known about T cell trafficking through the lymphatic vasculature. This migratory process occurs in one manner within lymph nodes (LNs), where recirculating T cells continuously exit into efferent lymphatics to return to the blood circulation. In another manner, T cell trafficking through lymphatics also occurs in peripheral tissues, where T cells exit the tissue by means of afferent lymphatics, to migrate to draining LNs and back into blood. In this review, we highlight how the anatomy of the lymphatic vasculature supports T cell trafficking and review current knowledge regarding the molecular and cellular requirements of T cell migration through LVs. Finally, we summarize and discuss recent insights regarding the presumed relevance of T cell trafficking through afferent lymphatics. PMID:28066423

  7. Lymphatic vessels clean up your arteries.

    PubMed

    Fernández-Hernando, Carlos

    2013-04-01

    Reverse cholesterol transport (RCT) is the pathway by which cholesterol accumulated in peripheral tissues, including the artery wall, is transported to the liver for excretion. There is strong evidence suggesting that interventions that increase macrophage cholesterol efflux and RCT would be antiatherogenic. In this issue of the JCI, Martel et al. investigate the contribution of lymphatic vasculature to RCT. Their results support the concept that the lymphatic vessel route is critical for RCT from atherosclerotic plaques. Therefore, strategies to improve lymphatic transport might be useful for treating atherosclerotic vascular disease.

  8. Rapid Lymphatic Dissemination of Encapsulated Group A Streptococci via Lymphatic Vessel Endothelial Receptor-1 Interaction.

    PubMed

    Lynskey, Nicola N; Banerji, Suneale; Johnson, Louise A; Holder, Kayla A; Reglinski, Mark; Wing, Peter A C; Rigby, David; Jackson, David G; Sriskandan, Shiranee

    2015-09-01

    The host lymphatic network represents an important conduit for pathogen dissemination. Indeed, the lethal human pathogen group A streptococcus has a predilection to induce pathology in the lymphatic system and draining lymph nodes, however the underlying basis and subsequent consequences for disease outcome are currently unknown. Here we report that the hyaluronan capsule of group A streptococci is a crucial virulence determinant for lymphatic tropism in vivo, and further, we identify the lymphatic vessel endothelial receptor-1 as the critical host receptor for capsular hyaluronan in the lymphatic system. Interference with this interaction in vivo impeded bacterial dissemination to local draining lymph nodes and, in the case of a hyper-encapsulated M18 strain, redirected streptococcal entry into the blood circulation, suggesting a pivotal role in the manifestation of streptococcal infections. Our results reveal a novel function for bacterial capsular polysaccharide in directing lymphatic tropism, with potential implications for disease pathology.

  9. Rapid Lymphatic Dissemination of Encapsulated Group A Streptococci via Lymphatic Vessel Endothelial Receptor-1 Interaction

    PubMed Central

    Johnson, Louise A.; Holder, Kayla A.; Reglinski, Mark; Wing, Peter A. C.; Rigby, David; Jackson, David G.; Sriskandan, Shiranee

    2015-01-01

    The host lymphatic network represents an important conduit for pathogen dissemination. Indeed, the lethal human pathogen group A streptococcus has a predilection to induce pathology in the lymphatic system and draining lymph nodes, however the underlying basis and subsequent consequences for disease outcome are currently unknown. Here we report that the hyaluronan capsule of group A streptococci is a crucial virulence determinant for lymphatic tropism in vivo, and further, we identify the lymphatic vessel endothelial receptor-1 as the critical host receptor for capsular hyaluronan in the lymphatic system. Interference with this interaction in vivo impeded bacterial dissemination to local draining lymph nodes and, in the case of a hyper-encapsulated M18 strain, redirected streptococcal entry into the blood circulation, suggesting a pivotal role in the manifestation of streptococcal infections. Our results reveal a novel function for bacterial capsular polysaccharide in directing lymphatic tropism, with potential implications for disease pathology. PMID:26352587

  10. MR imaging of the lymphatic system in patients with lipedema and lipo-lymphedema.

    PubMed

    Lohrmann, Christian; Foeldi, Etelka; Langer, Mathias

    2009-05-01

    To assess for the first time the morphology of the lymphatic system in patients with lipedema and lipo-lymphedema of the lower extremities by MR lymphangiography. 26 lower extremities in 13 consecutive patients (5 lipedema, 8 lipo-lymphedema) were examined by MR lymphangiography. 18 mL of gadoteridol and 1 mL of mepivacainhydrochloride 1% were subdivided into 10 portions and injected intracutaneously in the forefoot. MR imaging was performed with a 1.5-T system equipped with high-performance gradients. For MR lymphangiography, a 3D-spoiled gradient-echo sequence was used. For evaluation of the lymphedema a heavily T2-weighted 3D-TSE sequence was performed. In all 16 lower extremities (100%) with lipo-lymphedema, high signal intensity areas in the epifascial region could be detected on the 3D-TSE sequence. In the 16 examined lower extremities with lipo-lymphedema, 8 lower legs and 3 upper legs demonstrated enlarged lymphatic vessels up to a diameter of 3 mm. In two lower legs with lipo-lymphedema, an area of dermal back-flow was seen, indicating lymphatic outflow obstruction. In the 10 examined lower extremities with clinically pure lipedema, 4 lower legs and 2 upper legs demonstrated enlarged lymphatic vessels up to a diameter of 2 mm, indicating a subclinical status of lymphedema. In all examined extremities, the inguinal lymph nodes demonstrated a contrast material enhancement in the first image acquisition 15 min after injection. MR lymphangiography is a safe and accurate minimal-invasive imaging modality for the evaluation of the lymphatic circulation in patients with lipedema and lipo-lymphedema of the lower extremities. If the extent of lymphatic involvement is unclear at the initial clinical examination or requires a better definition for optimal therapeutic planning, MR lymphangiography is able to identify the anatomic and physiological derangements and to establish an objective baseline.

  11. Use of a PEG-conjugated bright near-infrared dye for functional imaging of rerouting of tumor lymphatic drainage after sentinel lymph node metastasis

    PubMed Central

    Proulx, Steven T.; Luciani, Paola; Christiansen, Ailsa; Karaman, Sinem; Blum, Katrin S.; Rinderknecht, Matthias; Leroux, Jean-Christophe; Detmar, Michael

    2013-01-01

    Tumor lymphangiogenesis promotes metastatic cancer spread to lymph nodes and beyond. However, the potential remodeling and functionality of tumor-draining lymphatic vessels has remained unclear. Thus, we aimed to develop non-invasive imaging methods for repeated quantitative imaging of lymphatic drainage and of contractile collecting lymphatic vessel function in mice, with colloidal near-infrared (NIR) tracers and a custom fluorescence stereomicroscope specially adapted for NIR sensitive imaging. Using these tools, we quantitatively determined pulse rates and valvular function of collecting lymphatic vessels with high resolution. Unexpectedly, we found that tumor-draining lymphatic vessels in a melanoma footpad model initially were dilated but remained functional, despite lower pulse rates. In two independent tumor models, impaired lymphatic function was detected once metastases were present in draining lymph nodes. Importantly, we found that lymphatic dysfunction, induced by metastatic tumor spread to sentinel lymph nodes, can lead to a rerouting of lymphatic flow away from the metastatic lymph node, via collateral lymphatic vessels, to alternate lymph nodes. These findings might have important clinical implications for the procedure of sentinel lymph node mapping that represents the standard of care for determining prognosis and treatment of melanoma and breast cancer patients. PMID:23566803

  12. Molecular and cellular mechanisms of lymphatic vascular maturation

    PubMed Central

    Chen, Hong; Griffin, Courtney; Xia, Lijun; Srinivasan, R. Sathish

    2014-01-01

    Lymphatic vasculature is necessary for maintaining fluid homeostasis in vertebrates. During embryogenesis lymphatic endothelial cells originate from the veins as a homogeneous population. These cells undergo a series of changes at the morphological and molecular levels to become mature lymphatic vasculature that consists of lymphatic capillaries, collecting lymphatic vessels and valves. In this article we summarize our current knowledge about these steps and highlight some black boxes that require further clarification. PMID:24928499

  13. In vivo determination of collecting lymphatic vessel permeability to albumin: a role for lymphatics in exchange

    PubMed Central

    Scallan, Joshua P; Huxley, Virginia H

    2010-01-01

    While it is well established that the lymphatic vasculature is central to fluid and solute homeostasis, how it accomplishes this task is not well defined. To clarify the basic mechanisms underlying basal fluid and solute homeostasis, we assessed permeability to rat serum albumin () in mesenteric collecting lymphatic vessels and venules of juvenile male rats. Using the quantitative microfluorometric technique originally developed for blood capillaries, we tested the hypothesis that as a consequence of venules and collecting lymphatics sharing a common embryological origin, their would not differ significantly. Supporting our hypothesis, the median collecting lymphatic (3.5 ± 1.0 × 10−7 cm s−1, N= 22) did not differ significantly from the median venular (4.0 ± 1.0 × 10−7 cm s−1, N= 8, P= 0.61). For collecting lymphatics the diffusive permeability (Pd= 2.5 × 10−7 cm s−1) was obtained from the relationship of apparent and pressure. While the measured , Pd and estimated hydraulic conductivity of collecting lymphatics and venules were similar, the contribution of convective coupling differs as a result of the higher hydrostatic pressure experienced by venules relative to collecting lymphatics in vivo. In summary, the data demonstrate the capacity for collecting lymphatics to act as exchange vessels, able to extravasate solute and filter fluid. As a consequence these data provide experimental support for the theory that prenodal lymphatic vessels concentrate intraluminal protein. PMID:19917564

  14. Macrophages define dermal lymphatic vessel calibre during development by regulating lymphatic endothelial cell proliferation.

    PubMed

    Gordon, Emma J; Rao, Sujata; Pollard, Jeffrey W; Nutt, Stephen L; Lang, Richard A; Harvey, Natasha L

    2010-11-01

    Macrophages have been suggested to stimulate neo-lymphangiogenesis in settings of inflammation via two potential mechanisms: (1) acting as a source of lymphatic endothelial progenitor cells via the ability to transdifferentiate into lymphatic endothelial cells and be incorporated into growing lymphatic vessels; and (2) providing a crucial source of pro-lymphangiogenic growth factors and proteases. We set out to establish whether cells of the myeloid lineage are important for development of the lymphatic vasculature through either of these mechanisms. Here, we provide lineage tracing evidence to demonstrate that lymphatic endothelial cells arise independently of the myeloid lineage during both embryogenesis and tumour-stimulated lymphangiogenesis in the mouse, thus excluding macrophages as a source of lymphatic endothelial progenitor cells in these settings. In addition, we demonstrate that the dermal lymphatic vasculature of PU.1(-/-) and Csf1r(-/-) macrophage-deficient mouse embryos is hyperplastic owing to elevated lymphatic endothelial cell proliferation, suggesting that cells of the myeloid lineage provide signals that act to restrain lymphatic vessel calibre in the skin during development. In contrast to what has been demonstrated in settings of inflammation, macrophages do not comprise the principal source of pro-lymphangiogenic growth factors, including VEGFC and VEGFD, in the embryonic dermal microenvironment, illustrating that the sources of patterning and proliferative signals driving embryonic and disease-stimulated lymphangiogenesis are likely to be distinct.

  15. Phosphorylation of ERK/MAP Kinase Is Required for Long-Term Potentiation in Anatomically Restricted Regions of the Lateral Amygdala in Vivo

    ERIC Educational Resources Information Center

    Schafe, Glenn E.; Swank, Michael W.; Rodriguez, Sarina M.; Debiec, Jacek; Doyere, Valerie

    2008-01-01

    We have previously shown that the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/ MAPK) is transiently activated in anatomically restricted regions of the lateral amygdala (LA) following Pavlovian fear conditioning and that blockade of ERK/MAPK activation in the LA impairs both fear memory consolidation and long-term…

  16. Phosphorylation of ERK/MAP Kinase Is Required for Long-Term Potentiation in Anatomically Restricted Regions of the Lateral Amygdala in Vivo

    ERIC Educational Resources Information Center

    Schafe, Glenn E.; Swank, Michael W.; Rodriguez, Sarina M.; Debiec, Jacek; Doyere, Valerie

    2008-01-01

    We have previously shown that the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/ MAPK) is transiently activated in anatomically restricted regions of the lateral amygdala (LA) following Pavlovian fear conditioning and that blockade of ERK/MAPK activation in the LA impairs both fear memory consolidation and long-term…

  17. Cardiac Lymphatics - A New Avenue for Therapeutics?

    PubMed

    Vuorio, Taina; Tirronen, Annakaisa; Ylä-Herttuala, Seppo

    2017-01-10

    Recent progress in lymphatic vessel biology and in novel imaging techniques has established the importance of the lymphatic vasculature as part of the cardiovascular system. The lymphatic vessel network regulates many physiological processes important for heart function such as fluid balance, transport of extravasated proteins, and trafficking of immune cells. Therefore, lymphangiogenic therapy could be beneficial in the treatment of cardiovascular diseases, for example by improving reverse cholesterol transport (RCT) from atherosclerotic lesions or by resolving edema and fibrosis after myocardial infarction. In this review we first describe recent findings on the development and function of cardiac lymphatic vessels, and subsequently focus on the prospects of pro- and anti-lymphangiogenic therapies in cardiovascular diseases.

  18. Lymphatic vessels in inflamed human dental pulp.

    PubMed

    Marchetti, C; Piacentini, C; Menghini, P

    1990-01-01

    Investigation has been performed on both the light and electron microscopic characteristics of the lymphatic vessels present in the dental pulp of human teeth which have been affected by serious carious lesions. These conditions provoke a severe inflammatory response resulting in structural and functional modifications of the tissue; increase of the tissue pressure is followed by the need for a more intensive lymphatic drainage. In the inflamed pulps, dilated lymphatic vessels with distended walls and "open junctions" between endothelial cells are detectable. On the other hand they lack certain endothelial structures which characterize the morphology of these vessels under normal conditions. In the pulpal regions affected by fibrotic proliferation shrunken vessels with irregular profiles are present. From these observations it is possible to obtain other information on the mechanisms regulating the lymphatic drainage in different structural and functional conditions of the interstitium.

  19. Lymphatic system anomalies in Crouzon syndrome

    PubMed Central

    Bourgeois, Pierre; Moniotte, Stéphane

    2009-01-01

    Crouzon syndrome is a rare genetic disorder characterised mainly by distinctive malformations of the skull and facial region and caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. No study reported on oedemas related to lymphatic system abnormalities in these patients. A case of Crouzon syndrome displaying classic facial anomalies but also with bilateral lower limb oedema is reported in whom lymphoscintigraphic investigation of the limbs clearly delineated the presence of lymphatic system anomalies. PMID:21686735

  20. Near-infrared fluorescence imaging of lymphatics in head and neck lymphedema

    NASA Astrophysics Data System (ADS)

    Tan, I.-Chih; Maus, Erik A.; Rasmussen, John C.; Marshall, Milton V.; Fife, Caroline E.; Smith, Latisha A.; Sevick-Muraca, Eva M.

    2011-03-01

    Treatment of lymphatic disease is complicated and controversial, due in part to the limited understanding of the lymphatic system. Lymphedema (LE) is a frequent complication after surgical resection and radiation treatment in cancer survivors, and is especially debilitating in regions where treatment options are limited. Although some extremity LE can be effectively treated with manual lymphatic drainage (MLD) therapy or compression devices to direct proximal lymph transport, head and neck LE is more challenging, due to complicated geometry and complex lymphatic structure in head and neck region. Herein, we describe the compassionate use of an investigatory technique of near-infrared (NIR) fluorescence imaging to understand the lymphatic anatomy and function, and to help direct MLD in a patient with head and neck LE. Immediately after 9 intradermal injections of 25 μg indocyanine green each around the face and neck region, NIR fluorescence images were collected using a custom-built imaging system with diffused excitation light illumination. These images were then used to direct MLD therapy. In addition, 3-dimensional (3D) surface profilometry was used to monitor response to therapy. NIR fluorescence images of functioning lymphatic vessels and abnormal structures were obtained. Precise geometries of facial structures were obtained using 3D profilometry, and detection of small changes in edema between therapy sessions was achieved. NIR fluorescence imaging provides a mapping of lymphatic architecture to direct MLD therapy and thus improve treatment efficacy in the head and neck LE, while 3D profilometry allowed longitudinal assessment of edema to evaluate the efficacy of therapy.

  1. Comparative and Developmental Anatomy of Cardiac Lymphatics

    PubMed Central

    Ratajska, A.; Gula, G.; Flaht-Zabost, A.; Czarnowska, E.; Ciszek, B.; Jankowska-Steifer, E.; Niderla-Bielinska, J.; Radomska-Lesniewska, D.

    2014-01-01

    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. PMID:24592145

  2. Advances in Lymphatic Imaging and Drug Delivery

    SciTech Connect

    Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.; Thallapally, Praveen K.; Laird, Forrest M.

    2011-09-10

    Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases will have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastly improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.

  3. Lymphatic fluid: exchange mechanisms and regulation

    PubMed Central

    Huxley, Virginia H; Scallan, Joshua

    2011-01-01

    Abstract Regulation of fluid and material movement between the vascular space of microvessels penetrating functioning organs and the cells therein has been studied extensively. Unanswered questions as to the regulatory mechanisms and routes remain. Significantly less is known about the lymphatic vascular system given the difficulties in seeing, no less isolating, these vessels lying deeper in these same tissues. It has become evident that the exchange microvasculature is not simply a passive biophysical barrier separating the vascular and interstitial compartments but a dynamic, multicellular structure subject to acute regulation and chronic adaptation to stimuli including inflammation, sepsis, diabetes, injury, hypoxia and exercise. Similarly lymphatic vessels range, in their simplest form, from lymphatic endothelium attached to the interstitial matrix, to endothelia and phasic lymphatic smooth muscle that act as Starling resistors. Recent work has demonstrated that among the microvascular lymphatic elements, the collecting lymphatics have barrier properties similar to venules, and thus participate in exchange. As with venules, vasoactive agents can alter both the permeability and contractile properties thereby setting up previously unanticipated gradients in the tissue space and providing potential targets for the pharmacological prevention and/or resolution of oedema. PMID:21521763

  4. Lymphatic vessel density in radical prostatectomy specimens.

    PubMed

    Cheng, Liang; Bishop, Elena; Zhou, Honghong; Maclennan, Gregory T; Lopez-Beltran, Antonio; Zhang, Shaobo; Badve, Sunil; Baldridge, Lee Ann; Montironi, Rodolfo

    2008-04-01

    Formation of new lymphatic channels, or lymphangiogenesis, has been associated with poor prognosis in a number of human cancers. Its prognostic significance in prostate cancer is uncertain. We analyzed 122 radical prostatectomy specimens. Immunohistochemistry for lymphatic vessels was performed using a mouse monoclonal antibody reactive with an O-linked sialoglycoprotein found on lymphatic endothelium (clone D2-40, Signet Laboratories, Dedham, Mass). The mean lymphatic vessel densities (LVDs) of the 3 prostate compartments were compared. Lymphatic vessel densities were correlated with other clinical and pathologic characteristics. Mean values for intratumoral, peritumoral, and normal prostate LVD were 3.0, 5.2, and 4.8 lymphatic vessels per 200x field, respectively. The intratumoral LVD was significantly lower than the peritumoral or normal LVD (P < .001), and the LVD of the latter 2 compartments was not significantly different (P = .29). The prostate LVD did not correlate with other clinical and pathologic parameters. In conclusion, LVD is reduced in the intratumoral compartment compared with the peritumoral and normal prostate compartments, whereas the latter 2 have similar LVD. In contrast to other malignancies, quantitation of lymphangiogenesis in prostatic adenocarcinoma does not appear to offer useful prognostic information.

  5. TGF-β1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by the activation of CCR7/CCL21-mediated chemotaxis.

    PubMed

    Pang, M-F; Georgoudaki, A-M; Lambut, L; Johansson, J; Tabor, V; Hagikura, K; Jin, Y; Jansson, M; Alexander, J S; Nelson, C M; Jakobsson, L; Betsholtz, C; Sund, M; Karlsson, M C I; Fuxe, J

    2016-02-11

    Tumor cells frequently disseminate through the lymphatic system during metastatic spread of breast cancer and many other types of cancer. Yet it is not clear how tumor cells make their way into the lymphatic system and how they choose between lymphatic and blood vessels for migration. Here we report that mammary tumor cells undergoing epithelial-mesenchymal transition (EMT) in response to transforming growth factor-β (TGF-β1) become activated for targeted migration through the lymphatic system, similar to dendritic cells (DCs) during inflammation. EMT cells preferentially migrated toward lymphatic vessels compared with blood vessels, both in vivo and in 3D cultures. A mechanism of this targeted migration was traced to the capacity of TGF-β1 to promote CCR7/CCL21-mediated crosstalk between tumor cells and lymphatic endothelial cells. On one hand, TGF-β1 promoted CCR7 expression in EMT cells through p38 MAP kinase-mediated activation of the JunB transcription factor. Blockade of CCR7, or treatment with a p38 MAP kinase inhibitor, reduced lymphatic dissemination of EMT cells in syngeneic mice. On the other hand, TGF-β1 promoted CCL21 expression in lymphatic endothelial cells. CCL21 acted in a paracrine fashion to mediate chemotactic migration of EMT cells toward lymphatic endothelial cells. The results identify TGF-β1-induced EMT as a mechanism, which activates tumor cells for targeted, DC-like migration through the lymphatic system. Furthermore, it suggests that p38 MAP kinase inhibition may be a useful strategy to inhibit EMT and lymphogenic spread of tumor cells.

  6. Label-free 3D imaging of microstructure, blood, and lymphatic vessels within tissue beds in vivo.

    PubMed

    Zhi, Zhongwei; Jung, Yeongri; Wang, Ruikang K

    2012-03-01

    This Letter reports the use of an ultrahigh resolution optical microangiography (OMAG) system for simultaneous 3D imaging of microstructure and lymphatic and blood vessels without the use of an exogenous contrast agent. An automatic algorithm is developed to segment the lymphatic vessels from the microstructural images based on the fact that the lymph fluid is optically transparent. An OMAG system is developed that utilizes a broadband supercontinuum light source, providing an axial resolution of 2.3 μm and lateral resolution of 5.8 μm, capable of resolving the capillary vasculature and lymphatic vessels innervating microcirculatory tissue beds. Experimental demonstration is performed by showing detailed 3D lymphatic and blood vessel maps, coupled with morphology, within mouse ears in vivo. © 2012 Optical Society of America

  7. Superselective retrograde lymphatic duct embolization for management of postoperative lymphatic leak.

    PubMed

    Arslan, Bülent; Masrani, Abdulrahman; Tasse, Jordan Cameron; Stenson, Kerstin; Turba, Ülkü Cenk

    2017-01-01

    Lymphatic leak is a well-documented complication following neck dissection surgeries. When conservative methods fail to control the leak, thoracic duct embolization becomes an option. Transabdominal access is the standard for this procedure; however, it is not always feasible. We discuss a technique of selective lymphatic vessel embolization utilizing retrograde transvenous access.

  8. Superselective retrograde lymphatic duct embolization for management of postoperative lymphatic leak

    PubMed Central

    Arslan, Bülent; Masrani, Abdulrahman; Tasse, Jordan Cameron; Stenson, Kerstin; Turba, Ülkü Cenk

    2017-01-01

    Lymphatic leak is a well-documented complication following neck dissection surgeries. When conservative methods fail to control the leak, thoracic duct embolization becomes an option. Transabdominal access is the standard for this procedure; however, it is not always feasible. We discuss a technique of selective lymphatic vessel embolization utilizing retrograde transvenous access. PMID:28724508

  9. Sentinel lymph node mapping in melanoma of the ear.

    PubMed

    Wey, P D; De La Cruz, C; Goydos, J S; Choi, M L; Borah, G L

    1998-05-01

    Primary nodal drainage basins in melanoma of the head and neck are often unpredictable. The ear is a notorious example of an anatomic site with ambiguous patterns of lymphatic drainage. Preoperative lymphoscintigraphy has recently emerged as one modality to assist in identifying clinically relevant nodes. We propose that the addition of intraoperative lymph node mapping techniques that utilize radioactive tracers ("intraoperative lymphoscintigraphy") can increase the accuracy of identifying sentinel nodes and help to determine which patients may benefit from a complete neck dissection. This report demonstrates the ambiguity in identifying drainage patterns in melanoma of the ear and offers a reliable method of sentinel lymph node mapping. This report also addresses current issues regarding treatment protocols of patients with micrometastatic disease in the periauricular region.

  10. Role of lymphatic vasculature in regional and distant metastases.

    PubMed

    Podgrabinska, Simona; Skobe, Mihaela

    2014-09-01

    In cancer, lymphatic vasculature has been traditionally viewed only as a transportation system for metastatic cells. It has now become clear that lymphatics perform many additional functions which could influence cancer progression. Lymphangiogenesis, induced at the primary tumor site and at distant sites, potently augments metastasis. Lymphatic endothelial cells (LECs) control tumor cell entry and exit from the lymphatic vessels. LECs also control immune cell traffic and directly modulate adaptive immune responses. This review highlights advances in our understanding of the mechanisms by which lymphatic vessels, and in particular lymphatic endothelium, impact metastasis. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. The Lymphatic System in Disease Processes and Cancer Progression

    PubMed Central

    Padera, Timothy P.; Meijer, Eelco F.J.; Munn, Lance L.

    2016-01-01

    Advances in our understanding of the structure and function of the lymphatic system have made it possible to identify its role in a variety of disease processes. Because it is involved not only in fluid homeostasis but also in immune cell trafficking, the lymphatic system can mediate and ultimately alter immune responses. Our rapidly increasing knowledge of the molecular control of the lymphatic system will inevitably lead to new and effective therapies for patients with lymphatic dysfunction. In this review, we discuss the molecular and physiological control of lymphatic vessel function and explore how the lymphatic system contributes to many disease processes, including cancer and lymphedema. PMID:26863922

  12. Lymphoedema caused by idiopathic lymphatic thrombus.

    PubMed

    Hara, Hisako; Mihara, Makoto; Seki, Yukio; Koshima, Isao

    2013-12-01

    Primary lymphoedema includes some diseases whose genetic anomaly is detected and others whose pathology is unknown. In this article, we report a lymphatic thrombus found in a limb with lymphoedema during lymphatico-venous anastomosis (LVA). A 32-year-old man was aware of oedema in his left calcar pedis 3 years previously, which appeared without any trigger. Indocyanine green lymphography indicated lymphatic stasis in the left calf and thigh region, and we performed LVA for the patient. During the operation, we found yellow vessels, which were thought to be lymphatic vessels filled with a yellow solid substance, just beneath the superficial fascia at the left ankle. Pathological examination of the thrombi revealed hyaline material mixed with cell components. The cells were categorised as lymphatic endothelial cells, as they were positive for podoplanin. There was no evidence of malignancy. Causes of idiopathic lymphatic thrombus such as this may be one of the causes of so-called primary lymphoedema, and evaluation of such cases may be the first step towards elucidating the mechanisms involved in the development of primary lymphoedema.

  13. Cholinergic innervation of human mesenteric lymphatic vessels.

    PubMed

    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.

  14. Exercise training improves obesity-related lymphatic dysfunction.

    PubMed

    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 < 0.01). Aerobic 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

  15. Interaction between the extracellular matrix and lymphatics - consequences for lymphangiogenesis and lymphatic function

    PubMed Central

    Wiig, Helge; Keskin, Doruk; Kalluri, Raghu

    2014-01-01

    The lymphatic system is important for body fluid balance as well as immunological surveillance. Due to the identification of new molecular markers during the last decade, there has been a recent dramatic increase in our knowledge on the molecular mechanisms involved in lymphatic vessel growth (lymphangiogenesis) and lymphatic function. Here we review data showing that although it is often overlooked, the extracellular matrix plays an important role in the generation of new lymphatic vessels as a response to physiological and pathological stimuli. Extracellular matrix-lymphatic interactions as well as biophysical characteristics of the stroma have consequences for tumor formation, growth and metastasis. During the recent years, anti-lymphangiogenesis has emerged as an additional therapeutic modality to the clinically applied anti-angiogenesis strategy. Oppositely, enhancement of lymphangiogenesis in situations of lymph accumulation is seen as a promising strategy to a set of conditions where few therapeutic avenues are available. Knowledge on the interaction between the extracellular matrix and the lymphatics may enhance our understanding of the underlying mechanisms and may ultimately lead to better therapies for conditions where reduced or increased lymphatic function is the therapeutic target PMID:20727409

  16. Lymphatic Vessels: The Next Frontier in Lung Transplant.

    PubMed

    Cui, Ye; Liu, Kaifeng; Lamattina, Anthony Mark; Visner, Gary; El-Chemaly, Souheil

    2017-09-01

    Lymphatic vessels are essential for the uptake of fluid, immune cells, macromolecules, and lipids from the interstitial space. During lung transplant surgery, the pulmonary lymphatic vessel continuum is completely disrupted, and, as a result, lymphatic drainage function is severely compromised. After transplantation, the regeneration of an effective lymphatic drainage system plays a crucial role in maintaining interstitial fluid balance in the lung allograft. In the meantime, these newly formed lymphatic vessels are commonly held responsible for the development of immune responses leading to graft rejection, because they are potentially capable of transporting antigen-presenting cells loaded with allogeneic antigens to the draining lymph nodes. However, despite remarkable progress in the understanding of lymphatic biology, there is still a paucity of consistent evidence that demonstrates the exact impacts of lymphatic vessels on lung graft function. In this review, we examine the current literature related to roles of lymphatic vessels in the pathogenesis of lung transplant rejection.

  17. Endothelial Cell Responses to Biomechanical Forces in Lymphatic Vessels.

    PubMed

    Sabine, Amélie; Saygili Demir, Cansaran; Petrova, Tatiana V

    2016-09-01

    Lymphatic vessels are important components of the cardiovascular and immune systems. They contribute both to the maintenance of normal homeostasis and to many pathological conditions, such as cancer and inflammation. The lymphatic vasculature is subjected to a variety of biomechanical forces, including fluid shear stress and vessel circumferential stretch. This review will discuss recent advances in our understanding of biomechanical forces in lymphatic vessels and their role in mammalian lymphatic vascular development and function. We will highlight the importance of fluid shear stress generated by lymph flow in organizing the lymphatic vascular network. We will also describe how mutations in mechanosensitive genes lead to lymphatic vascular dysfunction. Better understanding of how biomechanical and biochemical stimuli are perceived and interpreted by lymphatic endothelial cells is important for targeting regulation of lymphatic function in health and disease. Important remaining critical issues and future directions in the field will be discussed in this review. Antioxid. Redox Signal. 25, 451-465.

  18. Lattice Boltzmann simulations of lymphatic pumping

    NASA Astrophysics Data System (ADS)

    Kunert, Christian; Padera, Tim P.; Munn, Lance L.

    2012-02-01

    Lymphatic flow plays an important role in the progress of many diseases, including lymphedema and metastasis. However lymphatic pumping and flow is poorly understood. Here, we present a computer model that is based on biological observations of lymphatic pumping. Fluid flow is simulated by a D2Q9 lattice Boltzmann model. The boundary of the vessels moves according to shear-induced nitric oxide production, and wall motion transfers momentum to the fluid to induce flow. Because the model only includes local properties, it can be highly parallelized. In our case we utilize graphic processors (GPU) to achieve high performance computation. We show that the model provides stable pumping over a wide range of parameter values, with optimum flow achieved in the biological ranges. Furthermore, we investigate the efficiency by analyzing the flow rate and pumping frequency in order to compare the behavior of the model with existing in vivo data.

  19. Morphogenesis of the lymphatic vasculature: A focus on new progenitors and cellular mechanisms important for constructing lymphatic vessels.

    PubMed

    Kazenwadel, Jan; Harvey, Natasha L

    2016-03-01

    Lymphatic vessels serve crucial roles in the regulation of tissue fluid homeostasis, dietary lipid absorption and immune cell trafficking. Defects in lymphatic vessel morphogenesis and function have been associated with lymphedema, obesity, hypertension and tumour metastasis. Morphogenetic events important for construction of the lymphatic vasculature during development include the specification and emergence of lymphatic endothelial progenitor cells, their differentiation and assembly into interconnected vessels and vascular remodeling, ultimately giving rise to a functional vascular network. Despite the embryonic origins of lymphatic endothelial progenitor cells being long debated, work performed over the last decade had overwhelmingly supported at least a great majority of progenitor cells arising from the venous vasculature. Here, we review the most recent advances in the field of lymphatic vessel morphogenesis, with a focus on studies that have identified novel sources of embryonic lymphatic endothelial progenitor cells, together with the cellular mechanisms by which lymphatic vessels are initially assembled. © 2015 Wiley Periodicals, Inc.

  20. Cerebral Lipiodol Embolism after Lymphatic Embolization for Plastic Bronchitis

    PubMed Central

    Kirschen, Matthew P.; Dori, Yoav; Itkin, Maxim; Licht, Daniel J.; Ichord, Rebecca; Vossough, Arastoo

    2016-01-01

    An adolescent with plastic bronchitis due to congenital heart disease had altered mental status after an interventional lymphatic procedure in which lipiodol contrast was used. Neuroimaging revealed cerebral lipiodol embolization due to direct shunting between lymphatic channels and pulmonary veins. Cerebral lipiodol embolization is a potential neurologic morbidity associated with interventional lymphatic procedures. PMID:27297208

  1. Cerebral Lipiodol Embolism after Lymphatic Embolization for Plastic Bronchitis.

    PubMed

    Kirschen, Matthew P; Dori, Yoav; Itkin, Maxim; Licht, Daniel J; Ichord, Rebecca; Vossough, Arastoo

    2016-09-01

    An adolescent with plastic bronchitis due to congenital heart disease had altered mental status after an interventional lymphatic procedure in which lipiodol contrast was used. Neuroimaging revealed cerebral lipiodol embolization due to direct shunting between lymphatic channels and pulmonary veins. Cerebral lipiodol embolization is a potential neurologic morbidity associated with interventional lymphatic procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The human renal lymphatics under normal and pathological conditions.

    PubMed

    Ishikawa, Y; Akasaka, Y; Kiguchi, H; Akishima-Fukasawa, Y; Hasegawa, T; Ito, K; Kimura-Matsumoto, M; Ishiguro, S; Morita, H; Sato, S; Soh, S; Ishii, T

    2006-09-01

    The renal lymphatics have not been fully documented in humans. The aim of this study was to clarify the morphology of the human renal lymphatic system under normal and pathological conditions by immunohistochemistry using anti-D2-40 antibody. Normal and pathological renal tissues obtained at autopsy as well as nephrectomy specimens with renal cell carcinoma (RCC) were used. Thin sections were immunostained with antibodies against D2-40 and CD31. In normal kidney, D2-40+ lymphatics were abundant in the interstitium around the interlobar and arcuate arteries/veins but sporadic in those around the glomeruli or between the tubules in the cortex. A few lymphatics contained erythrocytes in their lumina. Lymphatics were seldom present in the medulla. In RCC cases, lymphatics were evident at the tumour margin, whereas CD31+ capillaries were abundant throughout the tumour and lymphatics were increased in the fibrous interstitium around the tumour. Lymphatic invasion by RCC cells was also detectable. D2-40+ lymphatics were evident in other pathological conditions and end-stage kidney had a denser lymphatic distribution than normal kidney. Lymphatics are abundant around the arteries/veins and are also present in the renal cortex and medulla. D2-40 immunostaining is helpful for investigating the pathophysiological role of renal lymphatics.

  3. Development of the lymphatic vascular system: a mystery unravels.

    PubMed

    Hong, Young-Kwon; Shin, Jay W; Detmar, Michael

    2004-11-01

    The blood vascular and the lymphatic system play complementary roles in tissue perfusion and fluid reabsorption. Despite its critical role in mediating tissue fluid homeostasis, intestinal lipid absorption, and the immune response, the lymphatic system has not received as much attention as the blood vascular system, largely due to a lack of lymphatic-specific markers and to the dearth of knowledge about the molecular regulation of lymphatic development and function. A series of recent landmark studies now significantly has advanced our understanding of the lymphatic system. Based upon the discovery and characterization of lymphatic-specific growth factors, receptors, and transcriptional regulators, the mystery of lymphatic vascular system development begins to be unraveled. The successful isolation and cultivation of blood vascular and lymphatic endothelial cells has enabled comparative molecular and cellular analyses of these two genetically and developmentally closely related cell lineages. Moreover, studies of several genetic mouse models have set the framework for a new molecular model of embryonic lymphatic vascular development and have identified molecular pathways whose mutational inactivation leads to human diseases associated with lymphedema. Although these rapid advances already have led to development of the first lymphatic-targeted molecular therapies, there still remain many unanswered questions regarding almost every aspect of lymphatic vascular biology, making the lymphatic system a highly exciting and rewarding field of study.

  4. Mapping.

    ERIC Educational Resources Information Center

    Kinney, Douglas M.; McIntosh, Willard L.

    1979-01-01

    The area of geological mapping in the United States in 1978 increased greatly over that reported in 1977; state geological maps were added for California, Idaho, Nevada, and Alaska last year. (Author/BB)

  5. Lymphatic Muscle Cells in Rat Mesenteric Lymphatic Vessels of Various Ages

    PubMed Central

    Bridenbaugh, Eric A.; Nizamutdinova, Irina Tsoy; Jupiter, Daniel; Nagai, Takashi; Thangaswamy, Sangeetha; Chatterjee, Victor

    2013-01-01

    Abstract Background Recent studies on aging-associated changes in mesenteric lymph flow in situ demonstrated predominance of the severe negative chronotropic effect of aging on the contractility of aged mesenteric lymphatic vessels (MLV). At the same time, contraction amplitude of the aged vessels was only slightly diminished by aging and can be rapidly stimulated within 5–15 minutes. However, the detailed quantitative evaluation of potential aging-associated changes in muscle cells investiture in MLV has never been performed. Methods and Results In this study we, for the first time, performed detailed evaluation of muscle cells investiture in MLV in reference to the position of lymphatic valve in different zones of lymphangion within various age groups (3-mo, 9-mo and 24-mo Fischer-344 rats). Using visual and quantitative analyses of the images of MLV immunohistochemically labeled for actin, we confirmed that the zones located close upstream (pre-valve zones) and above lymphatic valves (valve zones) possess the lowest investiture of lymphatic muscle cells. Most of the high muscle cells investiture zones exist downstream to the lymphatic valve (post-valve zones). The muscle cells investiture of these zones is not affected by aging, while pre-valve and valve zones demonstrate significant aging-associated decrease in muscle cells investiture. Conclusions The low muscle cells investiture zones in lymphatic vessels consist of predominantly longitudinally oriented muscle cells which are positioned in pre-valve and valve zones and connect adjacent lymphangions. These cells may provide important functional impact on the biomechanics of the lymphatic valve gating and electrical coupling between lymphangions, while their aging-associated changes may delimit adaptive reserves of aged lymphatic vessels. PMID:23531183

  6. Lymphatic muscle cells in rat mesenteric lymphatic vessels of various ages.

    PubMed

    Bridenbaugh, Eric A; Nizamutdinova, Irina Tsoy; Jupiter, Daniel; Nagai, Takashi; Thangaswamy, Sangeetha; Chatterjee, Victor; Gashev, Anatoliy A

    2013-03-01

    Recent studies on aging-associated changes in mesenteric lymph flow in situ demonstrated predominance of the severe negative chronotropic effect of aging on the contractility of aged mesenteric lymphatic vessels (MLV). At the same time, contraction amplitude of the aged vessels was only slightly diminished by aging and can be rapidly stimulated within 5-15 minutes. However, the detailed quantitative evaluation of potential aging-associated changes in muscle cells investiture in MLV has never been performed. In this study we, for the first time, performed detailed evaluation of muscle cells investiture in MLV in reference to the position of lymphatic valve in different zones of lymphangion within various age groups (3-mo, 9-mo and 24-mo Fischer-344 rats). Using visual and quantitative analyses of the images of MLV immunohistochemically labeled for actin, we confirmed that the zones located close upstream (pre-valve zones) and above lymphatic valves (valve zones) possess the lowest investiture of lymphatic muscle cells. Most of the high muscle cells investiture zones exist downstream to the lymphatic valve (post-valve zones). The muscle cells investiture of these zones is not affected by aging, while pre-valve and valve zones demonstrate significant aging-associated decrease in muscle cells investiture. The low muscle cells investiture zones in lymphatic vessels consist of predominantly longitudinally oriented muscle cells which are positioned in pre-valve and valve zones and connect adjacent lymphangions. These cells may provide important functional impact on the biomechanics of the lymphatic valve gating and electrical coupling between lymphangions, while their aging-associated changes may delimit adaptive reserves of aged lymphatic vessels.

  7. Lymphatic and venous function in lipoedema.

    PubMed

    Harwood, C A; Bull, R H; Evans, J; Mortimer, P S

    1996-01-01

    Lipoedema is a common but infrequently recognized condition causing bilateral enlargement of the legs in women. Although generally considered to be the result of an abnormal deposition of subcutaneous fat with associated oedema, the precise mechanisms responsible for oedema formation have yet to be fully established. In order to evaluate the possible role of lymphatic or venous dysfunction in the pathogenesis of lipoedema, 10 patients were investigated by photoplethysmography (venous function) and quantitative lymphoscintigraphy (lymphatic function). The results were compared with those from patients with primary lymphoedema and those from healthy volunteers. The results demonstrated minor abnormalities of venous function in only two patients. One patient had moderately impaired lymphatic function in both legs and seven patients had a marginal degree of impairment in one or both legs. However, in none of these cases did the impairment attain the low levels seen in true lymphoedema. Lipoedema appears to be a distinct clinical entity best classified as a lipodystrophy rather than a direct consequence of any primary venous or lymphatic insufficiency.

  8. Lymphatic Leak Complicating Central Venous Catheter Insertion

    SciTech Connect

    Barnacle, Alex M. Kleidon, Tricia M.

    2005-12-15

    Many of the risks associated with central venous access are well recognized. We report a case of inadvertent lymphatic disruption during the insertion of a tunneled central venous catheter in a patient with raised left and right atrial pressures and severe pulmonary hypertension, which led to significant hemodynamic instability. To our knowledge, this rare complication is previously unreported.

  9. Breast cancer metastasis and the lymphatic system

    PubMed Central

    RAHMAN, MUNAZZAH; MOHAMMED, SULMA

    2015-01-01

    Breast cancer remains the leading cause of cancer mortality worldwide, despite a significant decline in death rates due to early detection. The majority of cancer mortalities are due to the metastasis of tumor cells to other organs. Metastasis or tumor cell dissemination occurs via the hematogenous and lymphatic systems. For many carcinomas, the dissemination of tumor cells via lymphatic drainage of the tumor is the most common metastatic route. Such lymphatic drainage collects at the regional lymph nodes and the dissection and pathological examination of these nodes for lodged cancer cells is the gold standard procedure to detect metastasis. The present report provides an overview of the lymphatic system and its clinical significance as a prognostic factor, in addition to the interactions between the primary tumor and its microenvironment, and the influence of genomic subtypes on the resulting organ-specific pattern of tumor cell dissemination. It also examines the seemingly protracted asymptomatic period, during which the disseminated cells remain dormant, leading to the manifestation of metastasis decades after the successful treatment of the primary tumor. PMID:26622656

  10. The embryonic origins of lymphatic vessels: an historical review.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2010-06-01

    Work on the lymphatic system began in the 17th century, and by the beginning of the 19th century the anatomy of most of the lymphatic system had been described. One of the most important questions in this field has been the determination of the embryological origin of the lymphatic endothelium. Two theories were proposed. The first suggested that lymphatic endothelium derived by sprouting from venous endothelium, the so-called centrifugal theory. The second, the so-called centripetal theory, suggested that lymphatic endothelium differentiates in situ from primitive mesenchyme, and secondarily acquires connection with the vascular system. More recent evidence has provided support for both hypotheses.

  11. Lymphoscintigraphy patterns in newborns and children with congenital lymphatic dysplasia.

    PubMed

    Bellini, C; Villa, G; Sambuceti, G; Traggiai, C; Campisi, C; Bellini, T; Morcaldi, G; Massocco, D; Bonioli, E; Boccardo, F

    2014-03-01

    We performed lymphoscintigraphy on 31 patients (newborns and children) affected by congenital lymphatic dysplasia according to our previously published protocol. Congenital lymphatic dysplasia may present with various degrees of clinical severity, ranging from nonimmune hydrops fetalis with visceral effusions to lymphedema alone. We recommend that lymphoscintigraphy should be strongly considered in all patients with signs of lymphatic dysplasia, including those with minimal and initial signs of lymphatic impairment, in order to obtain a very early diagnosis and to start treatment. Lymphoscintigraphy is safe and useful in the diagnosis of lymphatic dysplasia in the newborn and children. Moreover, it is well tolerated by patients and well accepted by their parents.

  12. Blocking of the Lymphatic Vessel in Lymphedema

    PubMed Central

    Mihara, Makoto

    2017-01-01

    Objective: In this case report, we present a case wherein we observed a blocking of lymphatic vessels in indocyanine green lymphography and found a shrunken lymphatic vessel intraoperatively. Methods: We performed indocyanine green lymphography and lymphaticovenous anastomosis on a 77-year-old woman. She had previously undergone right mastectomy and axillary lymph node dissection accompanied by radiotherapy and chemotherapy for right breast cancer. She noticed swelling in the right upper limb 22 years after the surgery and consulted our hospital. Although she started wearing elastic sleeve, there was still stiffness in the right upper limb, and we decided to perform lymphaticovenous anastomosis 5 months after the first consultation. Results: In the preoperative indocyanine green lymphography, we observed a linear pattern in the medial side of the right forearm, which suddenly blocked in the middle of the forearm. At that point, we observed dilated lymphatic vessels that were suddenly shrunken at the proximal side intraoperatively. We performed lymphaticovenous anastomosis with the dilated part of this lymphatic vessel. We also performed 4 additional lymphaticovenous anastomoses. The operation time was 2 hours 10 minutes, and the amount of bleeding was minimal. The right upper limb of the patient got softer, and she was satisfied with the result 3 months after the operation. The average circumference change at the 5 points in the right upper limb was −1.26 cm (range, −2.3 to −0.3 cm). Conclusions: There was a possibility that the blocking of the lymphatic vessels was a cause of lymphedema in the upper extremity. PMID:28405261

  13. Aged lymphatic contractility: recent answers and new questions.

    PubMed

    Gashev, Anatoliy A; Chatterjee, Victor

    2013-03-01

    Abstract An overview is presented of recent findings related to biology of aging of the lymph transport system. The authors discuss recently obtained data on the aging-associated alterations of lymphatic contractility in thoracic duct and mesenteric lymphatic vessels; on comparisons of function of aged mesenteric lymphatic vessels in situ versus isolated specimens and important conclusions which arose from these studies; on aging-associated changes in functional status of mast cells located close to aged mesenteric lymphatic vessels; on evidence of presence of oxidative stress in aged lymphatic vessels and changes in arrangement of muscle cells in their walls. The authors conclude that future continuation of the research efforts in this area is necessary and will be able to provide not only novel fundamental knowledge on the biology of lymphatic aging, but also will create solid foundation for the subsequent developments of lymphatic-oriented therapeutic interventions in many diseases of the elderly.

  14. Use of Indocyanine Green-SPY Angiography for Tracking Lymphatic Recovery After Lymphaticovenous Anastomosis.

    PubMed

    Shih, Hubert B; Shakir, Afaaf; Nguyen, Dung H

    2016-05-01

    Lymphaticovenous anastomosis (LVA) is a surgical treatment option for patients with early stage lymphedema. To date, no ideal imaging modality exists for tracking patency of the LVA postoperatively. We hypothesize that laser angiography utilizing indocyanine green (ICG) via the SPY system (Lifecell Corp.) would be a useful methodology for assessing the patency of the LVA and lymphatic recovery postoperatively. A prospective trial was performed on patients with stage II lymphedema who underwent LVA from 2013 to 2014 by a single surgeon. All candidates underwent preoperative and postoperative lymphatic mapping using ICG-SPY angiography. Postoperative analyses were performed at 1 month and at 9 months after surgery and assessed for patency at the site of the LVAs and for changes in lymphatic pattern. Five patients underwent LVA, 3 for upper extremity and 2 for lower extremity stage II lymphedema. The number of LVAs per extremity was 1 to 3 (total, 11). One month postoperative ICG-SPY angiography demonstrated flow through 9 of 11 anastomoses. Evaluation at 9 months postoperative showed improvement in lymphatic drainage. Indocyanine green-SPY angiography may be used to objectively evaluate the surgical outcome of LVA.

  15. Nanoparticle-enhanced MRI to evaluate radiation delivery to the regional lymphatics for patients with breast cancer.

    PubMed

    MacDonald, Shannon M; Harisinghani, Mukesh G; Katkar, Amol; Napolitano, Brian; Wolfgang, John; Taghian, Alphonse G

    2010-07-15

    At present, radiation (RT) fields are based largely, and often solely, on bony anatomy. Recent efforts have been taken to better define lymphatic regions for RT planning. Lymphotrophic nanoparticle-enhanced MRI (LN-MRI) allows for accurate identification of malignant and benign lymph nodes. We sought to evaluate RT delivery to lymphatics for breast cancer using LN-MRI. Twenty-three patients with breast cancer underwent LN-MRI. MRIs were anatomically registered to a reference CT; benign and malignant lymph nodes were contoured. Standard RT fields were planned and dose calculated to prescribe 45-50 Gy. Lymphatic regions were contoured on CT. Coverage of LN-MRI lymph nodes by RT fields and contoured lymphatics were assessed. Eighty-one percent of all lymph nodes defined by LN-MRI were covered by the 45-Gy isodose line; 82% of malignant and 79% of benign. The 50-Gy isodose line only encompassed 60% of LN-MRI defined lymph nodes-64% of malignant and 59% of benign. For nodal volumes contoured in the absence of a margin, 86% of actual lymph nodes were within contoured volumes. When a 5-mm expansion was added, 99% were included. LN-MRI is a useful tool to delineate the location of breast regional lymphatics. These results suggest less than desired coverage of lymph nodes using standard RT fields and that a margin may be advisable when defining nodal volumes by CT. The use of IMRT and RT in lieu of surgery makes accurate definition of the location of breast regional lymphatics of paramount importance. Published by Elsevier Inc.

  16. Nanoparticle-Enhanced MRI to Evaluate Radiation Delivery to the Regional Lymphatics for Patients With Breast Cancer

    SciTech Connect

    MacDonald, Shannon M.; Harisinghani, Mukesh G.; Katkar, Amol; Napolitano, Brian; Wolfgang, John; Taghian, Alphonse G.

    2010-07-15

    Purpose: At present, radiation (RT) fields are based largely, and often solely, on bony anatomy. Recent efforts have been taken to better define lymphatic regions for RT planning. Lymphotrophic nanoparticle-enhanced MRI (LN-MRI) allows for accurate identification of malignant and benign lymph nodes. We sought to evaluate RT delivery to lymphatics for breast cancer using LN-MRI. Methods and Materials: Twenty-three patients with breast cancer underwent LN-MRI. MRIs were anatomically registered to a reference CT; benign and malignant lymph nodes were contoured. Standard RT fields were planned and dose calculated to prescribe 45-50 Gy. Lymphatic regions were contoured on CT. Coverage of LN-MRI lymph nodes by RT fields and contoured lymphatics were assessed. Results: Eighty-one percent of all lymph nodes defined by LN-MRI were covered by the 45-Gy isodose line; 82% of malignant and 79% of benign. The 50-Gy isodose line only encompassed 60% of LN-MRI defined lymph nodes-64% of malignant and 59% of benign. For nodal volumes contoured in the absence of a margin, 86% of actual lymph nodes were within contoured volumes. When a 5-mm expansion was added, 99% were included. Conclusions: LN-MRI is a useful tool to delineate the location of breast regional lymphatics. These results suggest less than desired coverage of lymph nodes using standard RT fields and that a margin may be advisable when defining nodal volumes by CT. The use of IMRT and RT in lieu of surgery makes accurate definition of the location of breast regional lymphatics of paramount importance.

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

    PubMed

    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.

  18. Reconstructive microsurgery of lymph vessels: the personal method of lymphatic-venous-lymphatic (LVL) interpositioned grafted shunt.

    PubMed

    Campisi, C; Boccardo, F; Tacchella, M

    1995-01-01

    Our clinical observations in 64 patients affected by chronic obstructive lymphedema (either arm or leg) undergoing interposition autologous lymphatic-venous-lymphatic (LVL) anastomoses are reported. This microsurgical technique is an alternative to other lymphatic shunting methods, especially when venous dysfunction coexists in the same limb and, therefore, when direct lymphatic-venous anastomosis is accordingly inadequate. Preoperative diagnostic evaluation (including lymphatic and venous isotopic scintigraphy, Doppler venous flowmetrics, and pressure manometry) plays an essential role in assessing the conditions of both the lymphatic and venous systems and in establishing which microsurgical procedure, if any, is indicated. Our microsurgical technique consists of inserting suitably large and lengthy autologous venous grafts between lymphatic collectors above and below the site of obstruction to lymph flow. The data show that, using this technique, both limb function and edema improved, and in all patients followed up for over 5 years edema regression was permanent.

  19. High-Resolution Mapping of Anatomical Connections in Marmoset Extrastriate Cortex Reveals a Complete Representation of the Visual Field Bordering Dorsal V2

    PubMed Central

    Jeffs, Janelle; Federer, Frederick; Ichida, Jennifer M.

    2013-01-01

    The primate visual cortex consists of many areas. The posterior areas (V1, V2, V3, and middle temporal) are thought to be common to all primate species. However, the organization of cortex immediately anterior to area V2 (the “third tier” cortex) remains controversial, particularly in New World primates. The main point of contention has been whether the third tier cortex consists of a single area V3, representing lower and upper visual quadrants in dorsal and ventral cortex, respectively, or of 2 distinct areas (the dorsomedial [DM] area and a V3-like area). Resolving this controversy is crucial to understand the function and evolution of the third tier cortex. We have addressed this issue in marmosets, by performing high-precision mapping of corticocortical connections in cortex bordering dorsal V2. Multiple closely spaced neuroanatomical tracer injections were placed across the full width of dorsal V2 or adjacent anterior cortex, and the location of resulting labeled cells mapped throughout whole flattened visual cortex. The resulting topographic patterns of labeled connections allowed us to define areas and their boundaries. We found that a complete representation of the visual field borders dorsal V2 and that the third tier cortex consists of 2 distinct areas. These results unequivocally support the DM model. PMID:22523183

  20. Laminar flow downregulates Notch activity to promote lymphatic sprouting.

    PubMed

    Choi, Dongwon; Park, Eunkyung; Jung, Eunson; Seong, Young Jin; Yoo, Jaehyuk; Lee, Esak; Hong, Mingu; Lee, Sunju; Ishida, Hiroaki; Burford, James; Peti-Peterdi, Janos; Adams, Ralf H; Srikanth, Sonal; Gwack, Yousang; Chen, Christopher S; Vogel, Hans J; Koh, Chester J; Wong, Alex K; Hong, Young-Kwon

    2017-04-03

    The major function of the lymphatic system is to drain interstitial fluid from tissue. Functional drainage causes increased fluid flow that triggers lymphatic expansion, which is conceptually similar to hypoxia-triggered angiogenesis. Here, we have identified a mechanotransduction pathway that translates laminar flow-induced shear stress to activation of lymphatic sprouting. While low-rate laminar flow commonly induces the classic shear stress responses in blood endothelial cells and lymphatic endothelial cells (LECs), only LECs display reduced Notch activity and increased sprouting capacity. In response to flow, the plasma membrane calcium channel ORAI1 mediates calcium influx in LECs and activates calmodulin to facilitate a physical interaction between Krüppel-like factor 2 (KLF2), the major regulator of shear responses, and PROX1, the master regulator of lymphatic development. The PROX1/KLF2 complex upregulates the expression of DTX1 and DTX3L. DTX1 and DTX3L, functioning as a heterodimeric Notch E3 ligase, concertedly downregulate NOTCH1 activity and enhance lymphatic sprouting. Notably, overexpression of the calcium reporter GCaMP3 unexpectedly inhibited lymphatic sprouting, presumably by disturbing calcium signaling. Endothelial-specific knockouts of Orai1 and Klf2 also markedly impaired lymphatic sprouting. Moreover, Dtx3l loss of function led to defective lymphatic sprouting, while Dtx3l gain of function rescued impaired sprouting in Orai1 KO embryos. Together, the data reveal a molecular mechanism underlying laminar flow-induced lymphatic sprouting.

  1. Lymph flow regulates collecting lymphatic vessel maturation in vivo

    PubMed Central

    Sweet, Daniel T.; Jiménez, Juan M.; Chang, Jeremy; Hess, Paul R.; Mericko-Ishizuka, Patricia; Fu, Jianxin; Xia, Lijun; Davies, Peter F.; Kahn, Mark L.

    2015-01-01

    Fluid shear forces have established roles in blood vascular development and function, but whether such forces similarly influence the low-flow lymphatic system is unknown. It has been difficult to test the contribution of fluid forces in vivo because mechanical or genetic perturbations that alter flow often have direct effects on vessel growth. Here, we investigated the functional role of flow in lymphatic vessel development using mice deficient for the platelet-specific receptor C-type lectin–like receptor 2 (CLEC2) as blood backfills the lymphatic network and blocks lymph flow in these animals. CLEC2-deficient animals exhibited normal growth of the primary mesenteric lymphatic plexus but failed to form valves in these vessels or remodel them into a structured, hierarchical network. Smooth muscle cell coverage (SMC coverage) of CLEC2-deficient lymphatic vessels was both premature and excessive, a phenotype identical to that observed with loss of the lymphatic endothelial transcription factor FOXC2. In vitro evaluation of lymphatic endothelial cells (LECs) revealed that low, reversing shear stress is sufficient to induce expression of genes required for lymphatic valve development and identified GATA2 as an upstream transcriptional regulator of FOXC2 and the lymphatic valve genetic program. These studies reveal that lymph flow initiates and regulates many of the key steps in collecting lymphatic vessel maturation and development. PMID:26214523

  2. Development of the larval lymphatic system in zebrafish.

    PubMed

    Jung, Hyun Min; Castranova, Daniel; Swift, Matthew R; Pham, Van N; Venero Galanternik, Marina; Isogai, Sumio; Butler, Matthew G; Mulligan, Timothy S; Weinstein, Brant M

    2017-06-01

    The lymphatic vascular system is a hierarchically organized complex network essential for tissue fluid homeostasis, immune trafficking and absorption of dietary fats in the human body. Despite its importance, the assembly of the lymphatic network is still not fully understood. The zebrafish is a powerful model organism that enables study of lymphatic vessel development using high-resolution imaging and sophisticated genetic and experimental manipulation. Although several studies have described early lymphatic development in the fish, lymphatic development at later stages has not been completely elucidated. In this study, we generated a new Tg(mrc1a:egfp)(y251) transgenic zebrafish that uses a mannose receptor, C type 1 (mrc1a) promoter to drive strong EGFP expression in lymphatic vessels at all stages of development and in adult zebrafish. We used this line to describe the assembly of the major vessels of the trunk lymphatic vascular network, including the later-developing collateral cardinal, spinal, superficial lateral and superficial intersegmental lymphatics. Our results show that major trunk lymphatic vessels are conserved in the zebrafish, and provide a thorough and complete description of trunk lymphatic vessel assembly. © 2017. Published by The Company of Biologists Ltd.

  3. Lymphatic System: An Active Pathway for Immune Protection

    PubMed Central

    Liao, Shan; von der Weid, Pierre-Yves

    2015-01-01

    Lymphatic vessels are well known to participate in the immune response by providing the structural and functional support for the delivery of antigens and antigen presenting cells to draining lymph nodes. Recent advances have improved our understanding of how the lymphatic system works and how it participates to the development of immune responses. New findings suggest that the lymphatic system may control the ultimate immune response through a number of ways which include guiding antigen/dendritic cells (DC) entry into initial lymphatics at the periphery; promoting antigen/DC trafficking through afferent lymphatic vessels by actively facilitating lymph and cell movement; enabling antigen presentation in lymph nodes via a network of lymphatic endothelial cells and lymph node stroma cell and finally by direct lymphocytes exit from lymph nodes. The same mechanisms are likely also important to maintain peripheral tolerance. In this review we will discuss how the morphology and gene expression profile of the lymphatic endothelial cells in lymphatic vessels and lymph nodes provides a highly efficient pathway to initiate immune responses. The fundamental understanding of how lymphatic system participates in immune regulation will guide the research on lymphatic function in various diseases. PMID:25534659

  4. The lymphatic vasculature: development and role in shaping immunity.

    PubMed

    Betterman, Kelly L; Harvey, Natasha L

    2016-05-01

    The lymphatic vasculature is an integral component of the immune system. Lymphatic vessels are a key highway via which immune cells are trafficked, serving not simply as a passive route of transport, but to actively shape and coordinate immune responses. Reciprocally, immune cells provide signals that impact the growth, development, and activity of the lymphatic vasculature. In addition to immune cell trafficking, lymphatic vessels are crucial for fluid homeostasis and lipid absorption. The field of lymphatic vascular research is rapidly expanding, fuelled by rapidly advancing technology that has enabled the manipulation and imaging of lymphatic vessels, together with an increasing recognition of the involvement of lymphatic vessels in a myriad of human pathologies. In this review we provide an overview of the genetic pathways and cellular processes important for development and maturation of the lymphatic vasculature, discuss recent work revealing important roles for the lymphatic vasculature in directing immune cell traffic and coordinating immune responses and highlight the involvement of lymphatic vessels in a range of pathological settings. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Lymphatic system: an active pathway for immune protection.

    PubMed

    Liao, Shan; von der Weid, P Y

    2015-02-01

    Lymphatic vessels are well known to participate in the immune response by providing the structural and functional support for the delivery of antigens and antigen presenting cells to draining lymph nodes. Recent advances have improved our understanding of how the lymphatic system works and how it participates to the development of immune responses. New findings suggest that the lymphatic system may control the ultimate immune response through a number of ways which may include guiding antigen/dendritic cells (DC) entry into initial lymphatics at the periphery; promoting antigen/DC trafficking through afferent lymphatic vessels by actively facilitating lymph and cell movement; enabling antigen presentation in lymph nodes via a network of lymphatic endothelial cells and lymph node stroma cell and finally by direct lymphocytes exit from lymph nodes. The same mechanisms are likely also important to maintain peripheral tolerance. In this review we will discuss how the morphology and gene expression profile of the lymphatic endothelial cells in lymphatic vessels and lymph nodes provides a highly efficient pathway to initiate immune responses. The fundamental understanding of how lymphatic system participates in immune regulation will guide the research on lymphatic function in various diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Comparison of approaches for microscopic imaging of skin lymphatic vessels.

    PubMed

    Wu, Xiufeng; Yu, Zheyuan; Liu, Ningfei

    2012-01-01

    Assessment of skin lymphatic vessels is of great significance in understanding their roles in many pathological conditions. Our aim was to identify the optimal approach for investigation of cutaneous lymphatic system. We performed comparative studies on skin lymphatic vessels using immunohistochemistry of tissue sections, computer graphic reconstruction method together with immunohistochemically stained serial sections and whole mount fluorescence in human lower limb. Lymphatic vessels were identified with podoplanin antibody. The relative merits and drawbacks of each method in evaluation of structure, spatial organization, and distribution of cutaneous lymphatic vessels were described. Immunohistology of tissue sections enabled the investigation of the structure and distribution of the whole cutaneous lymphatic system in two-dimensional slices, whereas three-dimensional morphology of only the most superficial lymph capillary network immediately under the epidermis could be evaluated with the whole mount technique. Meanwhile, only little segmentation of skin lymphatic vessel from five immunohistochemically stained serial sections was reconstructed and evaluated due to expense and special skills required using computer graphic three-dimensional reconstruction. Furthermore, a great number of artifacts and special skills required in its processes leaded to less accurate structure of skin lymphatic vessels. Our findings demonstrated that the use of either of the proposed techniques alone could not allow a comprehensive analysis of the skin lymphatic system due to their relative drawbacks. Combination of immunohistology of tissue sections and three-dimensional whole-mount preparations appears to be the best candidate for comprehensive evaluation of skin lymphatic system. © Wiley Periodicals, Inc.

  7. Fluorescence imaging of lymphatic outflow of cerebrospinal fluid in mice.

    PubMed

    Kwon, Sunkuk; Janssen, Christopher F; Velasquez, Fred Christian; Sevick-Muraca, Eva M

    2017-10-01

    Cerebrospinal fluid (CSF) is known to be reabsorbed by the lymphatic vessels and drain into the lymph nodes (LNs) through peripheral lymphatic vessels. In the peripheral lymphatics, the contractile pumping action of lymphangions mediates lymph drainage; yet it is unknown whether lymphatic vessels draining cranial and spinal CSF show similar function. Herein, we used non-invasive near-infrared fluorescence imaging (NIRFI) to image (i) indocyanine green (ICG) distribution along the neuraxis and (ii) routes of ICG-laden CSF outflow into the lymphatics following intrathecal lumbar administration. We demonstrate lymphatic contractile function in peripheral lymphatics draining from the nasal lymphatics to the mandibular LNs. In addition, we observed afferent sciatic lymphatic vessels, which also show contractile activity and transport spinal CSF into the sciatic LNs. This drainage pattern was also visualized by NIRFI following intrathecal thoracic injection. In situ intravital imaging following intrathecal lumbar injection of blue dye shows similar distributions to that seen in vivo with ICG. NIRFI could be used as a tool to probe CSF pathology including neurological disorders by imaging CSF outflow dynamics to lymphatics. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The lymphatic vascular system of the mouse head.

    PubMed

    Lohrberg, Melanie; Wilting, Jörg

    2016-12-01

    Histological studies of the lymphatic vascular system in adult mice are hampered because bones cannot be sectioned properly. Here, we decalcified the heads of 14-day-old mice, embedded them in paraffin and stained resultant serial sections with the lymphendothelial-specific antibodies Lyve-1 and Podoplanin. We show that the tissues with the highest lymphatic vascular density are the dermis and the oral mucous membranes. In contrast, the nasal mucous membrane is devoid of lymphatics, except for its most basal parts below the vomeronasal organ. The inferior nasal turbinate contains numerous lymphatics and is connected to the nasolacrimal duct (NLD), which is ensheathed by a dense network of lymphatics. The lymphatics of the eye lids and conjunctiva are connected to those of the inferior nasal turbinate. We suggest that cerebro-spinal fluid (CSF) can drain via the optic nerve and NLD lymphatics, whereas CSF drained via the Fila olfactoria into the nasal mucous membrane is used for moisturization of the respiratory air. Tongue, palatine and buccal mucous membranes possess numerous lymphatics, whereas the dental pulp has none. Lymphatics are present in the maxillary gland and close to the temporomandibular joint, suggesting the augmentation of lymph flow by chewing and yawning. Lymphatics can also be found in the dura mater and in the dural septae entering into deeper parts of the brain. Our findings are discussed with regard to CSF drainage and potential routes for ocular tumor dissemination.

  9. Program requirements for fellowship education in venous and lymphatic medicine.

    PubMed

    Comerota, Anthony J; Min, Robert J; Rathbun, Suman W; Khilnani, Neil; Rooke, Thom; Wakefield, Thomas W; Carman, Teresa L; Lurie, Fedor; Vedantham, Suresh; Zimmet, Steven E

    2017-08-01

    Background In every field of medicine, comprehensive education should be delivered at the graduate level. Currently, no single specialty routinely provides a standardized comprehensive curriculum in venous and lymphatic disease. Method The American Board of Venous & Lymphatic Medicine formed a task force, made up of experts from the specialties of dermatology, family practice, interventional radiology, interventional cardiology, phlebology, vascular medicine, and vascular surgery, to develop a consensus document describing the program requirements for fellowship medical education in venous and lymphatic medicine. Result The Program Requirements for Fellowship Education in Venous and Lymphatic Medicine identify the knowledge and skills that physicians must master through the course of fellowship training in venous and lymphatic medicine. They also specify the requirements for venous and lymphatic training programs. The document is based on the Core Content for Training in Venous and Lymphatic Medicine and follows the ACGME format that all subspecialties in the United States use to specify the requirements for training program accreditation. The American Board of Venous & Lymphatic Medicine Board of Directors approved this document in May 2016. Conclusion The pathway to a vein practice is diverse, and there is no standardized format available for physician education and training. The Program Requirements for Fellowship Education in Venous and Lymphatic Medicine establishes educational standards for teaching programs in venous and lymphatic medicine and will facilitate graduation of physicians who have had comprehensive training in the field.

  10. The human renal lymphatics under normal and pathological conditions

    PubMed Central

    Ishikawa, Y; Akasaka, Y; Kiguchi, H; Akishima-Fukasawa, Y; Hasegawa, T; Ito, K; Kimura-Matsumoto, M; Ishiguro, S; Morita, H; Sato, S; Soh, S; Ishii, T

    2006-01-01

    Ishikawa Y, Akasaka Y, Kiguchi H, Akishima-Fukasawa Y, Hasegawa T, Ito K, Kimura-Matsumoto M, Ishiguro S, Morita H, Sato S, Soh S & Ishii T (2006) Histopathology 49, 265–273 The human renal lymphatics under normal and pathological conditions Aims The renal lymphatics have not been fully documented in humans. The aim of this study was to clarify the morphology of the human renal lymphatic system under normal and pathological conditions by immunohistochemistry using anti-D2-40 antibody. Methods and results Normal and pathological renal tissues obtained at autopsy as well as nephrectomy specimens with renal cell carcinoma (RCC) were used. Thin sections were immunostained with antibodies against D2-40 and CD31. In normal kidney, D2-40+ lymphatics were abundant in the interstitium around the interlobar and arcuate arteries/veins but sporadic in those around the glomeruli or between the tubules in the cortex. A few lymphatics contained erythrocytes in their lumina. Lymphatics were seldom present in the medulla. In RCC cases, lymphatics were evident at the tumour margin, whereas CD31+ capillaries were abundant throughout the tumour and lymphatics were increased in the fibrous interstitium around the tumour. Lymphatic invasion by RCC cells was also detectable. D2-40+ lymphatics were evident in other pathological conditions and end-stage kidney had a denser lymphatic distribution than normal kidney. Conclusions Lymphatics are abundant around the arteries/veins and are also present in the renal cortex and medulla. D2-40 immunostaining is helpful for investigating the pathophysiological role of renal lymphatics. PMID:16918973

  11. Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis

    PubMed Central

    Lahdenranta, Johanna; Hagendoorn, Jeroen; Padera, Timothy P.; Hoshida, Tohru; Nelson, Gregory; Kashiwagi, Satoshi; Jain, Rakesh K.; Fukumura, Dai

    2009-01-01

    Lymphatic metastasis is a critical determinant of cancer prognosis. Recently, several lymphangiogenic molecules such as vafscular endothelial growth factor (VEGF)-C and -D were identified. However, the mechanistic understanding of lymphatic metastasis is still in infancy. Nitric oxide (NO) plays a crucial role in regulating blood vessel growth and function as well as lymphatic vessel function. NOS expression correlates with lymphatic metastasis. However, causal relationship between NOS and lymphatic metastasis has not been documented. To this end, we first show that both VEGF receptor-2 and -3 stimulation activate eNOS in lymphatic endothelial cells and that NO donors induce proliferation and/or survival of cultured lymphatic endothelial cells in a dose dependent manner. We find that an NOS inhibitor L-NMMA blocked regeneration of lymphatic vessels. Using intravital microscopy that allows us to visualize the steps of lymphatic metastasis, we show that genetic deletion of eNOS as well as NOS blockade attenuates peritumor lymphatic hyperplasia of VEGF-C-overexpressing T241 fibrosarcomas and decreases the delivery of metastatic tumor cells to the draining lymph nodes. Genetic deletion of eNOS in the host also leads to a decrease in T241 tumor cell dissemination to the lymph nodes and macroscopic lymph node metastasis of B16F10 melanoma. These findings indicate that eNOS mediates VEGF-C induced lymphangiogenesis and, consequently, plays a critical role in lymphatic metastasis. Our findings explain the correlation between NOS and lymphatic metastasis seen in a number of human tumors and open the door for potential therapies exploiting NO signaling to treat diseases of the lymphatic system. PMID:19318557

  12. Manual lymphatic drainage in chronic venous disease: a duplex ultrasound study.

    PubMed

    Dos Santos Crisóstomo, Rute Sofia; Candeias, Miguel Sandu; Ribeiro, Ana Margarida Martins; da Luz Belo Martins, Catarina; Armada-da-Silva, Paulo As

    2014-12-01

    To compare the effect of call-up and reabsorption maneuvers of manual lymphatic drainage on blood flow in femoral vein and great saphenous vein in patients with chronic venous disease and healthy controls. Forty-one subjects participated in this study (mean age: 42.68(15.23)), 23 with chronic venous disease (chronic venous disease group) with clinical classification C1-5 of clinical-etiological-anatomical-pathological (CEAP) and 18 healthy subjects (control group). Call-up and reabsorption maneuvers were randomly applied in the medial aspect of the thigh. The cross-sectional areas, as well as the peak and the mean blood flow velocity at femoral vein and great saphenous vein, were assessed by Duplex ultrasound at the baseline and during maneuvers. The venous flow volume changes were calculated. The venous flow volume in femoral vein and great saphenous vein increased during both manual lymphatic drainage maneuvers and in both groups (P < 0.05). The two maneuvers had a similar effect on femoral vein and great saphenous vein hemodynamics, and in both the chronic venous disease and control groups. As a result of the call-up maneuver, the flow volume augmentations, as a result of call-up maneuver, decreased with the severity of chronic venous disease in those patients measured by the clinical classification of CEAP (r = -0.64; P = 0.03). Manual lymphatic drainage increases the venous blood flow in the lower extremity with a magnitude that is independent from the specific maneuver employed or the presence of chronic venous disease. Therefore, manual lymphatic drainage may be an alternative strategy for the treatment and prevention of venous stasis complications in chronic venous disease. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  13. Higher blood vessel density in comparison to the lymphatic vessels in oral squamous cell carcinoma

    PubMed Central

    Maturana-Ramírez, Andrea; Espinoza, Iris; Reyes, Montserrat; Aitken, Juan Pablo; Aguayo, Francisco; Hartel, Steffen; Rojas-Alcayaga, Gonzalo

    2015-01-01

    Introduction: Oral squamous cell carcinoma (OSCC) is characterized by local invasion and the development of cervical metastasis. In the tongue, an association between the invasion of the lymphatic vessels and the development of metastasis in the regional lymph nodes has been demonstrated. Moreover, invasion of the blood vessels is associated with greater recurrence and poorer prognoses. Therefore, the presence and density of lymphatic and blood vessels in intra- and peritumoral tissues should play an important role in the progression, dissemination and metastasis of carcinomas. However, the evidence regarding OSCC is inconclusive. The aim of this study was to determine the comparison and association between the lymphatic (D2-40) and blood vessel (CD34) densities in intratumoral OSCC tissue. Materials and Methods: Thirty-seven cases diagnosed as OSCC between the years 2000 and 2008 were obtained from the Anatomic Pathology Service of the School of Dentistry, University of Chile. The immunohistochemical markers D2-40 and CD34 were used, and the densities (mm2) of lymphatic vessels (LVD) and blood vessels (BVD) in the intratumoral region were determined. The relationship between LVD and BVD values was evaluated. Results: There were significant association between the CD34 and D2-40 expression (rho=0.4, P<0.05) and between the LVD and the location in the tongue (P=0.019). The BVD was greater (128.0 vessels/mm2) than the LVD (42.9 vessels/mm2), and there was a positive correlation between the LVD and BVD. Conclusions: In OSCC, the BVD is greater than the LVD, and there is a moderate correlation between the two quantities. PMID:26722595

  14. Higher blood vessel density in comparison to the lymphatic vessels in oral squamous cell carcinoma.

    PubMed

    Maturana-Ramírez, Andrea; Espinoza, Iris; Reyes, Montserrat; Aitken, Juan Pablo; Aguayo, Francisco; Hartel, Steffen; Rojas-Alcayaga, Gonzalo

    2015-01-01

    Oral squamous cell carcinoma (OSCC) is characterized by local invasion and the development of cervical metastasis. In the tongue, an association between the invasion of the lymphatic vessels and the development of metastasis in the regional lymph nodes has been demonstrated. Moreover, invasion of the blood vessels is associated with greater recurrence and poorer prognoses. Therefore, the presence and density of lymphatic and blood vessels in intra- and peritumoral tissues should play an important role in the progression, dissemination and metastasis of carcinomas. However, the evidence regarding OSCC is inconclusive. The aim of this study was to determine the comparison and association between the lymphatic (D2-40) and blood vessel (CD34) densities in intratumoral OSCC tissue. Thirty-seven cases diagnosed as OSCC between the years 2000 and 2008 were obtained from the Anatomic Pathology Service of the School of Dentistry, University of Chile. The immunohistochemical markers D2-40 and CD34 were used, and the densities (mm(2)) of lymphatic vessels (LVD) and blood vessels (BVD) in the intratumoral region were determined. The relationship between LVD and BVD values was evaluated. There were significant association between the CD34 and D2-40 expression (rho=0.4, P<0.05) and between the LVD and the location in the tongue (P=0.019). The BVD was greater (128.0 vessels/mm(2)) than the LVD (42.9 vessels/mm(2)), and there was a positive correlation between the LVD and BVD. In OSCC, the BVD is greater than the LVD, and there is a moderate correlation between the two quantities.

  15. An overview of lymphatic vessels and their emerging role in cardiovascular disease.

    PubMed

    Jones, Dennis; Min, Wang

    2011-07-01

    Over the past decade, molecular details of lymphatic vessels (lymphatics) have been rapidly acquired due to the identification of lymphatic endothelial-specific markers. Separate from the cardiovascular system, the lymphatic system is also an elaborate network of vessels that are important in normal physiology. Lymphatic vessels have the unique task to regulate fluid homeostasis, assist in immune surveillance, and transport dietary lipids. However, dysfunctional lymphatic vessels can cause pathology, while normal lymphatics can exacerbate pathology. This review summarizes the development and growth of lymphatic vessels in addition to highlighting their critical roles in physiology and pathology. Also, we discuss recent work that suggests a connection between lymphatic dysfunction and cardiovascular disease.

  16. Lymphatic endothelium forms integrin-engaging 3D structures during DC transit across inflamed lymphatic vessels.

    PubMed

    Teijeira, Alvaro; Garasa, Saray; Peláez, Rafael; Azpilikueta, Arantza; Ochoa, Carmen; Marré, Diego; Rodrigues, Magda; Alfaro, Carlos; Aubá, Cristina; Valitutti, Salvatore; Melero, Ignacio; Rouzaut, Ana

    2013-09-01

    Dendritic cell (DC) transmigration across the lymphatic endothelium is critical for the initiation and sustenance of immune responses. Under noninflammatory conditions, DC transit across the lymphatic endothelial cell (LEC) has been shown to be integrin independent. In contrast, there is increasing evidence for the participation of integrins and their ligands in DC transit across lymphatic endothelium under inflammation. In this sense, we describe the formation of ICAM-1 (CD54)-enriched three-dimensional structures on LEC/DC contacts, as these DCs adhere to inflamed skin lymphatic vessels and transmigrate into them. In vitro imaging revealed that under inflammation ICAM-1 accumulated on microvilli projections surrounding 60% of adhered DCs. In contrast, these structures were scarcely formed in noninflammatory conditions. Furthermore, ICAM-1-enriched microvilli were important in promoting DC transendothelial migration and DC crawling over the LEC surface. Microvilli formation was dependent on the presence of β-integrins on the DC side and on integrin conformational affinity to ligand. Finally, we observed that LEC microvilli structures appeared in close vicinity of CCL21 depots and that their assembly was partially inhibited by CCL21-neutralizing antibodies. Therefore, under inflammatory conditions, integrin ligands form three-dimensional membrane projections around DCs. These structures offer docking sites for DC transit from the tissue toward the lymphatic vessel lumen.

  17. Interactions of immune cells and lymphatic vessels.

    PubMed

    Kataru, Raghu P; Lee, Yulia G; Koh, Gou Young

    2014-01-01

    In addition to fluid and lipid absorption, immune cell trafficking has now become recognized as one of the major functions of the lymphatic system. Recently, several critical roles of the lymphatic vessels (LVs) in modulating immune reactions during both physiological and pathological conditions have been emerging. As LVs serve as conduits for immune cells, they come to closely interact with macrophages/monocytes, dendritic cells, and T and B lymphocytes. Accumulating evidences indicate that reciprocal interactions between the LVs and immune cells exist which cause considerable influence over the process of immune cell migration, LV growth, and ultimately certain immune reactions. This chapter discusses on the interactions of macrophages/monocytes and dendritic cells with peripheral LVs and on those of sinusoidal macrophages and T and B lymphocytes with lymph node LVs.

  18. MAPS

    Atmospheric Science Data Center

    2014-07-03

    ... Measurement of Air Pollution from Satellites (MAPS) data were collected during Space Shuttle flights in 1981, ... Facts Correlative Data  - CDIAC - Spring & Fall 1994 - Field and Aircraft Campaigns SCAR-B Block:  ...

  19. Clinical feasibility study of combined opto-acoustic and ultrasonic imaging modality providing coregistered functional and anatomical maps of breast tumors

    NASA Astrophysics Data System (ADS)

    Zalev, Jason; Clingman, Bryan; Smith, Remie J.; Herzog, Don; Miller, Tom; Stavros, A. Thomas; Ermilov, Sergey; Conjusteau, André; Tsyboulski, Dmitri; Oraevsky, Alexander A.; Kist, Kenneth; Dornbluth, N. C.; Otto, Pamela

    2013-03-01

    We report on findings from the clinical feasibility study of the ImagioTM. Breast Imaging System, which acquires two-dimensional opto-acoustic (OA) images co-registered with conventional ultrasound using a specialized duplex hand-held probe. Dual-wavelength opto-acoustic technology is used to generate parametric maps based upon total hemoglobin and its oxygen saturation in breast tissues. This may provide functional diagnostic information pertaining to tumor metabolism and microvasculature, which is complementary to morphological information obtained with conventional gray-scale ultrasound. We present co-registered opto-acoustic and ultrasonic images of malignant and benign tumors from a recent clinical feasibility study. The clinical results illustrate that the technology may have the capability to improve the efficacy of breast tumor diagnosis. In doing so, it may have the potential to reduce biopsies and to characterize cancers that were not seen well with conventional gray-scale ultrasound alone.

  20. Anatomy of the transverse colon revisited with respect to complete mesocolic excision and possible pathways of aberrant lymphatic tumor spread.

    PubMed

    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.

  1. CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance.

    PubMed

    Kida, S; Pantazis, A; Weller, R O

    1993-12-01

    Cerebrospinal fluid (CSF) drainage pathways from the rat brain were investigated by the injection of 50 microliters Indian ink into the cisterna magna. The distribution of the ink, as it escaped from the cranial CSF space, was documented in 2 mm thick slices of brain and skull cleared in cedar wood oil and in decalcified paraffin sections. Following injection of the ink, deep cervical lymph nodes were selectively blackened within 30 min and lumbar para-aortic nodes within 6 h. Within the cranial cavity, carbon particles accumulated in the basal cisterns but were also distributed in the paravascular spaces around the middle cerebral arteries and the nasal-olfactory artery. Carbon particles in the subarachnoid space beneath the olfactory bulbs drained directly into discrete channels which passed through the cribriform plate and into lymphatics in the nasal submucosa. Although ink was distributed along the subarachnoid space of the optic nerves and entered the cochlea, the nasal route was the only direct connection between cranial CSF and lymphatics. Arachnoid villi associated with superior and inferior sagittal sinuses were identified and a minor amount of drainage of ink into dural lymphatics was also observed. This study demonstrates the direct drainage of cerebrospinal fluid through the cribriform plate in anatomically defined channels which connect with the nasal lymphatics.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Non-endemic cases of lymphatic filariasis.

    PubMed

    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. Lymphatic Filariasis Disseminating to the Upper Extremity

    PubMed Central

    Maldjian, Catherine; Khanna, Vineet; Tandon, Bevan; Then, Matthew; Yassin, Mohamed; Adam, Richard; Klein, Michael J.

    2014-01-01

    Lymphatic filariasis is the most common cause of acquired lymphedema worldwide (Szuba and Rockson, 1998). It is endemic to tropical and subtropical regions, and its effects are devastating. With over 100 million infected persons, it ranks second only to leprosy as the leading cause of permanent and long-term disability. Wuchereria bancrofti is the etiologic agent in 90% of cases. There is a dearth of published MRI findings with pathologically proven active infections, making this entity even more of a diagnostic dilemma. Imaging may provide the first clue that one is dealing with a parasite and may facilitate proper treatment and containment of this disease. This is the first report of pathologic correlation with MRI findings in the extremity in active filariasis. The magnetic resonance images demonstrate an enhancing, infiltrative, mass-like appearance with partial encasement of vasculature that has not been previously described in filariasis. Low signal strands in T2-hyperintense dilated lymphatic channels are seen and may depict live adult worms. We hypothesize that the low signal strands correspond to the collagen rich acellular cuticle. This, in combination with the surrounding hyperintense T2 signal, corresponding to a dilated lymphatic channel, may provide more specific MRI findings for active nematodal infection, which can prompt early biopsy, pathological correlation, and diagnosis. PMID:24707427

  4. STUDIES ON THE PERMEABILITY OF LYMPHATIC CAPILLARIES

    PubMed Central

    Leak, Lee V.

    1971-01-01

    The passageway for interstitial fluids and large molecules across the connective tissue lymph interface has been investigated in dermal lymphatic capillaries in the ears of guinea pigs. Numerous endothelial cells overlap extensively at their margins and lack adhesion devices at many points. The observations suggest that these sites are free to move as a result of slight pressure changes. Immediately following interstitial injections of tracer particles (ferritin, thorium, carbon, and latex spheres), many of the overlapped endothelial cells are separated and thus passageways are provided between the interstitium and lymphatic lumen. Tracer particles also occur in plasmalemmal invaginations along both connective tissue and luminal fronts. All of the tracer particles accumulate within large autophagic-like vacuoles. Very few particles of ferritin are observed in the endothelium after 24 hr; however, the vesicles containing the nonprotein tracer particles (carbon, thorium, and latex) increase in size and content and remain within the lymphatic endothelial cells up to 6 months. The role of vesicles in the transport of large molecules and particles is discussed in relation to the accretion of tracer particles within large vesicles and autophagic-like vacuoles in the endothelial cytoplasm. PMID:4329612

  5. Aberrant mural cell recruitment to lymphatic vessels and impaired lymphatic drainage in a murine model of pulmonary fibrosis.

    PubMed

    Meinecke, Anna-Katharina; Nagy, Nadine; Lago, Gabriela D'Amico; Kirmse, Santina; Klose, Ralph; Schrödter, Katrin; Zimmermann, Annika; Helfrich, Iris; Rundqvist, Helene; Theegarten, Dirk; Anhenn, Olaf; Orian-Rousseau, Véronique; Johnson, Randall S; Alitalo, Kari; Fischer, Jens W; Fandrey, Joachim; Stockmann, Christian

    2012-06-14

    Pulmonary fibrosis is a progressive disease with unknown etiology that is characterized by extensive remodeling of the lung parenchyma, ultimately resulting in respiratory failure. Lymphatic vessels have been implicated with the development of pulmonary fibrosis, but the role of the lymphatic vasculature in the pathogenesis of pulmonary fibrosis remains enigmatic. Here we show in a murine model of pulmonary fibrosis that lymphatic vessels exhibit ectopic mural coverage and that this occurs early during the disease. The abnormal lymphatic vascular patterning in fibrotic lungs was driven by expression of platelet-derived growth factor B (PDGF-B) in lymphatic endothelial cells and signaling through platelet-derived growth factor receptor (PDGFR)-β in associated mural cells. Because of impaired lymphatic drainage, aberrant mural cell coverage fostered the accumulation of fibrogenic molecules and the attraction of fibroblasts to the perilymphatic space. Pharmacologic inhibition of the PDGF-B/PDGFR-β signaling axis disrupted the association of mural cells and lymphatic vessels, improved lymphatic drainage of the lung, and prevented the attraction of fibroblasts to the perilymphatic space. Our results implicate aberrant mural cell recruitment to lymphatic vessels in the pathogenesis of pulmonary fibrosis and that the drainage capacity of pulmonary lymphatics is a critical mediator of fibroproliferative changes.

  6. Lymphatic Vessels in Regenerative Medicine and Tissue Engineering.

    PubMed

    Schaupper, Mira; Jeltsch, Michael; Rohringer, Sabrina; Redl, Heinz; Holnthoner, Wolfgang

    2016-10-01

    The lymphatic system is involved in maintaining interstitial fluid homeostasis, fat absorption, and immune surveillance. Dysfunction of lymphatic fluid uptake can lead to lymphedema. Worldwide up to 250 million people are estimated to suffer from this disfiguring and disabling disease, which places a strain on the healthcare system as well as on the affected patients. The severity of lymphatic diseases calls for the establishment of new treatment methods. One approach is to replace dysfunctional lymphatic vessels with bioengineered ones. In this study, we mainly focus on hydrogels, scaffolds with cellular constructs, interstitial flow, and extracorporeal shockwave therapy. This review provides an overview on the current status of lymphatic biology and approaches of reconstruction and regeneration of lymphatic vascular tissues.

  7. The optimum marker for the detection of lymphatic vessels.

    PubMed

    Kong, Ling-Ling; Yang, Nian-Zhao; Shi, Liang-Hui; Zhao, Guo-Hai; Zhou, Wenbin; Ding, Qiang; Wang, Ming-Hai; Zhang, Yi-Sheng

    2017-10-01

    Podoplanin, lymphatic vessel endothelial hyaluronic acid receptor-1, prospero-related homeobox-1 and vascular endothelial growth factor receptor 3 have been demonstrated to have crucial roles in the development of the lymphatic system and lymphangiogenesis process by combining with their corresponding receptors. Thus, the four markers have been widely used in labelling lymphatic vessels for the detection of lymphangiogenesis and lymphatic vessel invasion. Numerous authors have aimed to identify the roles of these four markers in the lymphatic system and the mechanisms have been partly clarified at the molecular level. The aim of the present review was to comprehensively clarify the characteristics and latent action modes of the four markers in order to determine which is the best one for the detection of lymphangiogenesis and lymphatic vessel invasion.

  8. Lymphatic vessels arise from specialized angioblasts within a venous niche.

    PubMed

    Nicenboim, J; Malkinson, G; Lupo, T; Asaf, L; Sela, Y; Mayseless, O; Gibbs-Bar, L; Senderovich, N; Hashimshony, T; Shin, M; Jerafi-Vider, A; Avraham-Davidi, I; Krupalnik, V; Hofi, R; Almog, G; Astin, J W; Golani, O; Ben-Dor, S; Crosier, P S; Herzog, W; Lawson, N D; Hanna, J H; Yanai, I; Yaniv, K

    2015-06-04

    How cells acquire their fate is a fundamental question in developmental and regenerative biology. Multipotent progenitors undergo cell-fate restriction in response to cues from the microenvironment, the nature of which is poorly understood. In the case of the lymphatic system, venous cells from the cardinal vein are thought to generate lymphatic vessels through trans-differentiation. Here we show that in zebrafish, lymphatic progenitors arise from a previously uncharacterized niche of specialized angioblasts within the cardinal vein, which also generates arterial and venous fates. We further identify Wnt5b as a novel lymphatic inductive signal and show that it also promotes the ‘angioblast-to-lymphatic’ transition in human embryonic stem cells, suggesting that this process is evolutionarily conserved. Our results uncover a novel mechanism of lymphatic specification, and provide the first characterization of the lymphatic inductive niche. More broadly, our findings highlight the cardinal vein as a heterogeneous structure, analogous to the haematopoietic niche in the aortic floor.

  9. Emerging trends in the pathophysiology of lymphatic contractile function

    PubMed Central

    Chakraborty, Sanjukta; Davis, Michael J.; Muthuchamy, Mariappan

    2015-01-01

    Lymphatic contractile dysfunction is central to a number of pathologies that affect millions of people worldwide. Due to its critical role in the process of inflammation, a dysfunctional lymphatic system also compromises the immune response, further exacerbating a number of inflammation related diseases. Despite the critical physiological functions accomplished by the transport of lymph, a complete understanding of the contractile machinery of the lymphatic system lags far behind that of the blood vasculature. However, there has been a surge of recent research focusing on different mechanisms that underlie both physiological and pathophysiological aspects of lymphatic contractile function. This review summarizes those emerging paradigms that shed some novel insights into the contractile physiology of the lymphatics in normal as well as different disease states. In addition, this review emphasizes the recent progress made in our understanding of various contractile parameters and regulatory elements that contribute to the normal functioning of the lymphatics. PMID:25617600

  10. Effect of lymphatic outflow pressure on lymphatic albumin transport in humans.

    PubMed

    Wu, J; Mack, G W

    2001-09-01

    The effects of posture on the lymphatic outflow pressure and lymphatic return of albumin were examined in 10 volunteers. Lymph flow was stimulated with a bolus infusion of isotonic saline (0.9%, 12.6 ml/kg body wt) under four separate conditions: upright rest (Up), upright rest with lower body positive pressure (LBPP), supine rest (Sup), and supine rest with lower body negative pressure (LBNP). The increase in plasma albumin content (Delta Alb) during the 2 h after bolus saline infusion was greater in Up than in LBPP: 82.9 +/- 18.5 vs. -28.4 mg/kg body wt. Delta Alb was greater in LBNP than in Sup: 92.6 vs. -22.5 +/- 18.9 mg/kg body wt (P < 0.05). The greater Delta Alb in Up and Sup with LBNP were associated with a lower estimated lymphatic outflow pressure on the basis of the difference in central venous pressure (Delta CVP). During LBPP, CVP was increased compared with Up: 3.8 +/- 1.4 vs. -1.2 +/- 1.2 mmHg. During LBNP, CVP was reduced compared with Sup: -3.0 +/- 2.2 vs. 1.7 +/- 1.0 mmHg. The translocation of protein into the vascular space after bolus saline infusion reflects lymph return of protein and is higher in Up than in Sup. Modulation of CVP with LBPP or LBNP in Up and Sup, respectively, reversed the impact of posture on lymphatic outflow pressure. Thus posture-dependent changes in lymphatic protein transport are modulated by changes in CVP through its mechanical impact on lymphatic outflow pressure.

  11. Tissue Engineering of Dermal Blood and Lymphatic Microvascular Networks

    DTIC Science & Technology

    2014-03-06

    SECURITY CLASSIFICATION OF: This proposal focused on establishing the conditions necessary to induce lymphatic endothelial cell (EC) tube...morphogenesis in 3D collagen matrices with the long-term goal of establishing separate networks of lymphatic tubes and co-existing, but not interconnecting...networks of blood EC-lined tubes. In addition, we hoped that pericytes, which support blood EC tube networks, but not lymphatic vessel networks, would

  12. Lymphatic vessels in the healthy human dental pulp.

    PubMed

    Marchetti, C; Poggi, P; Calligaro, A; Casasco, A

    1991-01-01

    The lymphatic vessels of the dental pulp have been studied in non-carious teeth of young people. A network of lymphatic vessels drains the pulpal tissue. The lymphatic capillaries are characterized by a thin wall with an irregular profile. Cellular projections rise from the endothelial cells. Micropinocytotic vesicles and intercellular adjoining structures are the main mechanisms for the lymph formation. Multivesicular structures, Weibel-Palade bodies and paracrystalline inclusions have been observed.

  13. Anatomical Basis for the Cardiac Interventional Electrophysiologist

    PubMed Central

    Sánchez-Quintana, Damián; Doblado-Calatrava, Manuel; Cabrera, José Angel; Macías, Yolanda; Saremi, Farhood

    2015-01-01

    The establishment of radiofrequency catheter ablation techniques as the mainstay in the treatment of tachycardia has renewed new interest in cardiac anatomy. The interventional arrhythmologist has drawn attention not only to the gross anatomic details of the heart but also to architectural and histological characteristics of various cardiac regions that are relevant to the development or recurrence of tachyarrhythmias and procedural related complications of catheter ablation. In this review, therefore, we discuss some anatomic landmarks commonly used in catheter ablations including the terminal crest, sinus node region, Koch's triangle, cavotricuspid isthmus, Eustachian ridge and valve, pulmonary venous orifices, venoatrial junctions, and ventricular outflow tracts. We also discuss the anatomical features of important structures in the vicinity of the atria and pulmonary veins, such as the esophagus and phrenic nerves. This paper provides basic anatomic information to improve understanding of the mapping and ablative procedures for cardiac interventional electrophysiologists. PMID:26665006

  14. Tissue-engineered lymphatic graft for the treatment of lymphedema

    PubMed Central

    Kanapathy, Muholan; Patel, Nikhil M.; Kalaskar, Deepak M.; Mosahebi, Afshin; Mehrara, Babak J.; Seifalian, Alexander M.

    2015-01-01

    Background Lymphedema is a chronic debilitating condition and curative treatment is yet to be found. Tissue engineering approach, which combines cellular components, scaffold, and molecular signals hold great potential in the treatment of secondary lymphedema with the advent of lymphatic graft to reconstruct damaged collecting lymphatic vessel. This review highlights the ideal characteristics of lymphatic graft, the limitation and challenges faced, and the approaches in developing tissue-engineered lymphatic graft. Methods Literature on tissue engineering of lymphatic system and lymphatic tissue biology was reviewed. Results The prime challenge in the design and manufacturing of this graft is producing endothelialized conduit with intraluminal valves. Suitable scaffold material is needed to ensure stability and functionality of the construct. Endothelialization of the construct can be enhanced via biofunctionalization and nanotopography, which mimics extracellular matrix. Nanocomposite polymers with improved performance over existing biomaterials are likely to benefit the development of lymphatic graft. Conclusions With the in-depth understanding of tissue engineering, nanotechnology, and improved knowledge on the biology of lymphatic regeneration, the aspiration to develop successful lymphatic graft is well achievable. PMID:25248852

  15. New developments in clinical aspects of lymphatic disease

    PubMed Central

    Mortimer, Peter S.; Rockson, Stanley G.

    2014-01-01

    The lymphatic system is fundamentally important to cardiovascular disease, infection and immunity, cancer, and probably obesity — the four major challenges in healthcare in the 21st century. This Review will consider the manner in which new knowledge of lymphatic genes and molecular mechanisms has demonstrated that lymphatic dysfunction should no longer be considered a passive bystander in disease but rather an active player in many pathological processes and, therefore, a genuine target for future therapeutic developments. The specific roles of the lymphatic system in edema, genetic aspects of primary lymphedema, infection (cellulitis/erysipelas), Crohn’s disease, obesity, cancer, and cancer-related lymphedema are highlighted. PMID:24590276

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

    SciTech Connect

    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).

  17. The Lymphatic Circulation in Adaptations to the Fontan Circulation.

    PubMed

    Menon, Sabarinath; Chennapragada, Murthy; Ugaki, Shinya; Sholler, Gary F; Ayer, Julian; Winlaw, David S

    2017-06-01

    Failing Fontan continues to be major problem for patients on the univentricular pathway. Failing Fontan is often complicated by chylothorax, plastic bronchitis and protein loosing enteropathy. The role of lymphatic circulation in Fontan circulation is still being researched. Newer imaging modalities give insight into the role of abnormal dilatation and retrograde flow in lymphatic channels post Fontan. Interventional strategies targeting abnormal lymphatic channels, provides an alternative management strategy for patients with failing Fontan. This review focuses on the role of lymphatic system in adaptations to Fontan circulation.

  18. Insights into the pathogenesis of disease in human lymphatic filariasis.

    PubMed

    Nutman, Thomas B

    2013-09-01

    Although two thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ∼40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce lymphatic dilatation. Progressive lymphatic damage and pathology results primarily from the host inflammatory response to the parasites but also perhaps from the host inflammatory response to the parasite's Wolbachia endosymbiont and as a consequence of superimposed bacterial or fungal infections. This review will attempt to shed light on disease pathogenesis in lymphatic filariasis.

  19. Recent advances in the research of lymphatic stomata.

    PubMed

    Wang, Zi-Bin; Li, Meng; Li, Ji-Cheng

    2010-05-01

    Lymphatic stomata are small openings of lymphatic capillaries on the free surface of the mesothelium. The peritoneal cavity, pleural cavity, and pericardial cavity are connected with lymphatic system via these small openings, which have the function of active absorption. The ultrastructure of the lymphatic stomata and their absorption from the body cavities are important clinically, such as ascites elimination, neoplasm metastasis, and inflammatory reaction. The lymphatic stomata play an important role in the physiological and pathological conditions. Our previous study indicated for the first time that nitric oxide (NO) could regulate the opening and absorption of the lymphatic stomata. It could decrease the level of free intracellular calcium [Ca(2+)] through increasing the cyclic guanosine monophosphate (cGMP) level in the rat peritoneal mesothelial cells, thus regulating the lymphatic stomata. This process is related with the NO-cGMP-[Ca(2+)] signal pathway. In this review, we summarize the recent advances in understanding the development and the function of the lymphatic stomata. The ultrastructure and regulations of the lymphatic stomata are also discussed in this review.

  20. Visualization of lymphatic vessel development, growth, and function.

    PubMed

    Pollmann, Cathrin; Hägerling, René; Kiefer, Friedemann

    2014-01-01

    Despite their important physiological and pathophysiological functions, lymphatic endothelial cells and lymphatic vessels remain less well studied compared to the blood vascular system. Lymphatic endothelium differentiates from venous blood vascular endothelium after initial arteriovenous differentiation. Only recently by the use of light sheet microscopy, the precise mechanism of separation of the first lymphatic endothelial progenitors from the cardinal vein has been described as delamination followed by mesenchymal cell migration of lymphatic endothelial cells. Dorsolaterally of the embryonic cardinal vein, lymphatic endothelial cells reaggregate to form the first lumenized lymphatic vessels, the dorsal peripheral longitudinal vessel and the more ventrally positioned primordial thoracic duct. Despite this progress in our understanding of the first lymph vessel formation, intravital observation of lymphatic vessel behavior in the intact organism, during development and in the adult, is prerequisite to a precise understanding of this tissue. Transgenic models and two-photon microscopy, in combination with optical windows, have made live intravital imaging possible: however, new imaging modalities and novel approaches promise gentler, more physiological, and longer intravital imaging of lymphatic vessels.

  1. Ultrasound visualization of the lymphatic vessels in the lower leg.

    PubMed

    Hayashi, Akitatsu; Yamamoto, Takumi; Yoshimatsu, Hidehiko; Hayashi, Nobuko; Furuya, Megumi; Harima, Mitsunobu; Narushima, Mitsunaga; Koshima, Isao

    2015-04-08

    Identification of lymphatic vessels for lymphaticovenular anastomosis (LVA), which is an effective surgical treatment for obstructive lymphedema, is important. Indocyanine green (ICG) lymphography is useful for that purpose, but is not common in many institutions. Although ultrasound is a very common modality, no research has yet underlined the feasibility of the device to detect the lymphatic vessels. First, identification of lymphatic vessels in the lower legs using ultrasound was performed in non-edematous limbs with linear-pattern on ICG lymphography (n = 12). The imaging findings and characteristic of the lymphatic vessels in ultrasonography were investigated on transverse scans. Second, to assess the ultrasound detection technique, ICG was injected to healthy volunteers after identification and marking of the lymphatic vessels using ultrasound (n = 14). Sensitivity and specificity of the examination were calculated. In the first part, the lymphatic vessels were detected by ultrasound in all cases. Characteristic ultrasonography findings of lymphatic vessels included homogeneous, hypoechoic and spicular misshapen images in all cases. In the second part, the overall sensitivity and specificity were 95.5 and 92.9%, respectively. Ultrasonography can identify lymphatic vessels of the lower leg with precision and may aid lymphatic microsurgery for lymphedema. © 2015 Wiley Periodicals, Inc. Microsurgery, 2015. © 2015 Wiley Periodicals, Inc.

  2. Near-Infrared Fluorescence Lymphatic Imaging to Reconsider Occlusion Pressure of Superficial Lymphatic Collectors in Upper Extremities of Healthy Volunteers

    PubMed Central

    Vandermeeren, Liesbeth; Vankerckhove, Sophie; Valsamis, Jean-Baptiste; Malloizel-Delaunay, Julie; Moraine, Jean-Jacques; Liebens, Fabienne

    2016-01-01

    Abstract Background: There are very little scientific data on occlusion pressure for superficial lymphatic collectors. Given its importance in determining the transport capacity of lymphatic vessels, it is crucial to know its value. The novel method of near-infrared fluorescence lymphatic imaging (NIRFLI) can be used to visualize lymphatic flow in real time. The goal of this study was to see if this method could be used to measure the lymphatic occlusion pressure. Methods: We observed and recorded lymph flow in the upper limb of healthy volunteers through a transparent cuff using near-infrared fluorescence lymphatic imaging. After obtaining a baseline of the lymph flow without pressure inside the cuff, the cuff was inflated by increments of 10 mm Hg starting at 30 mm Hg. A NIRFLI guided manual lymphatic drainage technique named “Fill & Flush Drainage Method” was performed during the measurement to promote lymph flow. Lymphatic occlusion pressure was determined by observing when lymph flow stopped under the cuff. Results: We measured the lymphatic occlusion pressure on 30 healthy volunteers (11 men and 19 women). Mean lymphatic occlusion pressure in the upper limb was 86 mm Hg (CI ±3.7 mm Hg, α = 0.5%). No significant differences were found between age groups (p = 0.18), gender (p = 0.12), or limb side (p = 0.85). Conclusions: NIRFLI, a transparent sphygmomanometer cuff and the “Fill and Flush” manual lymphatic drainage method were used to measure the lymphatic occlusion pressure in 30 healthy humans. That combination of these techniques allows the visualization of the lymph flow in real time, while ensuring the continuous filling of the lymph collectors during the measurement session, reducing false negative observations. The measured occlusion pressures are much higher than previously described in the medical literature. PMID:27167187

  3. Anatomical Ablation Strategy for Noninducible Fascicular Tachycardia.

    PubMed

    Talib, Ahmed Karim; Nogami, Akihiko

    2016-03-01

    The presence of structural heart disease does not exclude fascicular ventricular tachycardia (VT), especially if the VT is verapamil sensitive. An empirical anatomic approach is effective when fascicular VT is noninducible or if diastolic Purkinje potential (P1) cannot be recorded during VT mapping. Pace mapping at the successful ablation site is usually not effective because selective pacing of P1 is difficult and there is an antidromic activation of the proximal P1 potential.

  4. Weibel-Palade bodies and lymphatic endothelium: observations in the lymphatic vessels of normal and inflamed human dental pulps.

    PubMed

    Marchetti, C

    1996-01-01

    The Weibel-Palade bodies, cytoplasmic organelles characterizing endothelial cells, are abundant in lymphatic capillary endothelium of human dental pulp. Their number almost double in the lymphatic vessels of inflamed dental pulps. The data were discussed and compared with others concerning the demonstration of the presence of von Willebrand factor and P-selectin in the Weibel-Palade bodies of lymphatic vessels in mesentery. It is suggested that the increase in the number of Weibel-Palade bodies observed in dental pulp may be connected along with those in the lymphatic vessels to the function that these adhesive molecules play during inflammatory states.

  5. The position- and lymphatic lumen-controlled tissue chambers to study live lymphatic vessels and surrounding tissues ex vivo.

    PubMed

    Maejima, Daisuke; Nagai, Takashi; Bridenbaugh, Eric A; Cromer, Walter E; Gashev, Anatoliy A

    2014-09-01

    Until now, there has been no tool available to provide lymphatic researchers the ability to perform experiments in tissue explants containing lymphatic vessels under tissue position- and lymphatic lumen-controlled conditions. In this article we provide technical details and description of the method of using the newly developed and implemented the position- and lymphatic lumen-controlled tissue chambers to study live lymphatic vessels and surrounding tissues ex vivo. In this study, we, for the first time, performed detailed comparative analysis of the contractile and pumping activity of rat mesenteric lymphatic vessels (MLVs) situated within tissue explants mounted in new tissue chambers and isolated, cannulated, and pressurized rat MLVs maintained in isolated vessel setups. We found no significant differences of the effects of both transmural pressure- and wall shear stress sensitivities of MLVs in tissue chambers and isolated MLVs. We conclude that this new experimental tool, a position- and lymphatic lumen-controlled tissue chamber, allows precise investigation of lymphatic function of MLVs interacting with elements of the tissue microenvironment. This method provides an important new set of experimental tools to investigate lymphatic function.

  6. Standardized anatomic space for abdominal fat quantification

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, Jayaram K.; Torigian, Drew A.

    2014-03-01

    The ability to accurately measure subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from images is important for improved assessment and management of patients with various conditions such as obesity, diabetes mellitus, obstructive sleep apnea, cardiovascular disease, kidney disease, and degenerative disease. Although imaging and analysis methods to measure the volume of these tissue components have been developed [1, 2], in clinical practice, an estimate of the amount of fat is obtained from just one transverse abdominal CT slice typically acquired at the level of the L4-L5 vertebrae for various reasons including decreased radiation exposure and cost [3-5]. It is generally assumed that such an estimate reliably depicts the burden of fat in the body. This paper sets out to answer two questions related to this issue which have not been addressed in the literature. How does one ensure that the slices used for correlation calculation from different subjects are at the same anatomic location? At what anatomic location do the volumes of SAT and VAT correlate maximally with the corresponding single-slice area measures? To answer these questions, we propose two approaches for slice localization: linear mapping and non-linear mapping which is a novel learning based strategy for mapping slice locations to a standardized anatomic space so that same anatomic slice locations are identified in different subjects. We then study the volume-to-area correlations and determine where they become maximal. We demonstrate on 50 abdominal CT data sets that this mapping achieves significantly improved consistency of anatomic localization compared to current practice. Our results also indicate that maximum correlations are achieved at different anatomic locations for SAT and VAT which are both different from the L4-L5 junction commonly utilized.

  7. Anatomical Abnormalities in Autism?

    PubMed

    Haar, Shlomi; Berman, Sigal; Behrmann, Marlene; Dinstein, Ilan

    2016-04-01

    Substantial controversy exists regarding the presence and significance of anatomical abnormalities in autism spectrum disorders (ASD). The release of the Autism Brain Imaging Data Exchange (∼1000 participants, age 6-65 years) offers an unprecedented opportunity to conduct large-scale comparisons of anatomical MRI scans across groups and to resolve many of the outstanding questions. Comprehensive univariate analyses using volumetric, thickness, and surface area measures of over 180 anatomically defined brain areas, revealed significantly larger ventricular volumes, smaller corpus callosum volume (central segment only), and several cortical areas with increased thickness in the ASD group. Previously reported anatomical abnormalities in ASD including larger intracranial volumes, smaller cerebellar volumes, and larger amygdala volumes were not substantiated by the current study. In addition, multivariate classification analyses yielded modest decoding accuracies of individuals' group identity (<60%), suggesting that the examined anatomical measures are of limited diagnostic utility for ASD. While anatomical abnormalities may be present in distinct subgroups of ASD individuals, the current findings show that many previously reported anatomical measures are likely to be of low clinical and scientific significance for understanding ASD neuropathology as a whole in individuals 6-35 years old.

  8. D2-40 lymphatic marker for detecting lymphatic invasion in thin to intermediate thickness melanomas: association with sentinel lymph node status and prognostic value-a retrospective case study.

    PubMed

    Fohn, Laurel E; Rodriguez, Adrian; Kelley, Mark C; Ye, Fei; Shyr, Yu; Stricklin, George; Robbins, Jason B

    2011-02-01

    Sentinel lymph node (SLN) status is the greatest prognostic factor of morbidity in melanoma. D2-40 antibody specifically marks lymphatic endothelium and has been used for identifying lymphatic invasion (LI) in multiple cancers. We sought to determine the relationship between melanoma lymphatic invasion (as detected using D2-40 on primary melanoma biopsies/excisions) and the presence or absence of melanoma in subsequent SLN biopsy. We retrospectively evaluated LI using D2-40 on primary biopsies/excisions from patients with thin to intermediate thickness (Breslow thickness: ≤2.0 mm) melanomas, who underwent lymphatic mapping and SLN biopsy, and whose SLN status was known. Sixty-four cases met the criteria and were available for analysis. We analyzed patient age, patient sex, mitotic rate, ulceration, tumor depth, and D2-40 detected LI as predictors of SLN status. Lymphatic invasion detection increased from 3.1% using hematoxylin and eosin only to 21.9% using D2-40. Twelve of 14 patients with D2-40 LI were SLN positive (positive predictive value, 85.7%). D2-40 LI was detected in the primary biopsy specimen of 12 of 18 patients with a positive SLN (sensitivity 66.7%). Of 50 patients without D2-40 LI, 44 were SLN negative (negative predictive value, 88.0%). Of 46 SLN-negative patients, 44 did not have D2-40 LI (specificity, 95.7%). Results are retrospective and limited to SLN biopsy performed at one institution. On univariate and multivariate analysis, D2-40-detected LI was the most significant predictor of SLN status. D2-40 antibody staining to detect lymphatic invasion should be incorporated in routine melanoma biopsy evaluation. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  9. Quantitative Imaging of Lymphatic Function with Liposomal Indocyanine Green

    PubMed Central

    Proulx, Steven T.; Luciani, Paola; Derzsi, Stefanie; Rinderknecht, Matthias; Mumprecht, Viviane; Leroux, Jean-Christophe; Detmar, Michael

    2010-01-01

    Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system but it is unstable in solution and may rapidly enter venous capillaries after local injection. We developed a novel liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in solution and an increased fluorescence signal with a shift towards longer wavelength absorption and emission. When injected intradermally to mice, LP-ICG was specifically taken up by lymphatic vessels and allowed improved visualization of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from the injection site. In mice bearing B16 luciferase expressing melanomas expressing vascular endothelial growth factor-C (VEGF-C), sequential near infrared imaging of intradermally-injected LP-ICG enabled quantification of lymphatic flow. Increased flow through draining lymph nodes was observed in mice bearing VEGF-C expressing tumors without metastases while a decreased flow pattern was seen in mice with a higher lymph node tumor burden. This new method likely will facilitate quantitative studies of lymphatic function in preclinical studies and may also have potential for imaging of lymphedema or improved sentinel lymph detection in cancer. PMID:20823159

  10. Lymphatic vessels: new targets for the treatment of inflammatory diseases.

    PubMed

    Dieterich, Lothar C; Seidel, Catharina D; Detmar, Michael

    2014-04-01

    The lymphatic system plays an important role in the physiological control of the tissue fluid balance and in the initiation of immune responses. Recent studies have shown that lymphangiogenesis, the growth of new lymphatic vessels and/or the expansion of existing lymphatic vessels, is a characteristic feature of acute inflammatory reactions and of chronic inflammatory diseases. In these conditions, lymphatic vessel expansion occurs at the tissue level but also within the draining lymph nodes. Surprisingly, activation of lymphatic vessel function by delivery of vascular endothelial growth factor-C exerts anti-inflammatory effects in several models of cutaneous and joint inflammation. These effects are likely mediated by enhanced drainage of extravasated fluid and inflammatory cells, but also by lymphatic vessel-mediated modulation of immune responses. Although some of the underlying mechanisms are just beginning to be identified, lymphatic vessels have emerged as important targets for the development of new therapeutic strategies to treat inflammatory conditions. In this context, it is of great interest that some of the currently used anti-inflammatory drugs also potently activate lymphatic vessels.

  11. Heterogeneity in the lymphatic vascular system and its origin.

    PubMed

    Ulvmar, Maria H; Mäkinen, Taija

    2016-09-01

    Lymphatic vessels have historically been viewed as passive conduits for fluid and immune cells, but this perspective is increasingly being revised as new functions of lymphatic vessels are revealed. Emerging evidence shows that lymphatic endothelium takes an active part in immune regulation both by antigen presentation and expression of immunomodulatory genes. In addition, lymphatic vessels play an important role in uptake of dietary fat and clearance of cholesterol from peripheral tissues, and they have been implicated in obesity and arteriosclerosis. Lymphatic vessels within different organs and in different physiological and pathological processes show a remarkable plasticity and heterogeneity, reflecting their functional specialization. In addition, lymphatic endothelial cells (LECs) of different organs were recently shown to have alternative developmental origins, which may contribute to the development of the diverse lymphatic vessel and endothelial functions seen in the adult. Here, we discuss recent developments in the understanding of heterogeneity within the lymphatic system considering the organ-specific functional and molecular specialization of LECs and their developmental origin. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

  12. Blood flow reprograms lymphatic vessels to blood vessels

    PubMed Central

    Chen, Chiu-Yu; Bertozzi, Cara; Zou, Zhiying; Yuan, Lijun; Lee, John S.; Lu, MinMin; Stachelek, Stan J.; Srinivasan, Sathish; Guo, Lili; Vincente, Andres; Mericko, Patricia; Levy, Robert J.; Makinen, Taija; Oliver, Guillermo; Kahn, Mark L.

    2012-01-01

    Human vascular malformations cause disease as a result of changes in blood flow and vascular hemodynamic forces. Although the genetic mutations that underlie the formation of many human vascular malformations are known, the extent to which abnormal blood flow can subsequently influence the vascular genetic program and natural history is not. Loss of the SH2 domain–containing leukocyte protein of 76 kDa (SLP76) resulted in a vascular malformation that directed blood flow through mesenteric lymphatic vessels after birth in mice. Mesenteric vessels in the position of the congenital lymphatic in mature Slp76-null mice lacked lymphatic identity and expressed a marker of blood vessel identity. Genetic lineage tracing demonstrated that this change in vessel identity was the result of lymphatic endothelial cell reprogramming rather than replacement by blood endothelial cells. Exposure of lymphatic vessels to blood in the absence of significant flow did not alter vessel identity in vivo, but lymphatic endothelial cells exposed to similar levels of shear stress ex vivo rapidly lost expression of PROX1, a lymphatic fate–specifying transcription factor. These findings reveal that blood flow can convert lymphatic vessels to blood vessels, demonstrating that hemodynamic forces may reprogram endothelial and vessel identity in cardiovascular diseases associated with abnormal flow. PMID:22622036

  13. Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles

    PubMed Central

    Cai, Shuang; Zhang, Qiuhong; Bagby, Taryn; Forrest, M. Laird

    2011-01-01

    The lymphatic system plays a crucial role in the immune system’s recognition and response to disease, and most solid cancers initially spread from the primary site via the tumor’s surrounding lymphatics before hematological dissemination. Hence, the lymphatic system is an important target for developing new vaccines, cancer treatments, and diagnostic agents. Targeting the lymphatic system by subcutaneous, intestinal, and pulmonary routes has been evaluated and subsequently utilized to improve lymphatic penetration and retention of drug molecules, reduce drug-related systemic toxicities, and enhance bioavailability of poorly soluble and unstable drugs. Lymphatic imaging is an essential tool for the detection and staging of cancer. New nano-based technologies offer improved detection and characterization of the nodal diseases, while new delivery devices can better target and confine treatments to tumors within the nodal space while sparing healthy tissues. This manuscript reviews recent advances in the field of lymphatic drug delivery and imaging and focuses specifically on the development ofliposomes and solid lipid nanoparticles for lymphatic introduction via the subcutaneous, intestinal, and pulmonary routes. PMID:21712055

  14. Isolation and Characterization of Circulating Lymphatic Endothelial Colony Forming Cells

    PubMed Central

    DiMaio, Terri A.; Wentz, Breanna L.; Lagunoff, Michael

    2016-01-01

    Rationale The identification of circulating endothelial progenitor cells has led to speculation regarding their origin as well as their contribution to neovascular development. Two distinct types of endothelium make up the blood and lymphatic vessel system. However, it has yet to be determined whether there are distinct lymphatic-specific circulating endothelial progenitor cells. Objective This study aims to isolate and characterize the cellular properties and global gene expression of lymphatic-specific endothelial progenitor cells. Methods and Results We isolated circulating endothelial colony forming cells (ECFCs) from whole peripheral blood. These cells are endothelial in nature, as defined by their expression of endothelial markers and their ability to undergo capillary morphogenesis in three-dimensional culture. A subset of isolated colonies express markers of lymphatic endothelium, including VEGFR-3 and Prox-1, with low levels of VEGFR-1, a blood endothelial marker, while the bulk of the isolated cells express high VEGFR-1 levels with low VEGFR-3 and Prox-1 expression. The different isolates have differential responses to VEGF-C, a lymphatic endothelial specific cytokine, strongly suggesting that there are lymphatic specific and blood specific ECFCs. Global analysis of gene expression revealed key differences in the regulation of pathways involved in cellular differentiation between blood and lymphatic-specific ECFCs. Conclusion These data indicate that there are two distinguishable circulating ECFC types, blood and lymphatic, which are likely to have discrete functions during neovascularization. PMID:26597759

  15. Blood flow reprograms lymphatic vessels to blood vessels.

    PubMed

    Chen, Chiu-Yu; Bertozzi, Cara; Zou, Zhiying; Yuan, Lijun; Lee, John S; Lu, MinMin; Stachelek, Stan J; Srinivasan, Sathish; Guo, Lili; Vicente, Andres; Vincente, Andres; Mericko, Patricia; Levy, Robert J; Makinen, Taija; Oliver, Guillermo; Kahn, Mark L

    2012-06-01

    Human vascular malformations cause disease as a result of changes in blood flow and vascular hemodynamic forces. Although the genetic mutations that underlie the formation of many human vascular malformations are known, the extent to which abnormal blood flow can subsequently influence the vascular genetic program and natural history is not. Loss of the SH2 domain-containing leukocyte protein of 76 kDa (SLP76) resulted in a vascular malformation that directed blood flow through mesenteric lymphatic vessels after birth in mice. Mesenteric vessels in the position of the congenital lymphatic in mature Slp76-null mice lacked lymphatic identity and expressed a marker of blood vessel identity. Genetic lineage tracing demonstrated that this change in vessel identity was the result of lymphatic endothelial cell reprogramming rather than replacement by blood endothelial cells. Exposure of lymphatic vessels to blood in the absence of significant flow did not alter vessel identity in vivo, but lymphatic endothelial cells exposed to similar levels of shear stress ex vivo rapidly lost expression of PROX1, a lymphatic fate-specifying transcription factor. These findings reveal that blood flow can convert lymphatic vessels to blood vessels, demonstrating that hemodynamic forces may reprogram endothelial and vessel identity in cardiovascular diseases associated with abnormal flow.

  16. Aged Lymphatic Vessels and Mast Cells in Perilymphatic Tissues.

    PubMed

    Pal, Sarit; Meininger, Cynthia J; Gashev, Anatoliy A

    2017-05-03

    This review provides a comprehensive summary of research on aging-associated alterations in lymphatic vessels and mast cells in perilymphatic tissues. Aging alters structure (by increasing the size of zones with low muscle cell investiture), ultrastructure (through loss of the glycocalyx), and proteome composition with a concomitant increase in permeability of aged lymphatic vessels. The contractile function of aged lymphatic vessels is depleted with the abolished role of nitric oxide and an increased role of lymphatic-born histamine in flow-dependent regulation of lymphatic phasic contractions and tone. In addition, aging induces oxidative stress in lymphatic vessels and facilitates the spread of pathogens from these vessels into perilymphatic tissues. Aging causes the basal activation of perilymphatic mast cells, which, in turn, restricts recruitment/activation of immune cells in perilymphatic tissues. This aging-associated basal activation of mast cells limits proper functioning of the mast cell/histamine/NF-κB axis that is essential for the regulation of lymphatic vessel transport and barrier functions as well as for both the interaction and trafficking of immune cells near and within lymphatic collecting vessels. Cumulatively, these changes play important roles in the pathogenesis of alterations in inflammation and immunity associated with aging.

  17. Heterogeneity in the lymphatic vascular system and its origin

    PubMed Central

    Ulvmar, Maria H.; Mäkinen, Taija

    2016-01-01

    Lymphatic vessels have historically been viewed as passive conduits for fluid and immune cells, but this perspective is increasingly being revised as new functions of lymphatic vessels are revealed. Emerging evidence shows that lymphatic endothelium takes an active part in immune regulation both by antigen presentation and expression of immunomodulatory genes. In addition, lymphatic vessels play an important role in uptake of dietary fat and clearance of cholesterol from peripheral tissues, and they have been implicated in obesity and arteriosclerosis. Lymphatic vessels within different organs and in different physiological and pathological processes show a remarkable plasticity and heterogeneity, reflecting their functional specialization. In addition, lymphatic endothelial cells (LECs) of different organs were recently shown to have alternative developmental origins, which may contribute to the development of the diverse lymphatic vessel and endothelial functions seen in the adult. Here, we discuss recent developments in the understanding of heterogeneity within the lymphatic system considering the organ-specific functional and molecular specialization of LECs and their developmental origin. PMID:27357637

  18. Exploiting lymphatic vessels for immunomodulation: Rationale, opportunities, and challenges.

    PubMed

    Maisel, Katharina; Sasso, Maria Stella; Potin, Lambert; Swartz, Melody A

    2017-05-15

    Lymphatic vessels are the primary route of communication from peripheral tissues to the immune system; as such, they represent an important component of local immunity. In addition to their transport functions, new immunomodulatory roles for lymphatic vessels and lymphatic endothelial cells have come to light in recent years, demonstrating that lymphatic vessels help shape immune responses in a variety of ways: promoting tolerance to self-antigens, archiving antigen for later presentation, dampening effector immune responses, and resolving inflammation, among others. In addition to these new biological insights, the growing field of immunoengineering has begun to explore therapeutic approaches to utilize or exploit the lymphatic system for immunotherapy. Copyright © 2017. Published by Elsevier B.V.

  19. How Do Meningeal Lymphatic Vessels Drain the CNS?

    PubMed

    Raper, Daniel; Louveau, Antoine; Kipnis, Jonathan

    2016-09-01

    The many interactions between the nervous and the immune systems, which are active in both physiological and pathological states, have recently become more clearly delineated with the discovery of a meningeal lymphatic system capable of carrying fluid, immune cells, and macromolecules from the central nervous system (CNS) to the draining deep cervical lymph nodes. However, the exact localization of the meningeal lymphatic vasculature and the path of drainage from the cerebrospinal fluid (CSF) to the lymphatics remain poorly understood. Here, we discuss the potential differences between peripheral and CNS lymphatic vessels and examine the purported mechanisms of CNS lymphatic drainage, along with how these may fit into established patterns of CSF flow. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Navigation lymphatic supermicrosurgery for the treatment of cancer-related peripheral lymphedema.

    PubMed

    Yamamoto, Takumi; Yamamoto, Nana; Numahata, Takao; Yokoyama, Ai; Tashiro, Kensuke; Yoshimatsu, Hidehiko; Narushima, Mitsunaga; Koshima, Isao

    2014-02-01

    Lymphatic supermicrosurgery is becoming the treatment of choice for refractory lymphedema. Detection and anastomosis of functional lymphatic vessels are important for lymphatic supermicrosurgery. Navigation lymphatic supermicrosurgery was performed using an operating microscope equipped with an integrated near-infrared illumination system (OPMI Pentero Infrared 800; Carl Zeiss, Oberkochen, Germany). Eight patients with extremity lymphedema who underwent navigation lymphatic supermicrosurgery were evaluated. A total of 21 lymphaticovenular anastomoses were performed on 8 limbs through 14 skin incisions. Lymphatic vessels were enhanced by intraoperative microscopic indocyanine green (ICG) lymphography in 12 of the 14 skin incisions, which resulted in early dissection of lymphatic vessels. All anastomoses showed good anastomosis patency after completion of anastomoses. Postoperative extremity lymphedema index decreased in all limbs. Navigation lymphatic supermicrosurgery, in which lymphatic vessels are visualized with intraoperative microscopic ICG lymphography, allows a lymphatic supermicrosurgeon to find and dissect lymphatic vessels earlier and facilitates successful performance of lymphaticovenular anastomosis.

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

    PubMed

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

    2013-10-25

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Lymphatic albumin clearance from psoriatic skin

    SciTech Connect

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

    1983-12-01

    In nine patients with untreated psoriasis vulgaris, human serum albumin labelled with /sup 125/I or /sup 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.

  3. Experimental chemotherapy of lymphatic filariasis. A review.

    PubMed

    Mak, J W; Navaratnam, V; Ramachandran, C P

    1991-02-01

    An intense global collaborative effort under the leadership of the Steering Committee of the Filariasis Scientific Working Group of the Tropical Diseases Research Programme, World Health Organization, has brought together researchers, pharmaceutical chemists and clinicians in the development and search for antifilarial compounds which are more effective and more convenient to administer than diethylcarbamazine citrate, the current drug of choice for lymphatic filariasis. The Brugia spp.-rodent model has been used extensively for the primary screening and B. pahangi infections in the dog or cat for the secondary screening, of potential filaricides. Recently, the leaf-monkey (Presbytis spp.) infected with subperiodic B. malayi or Wuchereria kalimantani has been used for the tertiary evaluation and pharmacokinetic studies of compounds which have shown effectiveness in the primary and secondary screens. Both P. cristata and P. melalophos are extremely susceptible to subperiodic B. malayi infection, but the former is a better host as a higher peak microfilaremia and adult worm recovery rate were obtained. Although more than 30 potential filaricides have been evaluated in the tertiary screen, only a few compounds have shown some promise against lymphatic filariasis. CGP 20376, a 5-methoxyl-6-dithiocarbamic-S-(2-carboxy-ethyl) ester derivative of benzothiazole, had complete adulticidal and microfilaricidal activities against the parasite at a single oral dose of 20 mg kg-1. However, as the compound or its metabolites caused hepatotoxicity, its clinical use in the present formulation is not recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed

    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.

  5. Apelin modulates pathological remodeling of lymphatic endothelium after myocardial infarction

    PubMed Central

    Renaud-Gabardos, Edith; Godet, Anne-Claire; Hantelys, Fransky; Pujol, Francoise; Calise, Denis; Viars, Fanny; Valet, Philippe; Masri, Bernard; Prats, Anne-Catherine; Garmy-Susini, Barbara

    2017-01-01

    Lymphatic endothelium serves as a barrier to control fluid balance and immune cell trafficking to maintain tissue homeostasis. Long-term alteration of lymphatic vasculature promotes edema and fibrosis, which is an aggravating factor in the onset of cardiovascular diseases such as myocardial infarction. Apelin is a bioactive peptide that plays a central role in angiogenesis and cardiac contractility. Despite an established role of apelin in lymphangiogenesis, little is known about its function in the cardiac lymphatic endothelium. Here, we show that apelin and its receptor APJ were exclusively expressed on newly formed lymphatic vasculature in a pathological model of myocardial infarction. Using an apelin-knockout mouse model, we identified morphological and functional defects in lymphatic vasculature associated with a proinflammatory status. Surprisingly, apelin deficiency increased the expression of lymphangiogenic growth factors VEGF-C and VEGF-D and exacerbated lymphangiogenesis after myocardial infarction. Conversely, the overexpression of apelin in ischemic heart was sufficient to restore a functional lymphatic vasculature and to reduce matrix remodeling and inflammation. In vitro, the expression of apelin prevented the alteration of cellular junctions in lymphatic endothelial cells induced by hypoxia. In addition, we demonstrated that apelin controls the secretion of the lipid mediator sphingosine-1-phosphate in lymphatic endothelial cells by regulating the level of expression of sphingosine kinase 2 and the transporter SPNS2. Taken together, our results show that apelin plays a key role in lymphatic vessel maturation and stability in pathological settings. Thus, apelin may represent a novel candidate to prevent pathological lymphatic remodeling in diseases. PMID:28614788

  6. Apelin modulates pathological remodeling of lymphatic endothelium after myocardial infarction.

    PubMed

    Tatin, Florence; Renaud-Gabardos, Edith; Godet, Anne-Claire; Hantelys, Fransky; Pujol, Francoise; Morfoisse, Florent; Calise, Denis; Viars, Fanny; Valet, Philippe; Masri, Bernard; Prats, Anne-Catherine; Garmy-Susini, Barbara

    2017-06-15

    Lymphatic endothelium serves as a barrier to control fluid balance and immune cell trafficking to maintain tissue homeostasis. Long-term alteration of lymphatic vasculature promotes edema and fibrosis, which is an aggravating factor in the onset of cardiovascular diseases such as myocardial infarction. Apelin is a bioactive peptide that plays a central role in angiogenesis and cardiac contractility. Despite an established role of apelin in lymphangiogenesis, little is known about its function in the cardiac lymphatic endothelium. Here, we show that apelin and its receptor APJ were exclusively expressed on newly formed lymphatic vasculature in a pathological model of myocardial infarction. Using an apelin-knockout mouse model, we identified morphological and functional defects in lymphatic vasculature associated with a proinflammatory status. Surprisingly, apelin deficiency increased the expression of lymphangiogenic growth factors VEGF-C and VEGF-D and exacerbated lymphangiogenesis after myocardial infarction. Conversely, the overexpression of apelin in ischemic heart was sufficient to restore a functional lymphatic vasculature and to reduce matrix remodeling and inflammation. In vitro, the expression of apelin prevented the alteration of cellular junctions in lymphatic endothelial cells induced by hypoxia. In addition, we demonstrated that apelin controls the secretion of the lipid mediator sphingosine-1-phosphate in lymphatic endothelial cells by regulating the level of expression of sphingosine kinase 2 and the transporter SPNS2. Taken together, our results show that apelin plays a key role in lymphatic vessel maturation and stability in pathological settings. Thus, apelin may represent a novel candidate to prevent pathological lymphatic remodeling in diseases.

  7. Thymus cell antigen 1 (Thy1, CD90) is expressed by lymphatic vessels and mediates cell adhesion to lymphatic endothelium.

    PubMed

    Jurisic, Giorgia; Iolyeva, Maria; Proulx, Steven T; Halin, Cornelia; Detmar, Michael

    2010-10-15

    The lymphatic vascular system plays an important role in inflammation and cancer progression, although the molecular mechanisms involved are poorly understood. As determined by comparative transcriptional profiling studies of ex vivo isolated mouse intestinal lymphatic endothelial cells versus blood vascular endothelial cells, thymus cell antigen 1 (Thy1, CD90) was expressed at much higher levels in lymphatic endothelial cells than in blood vascular endothelial cells. These findings were confirmed by quantitative PCR, and at the protein level by FACS and immunofluorescence analyses. Thy1 was also strongly expressed by tumor-associated lymphatic vessels, as evaluated in a B16 melanoma footpad model in mice. Blockade of Thy1 inhibited tumor cell adhesion to cultured mouse lymphatic endothelial cells. Importantly, treatment of human dermal microvascular endothelial cells with tumor necrosis factor or phorbol 12-myristate 13-acetate resulted in Thy1 upregulation in podoplanin-expressing lymphatic endothelial cells, but not in podoplanin-negative blood vascular endothelial cells. Moreover, adhesion of human polymorphonuclear and mononuclear leukocytes to human lymphatic endothelial cells was Thy1-dependent. Together, these results identify Thy1 as a novel lymphatic vessel expressed gene and suggest its potential role in the cell adhesion processes required for tumor progression and inflammation. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Different regions of latest electrical activation during left bundle-branch block and right ventricular pacing in cardiac resynchronization therapy patients determined by coronary venous electro-anatomic mapping.

    PubMed

    Mafi Rad, Masih; Blaauw, Yuri; Dinh, Trang; Pison, Laurent; Crijns, Harry J; Prinzen, Frits W; Vernooy, Kevin

    2014-11-01

    Current targeted left ventricular (LV) lead placement strategy is directed at the latest activated region during intrinsic activation. However, cardiac resynchronization therapy (CRT) is most commonly applied by simultaneous LV and right ventricular (RV) pacing without contribution from intrinsic conduction. Therefore, targeting the LV lead to the latest activated region during RV pacing might be more appropriate. We investigated the difference in LV electrical activation sequence between left bundle-branch block (LBBB) and RV apex (RVA) pacing using coronary venous electro-anatomic mapping (EAM). Twenty consecutive CRT candidates with LBBB underwent intra-procedural coronary venous EAM during intrinsic activation and RVA pacing using EnSite NavX. Left ventricular lead placement was aimed at the latest activated region during LBBB according to current recommendations. In all patients, LBBB was associated with a circumferential LV activation pattern, whereas RVA pacing resulted in activation from the apex of the heart to the base. In 10 of 20 patients, RVA pacing shifted the latest activated region relative to LBBB. In 18 of 20 patients, the LV lead was successfully positioned in the latest activated region during LBBB. For the whole study population, LV lead electrical delay, expressed as percentage of QRS duration, was significantly shorter during RVA pacing than during LBBB (72 ± 13 vs. 82 ± 5%, P = 0.035). Right ventricular apex pacing alters LV electrical activation pattern in CRT patients with LBBB, and shifts the latest activated region in a significant proportion of these patients. These findings warrant reconsideration of the current practice of LV lead targeting for CRT. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

  9. Discrimination of dementia with Lewy bodies from Alzheimer's disease using voxel-based morphometry of white matter by statistical parametric mapping 8 plus diffeomorphic anatomic registration through exponentiated Lie algebra.

    PubMed

    Nakatsuka, Tomoya; Imabayashi, Etsuko; Matsuda, Hiroshi; Sakakibara, Ryuji; Inaoka, Tsutomu; Terada, Hitoshi

    2013-05-01

    The purpose of this study was to identify brain atrophy specific for dementia with Lewy bodies (DLB) and to evaluate the discriminatory performance of this specific atrophy between DLB and Alzheimer's disease (AD). We retrospectively reviewed 60 DLB and 30 AD patients who had undergone 3D T1-weighted MRI. We randomly divided the DLB patients into two equal groups (A and B). First, we obtained a target volume of interest (VOI) for DLB-specific atrophy using correlation analysis of the percentage rate of significant whole white matter (WM) atrophy calculated using the Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD) based on statistical parametric mapping 8 (SPM8) plus diffeomorphic anatomic registration through exponentiated Lie algebra, with segmented WM images in group A. We then evaluated the usefulness of this target VOI for discriminating the remaining 30 DLB patients in group B from the 30 AD patients. Z score values in this target VOI obtained from VSRAD were used as the determinant in receiver operating characteristic (ROC) analysis. Specific target VOIs for DLB were determined in the right-side dominant dorsal midbrain, right-side dominant dorsal pons, and bilateral cerebellum. ROC analysis revealed that the target VOI limited to the midbrain exhibited the highest area under the ROC curves of 0.75. DLB patients showed specific atrophy in the midbrain, pons, and cerebellum. Midbrain atrophy demonstrated the highest power for discriminating DLB and AD. This approach may be useful for determining the contributions of DLB and AD pathologies to the dementia syndrome.

  10. Rho Kinase Enhances Contractions of Rat Mesenteric Collecting Lymphatics

    PubMed Central

    Kurtz, Kristine H.; Souza-Smith, Flavia M.; Moor, Andrea N.; Breslin, Jerome W.

    2014-01-01

    The mechanisms that control phasic and tonic contractions of lymphatic vessels are poorly understood. We hypothesized that rho kinase ROCK, previously shown to increase calcium (Ca2+) sensitivity in vascular smooth muscle, enhances lymphatic contractile activity in a similar fashion. Contractions of isolated rat mesenteric lymphatic vessels were observed at a luminal pressure of 2 cm H2O in a 37°C bath. The expression of ROCK in isolated rat mesenteric lymphatic vessels was assessed by Western blotting and confocal microscopy. The role of ROCK in contractile function was tested using two specific yet structurally distinct inhibitors: H1152 (0.1–10 μM) and Y-27632 (0.5–50 μM). In addition, lymphatics were transfected with constitutively active (ca)-ROCK protein (2 μg/ml) to assess gain of contractile function. Vessel diameter and the concentration of intracellular free Ca2+ ([Ca2+]i) were simultaneously measured in a subset of isolated lymphatics loaded with the Ca2+-sensing dye fura-2. The results show expression of both the ROCK1 and ROCK2 isoforms in lymphatic vessels. Inhibition of ROCK increased lymphatic end diastolic diameter and end systolic diameter in a concentration-dependent manner. Significant reductions in lymphatic tone and contraction amplitude were observed after treatment 1–10 μM H1152 or 25–50 μM Y-27632. H1152 (10 μM) also significantly reduced contraction frequency. Transient increases in [Ca2+]i preceded each phasic contraction, however this pattern was disrupted by either 10 μM H1152 or 50 μM Y-27632 in the majority of lymphatics studied. The significant decrease in tone caused by H1152 or Y-27632 was not associated with a significant change in the basal [Ca2+]i between transients. Transfection with ca-ROCK protein enhanced lymphatic tone, but was not associated with a significant change in basal [Ca2+]i. Our data suggest that ROCK mediates normal tonic constriction and influences phasic contractions in lymphatics. We propose

  11. Lipopolysaccharide modulates neutrophil recruitment and macrophage polarization on lymphatic vessels and impairs lymphatic function in rat mesentery

    PubMed Central

    Chakraborty, Sanjukta; Zawieja, Scott D.; Wang, Wei; Lee, Yang; Wang, Yuan J.; von der Weid, Pierre-Yves; Zawieja, David C.

    2015-01-01

    Impairment of the lymphatic system is apparent in multiple inflammatory pathologies connected to elevated endotoxins such as LPS. However, the direct mechanisms by which LPS influences the lymphatic contractility are not well understood. We hypothesized that a dynamic modulation of innate immune cell populations in mesentery under inflammatory conditions perturbs tissue cytokine/chemokine homeostasis and subsequently influences lymphatic function. We used rats that were intraperitoneally injected with LPS (10 mg/kg) to determine the changes in the profiles of innate immune cells in the mesentery and in the stretch-mediated contractile responses of isolated lymphatic preparations. Results demonstrated a reduction in the phasic contractile activity of mesenteric lymphatic vessels from LPS-injected rats and a severe impairment of lymphatic pump function and flow. There was a significant reduction in the number of neutrophils and an increase in monocytes/macrophages present on the lymphatic vessels and in the clear mesentery of the LPS group. This population of monocytes and macrophages established a robust M2 phenotype, with the majority showing high expression of CD163 and CD206. Several cytokines and chemoattractants for neutrophils and macrophages were significantly changed in the mesentery of LPS-injected rats. Treatment of lymphatic muscle cells (LMCs) with LPS showed significant changes in the expression of adhesion molecules, VCAM1, ICAM1, CXCR2, and galectin-9. LPS-TLR4-mediated regulation of pAKT, pERK pI-κB, and pMLC20 in LMCs promoted both contractile and inflammatory pathways. Thus, our data provide the first evidence connecting the dynamic changes in innate immune cells on or near the lymphatics and complex cytokine milieu during inflammation with lymphatic dysfunction. PMID:26453331

  12. Lipopolysaccharide modulates neutrophil recruitment and macrophage polarization on lymphatic vessels and impairs lymphatic function in rat mesentery.

    PubMed

    Chakraborty, Sanjukta; Zawieja, Scott D; Wang, Wei; Lee, Yang; Wang, Yuan J; von der Weid, Pierre-Yves; Zawieja, David C; Muthuchamy, Mariappan

    2015-12-15

    Impairment of the lymphatic system is apparent in multiple inflammatory pathologies connected to elevated endotoxins such as LPS. However, the direct mechanisms by which LPS influences the lymphatic contractility are not well understood. We hypothesized that a dynamic modulation of innate immune cell populations in mesentery under inflammatory conditions perturbs tissue cytokine/chemokine homeostasis and subsequently influences lymphatic function. We used rats that were intraperitoneally injected with LPS (10 mg/kg) to determine the changes in the profiles of innate immune cells in the mesentery and in the stretch-mediated contractile responses of isolated lymphatic preparations. Results demonstrated a reduction in the phasic contractile activity of mesenteric lymphatic vessels from LPS-injected rats and a severe impairment of lymphatic pump function and flow. There was a significant reduction in the number of neutrophils and an increase in monocytes/macrophages present on the lymphatic vessels and in the clear mesentery of the LPS group. This population of monocytes and macrophages established a robust M2 phenotype, with the majority showing high expression of CD163 and CD206. Several cytokines and chemoattractants for neutrophils and macrophages were significantly changed in the mesentery of LPS-injected rats. Treatment of lymphatic muscle cells (LMCs) with LPS showed significant changes in the expression of adhesion molecules, VCAM1, ICAM1, CXCR2, and galectin-9. LPS-TLR4-mediated regulation of pAKT, pERK pI-κB, and pMLC20 in LMCs promoted both contractile and inflammatory pathways. Thus, our data provide the first evidence connecting the dynamic changes in innate immune cells on or near the lymphatics and complex cytokine milieu during inflammation with lymphatic dysfunction. Copyright © 2015 the American Physiological Society.

  13. The effect of lymphatic valve morphology on fluid transport

    NASA Astrophysics Data System (ADS)

    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.

  14. Interaction of tumor cells and lymphatic vessels in cancer progression.

    PubMed

    Alitalo, A; Detmar, M

    2012-10-18

    Metastatic spread of cancer through the lymphatic system affects hundreds of thousands of patients yearly. Growth of new lymphatic vessels, lymphangiogenesis, is activated in cancer and inflammation, but is largely inactive in normal physiology, and therefore offers therapeutic potential. Key mediators of lymphangiogenesis have been identified in developmental studies. During embryonic development, lymphatic endothelial cells derive from the blood vascular endothelium and differentiate under the guidance of lymphatic-specific regulators, such as the prospero homeobox 1 transcription factor. Vascular endothelial growth factor-C (VEGF-C) and VEGF receptor 3 signaling are essential for the further development of lymphatic vessels and therefore they provide a promising target for inhibition of tumor lymphangiogenesis. Lymphangiogenesis is important for the progression of solid tumors as shown for melanoma and breast cancer. Tumor cells may use chemokine gradients as guidance cues and enter lymphatic vessels through intercellular openings between endothelial cell junctions or, possibly, by inducing larger discontinuities in the endothelial cell layer. Tumor-draining sentinel lymph nodes show enhanced lymphangiogenesis even before cancer metastasis and they may function as a permissive 'lymphovascular niche' for the survival of metastatic cells. Although our current knowledge indicates that the development of anti-lymphangiogenic therapies may be beneficial for the treatment of cancer patients, several open questions remain with regard to the frequency, mechanisms and biological importance of lymphatic metastases.

  15. Lymphatic vessels regulate immune microenvironments in human and murine melanoma.

    PubMed

    Lund, Amanda W; Wagner, Marek; Fankhauser, Manuel; Steinskog, Eli S; Broggi, Maria A; Spranger, Stefani; Gajewski, Thomas F; Alitalo, Kari; Eikesdal, Hans P; Wiig, Helge; Swartz, Melody A

    2016-09-01

    Lymphatic remodeling in tumor microenvironments correlates with progression and metastasis, and local lymphatic vessels play complex and poorly understood roles in tumor immunity. Tumor lymphangiogenesis is associated with increased immune suppression, yet lymphatic vessels are required for fluid drainage and immune cell trafficking to lymph nodes, where adaptive immune responses are mounted. Here, we examined the contribution of lymphatic drainage to tumor inflammation and immunity using a mouse model that lacks dermal lymphatic vessels (K14-VEGFR3-Ig mice). Melanomas implanted in these mice grew robustly, but exhibited drastically reduced cytokine expression and leukocyte infiltration compared with those implanted in control animals. In the absence of local immune suppression, transferred cytotoxic T cells more effectively controlled tumors in K14-VEGFR3-Ig mice than in control mice. Furthermore, gene expression analysis of human melanoma samples revealed that patient immune parameters are markedly stratified by levels of lymphatic markers. This work suggests that the establishment of tumor-associated inflammation and immunity critically depends on lymphatic vessel remodeling and drainage. Moreover, these results have implications for immunotherapies, the efficacies of which are regulated by the tumor immune microenvironment.

  16. The lymphatic vasculature revisited-new developments in the zebrafish.

    PubMed

    Padberg, Y; Schulte-Merker, S; van Impel, A

    2017-01-01

    The lymphatic system is lined by endothelial cells and part of the vasculature. It is essential for tissue fluid homeostasis, absorption of dietary fats, and immune surveillance in vertebrates. Misregulation of lymphatic vessel formation and dysfunction of the lymphatic system have been indicated in a number of pathological conditions including lymphedema formation, obesity or chronic inflammatory diseases such as rheumatoid arthritis. In zebrafish, lymphatics were discovered about 10years ago, and the underlying molecular pathways involved in its development have since been studied in detail. Due to its superior live cell imaging possibilities and the broad tool kit for forward and reverse genetics, the zebrafish has become an important model organism to study the development of the lymphatic system during early embryonic development. In the current review, we will focus on the key players during zebrafish lymphangiogenesis and compare the roles of these genes to their mammalian counterparts. In particular, we will focus on novel findings that shed new light on the molecular mechanisms of lymphatic cell fate specification, as well as sprouting and migration of lymphatic precursor cells.

  17. Lymphatic vessel development: fluid flow and valve-forming cells.

    PubMed

    Kume, Tsutomu

    2015-08-03

    Hemodynamic forces regulate many aspects of blood vessel disease and development, including susceptibility to atherosclerosis and remodeling of primary blood vessels into a mature vascular network. Vessels of the lymphatic circulatory system are also subjected to fluid flow-associated forces, but the molecular and cellular mechanisms by which these forces regulate the formation and maintenance of lymphatic vessels remain largely uncharacterized. This issue of the JCI includes two articles that begin to address how fluid flow influences lymphatic vessel development and function. Sweet et al. demonstrate that lymph flow is essential for the remodeling of primary lymphatic vessels, for ensuring the proper distribution of smooth muscle cells (SMCs), and for the development and maturation of lymphatic valves. Kazenwadel et al. show that flow-induced lymphatic valve development is initiated by the upregulation of GATA2, which has been linked to lymphedema in patients with Emberger syndrome. Together, these observations and future studies inspired by these results have potential to lead to the development of strategies for the treatment of lymphatic disorders.

  18. Lymphangion coordination minimally affects mean flow in lymphatic vessels.

    PubMed

    Venugopal, Arun M; Stewart, Randolph H; Laine, Glen A; Dongaonkar, Ranjeet M; Quick, Christopher M

    2007-08-01

    The lymphatic system returns interstitial fluid to the central venous circulation, in part, by the cyclical contraction of a series of "lymphangion pumps" in a lymphatic vessel. The dynamics of individual lymphangions have been well characterized in vitro; their frequencies and strengths of contraction are sensitive to both preload and afterload. However, lymphangion interaction within a lymphatic vessel has been poorly characterized because it is difficult to experimentally alter properties of individual lymphangions and because the afterload of one lymphangion is coupled to the preload of another. To determine the effects of lymphangion interaction on lymph flow, we adapted an existing mathematical model of a lymphangion (characterizing lymphangion contractility, lymph viscosity, and inertia) to create a new lymphatic vessel model consisting of several lymphangions in series. The lymphatic vessel model was validated with focused experiments on bovine mesenteric lymphatic vessels in vitro. The model was then used to predict changes in lymph flow with different time delays between onset of contraction of adjacent lymphangions (coordinated case) and with different relative lymphangion contraction frequencies (noncoordinated case). Coordination of contraction had little impact on mean flow. Furthermore, orthograde and retrograde propagations of contractile waves had similar effects on flow. Model results explain why neither retrograde propagation of contractile waves nor the lack of electrical continuity between lymphangions adversely impacts flow. Because lymphangion coordination minimally affects mean flow in lymphatic vessels, lymphangions have flexibility to independently adapt to local conditions.

  19. Lymphatic vessels regulate immune microenvironments in human and murine melanoma

    PubMed Central

    Lund, Amanda W.; Wagner, Marek; Fankhauser, Manuel; Steinskog, Eli S.; Broggi, Maria A.; Spranger, Stefani; Gajewski, Thomas F.; Alitalo, Kari; Eikesdal, Hans P.

    2016-01-01

    Lymphatic remodeling in tumor microenvironments correlates with progression and metastasis, and local lymphatic vessels play complex and poorly understood roles in tumor immunity. Tumor lymphangiogenesis is associated with increased immune suppression, yet lymphatic vessels are required for fluid drainage and immune cell trafficking to lymph nodes, where adaptive immune responses are mounted. Here, we examined the contribution of lymphatic drainage to tumor inflammation and immunity using a mouse model that lacks dermal lymphatic vessels (K14-VEGFR3-Ig mice). Melanomas implanted in these mice grew robustly, but exhibited drastically reduced cytokine expression and leukocyte infiltration compared with those implanted in control animals. In the absence of local immune suppression, transferred cytotoxic T cells more effectively controlled tumors in K14-VEGFR3-Ig mice than in control mice. Furthermore, gene expression analysis of human melanoma samples revealed that patient immune parameters are markedly stratified by levels of lymphatic markers. This work suggests that the establishment of tumor-associated inflammation and immunity critically depends on lymphatic vessel remodeling and drainage. Moreover, these results have implications for immunotherapies, the efficacies of which are regulated by the tumor immune microenvironment. PMID:27525437

  20. Long-distance transportation of live isolated lymphatic vessels.

    PubMed

    Gashev, Anatoliy A; Davis, Michael J

    2010-12-01

    We performed experiments to test whether isolated lymphatic vessels would remain viable after overnight long-distance shipment. Freshly isolated segments of rat mesenteric lymphatic vessels were placed into tubes filled by chilled D-MEM/F12 supplemented with antibiotics and shipped via overnight by express mail from College Station, TX to Columbia, MO. Standard physiological and pharmacological tests were performed to investigate the influence of the long-distance transport procedure on the spontaneous contractility of isolated, cannulated, and pressurized rat mesenteric lymphatic vessels. The results demonstrate that normal contractile function of isolated lymphatic vessels can be preserved with long-distance shipping and subsequent overnight recovery if the proper precautions are taken. The method of lymphatic vessel transportation described in this report opens up the opportunity to perform in vitro functional tests on lymphatic tissues harvested and initially processed in a remote location. In addition, the described procedures may expand the options for potential sources of fresh human tissue, harvested during surgery or autopsy and allowed to be available to lymphatic researchers in remote locations.

  1. Itching for answers: how histamine relaxes lymphatic vessels.

    PubMed

    Scallan, Joshua P; Davis, Michael J

    2014-10-01

    In the current issue of Microcirculation, studies by Kurtz et al. and Nizamutdinova et al. together provide new evidence supporting a role for histamine as an endothelial-derived molecule that inhibits lymphatic muscle contraction. In particular, Nizamutdinova et al. show that the effects of flow-induced shear stress on lymphatic endothelium are mediated by both nitric oxide and histamine, since only blockade of both prevents contraction strength and frequency from being altered by flow. Separately, Kurtz et al. used confocal microscopy to determine a preferential expression of histamine receptors on the lymphatic endothelium and demonstrated that histamine applied to spontaneously contracting collecting lymphatics inhibits contractions. Previous studies disagreed on whether histamine stimulates or inhibits lymphatic contractions, but also used differing concentrations, species, and preparations. Together these new reports shed light on how histamine acts within the lymphatic vasculature, but also raise important questions about the cell type on which histamine exerts its effects and the signaling pathways involved. This editorial briefly discusses the contribution of each study and its relevance to lymphatic biology. © 2014 John Wiley & Sons Ltd.

  2. Distribution of the lymphatic vessels in the prostatic fascia.

    PubMed

    Soga, Hideo; Takenaka, Atsushi; Murakami, Gen; Haraguchi, Takahiro; Miyake, Hideaki; Tanaka, Kazushi; Fujisawa, Masato

    2011-09-01

    The prostatic fascia-preserving procedure is effective for the early recovery of erectile function after radical prostatectomy; however, the long-term influence of on cancer control was unknown. This study clarified the distribution of lymphatic vessels in the prostatic fascia. The lymphatic vessels were analyzed in 10 prostates obtained from fixed Japanese cadavers (aged, 71-90 years old). Specimens were taken from the apex, the middle part, and the base of the right-hand side of the prostate. Lymphatic vessels were detected by immunohistochemical stain using an antibody specific for the lymphatic endothelial cells (clone D2-40). The lymphatic vessels were counted in the prostate capsule and the prostatic fascia of each section by light microscopy at low power (100×). The median number of lymphatic vessels in the prostatic capsule per prostatic half was 21.0, 14.0, and 21.0 in the apex, middle, and base part of the prostate, respectively. In the prostatic facia the median number of lymphatic vessels per prostatic half was 8.0, 3.0, and 13.0 in the apex, middle, and the base part of the prostate, respectively. In the apex and the middle part the lymphatic vessels in the prostatic fascia were fewer than those in the prostatic capsule. However, in the base part the number of lymphatic vessels in the prostatic fascia was similar to that in the prostatic capsule. The present study suggested the surgeon to pay more attention for the dissection of the fascia at the base of the prostate. Copyright © 2011 Wiley-Liss, Inc.

  3. Can Lymphatic Filariasis Be Eliminated by 2020?

    PubMed

    Rebollo, Maria P; Bockarie, Moses J

    2017-02-01

    Interventions against neglected tropical diseases (NTD), including lymphatic filariasis (LF), scaled up dramatically after the signing of the London Declaration (LD) in 2012. LF is targeted for elimination by 2020, but some countries are considered not on track to meet the 2020 target using the recommended preventive chemotherapy and morbidity management strategies. In this Opinion article we review the prospects for achieving LF elimination by 2020 in the light of the renewed global action against NTDs and the global efforts to achieve the sustainable development goals (SDGs) by 2030. We conclude that LF can be eliminated by 2020 using cross-sectoral and integrated approaches because of the compound effect of the other SDG activities related to poverty reduction and water and sanitation.

  4. Lymphatic Vessels, Inflammation, and Immunity in Skin Cancer

    PubMed Central

    Lund, Amanda W.; Medler, Terry R.; Leachman, Sancy A.; Coussens, Lisa M.

    2015-01-01

    Skin is a highly ordered immune organ that coordinates rapid responses to external insult while maintaining self-tolerance. In healthy tissue, lymphatic vessels drain fluid and coordinate local immune responses; however, environmental factors induce lymphatic vessel dysfunction, leading to lymph stasis and perturbed regional immunity. These same environmental factors drive the formation of local malignancies, which are also influenced by local inflammation. Herein, we discuss clinical and experimental evidence supporting the tenet that lymphatic vessels participate in regulation of cutaneous inflammation and immunity, are important contributors to malignancy and potential biomarkers and targets for immunotherapy. PMID:26552413

  5. [Sonographic imaging of lymphatic vessels compared to other methods].

    PubMed

    Matter, D; Grosshans, E; Muller, J; Furderer, C; Mathelin, C; Warter, S; Bellocq, J P; Maillot, C

    2002-05-01

    This paper reviews for the first time the normal and abnormal appearances of lymphatic channels of the skin using ultrasound. After a review of anatomy and histology, the authors present the current imaging modalities available for lymph vessel imaging. The ultrasound examination is presented with a description of the author's technique as well as the technical requirements of the ultrasound unit (12 MHz linear probe with a resolution of 400 microns). They present the ultrasound appearance of normal lymphatic channels and their relationships to the dermis, hypodermis and lymph nodes, and at last the ultrasound appearance of abnormal lymphatic pathways

  6. A Giant Lymphatic Cyst of the Transverse Colon Mesentery

    PubMed Central

    Batool, Tayyaba; Ahmed, Soofia

    2010-01-01

    Mesenteric cysts are not uncommon in pediatric age group but giant lymphatic cysts of mesentery are reported infrequently. This is a report of six years old female who had vague abdominal pain with distension for two years. Investigations revealed a large cystic mass in abdomen. On exploration a giant lymphatic cyst in the mesentery of transverse colon found. More than 1500 ml of milky fluid was drained. The cyst was unilocular and appeared to be the collection of lymph (chyle) between two leaves of the mesentery of transverse colon. It is postulated that trauma to or malformation of lymphatics at the root of mesentery might have lead to this pathology. PMID:22953250

  7. A giant lymphatic cyst of the transverse colon mesentery.

    PubMed

    Batool, Tayyaba; Ahmed, Soofia; Akhtar, Jamshed

    2010-01-01

    Mesenteric cysts are not uncommon in pediatric age group but giant lymphatic cysts of mesentery are reported infrequently. This is a report of six years old female who had vague abdominal pain with distension for two years. Investigations revealed a large cystic mass in abdomen. On exploration a giant lymphatic cyst in the mesentery of transverse colon found. More than 1500 ml of milky fluid was drained. The cyst was unilocular and appeared to be the collection of lymph (chyle) between two leaves of the mesentery of transverse colon. It is postulated that trauma to or malformation of lymphatics at the root of mesentery might have lead to this pathology.

  8. A Three-Dimensional Lymphatic Endothelial Cell Tube Formation Assay to Identify Novel Kinases Involved in Lymphatic Vessel Remodeling.

    PubMed

    Gambino, T Jessica; Williams, Steven P; Caesar, Carol; Resnick, Daniel; Nowell, Cameron J; Farnsworth, Rae H; Achen, Marc G; Stacker, Steven A; Karnezis, Tara

    2017-01-01

    The lymphatic system is a series of vessels that transport cells and excess fluid from tissues to the blood vascular system. Normally quiescent, the lymphatics can grow or remodel in response to developmental, immunological, or cells pathological stimuli. Lymphatic vessels comprise lymphatic endothelial cells (LECs) that can respond to external growth factors by undergoing proliferation, migration, adhesion, and tube and lumen formation into new vessel structures, a process known as lymphangiogenesis. To understand the key gene and signaling pathways necessary for lymphangiogenesis and lymphatic vessel remodeling, we have developed a three-dimensional LEC tube formation assay to explore the role of kinase signaling in these processes. The collagen-overlay-based assay was used with primary human adult dermal LECs to investigate a library of 60 tyrosine kinase (TK) and TK-like genes by siRNA knockdown. Nine candidate genes were identified and characterized for their ability to modify key parameters of lymphatic tube formation, including tube length, area, thickness, branching, and number of blind-ended sacs. Four genes-ZAP70, IRAK4, RIPK1, and RIPK2-were identified as high-confidence hits after tertiary deconvolution screens and demonstrate the utility of the assay to define LEC genes critical for the formation of tube structures. This assay facilitates the identification of potential molecular targets for novel drugs designed to modulate the remodeling of lymphatics that is important for the metastatic spread of cancer and other pathologies.

  9. An investigation of the topography of the lymphatic system of the grey kangaroo (Macropus giganteus). 1. The superficial lymphatic system.

    PubMed Central

    Hopwood, P R

    1988-01-01

    The superficial lymphatic system of the grey kangaroo, Macropus giganteus is described. The description is based on dissections of 130 eastern grey kangaroos. The most significant difference found between the superficial lymphatic drainage pattern of kangaroos and that of the domestic species was the existence of large inguino-axillary lymphatic trunks in the kangaroo. Thus in the kangaroo, instead of lymph passing from the inguinal lymphocentre to the lumbar lymphatic trunks as is the situation in the domestic animals, lymph passes from the inguinal lymphocentre to the axillary lymphocentre. Apart from the lymph draining from the head and ventral neck (which passes to the superficial cervical lymphocentre) and lymph which may pass from the superficial lymphatic vessels to deeper lymphatic vessels, all the superficial lymphatic drainage of the kangaroo passes through the axillary lymphocentre. From the viewpoint of the meat inspection of the carcasses of kangaroos taken as game meat animals, pathology of the axillary lymphocentre may reflect disease in a much wider range of body regions than it would in a domestic animal. PMID:3198478

  10. Identification of lymphatic vessels and prognostic value of lymphatic microvessel density in lesions of the uterine cervix.

    PubMed

    Saptefraţi, L; Cîmpean, Anca Maria; Ciornîi, A; Ceauşu, Raluca; Eşanu, N; Raica, M

    2009-01-01

    Incomplete characterization of the uterine cervix cancer from molecular point of view represents the main problem for the use of a proper therapy in this disease. Few data are available about D2-40 expression in lymphatic endothelial cells and also in tumor cells from uterine cervix cancer. The aim of the present work was to study the involvement of lymphatics in prognosis and tumor progression of the uterine cervix lesions. We used D2-40 immunostaining to highlight lymphatic vessels from squamous cell metaplasia (n=17), cervical intraepithelial neoplasia (n=11), carcinoma in situ (n=3), microinvasive carcinoma (n=4) and invasive carcinoma (n=19) using Avidin-Biotin technique (LSAB+). Type and distribution of lymphatics in different lesions of the cervix were analyzed. We found significant correlation between lymphatic microvessel density and tumor grade and particular distribution of the lymphatics linked to histopathologic type of the lesions. Also, differences was found in lymphovascular invasion interpretation between routine Hematoxylin and Eosin staining specimens and immunohistochemical ones. Our results showed differences in the distribution and D2-40 expression in lymphatic vessels and tumor cells from the cervix lesions linked to histopathology and tumor grade.

  11. Baseline drivers of lymphatic filariasis in Burkina Faso.

    PubMed

    Stanton, Michelle C; Molyneux, David H; Kyelem, Dominique; Bougma, Roland W; Koudou, Benjamin G; Kelly-Hope, Louise A

    2013-11-01

    Lymphatic filariasis (LF) is a parasitic disease that is endemic throughout sub-Saharan Africa, infecting approximately 40 million people. In Burkina Faso, mass drug administration (MDA) for LF with ivermectin and albendazole has been ongoing since 2001, and by 2006 all endemic health districts were receiving MDA with a therapeutic coverage of at least 65%. As MDA activities scale down, the focus is now on targeting areas where LF transmission persists with alternative elimination strategies. This study explored the relationship between village-level, baseline LF prevalence data collected in 2000 with publicly available meteorological, environmental and demographic variables in order to determine the factors that influence the geographical distribution of the disease. A fitted multiple logistic regression model indicated that the length of the rainy season, variability in normalized difference vegetation index (NDVI) and population density were significantly positively associated with LF prevalence, whereas total annual rainfall, average June-September temperature, mean NDVI, elevation and the area of cotton crops were significantly negatively associated. This model was used to produce a baseline LF risk map for Burkina Faso. An extended model which incorporated potential socio-demographic risk factors also indicated a significant positive relationship between LF prevalence and wealth. In overlaying the baseline LF risk map with the number of MDA rounds, plus an insecticide-treated net (ITN) ownership measure, the central southern area of the country was highlighted as an area where baseline LF prevalence was high and ITN coverage relatively low (<50%), while at least 10 rounds of MDA had been undertaken, suggesting that more concentrated efforts will be needed to eliminate the disease in these areas.

  12. [Diseases of the pulmonary lymphatic system in children].

    PubMed

    Epaud, R; Fauroux, B; Boule, M; Clément, A

    2003-02-01

    Diseases of the lymphatic system in children include a group of exceptional conditions difficult to manage. The anatomy of lymphatic system is complex in the lung. Variable from one subject to another, its complex physiology plays an important role in air-blood exchanges occurring in the lung. In the pulmonary interstitium and in the pleura, the lymphatic system acts like an overflow valve capable of regulating variations in interstitial fluid. The presence or development of dysplasic lymphatics causes leakage, dilatation, and reflux of the lymph through incontinent valves leading to chylothorax and/or fluid overload in the pulmonary interstitium. Symptomatic care is usually proposed, based on a fat-free diet supplemented with light-chain triglycerides and liposoluble vitamins. Other therapeutic options can be proposed. Medical options include cytotoxic agents, somatostatin, and interferon-alpha. Surgery may also be useful, but an assessment of therapeutic efficacy is very difficult due to partial effects and the small number of cases studied.

  13. Roles of transcriptional network during the formation of lymphatic vessels.

    PubMed

    Watabe, Tetsuro

    2012-09-01

    The lymphatic vascular system, also known as the second vascular system in vertebrates, plays crucial roles in various physiological and pathological processes. It participates in the maintenance of normal tissue fluid balance, trafficking of the immune cells and absorption of fatty acids in the gut. Furthermore, lymphatic system is associated with the pathogenesis of a number of diseases, including lymphedema, inflammatory diseases and tumour metastasis. Lymphatic vessels are comprised of lymphatic endothelial cells (LECs), which are differentiated from blood vascular endothelial cells. This review highlights recent advances in our understanding of the transcriptional control of LEC fate determination and reflects on efforts to understand the roles of transcriptional networks during this discrete developmental process.

  14. Monocytes can be induced to express lymphatic phenotypes.

    PubMed

    Changming, W; Xin, L; Hua, T; Shikun, W; Qiong, X; Zhigeng, Z; Xueying, W

    2011-06-01

    Although it has been recently shown that monocytes can transdifferentiate into blood vascular endothelial cells which are involved in angiogenesis, little attention has been paid to their potential to transdifferentiate into lymphatic endothelial cells. Therefore, we examined this question in our study. We first stimulated monocytes with either fibronectin (FN), VEGF-C, TNF-alpha, LPS, or IL-3 for 24h. Then we examined the expression of several markers of lymphatic endothelium and found that the monocytes expressed specific lymphatic endothelial markers, LYVE-1, Podoplanin, and Prox-1, but not common endothelial markers vWF or eNOS. Next, monocytes were incubated in endothelial growth medium with FN and VEGF-C for 6d. These monocytes were also found to express LYVE-1, Podoplanin and Prox-1, but not vWF or eNOS. Our results indicate that monocytes in vitro can be easily induced to present lymphatic phenotypes in an inflammatory environment.

  15. Lymphatic vessel density and function in experimental bladder cancer

    PubMed Central

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

    2007-01-01

    Background 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. Methods 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. Results 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

  16. Validation of Simple Quantification Methods for (18)F-FP-CIT PET Using Automatic Delineation of Volumes of Interest Based on Statistical Probabilistic Anatomical Mapping and Isocontour Margin Setting.

    PubMed

    Kim, Yong-Il; Im, Hyung-Jun; Paeng, Jin Chul; Lee, Jae Sung; Eo, Jae Seon; Kim, Dong Hyun; Kim, Euishin E; Kang, Keon Wook; Chung, June-Key; Lee, Dong Soo

    2012-12-01

    (18)F-FP-CIT positron emission tomography (PET) is an effective imaging for dopamine transporters. In usual clinical practice, (18)F-FP-CIT PET is analyzed visually or quantified using manual delineation of a volume of interest (VOI) for the striatum. In this study, we suggested and validated two simple quantitative methods based on automatic VOI delineation using statistical probabilistic anatomical mapping (SPAM) and isocontour margin setting. Seventy-five (18)F-FP-CIT PET images acquired in routine clinical practice were used for this study. A study-specific image template was made and the subject images were normalized to the template. Afterwards, uptakes in the striatal regions and cerebellum were quantified using probabilistic VOI based on SPAM. A quantitative parameter, QSPAM, was calculated to simulate binding potential. Additionally, the functional volume of each striatal region and its uptake were measured in automatically delineated VOI using isocontour margin setting. Uptake-volume product (QUVP) was calculated for each striatal region. QSPAM and QUVP were compared with visual grading and the influence of cerebral atrophy on the measurements was tested. Image analyses were successful in all the cases. Both the QSPAM and QUVP were significantly different according to visual grading (P < 0.001). The agreements of QUVP or QSPAM with visual grading were slight to fair for the caudate nucleus (κ = 0.421 and 0.291, respectively) and good to perfect to the putamen (κ = 0.663 and 0.607, respectively). Also, QSPAM and QUVP had a significant correlation with each other (P < 0.001). Cerebral atrophy made a significant difference in QSPAM and QUVP of the caudate nuclei regions with decreased (18)F-FP-CIT uptake. Simple quantitative measurements of QSPAM and QUVP showed acceptable agreement with visual grading. Although QSPAM in some group may be influenced by cerebral atrophy, these simple methods are expected to be effective in the quantitative

  17. An Immunological Fingerprint Differentiates Muscular Lymphatics from Arteries and Veins

    PubMed Central

    Bridenbaugh, Eric A.; Wang, Wei; Srimushnam, Maya; Cromer, Walter E.; Zawieja, Scott D.; Schmidt, Susan E.; Jupiter, Daniel C.; Huang, Hung-Chung; Van Buren, Vincent

    2013-01-01

    Abstract The principal function of the lymphatic system is to transport lymph from the interstitium to the nodes and then from the nodes to the blood. In doing so lymphatics play important roles in fluid homeostasis, macromolecular/antigen transport and immune cell trafficking. To better understand the genes that contribute to their unique physiology, we compared the transcriptional profile of muscular lymphatics (prenodal mesenteric microlymphatics and large, postnodal thoracic duct) to axillary and mesenteric arteries and veins isolated from rats. Clustering of the differentially expressed genes demonstrated that the lymph versus blood vessel differences were more profound than between blood vessels, particularly the microvessels. Gene ontology functional category analysis indicated that microlymphatics were enriched in antigen processing/presentation, IgE receptor signaling, catabolic processes, translation and ribosome; while they were diminished in oxygen transport, regulation of cell proliferation, glycolysis and inhibition of adenylate cyclase activity by G-proteins. We evaluated the differentially expressed microarray genes/products by qPCR and/or immunofluorescence. Immunofluorescence documented that multiple MHC class II antigen presentation proteins were highly expressed by an antigen-presenting cell (APC) type found resident within the lymphatic wall. These APCs also expressed CD86, a co-stimulatory protein necessary for T-cell activation. We evaluated the distribution and phenotype of APCs within the pre and postnodal lymphatic network. This study documents a novel population of APCs resident within the walls of muscular, prenodal lymphatics that indicates novel roles in antigen sampling and immune responses. In conclusion, these prenodal lymphatics exhibit a unique profile that distinguishes them from blood vessels and highlights the role of the lymphatic system as an immunovascular system linking the parenchymal interstitium, lymph nodes and the

  18. [The macrophage contribution for maintaining lymphatic vessel in cornea].

    PubMed

    Maruyama, Kazuichi

    2014-11-01

    The presence of antigen-presenting cells and hem- and lymphangiogenesis in the cornea are risk factors for the rejection of corneal transplants. We previously reported that antigen-presenting cells such as macrophages (MPs) play an important role in the induction of lymphatic endothelial cells during inflammation. This prompted us to inquire whether the existence of lymphatic vessels in the cornea is associated with the activation of MPs during inflammation. To investigate this question, we performed suture placement on the cornea to induce inflammation. We found that a large number of MPs were recruited and that lymphatic vessels were formed in response. Next, as C57BL/6 mice have a higher rejection rate after corneal transplantation than BALB/c mice, we compared the corneas of C57BL/6 and BALB/c mice under normal and inflamed conditions. We found that the number of spontaneously formed lymphatic vessels in the C57BL/6 corneas was significantly greater than in the BALB/c corneas, and that there were more activated MPs in the C57BL/6 corneas than in the BALB/c corneas. Additionally, to confirm that activated MPs induced and maintained lymphatic vessels in the cornea, we depleted the number of MPs in C57BL/6 mice via clodronate liposomes. We found that MP depletion reduced the spontaneous formation of lymphatic vessels and reduced inflammation-induced lymphangiogenesis relative to control mice. Finally, we found that mice deficient in MP markers had fewer spontaneously formed lymphatic vessels and less lymphangiogenesis than control C57BL/6 mice. The evidence gathered in this study leads us to conclude that activated MPs appear to play an important role in the formation of new lymphatic vessels and in their maintenance.

  19. Current and Future Lymphatic Imaging Modalities for Tumor Staging

    PubMed Central

    Gao, Kuo; Liu, Tiegang; Tariq, Imran; Sajjad, Ashif; Niu, Meiying; Liu, Guokai; Mehmood, Zahid; Tian, Guihua

    2014-01-01

    Tumor progression is supported by the lymphatic system which should be scanned efficiently for tumor staging as well as the enhanced therapeutic outcomes. Poor resolution and low sensitivity is a limitation of traditional lymphatic imaging modalities; thus new noninvasive approaches like nanocarriers, magnetic resonance imaging, positron-emission tomography, and quantum dots are advantageous. Some newer modalities, which are under development, and their potential uses will also be discussed in this review. PMID:24757671

  20. Sensitivity analysis of near-infrared functional lymphatic imaging

    NASA Astrophysics Data System (ADS)

    Weiler, Michael; Kassis, Timothy; Dixon, J. Brandon

    2012-03-01

    Background - Near-infrared (NIR) imaging of lymphatic drainage of injected indocyanine green (ICG) has emerged as a new technology for clinical imaging of lymphatic architecture and quantification of vessel function, offering better spatial and temporal resolution than competing imaging modalities. While NIR lymphatic imaging has begun to be reported in the literature, the technology is still in its infancy and its imaging capabilities have yet to be quantitatively characterized. The objective of this study, therefore, was to characterize the parameters of NIR lymphatic imaging to quantify its capabilities as a diagnostic tool for evaluating lymphatic disease. Methods - An NIR imaging system was developed using a laser diode for excitation, ICG as a fluorescent agent, and a CCD camera to detect emission. A tissue phantom with mock lymphatic vessels of known depths and diameters was used as an alternative to in vivo lymphatic vessels due to the greater degree of control with the phantom. Results and Conclusions - When dissolved in an albumin physiological salt solution (APSS) to mimic interstitial fluid, ICG experiences shifts in the excitation/emission wavelengths such that it is maximally excited at 805nm and produces peak fluorescence at 840nm. Premixing ICG with albumin induces greater fluorescence intensity, with the ideal concentration being: 900μM (60g/L) albumin and 193.5μM (150μg/mL) ICG. ICG fluorescence can be detected as deep as 6mm, but spatial resolution deteriorates severely below 3mm, thus skewing vessel geometry measurements. ICG packet travel, a common measure of lymphatic transport, can be detected as deep as 5mm.

  1. Communication between lymphatic and venous systems in mice.

    PubMed

    Shao, Lenan; Takeda, Kazu; Kato, Shigeki; Mori, Shiro; Kodama, Tetsuya

    2015-09-01

    The lymphatic system in mice consists of lymphatic vessels and 22 types of lymph nodes. Metastatic tumor cells in the lymphatic system spread to distant organs through the venous system. However, the communication routes between the lymphatic and venous systems have not been fully elucidated. Here, we identify the communication routes between the lymphatic and venous systems in the axillary and subiliac regions of MXH10/Mo-lpr/lpr inbred mice, which develop systemic swelling of lymph nodes up to 10mm in diameter, allowing investigation of the topography of the lymph nodes and lymphatic vessels. Using a gross anatomy dissection approach, the efferent lymphatic vessels of the proper axillary lymph node were shown to communicate with the subclavian vein. Furthermore, we found that the thoracoepigastric vein, which connects the subclavian vein and inferior vena cava, runs adjacent to the subiliac and proper axillary lymph nodes, and receives venous blood from these lymph nodes routed through small branches. The direction of blood flow in the thoracoepigastric vein occurred in two directions in the intermediate region between the proper axillary lymph node and subiliac lymph node; one to the subclavian vein, the other to the inferior vena cava. This paper reveals the anatomy of the communication between the lymphatic and venous systems in the axillary and subiliac regions of the mouse, and provides new insights relevant to the investigation of the mechanisms of lymph node metastasis and cancer immunology, and the development of diagnostic and treatment methods for lymph node metastasis, including drug delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Neither normal nor diseased placentas contain lymphatic vessels.

    PubMed

    Castro, E; Tony Parks, W; Galambos, C

    2011-04-01

    Scant data on placental lymphatic vessels have pointed to the absence of lymphatic circulation. A recent study on mesenchymal dysplasia (MD), however, has identified pathologic lymphangiogenesis using the D2-40 lymphatic marker. These conflicting data have prompted us to investigate whether lymphatic vessels are present in normal developing placentas and in placental disorders characterized by cistern formation. Seventeen human placentas without significant pathological abnormality ranging from 12 to 39 weeks of gestational age were studied. Cisternal placental disorders were represented by mesenchymal dysplasia (n = 1), partial hydatitiform mole (n = 2), spontaneous abortion (n = 3) and complete hydatiform mole (n = 2). To identify lymphatic vessels, we used lymphatic endothelial markers Prox-1 and D2-40. The pan-endothelial marker CD31 was used to highlight overall placental vasculature and to determine if the lining cells of cisterns were of endothelial origin. Lymphatic marker positivity was assessed in maternal (decidual) as well as in fetal (chorionic villous) vasculature. No staining with Prox-1 or D2-40 was identified in fetal vessels in developing or term placentas, or in selected cisternal placental disorders, although both markers highlighted a number of thin-walled decidual vessels. Cistern lining cells were negative for Prox-1, D2-40 and CD31. D2-40 consistently marked stromal cells in chorionic villi and highlighted perivascular/pericellular extracellular matrix. We established that no lymphatic vasculature is present in the chorionic villi during development, at term or in selected edematous placental disorders. The cisternal lining cells are not endothelial cells; most likely they are of stromal cell origin. Lymphangiogenesis is a part of decidual vascular remodeling during gestation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Morphological and Molecular Characterization of Human Dermal Lymphatic Collectors

    PubMed Central

    Buttler, Kerstin; Ströbel, Philipp; Becker, Jürgen; Aung, Thiha; Felmerer, Gunther; Wilting, Jörg

    2016-01-01

    Millions of patients suffer from lymphedema worldwide. Supporting the contractility of lymphatic collectors is an attractive target for pharmacological therapy of lymphedema. However, lymphatics have mostly been studied in animals, while the cellular and molecular characteristics of human lymphatic collectors are largely unknown. We studied epifascial lymphatic collectors of the thigh, which were isolated for autologous transplantations. Our immunohistological studies identify additional markers for LECs (vimentin, CCBE1). We show and confirm differences between initial and collecting lymphatics concerning the markers ESAM1, D2-40 and LYVE-1. Our transmission electron microscopic studies reveal two types of smooth muscle cells (SMCs) in the media of the collectors with dark and light cytoplasm. We observed vasa vasorum in the media of the largest collectors, as well as interstitial Cajal-like cells, which are highly ramified cells with long processes, caveolae, and lacking a basal lamina. They are in close contact with SMCs, which possess multiple caveolae at the contact sites. Immunohistologically we identified such cells with antibodies against vimentin and PDGFRα, but not CD34 and cKIT. With Next Generation Sequencing we searched for highly expressed genes in the media of lymphatic collectors, and found therapeutic targets, suitable for acceleration of lymphatic contractility, such as neuropeptide Y receptors 1, and 5; tachykinin receptors 1, and 2; purinergic receptors P2RX1, and 6, P2RY12, 13, and 14; 5-hydroxytryptamine receptors HTR2B, and 3C; and adrenoceptors α2A,B,C. Our studies represent the first comprehensive characterization of human epifascial lymphatic collectors, as a prerequisite for diagnosis and therapy. PMID:27764183

  4. Zinc effect on human lymphatic malformation cells in vitro.

    PubMed

    O, Teresa Min-Jung; Lou, Man Si; Ma, Yupo

    2016-01-01

    Lymphatic malformations (LM) are clinically characterized by episodes of inflammatory episodes. Often, an upper respiratory illness or trauma will lead to painful swelling in the distribution of the LM. Zinc is an element involved in numerous aspects of cellular metabolism and is a common dietary supplement and cold remedy. We surmise that zinc may act as a therapeutic anti-inflammatory agent for lymphatic malformations and their cellular components. We investigate the apparent cytotoxic effect of zinc ion on lymphatic malformation cells in vitro. Fresh surgical lymphatic malformation specimens from 10 patients were collected and processed in a laboratory. Tissues were processed and lymphatic malformation cells were isolated and grown. Immunohistochemistry and cell morphology were used to confirm LM cells. HUVEC cells were used as controls. Zinc chloride solution was added to the cells and its effect observed. LM cells were isolated from five of the 10 specimens. Of these, the cells of only one specimen were able to be amplified to confluence. Five specimens were contaminated. Immunohistochemical staining (CD31, D2-40, and LYVE-1) and cell morphology of our specimens were consistent with lymphatic malformation while HUVEC control cells were negative. Zinc has a cytotoxic effect on BEL isolates in vitro with no obvious effect on cell morphology or growth rate of the control HUVEC cells. When compared with the published toxic zinc concentration for most cell types in the literature (100μM total zinc in vitro), our result indicates that LM cells may have a lower tolerance to zinc (10μM total zinc in vitro). Zinc has an apparent morphological effect on lymphatic malformation cells in vitro. Compared with other cell types, LM cells have a lower tolerance to zinc. While this result looks very promising for future therapeutic use of zinc in acute lymphangitis, further studies are necessary, such as finding the IC50 of zinc for lymphatic malformation in vitro and also in

  5. Lymphatic vessels: an emerging actor in atherosclerotic plaque development.

    PubMed

    Kutkut, Issa; Meens, Merlijn J; McKee, Thomas A; Bochaton-Piallat, Marie-Luce; Kwak, Brenda R

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease of large- to medium-sized arteries and is the main underlying cause of death worldwide. The lymphatic vasculature is critical for processes that are intimately linked to atherogenesis such as the immune response and cholesterol metabolism. However, whether lymphatic vessels truly contribute to the pathogenesis of atherosclerosis is less clear despite increasing research efforts in this field. PubMed and Ovid MEDLINE databases were searched. In addition, key review articles were screened for relevant original publications. Current knowledge about lymphatic vessels in the arterial wall came from studies that examined the presence and location of such vessels in human atherosclerotic plaque specimens, as well as in a variety of arteries in animal models for atherosclerosis (e.g. rabbits, dogs, rats and mice). Generally, three experimental approaches have been used to investigate the functional role of plaque-associated lymphatic vessels; experimental lymphostasis was used to investigate lymphatic drainage of the arterial wall, and more recently, studies with genetic interventions and/or surgical transplantation have been performed. Lymphatic vessels seem to be mostly present in the adventitial layer of the arterial walls of animals and humans. They are involved in reverse cholesterol transport from atherosclerotic lesions, and arteries with a dense lymphatic network seem naturally protected against atherosclerosis. Lymphangiogenesis is a process that is an important part of the inflammatory loop in atherosclerosis. However, how augmenting or impeding the distribution of lymphatic vessels impacts disease progression remains to be investigated in future studies. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

  6. Laparoscopic anatomic liver resection

    PubMed Central

    Vibert, Eric; Kouider, Ali

    2004-01-01

    Background Liver resection is reputed to be one of the most difficult procedures embraced in laparoscopy. This report shows that with adequate training, anatomical liver resection including major hepatectomies can be performed. Methods This is a retrospective study. Results From 1995 to 2004, among 84 laparoscopic liver resections, 46 (54%) anatomical laparoscopic hepatectomies were performed in our institution by laparoscopy. Nine (20%) patients had benign disease while 37 (80%) had malignant lesions. Among those with malignant lesions, 14 patients had hepatocellular carcinoma (HCC), 18 had colorectal metastasis (CRM), while 5 had miscellaneous tumours. For benign disease, minor (two Couinaud's segments or less) and major anatomic hepatectomies were performed in five and four patients, respectively. For malignant lesions, minor and major anatomic hepatectomies were performed in 15 and 22 patients, respectively. Overall, conversion to laparotomy was necessary in 7 (15%) patients. Blood transfusion was required in five (10%) patients. One patient died of cerebral infarction 8 days after a massive peroperative haemorrhage. The overall morbidity rate was 34% whatever the type of resection. Three patients required reoperation, either for haemorrhage (n=1) and/or biliary leak (n=2). For CRM (n=18), overall and disease-free survival at 24 months (mean follow-up of 17 months) were 100% and 56%, respectively. For HCC (n=14), overall and disease-free survival at 36 months (mean follow-up of 29 months) were 91% and 65%, respectively. No port site metastasis occurred in patients with malignancy. Conclusions After a long training with limited liver resection in superficial segments, laparoscopic anatomical minor and major resections are feasible. Short-term carcinological results seem to be similar to those obtained with laparotomy. PMID:18333079

  7. The association of adult Onchocerca volvulus with lymphatic vessels.

    PubMed

    Mackenzie, C D; Huntington, M K; Wanji, S; Lovato, R V; Eversole, R R; Geary, T G

    2010-02-01

    Immunocytochemical examination of onchocercal nodule tissues containing adult Onchocerca volvulus using immuno-markers for blood and lymphatic vessels (vWF, D2-40, podoplanin, Prox-1, and Lyve1) shows a distinct pattern of distribution of these vessels within nodules. Blood vessels were commonly seen associated with organized lymphoid cellular aggregates in the both the outer and inner areas of the nodules. In contrast, the majority of the lymphatic vessel positivity was seen in the central zone in close apposition to the adult parasites, and the remainder usually associated with microfilariae in the outer areas of the nodule. These findings suggest an intimate relationship between adult O. volvulus and lymphatic vessels, including the likely proliferation of lymphatic endothelial cells (lymphangectasia) akin to that seen with other filariae. These findings indicate that adult O. volvulus may migrate via the lymphatic system, and that clinical manifestations of this disease that involve tissue edema may be the result of the location of these worms in the lymphatic system.

  8. Photoacoustic lymphatic imaging with high spatial-temporal resolution

    NASA Astrophysics Data System (ADS)

    Martel, Catherine; Yao, Junjie; Huang, Chih-Hsien; Zou, Jun; Randolph, Gwendalyn J.; Wang, Lihong V.

    2014-11-01

    Despite its critical function in coordinating the egress of inflammatory and immune cells out of tissues and maintaining fluid balance, the causative role of lymphatic network dysfunction in pathological settings is still understudied. Engineered-animal models and better noninvasive high spatial-temporal resolution imaging techniques in both preclinical and clinical studies will help to improve our understanding of different lymphatic-related pathologic disorders. Our aim was to take advantage of our newly optimized noninvasive wide-field fast-scanning photoacoustic (PA) microcopy system to coordinately image the lymphatic vasculature and its flow dynamics, while maintaining high resolution and detection sensitivity. Here, by combining the optical-resolution PA microscopy with a fast-scanning water-immersible microelectromechanical system scanning mirror, we have imaged the lymph dynamics over a large field-of-view, with high spatial resolution and advanced detection sensitivity. Depending on the application, lymphatic vessels (LV) were spectrally or temporally differentiated from blood vessels. Validation experiments were performed on phantoms and in vivo to identify the LV. Lymphatic flow dynamics in nonpathological and pathological conditions were also visualized. These results indicate that our newly developed PA microscopy is a promising tool for lymphatic-related biological research.

  9. Sensitivity analysis of near-infrared functional lymphatic imaging

    NASA Astrophysics Data System (ADS)

    Weiler, Michael; Kassis, Timothy; Dixon, J. Brandon

    2012-06-01

    Near-infrared imaging of lymphatic drainage of injected indocyanine green (ICG) has emerged as a new technology for clinical imaging of lymphatic architecture and quantification of vessel function, yet the imaging capabilities of this approach have yet to be quantitatively characterized. We seek to quantify its capabilities as a diagnostic tool for lymphatic disease. Imaging is performed in a tissue phantom for sensitivity analysis and in hairless rats for in vivo testing. To demonstrate the efficacy of this imaging approach to quantifying immediate functional changes in lymphatics, we investigate the effects of a topically applied nitric oxide (NO) donor glyceryl trinitrate ointment. Premixing ICG with albumin induces greater fluorescence intensity, with the ideal concentration being 150 μg/mL ICG and 60 g/L albumin. ICG fluorescence can be detected at a concentration of 150 μg/mL as deep as 6 mm with our system, but spatial resolution deteriorates below 3 mm, skewing measurements of vessel geometry. NO treatment slows lymphatic transport, which is reflected in increased transport time, reduced packet frequency, reduced packet velocity, and reduced effective contraction length. NIR imaging may be an alternative to invasive procedures measuring lymphatic function in vivo in real time.

  10. Lymphatics at the crossroads of angiogenesis and lymphangiogenesis

    PubMed Central

    Scavelli, Claudio; Weber, Elisabetta; Aglianò, Margherita; Cirulli, Teresa; Nico, Beatrice; Vacca, Angelo; Ribatti, Domenico

    2004-01-01

    The lymphatic system is implicated in interstitial fluid balance regulation, immune cell trafficking, oedema and cancer metastasis. However, the sequence of events that initiate and coordinate lymphatic vessel development (lymphangiogenesis) remains obscure. In effect, the understanding of physiological regulation of lymphatic vasculature has been overshadowed by the greater emphasis focused on angiogenesis, and delayed by a lack of specific markers, thereby limiting this field to no more than a descriptive characterization. Recently, new insights into lymphangiogenesis research have been due to the discovery of lymphatic-specific markers and growth factors of vascular endothelial growth factor (VEGF) family, such as VEGF-C and VEGF-D. Studies using transgenic mice overexpressing VEGF-C and VEGF-D have demonstrated a crucial role for these factors in tumour lymphangiogenesis. Knowledge of lymphatic development has now been redefined at the molecular level, providing an interesting target for innovative therapies. This review highlights the recent insights and advances into the field of lymphatic vascular research, outlining the most important aspects of the embryo development, structure, specific markers and methods applied for studying lymphangiogenesis. Finally, molecular mechanisms involved in the regulation of lymphangiogenesis are described. PMID:15198686

  11. FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature

    PubMed Central

    Sabine, Amélie; Bovay, Esther; Demir, Cansaran Saygili; Kimura, Wataru; Jaquet, Muriel; Agalarov, Yan; Zangger, Nadine; Scallan, Joshua P.; Graber, Werner; Gulpinar, Elgin; Kwak, Brenda R.; Mäkinen, Taija; Martinez-Corral, Inés; Ortega, Sagrario; Delorenzi, Mauro; Kiefer, Friedemann; Davis, Michael J.; Djonov, Valentin; Miura, Naoyuki; Petrova, Tatiana V.

    2015-01-01

    Biomechanical forces, such as fluid shear stress, govern multiple aspects of endothelial cell biology. In blood vessels, disturbed flow is associated with vascular diseases, such as atherosclerosis, and promotes endothelial cell proliferation and apoptosis. Here, we identified an important role for disturbed flow in lymphatic vessels, in which it cooperates with the transcription factor FOXC2 to ensure lifelong stability of the lymphatic vasculature. In cultured lymphatic endothelial cells, FOXC2 inactivation conferred abnormal shear stress sensing, promoting junction disassembly and entry into the cell cycle. Loss of FOXC2-dependent quiescence was mediated by the Hippo pathway transcriptional coactivator TAZ and, ultimately, led to cell death. In murine models, inducible deletion of Foxc2 within the lymphatic vasculature led to cell-cell junction defects, regression of valves, and focal vascular lumen collapse, which triggered generalized lymphatic vascular dysfunction and lethality. Together, our work describes a fundamental mechanism by which FOXC2 and oscillatory shear stress maintain lymphatic endothelial cell quiescence through intercellular junction and cytoskeleton stabilization and provides an essential link between biomechanical forces and endothelial cell identity that is necessary for postnatal vessel homeostasis. As FOXC2 is mutated in lymphedema-distichiasis syndrome, our data also underscore the role of impaired mechanotransduction in the pathology of this hereditary human disease. PMID:26389677

  12. Quantum dots trace lymphatic drainage from the mouse eye.

    PubMed

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

    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.

  13. Quantum dots trace lymphatic drainage from the mouse eye

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

    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.

  14. Sensitivity analysis of near-infrared functional lymphatic imaging

    PubMed Central

    Weiler, Michael; Kassis, Timothy

    2012-01-01

    Abstract. Near-infrared imaging of lymphatic drainage of injected indocyanine green (ICG) has emerged as a new technology for clinical imaging of lymphatic architecture and quantification of vessel function, yet the imaging capabilities of this approach have yet to be quantitatively characterized. We seek to quantify its capabilities as a diagnostic tool for lymphatic disease. Imaging is performed in a tissue phantom for sensitivity analysis and in hairless rats for in vivo testing. To demonstrate the efficacy of this imaging approach to quantifying immediate functional changes in lymphatics, we investigate the effects of a topically applied nitric oxide (NO) donor glyceryl trinitrate ointment. Premixing ICG with albumin induces greater fluorescence intensity, with the ideal concentration being 150  μg/mL ICG and 60  g/L albumin. ICG fluorescence can be detected at a concentration of 150  μg/mL as deep as 6 mm with our system, but spatial resolution deteriorates below 3 mm, skewing measurements of vessel geometry. NO treatment slows lymphatic transport, which is reflected in increased transport time, reduced packet frequency, reduced packet velocity, and reduced effective contraction length. NIR imaging may be an alternative to invasive procedures measuring lymphatic function in vivo in real time. PMID:22734775

  15. Lymphatic Vessels, Inflammation, and Immunity in Skin Cancer.

    PubMed

    Lund, Amanda W; Medler, Terry R; Leachman, Sancy A; Coussens, Lisa M

    2016-01-01

    Skin is a highly ordered immune organ that coordinates rapid responses to external insult while maintaining self-tolerance. In healthy tissue, lymphatic vessels drain fluid and coordinate local immune responses; however, environmental factors induce lymphatic vessel dysfunction, leading to lymph stasis and perturbed regional immunity. These same environmental factors drive the formation of local malignancies, which are also influenced by local inflammation. Herein, we discuss clinical and experimental evidence supporting the tenet that lymphatic vessels participate in regulation of cutaneous inflammation and immunity, and are important contributors to malignancy and potential biomarkers and targets for immunotherapy. The tumor microenvironment and tumor-associated inflammation are now appreciated not only for their role in cancer progression but also for their response to therapy. The lymphatic vasculature is a less-appreciated component of this microenvironment that coordinates local inflammation and immunity and thereby critically shapes local responses. A mechanistic understanding of the complexities of lymphatic vessel function in the unique context of skin provides a model to understand how regional immune dysfunction drives cutaneous malignancies, and as such lymphatic vessels represent a biomarker of cutaneous immunity that may provide insight into cancer prognosis and effective therapy. ©2015 American Association for Cancer Research.

  16. Mechanotransduction activates canonical Wnt/β-catenin signaling to promote lymphatic vascular patterning and the development of lymphatic and lymphovenous valves

    PubMed Central

    Cha, Boksik; Geng, Xin; Mahamud, Md. Riaj; Fu, Jianxin; Mukherjee, Anish; Kim, Yeunhee; Jho, Eek-hoon; Kim, Tae Hoon; Kahn, Mark L.; Xia, Lijun; Dixon, J. Brandon; Chen, Hong; Srinivasan, R. Sathish

    2016-01-01

    Lymphatic vasculature regulates fluid homeostasis by returning interstitial fluid to blood circulation. Lymphatic endothelial cells (LECs) are the building blocks of the entire lymphatic vasculature. LECs originate as a homogeneous population of cells predominantly from the embryonic veins and undergo stepwise morphogenesis to become the lymphatic capillaries, collecting vessels or valves. The molecular mechanisms underlying the morphogenesis of the lymphatic vasculature remain to be fully understood. Here we show that canonical Wnt/β-catenin signaling is necessary for lymphatic vascular morphogenesis. Lymphatic vascular-specific ablation of β-catenin in mice prevents the formation of lymphatic and lymphovenous valves. Additionally, lymphatic vessel patterning is defective in these mice, with abnormal recruitment of mural cells. We found that oscillatory shear stress (OSS), which promotes lymphatic vessel maturation, triggers Wnt/β-catenin signaling in LECs. In turn, Wnt/β-catenin signaling controls the expression of several molecules, including the lymphedema-associated transcription factor FOXC2. Importantly, FOXC2 completely rescues the lymphatic vessel patterning defects in mice lacking β-catenin. Thus, our work reveals that mechanical stimulation is a critical regulator of lymphatic vascular development via activation of Wnt/β-catenin signaling and, in turn, FOXC2. PMID:27313318

  17. Progression of Inflammatory Bowel Disease to Cancer: Is the Patient Better Off without Lymphatic Vessels or Nodes (or Angiopoietin 2)?

    DTIC Science & Technology

    2012-10-01

    number of functioning lymphatic vessels and impaired lymph drainage (lymphatic vascular insufficiency) in the colon actually protects against...have remained elusive. We proposed that having a reduced number of functioning lymphatic vessels and impaired lymph drainage (lymphatic vascular...Lymphatics, Lymph and the Lymphomyeloid Complex. Academic Press, London, 942 p, 1970. Appendices None Supporting Data None

  18. Chronic High-Fat Diet Impairs Collecting Lymphatic Vessel Function in Mice

    PubMed Central

    Proulx, Steven T.; Ochsenbein, Alexandra M.; Luciani, Paola; Leroux, Jean-Christophe; Wolfrum, Christian; Detmar, Michael

    2014-01-01

    Lymphatic vessels play an essential role in intestinal lipid uptake, and impairment of lymphatic vessel function leads to enhanced adipose tissue accumulation in patients with lymphedema and in genetic mouse models of lymphatic dysfunction. However, the effects of obesity on lymphatic function have been poorly studied. We investigated if and how adipose tissue accumulation influences lymphatic function. Using a lymphatic specific tracer, we performed in vivo near-infrared (NIR) imaging to assess the function of collecting lymphatic vessels in mice fed normal chow or high-fat diet (HFD). Histological and whole mount analyses were performed to investigate the morphological changes in initial and the collecting lymphatic vessels. HFD was associated with impaired collecting lymphatic vessel function, as evidenced by reduced frequency of contractions and diminished response to mechanostimulation. Moreover, we found a significant negative correlation between collecting lymphatic vessel function and body weight. Whole mount analyses showed an enlargement of contractile collecting lymphatic vessels of the hind limb. In K14-VEGF-C mice, HFD resulted in a reduced spreading of the tracer within dermal lymphatic vessels. These findings indicate that adipose tissue expansion due to HFD leads to a functional impairment of the lymphatic vasculature, predominantly in collecting lymphatic vessels. PMID:24714646

  19. Tie1 is required for lymphatic valve and collecting vessel development

    PubMed Central

    Qu, Xianghu; Zhou, Bin; Baldwin, H. Scott

    2015-01-01

    Tie1 is a receptor tyrosine kinase with broad expression in embryonic endothelium. Reduction of Tie1 levels in mouse embryos with a hypomorphic Tie1 allele resulted in abnormal lymphatic patterning and architecture, decreased lymphatic draining efficiency, and ultimately, embryonic demise. Here we report that Tie1 is present uniformly throughout the lymphatics and from late embryonic/early postnatal stages, becomes more restricted to lymphatic valve regions. To investigate later events of lymphatic development, we employed Cre-loxP recombination utilizing a floxed Tie1 allele and an Nfatc1Cre line, to provide loxP excision predominantly in lymphatic endothelium and developing valves. Interestingly, unlike the early prenatal defects previously described by ubiquitous endothelial deletion, excision of Tie1 with Nfatc1Cre resulted in abnormal lymphatic defects in postnatal mice and was characterized by agenesis of lymphatic valves and a deficiency of collecting lymphatic vessels. Attenuation of Tie1 signaling in lymphatic endothelium prevented initiation of lymphatic valve specification by Prox1 high expression lymphatic endothelial cells that is associated with the onset of turbulent flow in the lymphatic circulation. Our findings reveal a fundamental role for Tie signaling during lymphatic vessel remodeling and valve morphogenesis and implicate it as a candidate gene involved in primary lymphedema. PMID:25576926

  20. Reconstitution of myocardial lymphatic vessels after acute infarction of rat heart.

    PubMed

    Sun, Q N; Wang, Y F; Guo, Z K

    2012-06-01

    We investigated the regeneration of cardiac lymphatic vessels and capillaries in the infarcted myocardiac zones after acute myocardial infarction in rats. The anterior descending artery of the heart was ligated for infarction and both immunohistochemistry and immunofluorescence were used to detect pathological changes of lymphatic vessels in infarcted zone (IZ), infarcted margin zone (MZ) and remote margin zone (RMZ) on days 7, 14, 21, and 28 after surgery. Dynamic variation of lymphatic vessels existed in IZ, MZ and RMZ at different stages after surgery. At day 7, lymphatic vessels and capillaries were not seen in the IZ, very thin lymphatic capillaries were obviously increased in the inner layer of the margin zone, and enlarged and increased lymphatic capillaries were found in the outer layer of margin zone. At 14 days, a few sparsely arranged lymphatic capillaries were observed in the IZ without marked changes in the MZ. At 21 days, constricted regenerating lymphatic capillaries in MZ were decreased, and lymphatic vessels exhibited sprouting towards the IZ. At 28 days, more lymphatic capillaries emerged in the IZ, and the morphology and number of lymphatic vessels and capillaries had returned to normal. There were no marked changes of lymphatic vessels and capillaries in RMZ compared to control myocardium at the 4 time points. This study demonstrates varied remodeling of lymphatic vessels and capillaries in the IZ and MZ after acute myocardial infarction, and these changes in lymphatic vessels likely play an important role for recovery of infarcted myocardiac function.

  1. Motivation and Organizational Principles for Anatomical Knowledge Representation

    PubMed Central

    Rosse, Cornelius; Mejino, José L.; Modayur, Bharath R.; Jakobovits, Rex; Hinshaw, Kevin P.; Brinkley, James F.

    1998-01-01

    Abstract Objective: Conceptualization of the physical objects and spaces that constitute the human body at the macroscopic level of organization, specified as a machine-parseable ontology that, in its human-readable form, is comprehensible to both expert and novice users of anatomical information. Design: Conceived as an anatomical enhancement of the UMLS Semantic Network and Metathesaurus, the anatomical ontology was formulated by specifying defining attributes and differentia for classes and subclasses of physical anatomical entities based on their partitive and spatial relationships. The validity of the classification was assessed by instantiating the ontology for the thorax. Several transitive relationships were used for symbolically modeling aspects of the physical organization of the thorax. Results: By declaring Organ as the macroscopic organizational unit of the body, and defining the entities that constitute organs and higher level entities constituted by organs, all anatomical entities could be assigned to one of three top level classes (Anatomical structure, Anatomical spatial entity and Body substance). The ontology accommodates both the systemic and regional (topographical) views of anatomy, as well as diverse clinical naming conventions of anatomical entities. Conclusions: The ontology formulated for the thorax is extendible to microscopic and cellular levels, as well as to other body parts, in that its classes subsume essentially all anatomical entities that constitute the body. Explicit definitions of these entities and their relationships provide the first requirement for standards in anatomical concept representation. Conceived from an anatomical viewpoint, the ontology can be generalized and mapped to other biomedical domains and problem solving tasks that require anatomical knowledge. PMID:9452983

  2. Impaired lymphatic function accelerates cancer growth

    PubMed Central

    Steinskog, Eli Sihn Samdal; Sagstad, Solfrid Johanne; Wagner, Marek; Karlsen, Tine Veronica; Yang, Ning; Markhus, Carl Erik; Yndestad, Synnøve; Wiig, Helge; Eikesdal, Hans Petter

    2016-01-01

    Increased lymphangiogenesis is a common feature of cancer development and progression, yet the influence of impaired lymphangiogenesis on tumor growth is elusive. C3HBA breast cancer and KHT-1 sarcoma cell lines were implanted orthotopically in Chy mice, harboring a heterozygous inactivating mutation of vascular endothelial growth factor receptor-3, resulting in impaired dermal lymphangiogenesis. Accelerated tumor growth was observed in both cancer models in Chy mice, coinciding with reduced peritumoral lymphangiogenesis. An impaired lymphatic washout was observed from the peritumoral area in Chy mice with C3HBA tumors, and the number of macrophages was significantly reduced. While fewer macrophages were detected, the fraction of CD163+ M2 macrophages remained constant, causing a shift towards a higher M2/M1 ratio in Chy mice. No difference in adaptive immune cells was observed between wt and Chy mice. Interestingly, levels of pro- and anti-inflammatory macrophage-associated cytokines were reduced in C3HBA tumors, pointing to an impaired innate immune response. However, IL-6 was profoundly elevated in the C3HBA tumor interstitial fluid, and treatment with the anti-IL-6 receptor antibody tocilizumab inhibited breast cancer growth. Collectively, our data indicate that impaired lymphangiogenesis weakens anti-tumor immunity and favors tumor growth at an early stage of cancer development. PMID:27329584

  3. Reference Man anatomical model

    SciTech Connect

    Cristy, M.

    1994-10-01

    The 70-kg Standard Man or Reference Man has been used in physiological models since at least the 1920s to represent adult males. It came into use in radiation protection in the late 1940s and was developed extensively during the 1950s and used by the International Commission on Radiological Protection (ICRP) in its Publication 2 in 1959. The current Reference Man for Purposes of Radiation Protection is a monumental book published in 1975 by the ICRP as ICRP Publication 23. It has a wealth of information useful for radiation dosimetry, including anatomical and physiological data, gross and elemental composition of the body and organs and tissues of the body. The anatomical data includes specified reference values for an adult male and an adult female. Other reference values are primarily for the adult male. The anatomical data include much data on fetuses and children, although reference values are not established. There is an ICRP task group currently working on revising selected parts of the Reference Man document.

  4. The National Programme to Eliminate Lymphatic Filariasis from Ethiopia

    PubMed Central

    Mengistu, Belete; Deribe, Kebede; Kebede, Fikreab; Martindale, Sarah; Hassan, Mohammed; Sime, Heven; Mackenzie, Charles; Mulugeta, Abate; Tamiru, Mossie; Sileshi, Mesfin; Hailu, Asrat; Gebre, Teshome; Fentaye, Amha; Kebede, Biruck

    2017-01-01

    Lymphatic filariasis (LF) is one of the most debilitating and disfiguring diseases common in Ethiopia and is caused by Wuchereria bancrofti. Mapping for LF has shown that 70 woredas (districts) are endemic and 5.9 million people are estimated to be at risk. The national government’s LF elimination programme commenced in 2009 in 5 districts integrated with the onchocerciasis programme. The programme developed gradually and has shown significant progress over the past 6 years, reaching 100% geographical coverage for mass drug administration (MDA) by 2016. To comply with the global LF elimination goals an integrated morbidity management and disability prevention (MMDP) guideline and a burden assessment programme has also been developed; MMDP protocols and a hydrocoele surgical handbook produced for country-wide use. In Ethiopia, almost all LF endemic districts are co-endemic with malaria and vector control aspects of the activities are conducted in the context of malaria programme as the vectors for both diseases are mosquitoes. In order to monitor the elimination, 11 sentinel and spot-check sites have been established and baseline information has been collected. Although significant achievements have been achieved in the scale up of the LF elimination programme, there is still a need to strengthen operational research to generate programme-relevant evidence, to increase access to morbidity management services, and to improve monitoring and evaluation of the LF programme. However, the current status of implementation of the LF national programme indicates that Ethiopia is poised to achieve the 2020 goal of elimination of LF. Nevertheless, to achieve this goal, high and sustained treatment coverage and strong monitoring and evaluation of the programme are essential. PMID:28878429

  5. Lymphatic Stomata in the Adult Human Pulmonary Ligament

    PubMed Central

    Miura, Masahiro; Iobe, Hiroaki; Kudo, Tomoo; Shimazu, Yoshihito; Aoba, Takaaki; Okudela, Koji; Nagahama, Kiyotaka; Sakamaki, Kentaro; Yoshida, Maki; Nagao, Toshitaka; Nakaya, Takeo; Kurata, Atsushi; Ohtani, Osamu

    2015-01-01

    Abstract Background: Lymphatic stomata are small lymphatic openings in the serosal membrane that communicate with the serosal cavity. Although these stomata have primarily been studied in experimental mammals, little is known concerning the presence and properties of lymphatic stomata in the adult human pleura. Thus, adult human pleurae were examined for the presence or absence of lymphatic stomata. Methods and Results: A total of 26 pulmonary ligaments (13 left and 13 right) were obtained from 15 adult human autopsy cases and examined using electron and light microscopy. The microscopic studies revealed the presence of apertures fringed with D2-40-positive, CD31-positive, and cytokeratin-negative endothelial cells directly communicating with submesothelial lymphatics in all of the pulmonary ligaments. The apertures' sizes and densities varied from case to case according to the serial tissue section. The medians of these aperture sizes ranged from 2.25 to 8.75 μm in the left pulmonary ligaments and from 2.50 to 12.50 μm in the right pulmonary ligaments. The densities of the apertures ranged from 2 to 9 per mm2 in the left pulmonary ligaments and from 2 to 18 per mm2 in the right pulmonary ligaments. However, no significant differences were found regarding the aperture size (p=0.359) and density (p=0.438) between the left and the right pulmonary ligaments. Conclusions: Our study revealed that apertures exhibit structural adequacy as lymphatic stomata on the surface of the pulmonary ligament, thereby providing evidence that lymphatic stomata are present in the adult human pleura. PMID:25526320

  6. Expression of lymphatic markers during avian and mouse cardiogenesis

    PubMed Central

    Karunamuni, Ganga; Yang, Ke; Doughman, Yong Qiu; Wikenheiser, Jamie; Bader, David; Barnett, Joey; Austin, Anita; Parsons-Wingerter, Patricia; Watanabe, Michiko

    2013-01-01

    The adult heart has been reported to have an extensive lymphatic system, yet the development of this important system during cardiogenesis is still largely unexplored. The nuclear-localized transcription factor Prox-1 identified a sheet of Prox-1-positive cells on the developing aorta and pulmonary trunk in avian and murine embryos just prior to septation of the four heart chambers. The cells coalesced into a branching lymphatic network that spread within the epicardium to cover the heart. These vessels eventually expressed the lymphatic markers LYVE-1, VEGFR-3, and podoplanin. Before the Prox-1-positive cells were detected in the mouse epicardium, LYVE-1, a homologue of the CD44 glycoprotein, was primarily expressed in individual epicardial cells. Similar staining patterns were observed for CD44 in avian embryos. The proximity of these LYVE-1/CD44-positive mesenchymal cells to Prox-1-positive vessels suggests that they may become incorporated into the lymphatics. Unexpectedly, we detected LYVE-1/PECAM/VEGFR-3-positive vessels within the embryonic and adult myocardium which remained Prox-1/podoplanin-negative. Lymphatic markers were surprisingly found in adult rat and embryonic mouse epicardial cell lines, with Prox-1 also exhibiting nuclear-localized expression in primary cultures of embryonic avian epicardial cells. Our data identified three types of cells in the embryonic heart expressing lymphatic markers: (1) Prox-1-positive cells from an extracardiac source that migrate within the serosa of the outflow tract into the epicardium of the developing heart, (2) individual LYVE-1-positive cells in the epicardium that may be incorporated into the Prox-1-positive lymphatic vasculature, and (3) LYVE-1-positive cells/vessels in the myocardium that do not become Prox-1-positive even in the adult heart. PMID:19938109

  7. Immunolocalization of lymphatic vessels in human fetal knee joint tissues.

    PubMed

    Melrose, James; Little, Christopher B

    2010-08-01

    We immunolocalized lymphatic and vascular blood vessels in 12- and 14-week-old human fetal knee joint tissues using a polyclonal antibody to a lymphatic vascular endothelium specific hyaluronan receptor (LYVE-1) and a monoclonal antibody to podoplanin (mAb D2-40). A number of lymphatic vessels were identified in the stratified connective tissues surrounding the cartilaginous knee joint femoral and tibial rudiments. These tissues also contained small vascular vessels with entrapped red blood cells which were imaged using Nomarsky DIC microscopy. Neither vascular nor lymphatic vessels were present in the knee joint cartilaginous rudiments. The menisci in 12-week-old fetal knees were incompletely demarcated from the adjacent tibial and femoral cartilaginous rudiments which was consistent with the ongoing joint cavitation process at the femoral-tibial junction. At 14 weeks of age the menisci were independent structural entities; they contained a major central blood vessel containing red blood cells and numerous communicating vessels at the base of the menisci but no lymphatic vessels. In contrast to the 12-week-old menisci, the 14-week meniscal rudiments contained abundant CD-31 and CD-34 positive but no lymphatic vessels. Isolated 14-week-old meniscal cells also were stained with the CD-31 and CD 34 antibodies; CD-68 +ve cells, also abundant in the 14-week-old menisci, were detectable to a far lesser degree in the 12-week menisci and were totally absent from the femoral and tibial rudiments. The distribution of lymphatic vessels and tissue macrophages in the fetal joint tissues was consistent with their roles in the clearance of metabolic waste and extracellular matrix breakdown products arising from the rapidly remodelling knee joint tissues.

  8. The history of sentinel node biopsy in head and neck cancer: From visualization of lymphatic vessels to sentinel nodes.

    PubMed

    de Bree, Remco; Nieweg, Omgo E

    2015-09-01

    The aim of this report is to describe the history of sentinel node biopsy in head and neck cancer. Sentinel node biopsy is a minimally invasive technique to select patients for treatment of metastatic lymph nodes in the neck. Although this procedure has only recently been accepted for early oral cancer, the first studies on visualization of the cervical lymphatic vessels were reported in the 1960s. In the 1980s mapping of lymphatic drainage from specific head and neck sites was introduced. Sentinel node biopsy was further developed in the 1990s and after validation in this century the procedure is routinely performed in early oral cancer in several head and neck centers. New techniques may improve the accuracy of sentinel node biopsy further, particularly in difficult subsites like the floor of mouth. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2016-03-01

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

  10. New model of macrophage acquisition of the lymphatic endothelial phenotype.

    PubMed

    Hall, Kelly L; Volk-Draper, Lisa D; Flister, Michael J; Ran, Sophia

    2012-01-01

    Macrophage-derived lymphatic endothelial cell progenitors (M-LECPs) contribute to new lymphatic vessel formation, but the mechanisms regulating their differentiation, recruitment, and function are poorly understood. Detailed characterization of M-LECPs is limited by low frequency in vivo and lack of model systems allowing in-depth molecular analyses in vitro. Our goal was to establish a cell culture model to characterize inflammation-induced macrophage-to-LECP differentiation under controlled conditions. Time-course analysis of diaphragms from lipopolysaccharide (LPS)-treated mice revealed rapid mobilization of bone marrow-derived and peritoneal macrophages to the proximity of lymphatic vessels followed by widespread (∼50%) incorporation of M-LECPs into the inflamed lymphatic vasculature. A differentiation shift toward the lymphatic phenotype was found in three LPS-induced subsets of activated macrophages that were positive for VEGFR-3 and many other lymphatic-specific markers. VEGFR-3 was strongly elevated in the early stage of macrophage transition to LECPs but undetectable in M-LECPs prior to vascular integration. Similar transient pattern of VEGFR-3 expression was found in RAW264.7 macrophages activated by LPS in vitro. Activated RAW264.7 cells co-expressed VEGF-C that induced an autocrine signaling loop as indicated by VEGFR-3 phosphorylation inhibited by a soluble receptor. LPS-activated RAW264.7 macrophages also showed a 68% overlap with endogenous CD11b(+)/VEGFR-3(+) LECPs in the expression of lymphatic-specific genes. Moreover, when injected into LPS- but not saline-treated mice, GFP-tagged RAW264.7 cells massively infiltrated the inflamed diaphragm followed by integration into 18% of lymphatic vessels. We present a new model for macrophage-LECP differentiation based on LPS activation of cultured RAW264.7 cells. This system designated here as the "RAW model" mimics fundamental features of endogenous M-LECPs. Unlike native LECPs, this model is

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

    PubMed

    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

  12. Lymphatic system: a prospective area for advanced targeting of particulate drug carriers.

    PubMed

    Singh, Indu; Swami, Rajan; Khan, Wahid; Sistla, Ramakrishna

    2014-02-01

    The lymphatic system has a critical role in the immune system's recognition and response to disease and it is an additional circulatory system throughout the entire body. Extensive multidisciplinary investigations have been carried out in the area of lymphatic delivery, and lymphatic targeting has attracted a lot of attention for providing preferential chemotherapy and improving bioavailability of drugs that undergo hepatic first-pass metabolism. This review focuses on progress in the field of lymphatic therapeutics and diagnosis. Moreover, the anatomy and physiology of the lymphatic system, particulate drug carriers and different physicochemical parameters of both modified and unmodified particulate drug carriers and their effect on lymphatic targeting are addressed. Particulate drug carriers have encouraged lymphatic targeting, but there are still challenges in targeting drugs and bioactives to specific sites, maintaining desired action and crossing all the physiological barriers. Lymphatic therapy using drug-encapsulated lipid carriers, especially liposomes and solid lipid nanoparticles, emerges as a new technology to provide better penetration into the lymphatics where residual disease exists. Size is the most important criteria when designing nanocarriers for targeting lymphatic vessels as the transportation of these particles into lymphatic vessels is size dependent. By increasing our understanding of lymphatic transport and uptake, and the role of lymphatics in various diseases, we can design new therapeutics for effective disease control.

  13. High relative density of lymphatic vessels predicts poor survival in tongue squamous cell carcinoma.

    PubMed

    Seppälä, Miia; Pohjola, Konsta; Laranne, Jussi; Rautiainen, Markus; Huhtala, Heini; Renkonen, Risto; Lemström, Karl; Paavonen, Timo; Toppila-Salmi, Sanna

    2016-12-01

    Tongue cancer has a poor prognosis due to its early metastasis via lymphatic vessels. The present study aimed at evaluating lymphatic vessel density, relative density of lymphatic vessel, and diameter of lymphatic vessels and its predictive role in tongue cancer. Paraffin-embedded tongue and lymph node specimens (n = 113) were stained immunohistochemically with a polyclonal antibody von Willebrand factor, recognizing blood and lymphatic endothelium and with a monoclonal antibody podoplanin, recognizing lymphatic endothelium. The relative density of lymphatic vessels was counted by dividing the mean number of lymphatic vessels per microscopic field (podoplanin) by the mean number of all vessels (vWf) per microscopic field. The high relative density of lymphatic vessels (≥80 %) was associated with poor prognosis in tongue cancer. The relative density of lymphatic vessels predicted poor prognosis in the group of primary tumor size T1-T2 and in the group of non-metastatic cancer. The lymphatic vessel density and diameter of lymphatic vessels were not associated with tongue cancer survival. The relative density of lymphatic vessels might have clinically relevant prognostic impact. Further studies with increased number of patients are needed.

  14. Elimination of Lymphatic Filariasis in The Gambia

    PubMed Central

    Rebollo, Maria P.; Sambou, Sana Malang; Thomas, Brent; Biritwum, Nana-Kwadwo; Jaye, Momodou C.; Kelly-Hope, Louise; Escalada, Alba Gonzalez; Molyneux, David H.; Bockarie, Moses J.

    2015-01-01

    Background The prevalence of Wuchereria bancrofti, which causes lymphatic filariasis (LF) in The Gambia was among the highest in Africa in the 1950s. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration (MDA). The decline in prevalence was partly attributed to a significant reduction in mosquito density through the widespread use of insecticidal nets. Based on findings elsewhere that vector control alone can interrupt LF, we asked the question in 2013 whether the rapid scale up in the use of insecticidal nets in The Gambia had interrupted LF transmission. Methodology/Principal Finding We present here the results of three independently designed filariasis surveys conducted over a period of 17 years (1997–2013), and involving over 6000 subjects in 21 districts across all administrative divisions in The Gambia. An immunochromatographic (ICT) test was used to detect W. bancrofti antigen during all three surveys. In 2001, tests performed on stored samples collected between 1997 and 2000, in three divisions, failed to show positive individuals from two divisions that were previously highly endemic for LF, suggesting a decline towards extinction in some areas. Results of the second survey conducted in 2003 showed that LF was no longer endemic in 16 of 21 districts surveyed. The 2013 survey used a WHO recommended LF transmission verification tool involving 3180 6–7 year-olds attending 60 schools across the country. We demonstrated that transmission of W. bancrofti has been interrupted in all 21 districts. Conclusions We conclude that LF transmission may have been interrupted in The Gambia through the extensive use of insecticidal nets for malaria control for decades. The growing evidence for the impact of malaria vector control activities on parasite transmission has been endorsed by WHO through a position statement in 2011 on integrated vector management to control malaria and LF. PMID

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

    PubMed

    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.

  16. Structural and functional features of central nervous system lymphatics

    PubMed Central

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

    2015-01-01

    One of the characteristics of the CNS is the lack of a classical lymphatic drainage system. Although it is now accepted that the CNS undergoes constant immune surveillance that takes place within the meningeal compartment1–3, the mechanisms governing the entrance and exit of immune cells from the CNS remain poorly understood4–6. 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 CSF, 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 CNS. The discovery of the CNS lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and shed new light on the etiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction. PMID:26030524

  17. Immunomodulatory roles of lymphatic vessels in cancer progression.

    PubMed

    Swartz, Melody A

    2014-08-01

    Lymphatic vessels in the tumor microenvironment are known to foster tumor metastasis in many cancers, and they can undergo activation, hyperplasia, and lymphangiogenesis in the tumor microenvironment and in the tumor-draining lymph node. The mechanism underlying this correlation was originally considered as lymphatic vessels providing a physical route for tumor cell dissemination, but recent studies have highlighted new roles of the lymphatic endothelium in regulating host immunity. These include indirectly suppressing T-cell function by secreting immunosuppressive factors and inhibiting dendritic cell (DC) maturation, as well as directly driving T-cell tolerance by antigen presentation in the presence of inhibitory ligands. Furthermore, lymphatic endothelium scavenges and regulates transendothelial transport actively, controlling the sustained delivery of lymph-borne antigens from chronically inflamed tissues to draining lymph nodes where immature DCs, in the absence of danger signals, along with lymph node stromal cells present these antigens to T cells for maintenance of peripheral tolerance to self-antigens, a mechanism that may be hijacked by some tumors. This Masters of Immunology primer aims to present an overview of research in this area and highlight emerging evidence that suggests lymphatic vessels, and lymphangiogenesis, play important immunomodulatory roles in the tumor microenvironment. ©2014 American Association for Cancer Research.

  18. Recent advances in standards for collaborative Digital Anatomic Pathology

    PubMed Central

    2011-01-01

    Context Collaborative Digital Anatomic Pathology refers to the use of information technology that supports the creation and sharing or exchange of information, including data and images, during the complex workflow performed in an Anatomic Pathology department from specimen reception to report transmission and exploitation. Collaborative Digital Anatomic Pathology can only be fully achieved using medical informatics standards. The goal of the international integrating the Healthcare Enterprise (IHE) initiative is precisely specifying how medical informatics standards should be implemented to meet specific health care needs and making systems integration more efficient and less expensive. Objective To define the best use of medical informatics standards in order to share and exchange machine-readable structured reports and their evidences (including whole slide images) within hospitals and across healthcare facilities. Methods Specific working groups dedicated to Anatomy Pathology within multiple standards organizations defined standard-based data structures for Anatomic Pathology reports and images as well as informatic transactions in order to integrate Anatomic Pathology information into the electronic healthcare enterprise. Results The DICOM supplements 122 and 145 provide flexible object information definitions dedicated respectively to specimen description and Whole Slide Image acquisition, storage and display. The content profile “Anatomic Pathology Structured Report” (APSR) provides standard templates for structured reports in which textual observations may be bound to digital images or regions of interest. Anatomic Pathology observations are encoded using an international controlled vocabulary defined by the IHE Anatomic Pathology domain that is currently being mapped to SNOMED CT concepts. Conclusion Recent advances in standards for Collaborative Digital Anatomic Pathology are a unique opportunity to share or exchange Anatomic Pathology structured

  19. Recent advances in standards for Collaborative Digital Anatomic Pathology.

    PubMed

    Daniel, Christel; Macary, François; Rojo, Marcial García; Klossa, Jacques; Laurinavičius, Arvydas; Beckwith, Bruce A; Della Mea, Vincenzo

    2011-03-30

    Collaborative Digital Anatomic Pathology refers to the use of information technology that supports the creation and sharing or exchange of information, including data and images, during the complex workflow performed in an Anatomic Pathology department from specimen reception to report transmission and exploitation. Collaborative Digital Anatomic Pathology can only be fully achieved using medical informatics standards. The goal of the international integrating the Healthcare Enterprise (IHE) initiative is precisely specifying how medical informatics standards should be implemented to meet specific health care needs and making systems integration more efficient and less expensive. To define the best use of medical informatics standards in order to share and exchange machine-readable structured reports and their evidences (including whole slide images) within hospitals and across healthcare facilities. Specific working groups dedicated to Anatomy Pathology within multiple standards organizations defined standard-based data structures for Anatomic Pathology reports and images as well as informatic transactions in order to integrate Anatomic Pathology information into the electronic healthcare enterprise. The DICOM supplements 122 and 145 provide flexible object information definitions dedicated respectively to specimen description and Whole Slide Image acquisition, storage and display. The content profile "Anatomic Pathology Structured Report" (APSR) provides standard templates for structured reports in which textual observations may be bound to digital images or regions of interest. Anatomic Pathology observations are encoded using an international controlled vocabulary defined by the IHE Anatomic Pathology domain that is currently being mapped to SNOMED CT concepts. Recent advances in standards for Collaborative Digital Anatomic Pathology are a unique opportunity to share or exchange Anatomic Pathology structured reports that are interoperable at an international

  20. [Guepar anatomical trapeziometacarpal prosthesis].

    PubMed

    Masmejean, E; Alnot, J Y; Chantelot, C; Beccari, R

    2003-02-01

    A choice of surgical techniques of treatment for trapeziometacarpal (TMC) Osteo-Arthritis (OA) have been described. Total arthroplasty is often used, especially in France. Many papers have been published, presenting various prostheses. In English literature, this device is not thoroughly used. [corrected] Guepar total arthroplasty is a cemented ball-in-socket prosthesis in metal-polyethylene. It includes an anatomical stem available in 4 sizes. After failure of the conservative treatment, total arthroplasty must be reserved to elderly patients, painful, with OA Dell stage III or IV aligned or not. The trapezial height must be sufficient. The authors reports the preliminary results of 64 Guepar prostheses, anatomical new design, implanted since 1995. Results of 63 prostheses are presented. One removal had been necessary at 9 months for metacarpal loosening (failure). Mean follow-up was 29 months. Clinical results were judged excellent or good in all cases. Regarding the radiological results, no modifications has been observed in 56 cases. Six radiolucent lines without displacement of the implants has been noted, with no incidence on clinical results. In one case, a metacarpal stem penetrated into the medullary canal in the bone axis but without any clinical modifications. Clinically, in addition to pain relief, trapeziometacarpal prosthesis allows to preserve the first column length and to obtain a better opposition of the thumb as well of a better thumb-digits pinch, compared after trapeziectomy. Radiologically, as for total hip arthroplasty, the exact adaptation of an anatomical stem (new design) to the canal has probably a better prognosis at long term follow-up.

  1. Anatomy and development of the cardiac lymphatic vasculature: Its role in injury and disease.

    PubMed

    Norman, Sophie; Riley, Paul R

    2016-04-01

    Lymphatic vessels are present throughout the entire body in all mammals and function to regulate tissue fluid balance, lipid transport and survey the immune system. Despite the presence of an extensive lymphatic plexus within the heart, until recently the importance of the cardiac lymphatic vasculature and its origins were unknown. Several studies have described the basic anatomy of the developing cardiac lymphatic vasculature and more recently the detailed development of the murine cardiac lymphatics has been documented, with important insight into their cellular sources during embryogenesis. In this review we initially describe the development of systemic lymphatic vasculature, to provide the background for a comparative description of the spatiotemporal development of the cardiac lymphatic vessels, including detail of both canonical, typically venous, and noncanonical (hemogenic endothelium) cellular sources. Subsequently, we address the response of the cardiac lymphatic network to myocardial infarction (heart attack) and the therapeutic potential of targeting cardiac lymphangiogenesis. © 2015 Wiley Periodicals, Inc.

  2. Near-infrared fluorescence lymphatic imaging of Klippel-Trénaunay syndrome.

    PubMed

    Rasmussen, John C; Zvavanjanja, Rodrick C; Aldrich, Melissa B; Greives, Matthew R; Sevick-Muraca, Eva M

    2017-07-01

    The relationship between lymphatic and venous malformations in Klippel-Trénaunay syndrome is difficult to assess. Herein the authors describe near-infrared fluorescence lymphatic imaging to assess the lymphatics of a subject with a large port-wine stain and right leg edema. Although lymphatic vessels in the medial, affected knee appeared dilated and perhaps tortuous, no definitive abnormal lymphatic pooling or propulsion was observed. The lymphatics in the affected limb were well defined but less numerous than in the contralateral limb, and active, contractile function was observed in all vessels. As demonstrated, near-infrared fluorescence lymphatic imaging enables the clinical assessment of lymphatics in lymphovenous malformations. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  3. From sewer to saviour - targeting the lymphatic system to promote drug exposure and activity.

    PubMed

    Trevaskis, Natalie L; Kaminskas, Lisa M; Porter, Christopher J H

    2015-11-01

    The lymphatic system serves an integral role in fluid homeostasis, lipid metabolism and immune control. In cancer, the lymph nodes that drain solid tumours are a primary site of metastasis, and recent studies have suggested intrinsic links between lymphatic function, lipid deposition, obesity and atherosclerosis. Advances in the current understanding of the role of the lymphatics in pathological change and immunity have driven the recognition that lymph-targeted delivery has the potential to transform disease treatment and vaccination. In addition, the design of lymphatic delivery systems has progressed from simple systems that rely on passive lymphatic access to sophisticated structures that use nanotechnology to mimic endogenous macromolecules and lipid conjugates that 'hitchhike' onto lipid transport processes. Here, we briefly summarize the lymphatic system in health and disease and the varying mechanisms of lymphatic entry and transport, as well as discussing examples of lymphatic delivery that have enhanced therapeutic utility. We also outline future challenges to effective lymph-directed therapy.

  4. Down-regulation of polycystin in lymphatic malformations: possible role in the proliferation of lymphatic endothelial cells.

    PubMed

    Ren, Jian-Gang; Xia, Hou-Fu; Yang, Jie-Gang; Zhu, Jun-Yi; Zhang, Wei; Chen, Gang; Zhao, Ji-Hong; Sun, Yan-Fang; Zhao, Yi-Fang

    2017-07-01

    Lymphatic malformations (LMs) are composed of aberrant lymphatic vessels and regarded as benign growths of the lymphatic system. Recent studies have demonstrated that the mutant embryos of PKD1 and PKD2, encoding polycystin-1 (PC-1) and polycystin-2 (PC-2), respectively, result in aberrant lymphatic vessels similar to those observed in LMs. In this study, for the first time, we investigated PC-1 and PC-2 expression and assessed their roles in the development of LMs. Our results demonstrated that PC-1 and PC-2 gene and protein expressions were obviously decreased in LMs compared with normal skin tissues. In addition, the expression of phosphorylated ERK but not total ERK was up-regulated in LMs and negatively correlated with the expression of PC-1 and PC-2. Moreover, up-regulation of Ki67 was detected in LMs and positively correlated with ERK phosphorylation levels. Furthermore, cluster analysis better reflected close correlation between these signals. All of the above results provided strong evidence suggesting that the hyperactivation of the ERK pathway may be caused by down-regulation of PC-1 and PC-2 in LMs, contributing to increased proliferation of lymphatic endothelial cells in LMs. Our present study sheds light on novel potential mechanisms involved in LMs and may help to explore novel treatments for LMs. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The Lymphatic Endothelial mCLCA1 Antibody Induces Proliferation and Growth of Lymph Node Lymphatic Sinuses

    PubMed Central

    Jordan-Williams, Kimberly L.; Ramanujam, Neela; Farr, Andrew G.

    2016-01-01

    Lymphocyte- and leukocyte-mediated lymph node (LN) lymphatic sinus growth (lymphangiogenesis) is involved in immune responses and in diseases including cancer and arthritis. We previously discovered a 10.1.1 Ab that recognizes the lymphatic endothelial cell (LEC) surface protein mCLCA1, which is an interacting partner for LFA1 and Mac-1 that mediates lymphocyte adhesion to LECs. Here, we show that 10.1.1 Ab treatment specifically induces LEC proliferation, and influences migration and adhesion in vitro. Functional testing by injection of mice with 10.1.1 Ab but not control hamster Abs identified rapid induction of LN LEC proliferation and extensive lymphangiogenesis within 23 h. BrdU pulse-chase analysis demonstrated incorporation of proliferating LYVE-1-positive LEC into the growing medullary lymphatic sinuses. The 10.1.1 Ab-induced LN remodeling involved coordinate increases in LECs and also blood endothelial cells, fibroblastic reticular cells, and double negative stroma, as is observed during the LN response to inflammation. 10.1.1 Ab-induced lymphangiogenesis was restricted to LNs, as mCLCA1-expressing lymphatic vessels of the jejunum and dermis were unaffected by 23 h 10.1.1 Ab treatment. These findings demonstrate that 10.1.1 Ab rapidly and specifically induces proliferation and growth of LN lymphatic sinuses and stroma, suggesting a key role of mCLCA1 in coordinating LN remodeling during immune responses. PMID:27224029

  6. Mechanosensitive β-catenin signaling regulates lymphatic vascular development

    PubMed Central

    Cha, Boksik; Srinivasan, R. Sathish

    2016-01-01

    The Wnt/β-catenin signaling is an evolutionarily conserved pathway that plays a pivotal role in embryonic development and adult homeostasis. However, we have limited information about the involvement of Wnt/β-catenin signaling in the lymphatic vascular system that regulates fluid homeostasis by absorbing interstitial fluid and returning it to blood circulation. In this recent publication we report that canonical Wnt/β-catenin signaling is highly active and critical for the formation of lymphovenus valves (LVVs) and lymphatic valves (LVs). β-catenin directly associates with the regulatory elements of the lymphedema-associated transcription factor, FOXC2 and activates its expression in an oscillatory shear stress (OSS)-dependent manner. The phenotype of β-catenin null embryos was rescued by FOXC2 overexpression. These results suggest that Wnt/β-catenin signaling is a mechanotransducer that links fluid force with lymphatic vascular development. [BMB Reports 2016; 49(8): 403-404] PMID:27418286

  7. Search for lymphatic drainage of the monkey orbit

    SciTech Connect

    McGetrick, J.J.; Wilson, D.G.; Dortzbach, R.K.; Kaufman, P.L.; Lemke, B.N.

    1989-02-01

    Colloid solutions of technetium Tc-99m and india ink injected into the retrobulbar space of the cynomolgus monkey outside the extraocular muscle cone were removed from the orbit by the lymphatic vessels of the conjunctiva and eyelids and were then concentrated within the lymph nodes that drained the conjunctival and eyelid areas. Colloid solutions injected into the retrobulbar space inside the extraocular muscle cone did not reach the conjunctiva and did not collect in any lymph nodes over a 24-hour period. Within the orbit, the injected colloids spread along the planes of the connective-tissue septa. No lymphatic vessels were identified within the orbits posterior to the conjunctiva. Small amounts of india ink left the posterior orbit and ultimately entered the contralateral orbit. This posterior pathway did not lead to lymphatic vessels or lymph nodes and therefore does not appear to represent a prelymphatic pathway.

  8. ACKR2: An Atypical Chemokine Receptor Regulating Lymphatic Biology

    PubMed Central

    Bonavita, Ornella; Mollica Poeta, Valeria; Setten, Elisa; Massara, Matteo; Bonecchi, Raffaella

    2017-01-01

    The lymphatic system plays an important role in the induction of the immune response by transporting antigens, inflammatory mediators, and leukocytes from peripheral tissues to draining lymph nodes. It is emerging that lymphatic endothelial cells (LECs) are playing an active role in this context via the expression of chemokines, inflammatory mediators promoting cell migration, and chemokine receptors. Particularly, LECs express atypical chemokine receptors (ACKRs), which are unable to promote conventional signaling and cell migration while they are involved in the regulation of chemokine availability. Here, we provide a summary of the data on the role of ACKR2 expressed by lymphatics, indicating an essential role for this ACKRs in the regulation of the inflammation and the immune response in different pathological conditions, including infection, allergy, and cancer. PMID:28123388

  9. Lymphatic vessels of the human dental pulp in different conditions.

    PubMed

    Marchetti, C; Poggi, P; Calligaro, A; Casasco, A

    1992-09-01

    The characteristics of the lymphatic vessel endothelial wall have been investigated in human normal and inflamed dental pulps. In normal pulps the endothelial wall is characterized by the presence of micropinocytotic vesicles and intraparietal channels. In the inflamed pulpal tissue, where an increase in interstitial fluid pressure occurs, the distended endothelial wall presents open junctions between endothelial cells and the openings of the intraparietal channels. Moreover the micropinocytotic vesicles disappear. The cytoplasm of the endothelial cells is characterized by the presence of numerous Weibel-Palade bodies, which increase in number in the dilated vessels. In the fibrillar apparatus surrounding the lymphatic vessel wall collagen fibrils are the prevalent component, while elastic fibers are not present. The different morphological properties of the lymphatic vessels are compared and discussed with regard to the variation of the functional conditions of the tissue.

  10. Anatomic hemispherectomy: historical perspective.

    PubMed

    Bahuleyan, Biji; Robinson, Shenandoah; Nair, Ajith Rajappan; Sivanandapanicker, Jyothish L; Cohen, Alan R

    2013-01-01

    The history of surgical treatment for hemispheric epilepsy is rich with colorful twists and turns. The authors trace the evolution of the surgical treatment of hemispheric epilepsy from radical anatomic resections to current less invasive disconnection procedures. Anatomic hemispherectomy (AH) was first described by Dandy in 1928 as a treatment for gliomas. The first report of this technique to control seizures was by McKenzie in 1938. AH gained wide popularity but began to fall out of favor after the description of superficial cerebral hemosiderosis in 1966. To reduce the morbidity and mortality associated with AH, Rasmussen introduced functional hemispherectomy in 1974. The technique of hemispherotomy was introduced in the 1990 s to minimize the extent of brain removal while maximizing the white matter disconnections. Thus, surgery for hemispheric epilepsy has undergone dramatic transformation since the technique was first introduced. Less invasive techniques have been developed to reduce surgical morbidity. Although optimal seizure control is best achieved with radical AH, the newer less invasive disconnection techniques appear to achieve near-comparable postoperative seizure control with a significantly lower rate of complications.

  11. Topography of Lymphatic Markers in Human Iris and Ciliary Body.

    PubMed

    Kaser-Eichberger, Alexandra; Schrödl, Falk; Trost, Andrea; Strohmaier, Clemens; Bogner, Barbara; Runge, Christian; Motloch, Karolina; Bruckner, Daniela; Laimer, Martin; Schlereth, Simona L; Heindl, Ludwig M; Reitsamer, Herbert A

    2015-07-01

    Reports of lymphatics in the anterior human uvea are contradictory. This might be caused due to a certain topography, which has not been considered yet. Therefore, here we systematically analyze iris and adjacent ciliary body with immunohistochemistry by combining various lymphatic markers. Human iris and ciliary body were obtained from cornea donors and prepared for cryosectioning. Cross sections of tissue blocks at 12/3/6/9 o'clock position and at corresponding intersections (1:30/4:30/7:30/10:30) were processed for immunohistochemistry of LYVE-1, PDPN, PROX1, FOXC2, VEGFR3, and CCL21, and when necessary, these lymphatic markers were combined with CD31, α-smooth muscle-actin, CD68, and 4',6-diamidino-2 phenylindole dihydrochloride (DAPI). Double, triple, and quadruple marker combinations were documented using confocal microscopy. Numerous podoplanin+ cells were mainly located at the anterior border of the iris while LYVE-1+ cells were distributed throughout the nonpigmented part. Both cell populations were PROX1/FOXC2/CCL21/VEGFR3-. Blood vessels, iris smooth muscles, and individual cells were VEGFR3+. While PDPN+ cells were rarely detected posteriorly of the iris root, many LYVE-1+ cells were present within the ciliary body muscle and villi. Within the muscle, occasionally PDPN+ vessel-like structures were detectable, but these were never colocalized with LYVE-1. Similar vessel-like structures were VEGFR3+/PROX1-/CCL21-, but CD31+. Further, ciliary muscle fibers and ciliary epithelium were immunoreactive for VEGFR3/CCL21, but were LYVE-1/PDPN-. A certain topography of structures at the various uvea-positions investigated was not obvious. The majority of LYVE-1+ cells displayed immunoreactivity for CD68. Lymphatic vessels colocalizing for at least two lymphatic markers were not detectable. Therefore, if present, putative lymphatic channels of the anterior uvea might display a different marker panel than generally presumed.

  12. Synthesis of a novel polyamidoamine dendrimer conjugating with alkali blue as a lymphatic tracer and study on the lymphatic targeting in vivo.

    PubMed

    Yang, Rui; Xia, Suxia; Ye, Tiantian; Yao, Jianhua; Zhang, Ruizhi; Wang, Shujun; Wang, Siling

    2016-09-01

    In this study, a novel lymphatic tracer polyamidoamin-alkali blue (PAMAM-AB) was synthesized in order to evaluate the intra-lymphatic targeting ability and lymphatic tropism of PAMAM-AB after subcutaneous administration. UV-Vis, FT-IR, NMR and HPLC characterization were performed to prove the successful synthesis of PAMAM-AB. The calculated AB payload of PAMAM-AB conjugate was seven per dendrimer molecule (27.16% by weight). Hydrolysis stability of PAMAM-AB in vitro was evaluated, which was stable in PBS and human plasma. Lymphatic tracing were studied to determine the blue-stained intensity of PAMAM-AB in right popliteral lymph nodes (PLNs), iliac lymph nodes (ILNs) and para-aortic lymph nodes (PALNs) after subcutaneous administration. The pharmacokinetics and biodistribution of PAMAM-AB in mice were investigated. PLNs, ILNs and PALNs could be obviously blue-stained within 10 min after PAMAM-AB administration, and displayed a more rapid lymphatic absorption, a higher AUC value in lymph nodes and a longer lymph nodes residence time compared with methylene blue solution (MB-S), MB water-in-oil microemulsion (MB-ME), MB multiple microemulsion (MB-MME). Enhanced lymphatic drainage from the injection site and uptake into lymph of PAMAM-AB indicated that PAMAM-AB possesses the double function of lymphatic tracing and lymphatic targeting, and suggested the potential for the development of lymphatic targeting vectors or as a lymphatic tracer in its own right.

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

    PubMed

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

    2016-09-01

    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. Recent developments in high-resolution imaging techniques have prompted a reassessment of the relationships between the CNS and the immune system. This review will take these developments into account in describing our present understanding of the anatomical connections of the CNS fluid drainage pathways towards regional lymph nodes and our current concept of immune cell trafficking into the CNS during immunosurveillance and neuroinflammation. Cerebrospinal fluid (CSF) and interstitial fluid are the two major components that drain from the CNS to regional lymph nodes. CSF drains via lymphatic vessels and appears to carry antigen-presenting cells. Interstitial fluid from the CNS parenchyma, on the other hand, drains to lymph nodes via narrow and restricted basement membrane pathways within the walls of cerebral capillaries and arteries that do not allow traffic of antigen-presenting cells. Lymphocytes targeting the CNS enter by a two-step process entailing receptor-mediated crossing of vascular endothelium and enzyme-mediated penetration of the glia limitans that covers the CNS. The contribution of the pathways into and out of the CNS as initiators or contributors to neurological disorders, such as multiple sclerosis and Alzheimer's disease, will be discussed. Furthermore, we propose a clear nomenclature allowing improved precision when describing the CNS-specific communication pathways with the immune system.

  14. Percutaneous sclerotherapy of pediatric lymphatic malformations: experience and outcomes according to the agent used.

    PubMed

    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.

  15. Thoracic involvement in generalised lymphatic anomaly (or lymphangiomatosis).

    PubMed

    Luisi, Francesca; Torre, Olga; Harari, Sergio

    2016-06-01

    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. Copyright ©ERS 2016.

  16. Lack of functioning intratumoral lymphatics in colon and pancreas cancer tissue.

    PubMed

    Olszewski, Waldemar L; Stanczyk, Marek; Gewartowska, Magdalena; Domaszewska-Szostek, Anna; Durlik, Marek

    2012-09-01

    There are controversial views as to whether intratumoral or peritumoral lymphatics play a dominant role in the metastatic process. Most clinical observations originate from studies of colon cancer. Colon contains mucosa and submucosa rich in lymphatics and with high lymph formation rate. This seems to be a prerequisite for easy metastasis of cancer cells to regional lymph nodes. However, there are other tissues as pancreas with a rudimentary lymphatic network where cancer metastasis formation is as intensive as in colon cancer. This contradicts the common notion that intratumor lymphatics play major role in metastases. We visualized interstitial space and lymphatics in the central and peripheral regions of colon and pancreas tumors using the color stereoscopic lymphography and simultaneously immunohistochemical performed stainings specific for lymphatic and blood endothelial cells. The density of open and compressed lymphatic and blood vessels was measured in the tumor core and edge. There were very few lymphatics in the colon and pancreas tumor core but numerous minor fluid "lakes" with no visible connection to the peritumoral lymphatics. Lining of "lakes" did not express molecular markers specific for lymphatic endothelial cells. Dense connective tissue surrounding tumor foci did not contain lymphatics. Peritumoral lymphatics were irregularly distributed in both types of tumor and only sporadically contained cells that might be tumor cells. Similar lymphoscintigraphic and histological pictures were seen in colon and pancreas cancer despite of different structure of both tissues. This suggests a uniform reaction of tissues to the growing cancer irrespective of the affected organ.

  17. 38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... and lymphatic systems. 4.117 Section 4.117 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Hemic and Lymphatic Systems § 4.117 Schedule of ratings—hemic and lymphatic systems. Rating 7700Anemia, hypochromic-microcytic...

  18. 38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and lymphatic systems. 4.117 Section 4.117 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Hemic and Lymphatic Systems § 4.117 Schedule of ratings—hemic and lymphatic systems. Rating 7700Anemia, hypochromic-microcytic...

  19. 38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... and lymphatic systems. 4.117 Section 4.117 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Hemic and Lymphatic Systems § 4.117 Schedule of ratings—hemic and lymphatic systems. Rating 7700Anemia, hypochromic-microcytic...

  20. 38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... and lymphatic systems. 4.117 Section 4.117 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Hemic and Lymphatic Systems § 4.117 Schedule of ratings—hemic and lymphatic systems. Rating 7700Anemia, hypochromic-microcytic...

  1. 38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... and lymphatic systems. 4.117 Section 4.117 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Hemic and Lymphatic Systems § 4.117 Schedule of ratings—hemic and lymphatic systems. Rating 7700Anemia, hypochromic-microcytic...

  2. Evaluation of lymphatic dysplasia in patients with congenital pleural effusion and ascites using indocyanine green lymphography.

    PubMed

    Shibasaki, Jun; Hara, Hisako; Mihara, Makoto; Adachi, Shinya; Uchida, Yasushi; Itani, Yasufumi

    2014-05-01

    To investigate the use of indocyanine green (ICG) lymphography in the diagnosis and assessment of the severity of lymphatic dysfunction in infants and neonates with congenital lymphatic pleural effusion and ascites. We performed ICG lymphography on 10 neonates and infants with congenital lymphatic pleural effusion and ascites. After the subcutaneous injection of ICG, circumferential fluorescent images of lymphatic drainage channels in the extremities and trunk were identified using an infrared camera system. The lymphographic findings were classifiable into 2 patterns-those showing a linear lymphatic pattern, suggesting normal lymphatic flow, and those showing lymphatic channels with retrograde lymphatic flow (dermal backflow pattern), suggesting an abnormal lymphatic flow. We analyzed the severity of the ICG lymphography findings and the clinical outcomes. Based on the ICG lymphography, the severity of lymphatic dysplasia were classified into 4 categories: mild dysplasia, moderate dysplasia, severe dysplasia, and lymphatic hypoplasia. All cases diagnosed with mild (n = 3) or moderate dysplasia (n = 2) survived, and 2 of the 4 cases diagnosed with severe dysplasia died. The duration of endotracheal intubation ranged from 1 to 17 days (median, 7) in the patients with mild or moderate dysplasia and from 25 to 110 days (median, 77) in those with severe dysplasia. The ICG lymphographic findings were consistent with the clinical conditions. This imaging technique may be important to the future clinical management of lymphatic dysplasia in neonates and infants. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Immunocytochemical localization of lymphatic and venous vessels in colonic polyps and adenomas.

    PubMed

    Tomita, Tatsuo

    2008-07-01

    Histopathological localization of lymphatic vessels has been hindered because of a lack of suitable immunocytochemical markers for lymphatic vessels. Using lymphatic vessels endothelial hyaluronan receptor-1 (LYVE-1) immunocytochemical staining, hyperplastic polyps, tubular adenomas to villous adenomas, were investigated for lymphatic vessels compared with immunostained blood vessels using factor-8. Four cases each of hyperplastic polyps, tubular adenomas to villous adenomas, were routinely fixed in formalin and embedded in paraffin and were immunostained using goat anti-LYVE-1 for lymphatic vessels and rabbit anti-factor-8 for blood vessels. In normal colon and hyperplastic polyps, slender lymphatic vessels were noted in muscularis mucosa, which spread into the base of colonic crypt, whereas round venous vessels, they extend into lamina propria. In tubular adenomas, small lymphatic and venous vessels were noted in broad fibrous stalks. In villous adenomas, smaller lymphatic and venous vessels were noted in fine intervillous stroma. In normal colon and hyperplastic polyps, slender, irregularly shaped lymphatic vessels were present in muscularis mucosa, spreading into the base of the colonic crypt. In tubular adenomas, small lymphatic and venous vessels were noted in fibrous stalks. In villous adenomas, smaller lymphatic and venous vessels were noted in intervillous stroma. There are no increased lymphatic and venous vessels in intermucosal stroma and stalks of adenomas compared with normal colon.

  4. A veterinary digital anatomical database.

    PubMed

    Snell, J R; Green, R; Stott, G; Van Baerle, S

    1991-01-01

    This paper describes the Veterinary Digital Anatomical Database Project. The purpose of the project is to investigate the construction and use of digitally stored anatomical models. We will be discussing the overall project goals and the results to date. Digital anatomical models are 3 dimensional, solid model representations of normal anatomy. The digital representations are electronically stored and can be manipulated and displayed on a computer graphics workstation. A digital database of anatomical structures can be used in conjunction with gross dissection in teaching normal anatomy to first year students in the professional curriculum. The computer model gives students the opportunity to "discover" relationships between anatomical structures that may have been destroyed or may not be obvious in the gross dissection. By using a digital database, the student will have the ability to view and manipulate anatomical structures in ways that are not available through interactive video disk (IVD). IVD constrains the student to preselected views and sections stored on the disk.

  5. MR lymphangiography for the assessment of the lymphatic system in patients undergoing microsurgical reconstructions of lymphatic vessels.

    PubMed

    Lohrmann, Christian; Felmerer, Gunther; Foeldi, Etelka; Bartholomä, J-P; Langer, Mathias

    2008-05-01

    To assess the morphology of the lymphatic system pre- and postoperatively in patients undergoing microsurgical reconstructions of the lymphatic vessels. 8 lower extremities in 4 consecutive patients with secondary unilateral lymphedema of the lower extremities were examined by MR lymphangiography. 18 mL of gadoteridol and 1 mL of mepivacainhydrochloride 1% were subdivided into 10 portions and injected intracutaneously into the dorsal aspect of each foot at the region of the four interdigital webs and medial to the first proximal phalanx. MR imaging was performed with a 1.5-T system equipped with high-performance gradients. For MR lymphangiography a 3D-spoiled gradient-echo sequence was used. For evaluation of the lymphedema a heavily T2-weighted 3D-TSE sequence was performed. In 2 patients the 3D-TSE sequence demonstrated a decrease of the epifascial lymphedema in the postoperative acquisitions, whereby MR lymphangiography displayed an improvement of dermal-back areas and collateral lymphatic vessels. In one patient the epifascial lymphedema of the lower extremity decreased, whereas the diameter of the lymphatic vessels showed a constant diameter of 2 mm. In one patient with a lymphocutaneous fistula at the level of the right groin, the feeding lymphatic vessels and contrast media extravasation could clearly be visualized. The 3D-TSE sequence demonstrated an epi- as well as subfascial lymphedema of the right leg. MR lymphangiography is a safe and accurate diagnostic imaging method for the pre- and postoperative evaluation of the lymphatic circulation in patients undergoing microlymphatic surgery. Due to the minimal-invasiveness and lack of radiation, diagnostic follow-up MR lymphangiography examinations can be performed routinely and with no risk for the patient.

  6. Occipital neuralgia: anatomic considerations.

    PubMed

    Cesmebasi, Alper; Muhleman, Mitchel A; Hulsberg, Paul; Gielecki, Jerzy; Matusz, Petru; Tubbs, R Shane; Loukas, Marios

    2015-01-01

    Occipital neuralgia is a debilitating disorder first described in 1821 as recurrent headaches localized in the occipital region. Other symptoms that have been associated with this condition include paroxysmal burning and aching pain in the distribution of the greater, lesser, or third occipital nerves. Several etiologies have been identified in the cause of occipital neuralgia and include, but are not limited to, trauma, fibrositis, myositis, fracture of the atlas, and compression of the C-2 nerve root, C1-2 arthrosis syndrome, atlantoaxial lateral mass osteoarthritis, hypertrophic cervical pachymeningitis, cervical cord tumor, Chiari malformation, and neurosyphilis. The management of occipital neuralgia can include conservative approaches and/or surgical interventions. Occipital neuralgia is a multifactorial problem where multiple anatomic areas/structures may be involved with this pathology. A review of these etiologies may provide guidance in better understanding occipital neuralgia. © 2014 Wiley Periodicals, Inc.

  7. Spectral contrast-enhanced optical coherence tomography for improved detection of tumor microvasculature and functional imaging of lymphatic drainage

    NASA Astrophysics Data System (ADS)

    SoRelle, Elliott D.; Liba, Orly; Sen, Debasish; de la Zerda, Adam

    2017-03-01

    Optical Coherence Tomography (OCT) is well-suited to study in vivo dynamics of blood circulation and lymphatic flow because of the technique's combination of rapid image acquisition, micron spatial resolution, and penetration depth in turbid tissues. However, OCT has been historically constrained by a dearth of contrast agents that are readily distinguished from the strong scattering intrinsic to biological tissues. In this study, we demonstrate large gold nanorods (LGNRs) as optimized contrast agents for OCT. LGNRs produce 32-fold greater backscattering than GNRs previously tested for contrast-enhanced OCT. Furthermore, LGNRs exhibit 110-fold stronger spectral signal than conventional GNRs when coupled with custom spectral detection algorithms. This signal enhancement enables picomolar OCT detection sensitivity in vivo and single-particle detection against optically-clear backgrounds. Moreover, the ability to synthesize LGNRs with tunable spectral peaks provides a viable platform for multiplexed imaging studies. To explore the advantages of LGNRs as OCT contrast agents, we implemented them for noninvasive 3D imaging of tumor blood supply and active lymphatic drainage in mice. Spectral detection of LGNRs enabled 100% improvement in imaging depth for detecting microvasculature (vessels 20 μm in diameter) in U87MG glioblastoma xenografts in mice pinnae. We also demonstrated our approach's ability to map the spatial dependence of lymph drainage and flow directionality within lymphatic capillaries. Using LGNRs with distinct spectra, we further identified the functional states of individual lymphatic valves in vivo. Thus, this approach provides a powerful new platform for functional imaging that may be extended for future molecular imaging studies with OCT.

  8. Relationship between high density of peritumoral lymphatic vessels and biological behavior of cervical cancer.

    PubMed

    En-Lin, Song; Wei-Wei, Yu; Xiao-Liang, Xiong; Juan, Xu

    2012-10-01

    To investigate the relationship between lymphangiogenesis and lymphatic metastasis in cervical squamous carcinoma. Eighty cases of invasive cervical squamous cancer were selected as objects of our study. Double immunohistochemical staining with antibodies against lymphatic vessel endothelial hyaluronan receptor 1 and Ki-67 was used to label the lymphatic vessels and mark the proliferative lymphatic vessels in cervical squamous cancer. The peritumoral lymphatic vessel density and intratumoral lymphatic vessel density was assessed. The lymphatic vessels proliferation index was evaluated by calculating Ki-67 proliferation index (PI) to reflect the lymphangiogenesis of cervical squamous cancer. Then the correlation between lymphangiogenesis and clinicopathologic features of cervical squamous cancer was analyzed. The LVD of cervical cancer (15.23 ± 3.6) was clearly higher than that of the adjacent normal cervical subepithelial tissues (9.9 ± 2.5, P < 0.001). The peritumoral lymphatic vessel density of cervical cancer (18.75 ± 4.3) was significantly higher than the intratumoral lymphatic vessel density of cervical cancer (11.71 ± 4.9, P < 0.001). Lymphatic PI (LPI) of cervical cancer (0.258 ± 0.07) was higher than that of the adjacent normal cervical subepithelial tissues (0.068 ± 0.08, P < 0.001). The peritumoral lymphatic vessel PI of cervical cancer (0.324 ± 0.06) was notably higher than the intratumoral lymphatic vessel PI of cervical cancer (0.232 ± 0.06, P < 0.001). Peritumoral lymphatic vessel density and peritumoral lymphatic vessel were clearly associated with the lymph node metastasis (P = 0.001 and P = 0.002, respectively) and lymphovascular space invasion (P = 0.024 and P = 0.01, respectively). The high density of peritumoral lymphatic vessels is a potential predictor of more aggressive phenotype of cervical squamous cancer.

  9. The Socioeconomic Impact of Lymphatic Filariasis in Tropical Countries

    ERIC Educational Resources Information Center

    Nwoke, Bertram Ekejiuba Bright; Nwoke, Eunice Anyalewechi; Dozie, Ikechukwu Nosike Simplicius

    2007-01-01

    Lymphatic filariasis (LF) is an endemic parasitic disease and a major cause of acute and chronic morbidity and incapacitation with devastating public health and socio-economic consequences. It exacerbates poor conditions of afflicted persons and endemic communities through reduced or lost labour supply and productivity. Stigmatisation and…

  10. Antifilarial compounds in the treatment and control of lymphatic filariasis.

    PubMed

    Mak, J W

    2004-12-01

    Diethylcarbamazine citrate (DEC) has been used for treatment and control of lymphatic filariasis since the 1950s. Although this remarkable drug is still useful and modified strategies in its usage have been developed, a number of newer antifilarial compounds are now available. Numerous field trials evaluating their efficacy in the control of lymphatic filariasis have been conducted. In particular, ivermectin (IVM), albendazole (ALB), and DEC have been tested singly and in combinations and the results of such field studies should be evaluated. While most of the studies were based on efficacy in the clearance of microfilaraemia, a few clinical trials evaluated the adulticidal activity of these compounds. Some antibiotics are effective in killing Wolbachia bacteria symbionts of filarial worms, but their role in the chemotherapy of lymphatic filariasis is still undefined. This review of randomised controlled field studies and randomised controlled clinical trials with these compounds will summarise the findings and give recommendations on their appropriate use for the control and treatment of lymphatic filariasis.

  11. Lymphatic vessels in the development of tissue and organ rejection.

    PubMed

    Hos, Deniz; Cursiefen, Claus

    2014-01-01

    The lymphatic vascular system-amongst other tasks-is critically involved in the regulation of adaptive immune responses as it provides an important route for APC trafficking to secondary lymphatic organs. In this context, the cornea, which is the transparent and physiologically avascular "windscreen" of the eye, has served as an excellent in vivo model to study the role of the blood and lymphatic vasculature in mediating allogenic immune responses after transplantation. Especially the mouse model of high-risk corneal transplantation, where corneal avascularity is abolished by a severe inflammatory stimulus prior to keratoplasty, allows for comparison to other transplantations performed in primarily vascularized tissues and solid organs. Using this model, we recently demonstrated that especially lymphatic vessels, but not blood vessels, define the high-risk status of vascularized corneas and that anti(lymph)angiogenic treatment significantly promotes corneal allograft survival. Since evidence for lymphangiogenesis and its potential association with graft rejection is nowadays also present in solid organ transplantation, studies are currently addressing the potential benefits of anti(lymph)angiogenic treatment as a novel therapeutic concept also in solid organ grafting with promising initial results.

  12. Utility of a microwave surgical instrument in sealing lymphatic vessels.

    PubMed

    Takebayashi, Katsushi; Shiomi, Hisanori; Naka, Shigeyuki; Murayama, Hiroyuki; Murakami, Koichiro; Akabori, Hiroya; Yamaguchi, Tsuyoshi; Shimizu, Tomoharu; Murata, Satoshi; Yamamoto, Hiroshi; Kurumi, Yoshimasa; Tani, Tohru

    2013-08-01

    This study assessed the ability of a novel microwave coagulation surgical instrument (MWCX) to seal lymphatic vessels when compared with LigaSure (Valleylab, Boulder, CO), the Harmonic Scalpel (HS; Ethicon Endo-Surgery, Cincinnati, OH), and electric cautery. The burst pressure of pig inguinal lymphatic vessels was assessed after the sealing of vessels with each surgical instrument. The rate of lymphorrhea from pig mesenteric lymphatic vessels was also investigated using indocyanine green and visualized with the Photodynamic Eye system (Hamamatsu Hotoniks, Hamamatsu, Japan). Burst pressures were higher with MWCX (average, 300 mm Hg), LigaSure (average, 290 mm Hg), and HS (average, 253 mm Hg) when compared with electric cautery (average, 152.3 mm Hg; vs MWCX: P = .002, vs LigaSure: P = .002, vs HS: P = .004). The rate of lymphorrhea was significantly lower with LigaSure (13.3%), HS (18.8%), and MWCX (13.3%) when compared with electric cautery (77.3%; vs LigaSure: P < .001, vs HS: P < .001, vs MWCX: P < .001). MWCX was equivalent to LigaSure and HS in terms of the ability to seal lymphatic vessels. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. The Socioeconomic Impact of Lymphatic Filariasis in Tropical Countries

    ERIC Educational Resources Information Center

    Nwoke, Bertram Ekejiuba Bright; Nwoke, Eunice Anyalewechi; Dozie, Ikechukwu Nosike Simplicius

    2007-01-01

    Lymphatic filariasis (LF) is an endemic parasitic disease and a major cause of acute and chronic morbidity and incapacitation with devastating public health and socio-economic consequences. It exacerbates poor conditions of afflicted persons and endemic communities through reduced or lost labour supply and productivity. Stigmatisation and…

  14. Radiation therapy causes loss of dermal lymphatic vessels and interferes with lymphatic function by TGF-β1-mediated tissue fibrosis

    PubMed Central

    Avraham, Tomer; Yan, Alan; Zampell, Jamie C.; Daluvoy, Sanjay V.; Haimovitz-Friedman, Adriana; Cordeiro, Andrew P.

    2010-01-01

    Although radiation therapy is a major risk factor for the development of lymphedema following lymphadenectomy, the mechanisms responsible for this effect remain unknown. The purpose of this study was therefore to determine the effects of radiation on lymphatic endothelial cells (LECs) and lymphatic function. The tails of wild-type or acid sphingomyelinase (ASM)-deficient mice were treated with 0, 15, or 30 Gy of radiation and then analyzed for LEC apoptosis and lymphatic function at various time points. To analyze the effects of radiation fibrosis on lymphatic function, we determined the effects of transforming growth factor (TGF)-β1 blockade after radiation in vivo. Finally, we determined the effects of radiation and exogenous TGF-β1 on LECs in vitro. Radiation caused mild edema that resolved after 12–24 wk. Interestingly, despite resolution of tail edema, irradiated animals displayed persistent lymphatic dysfunction. Radiation caused loss of capillary lymphatics and was associated with a dose-dependent increase in LEC apoptosis. ASM−/− mice had significantly less LEC apoptosis; however, this finding did not translate to improved lymphatic function at later time points. Short-term blockade of TGF-β1 function after radiation markedly decreased tissue fibrosis and significantly improved lymphatic function but did not alter LEC apoptosis. Radiation therapy decreases lymphatic reserve by causing depletion of lymphatic vessels and LECs as well as promoting soft tissue fibrosis. Short-term inhibition of TGF-β1 activity following radiation improves lymphatic function and is associated with decreased soft tissue fibrosis. ASM deficiency confers LEC protection from radiation-induced apoptosis but does not prevent lymphatic dysfunction. PMID:20519446

  15. Monoclonal Antibodies in the Lymphatics: Selective Delivery to Lymph Node Metastases of a Solid Tumor

    NASA Astrophysics Data System (ADS)

    Weinstein, John N.; Steller, Michael A.; Keenan, Andrew M.; Covell, David G.; Key, Marc E.; Sieber, Susan M.; Oldham, Robert K.; Hwang, Kou M.; Parker, Robert J.

    1983-10-01

    After subcutaneous injection, monoclonal antibodies directed against a tumor can enter local lymphatic vessels, pass to the draining lymph nodes, and bind to metastases there. Lymphatic delivery of antibody to early metastases is more efficient than intravenous administration, and the lymphatic route can be used to image smaller metastatic deposits. Perhaps more important, the lymphatic route minimizes binding of antibodies to circulating tumor antigens and to cross-reactive antigens present on normal tissues. Antibodies inappropriate for intravenous use because of binding to normal tissues may therefore be useful against lymph node metastases when injected subcutaneously or directly into lymphatic vessels.

  16. The dual role of tumor lymphatic vessels in dissemination of metastases and immune response development.

    PubMed

    Stachura, Joanna; Wachowska, Malgorzata; Kilarski, Witold W; Güç, Esra; Golab, Jakub; Muchowicz, Angelika

    2016-07-01

    Lymphatic vasculature plays a crucial role in the immune response, enabling transport of dendritic cells (DCs) and antigens (Ags) into the lymph nodes. Unfortunately, the lymphatic system has also a negative role in the progression of cancer diseases, by facilitating the metastatic spread of many carcinomas to the draining lymph nodes. The lymphatics can promote antitumor immune response as well as tumor tolerance. Here, we review the role of lymphatic endothelial cells (LECs) in tumor progression and immunity and mechanism of action in the newest anti-lymphatic therapies, including photodynamic therapy (PDT).

  17. Intestinal and peri-tumoral lymphatic endothelial cells are resistant to radiation-induced apoptosis

    SciTech Connect

    Sung, Hoon Ki; Morisada, Tohru; Cho, Chung-Hyun; Oike, Yuichi; Lee, Jayhun; Sung, Eon Ki; Chung, Jae Hoon; Suda, Toshio; Koh, Gou Young . E-mail: gykoh@kaist.ac.kr

    2006-06-30

    Radiation therapy is a widely used cancer treatment, but it is unable to completely block cancer metastasis. The lymphatic vasculature serves as the primary route for metastatic spread, but little is known about how lymphatic endothelial cells respond to radiation. Here, we show that lymphatic endothelial cells in the small intestine and peri-tumor areas are highly resistant to radiation injury, while blood vessel endothelial cells in the small intestine are relatively sensitive. Our results suggest the need for alternative therapeutic modalities that can block lymphatic endothelial cell survival, and thus disrupt the integrity of lymphatic vessels in peri-tumor areas.

  18. Bleomycin sclerotherapy for lymphatic malformation after unsuccessful surgical excision: case report.

    PubMed

    Vlahovic, A; Gazikalovic, A; Adjic, O

    2015-10-01

    Lymphatic malformations (LMs) are benign cystic masses resulting from the abnormal development of lymphatic channels. Lymphatic malformations occur primarily in the head and neck region. Surgical excision of lymphatic malformation is followed by high rate of recurrence and a high risk of complications. Bleomycin is an established antineoplastic drug. It can be used as a sclerosing agent in vascular anomalies. We present a child who was unsuccessfully treated with four surgical resections, with peripheral palsy of facial nerve as complication. The lymphatic malformation was successfully treated in our institution with intralesional administration of bleomycin.

  19. The dual role of tumor lymphatic vessels in dissemination of metastases and immune response development

    PubMed Central

    Stachura, Joanna; Wachowska, Malgorzata; Kilarski, Witold W.; Güç, Esra; Golab, Jakub; Muchowicz, Angelika

    2016-01-01

    ABSTRACT Lymphatic vasculature plays a crucial role in the immune response, enabling transport of dendritic cells (DCs) and antigens (Ags) into the lymph nodes. Unfortunately, the lymphatic system has also a negative role in the progression of cancer diseases, by facilitating the metastatic spread of many carcinomas to the draining lymph nodes. The lymphatics can promote antitumor immune response as well as tumor tolerance. Here, we review the role of lymphatic endothelial cells (LECs) in tumor progression and immunity and mechanism of action in the newest anti-lymphatic therapies, including photodynamic therapy (PDT). PMID:27622039

  20. [THE STRUCTURE OF LYMPHATIC CAPILLARIES OF THE CILIARY BODY OF THE HUMAN EYE].

    PubMed

    Borodin, Yu I; Bgatova, N P; Chernykh, V V; Trunov, A N; Pozhidayeva, A A; Konenkov, V I

    2015-01-01

    Using light microscopy, immunohistochemistry and electron microscopy, the structural organization of interstitial spaces and vessels of the ciliary body of the human eye (n = 5) were studied. The ciliary body was found to contain wide interstitial spaces--tissue clefts bound by collagen fibers and fibroblasts. Organ-specific lymphatic capillaries were also demonstrated in the ciliary body. According to the present findings and the lymphatic region concept, the first 2 elements of the lymphatic region of the eye were described: tissue clefts--prelymphatics and lymphatic capillaries of the ciliary body. The third element of the lymphatic region are the lymph nodes of the head and neck.

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

    PubMed

    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

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

    PubMed Central

    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

  3. Study on enhanced lymphatic exposure of polyamidoamin-alkali blue dendrimer for paclitaxel delivery and influence of the osmotic pressure on the lymphatic targeting.

    PubMed

    Yang, Rui; Mao, Yuling; Ye, Tiantian; Xia, Suxia; Wang, Shujun; Wang, Siling

    2016-09-01

    In this study, paclitaxel (PTX)-loaded polyamidoamin-alkali blue (PTX-P-AB) was prepared in order to investigate the intralymphatic targeting ability and anti-cancer effect after subcutaneous (s.c.) administration. The physicochemical properties and in vitro drug release were evaluated. The lymphatic drainage and lymph nodes (LNs) uptake were examined by pharmacokinetics and distribution recovery of PTX in plasma, LNs, injection site (IS) and tissues after s.c. injection in healthy mice and in tumor-bearing mice. The osmotic pressure of PTX-P-AB affecting the lymphatic targeting was studied. The anti-tumor activity of PTX-P-AB was investigated in mice bearing S180 metastatic tumors. Results showed that PTX-P-AB with suitable and stable physicochemical properties could be used for in vivo lymphatic studies, and displayed the more rapid lymphatic absorption, the higher AUC value in LNs, the longer LNs residence time and the higher metastasis-inhibiting rate compared with Taxol®. Enhanced lymphatic drainage from the IS and uptake into lymph by increasing the osmotic pressure of PTX-P-AB indicated that PTX-P-AB possesses the double function of lymphatic tracing and lymphatic targeting, and suggested the potential for the development of lymphatic targeting vectors and the lymphatic tracer for treatment and diagnosis.

  4. In vivo dual-modality imaging of lymphatic systems using indocyanine green in rats: three-dimensional photoacoustic imaging and planar fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Kim, Chulhong; Song, Kwang Hyun; Wang, Lihong V.

    2010-02-01

    The purpose of this study is to map non-invasively sentinel lymph nodes (SLNs) and lymphatic vessels of rats in vivo using FDA-approved indocyanine green (ICG) and two non-ionizing imaging modalities: volumetric spectroscopic photoacoustic (PA) imaging, which measures optical absorption, and planar fluorescence imaging, which measures fluorescent emission. SLNs and lymphatic vessels were clearly visible after a 0.2 ml-intradermal-injection of 1 mM ICG in both imaging systems. We also imaged deeply positioned lymph nodes in vivo by layering biological tissues on top of rats. These two modalities, when used together with ICG, have the potential to map SLNs in axillary staging and to study tumor metastasis in breast cancer patients.

  5. Lymphatic Contribution to the Cellular Niche in Heterotopic Ossification

    PubMed Central

    Loder, Shawn; Agarwal, Shailesh; Sorkin, Michael; Breuler, Chris; Li, John; Peterson, Joshua; Hsieh, Hsiao Hsin Sung; Wang, Stewart; Mehrara, Babak; Levi, Benjamin

    2016-01-01

    Objective The objective of this study was to determine the contribution of lymphatic tissue to heterotopic ossification. Background Heterotopic ossification (HO) is the pathologic development of ectopic bone within soft tissues often following severe trauma. Characterization of the tissue niche supporting HO is critical to identifying therapies directed against this condition. Lymphangiogenesis is up-regulated during incidents of trauma, thereby co-incident with the niche supportive of HO. We hypothesized that lymphatic tissues play a critical role in HO formation. Methods Mice underwent hindlimb Achilles’ tendon transection and dorsal burn injury(burn/tenotomy) to induce HO. The popliteal and inguinal lymph nodes were excised ipsilateral to the tenotomy site. Flow cytometry and immunostaining were used to quantify and localize lymphoendothelium. MicroCT was used to quantify HO. Results Enrichment of mature lymphatic tissues was noted 2 weeks after injury at the tendon transection sites when compared with the contralateral, intact tendon based on LYVE1+ tubules (10.9% v. 0.8%, p<0.05). Excision of the inguinal and popliteal nodes with draining popliteal lymphatic vessel significantly decreased the presence of mature lymphoendothelium 2 weeks after injury (10.9% v. 3.3%, p<0.05). Bone-cartilage-stromal progenitor cells (CD105+/AlphaV+/Tie2−/CD45−/CD90−/BP1−) were also significantly decreased after lymph node excision (10.2% v. 0.5%, p<0.05). A significant decrease was noted in the volume of de novo HO present within the soft tissues (0.12 mm^3 v. 0.02 mm^3). Conclusions These findings suggest that lymphatic vessels are intimately linked with the formation de novo bone within soft tissues following trauma, and their presence may facilitate bone formation. PMID:26779981

  6. [Graphic reconstruction of anatomic surfaces].

    PubMed

    Ciobanu, O

    2004-01-01

    The paper deals with the graphic reconstruction of anatomic surfaces in a virtual 3D setting. Scanning technologies and soft provides a greater flexibility in the digitization of surfaces and a higher resolution and accuracy. An alternative cheap method for the reconstruction of 3D anatomic surfaces is presented in connection with some studies and international projects developed by Medical Design research team.

  7. Collecting baseline information for national morbidity alleviation programs: different methods to estimate lymphatic filariasis morbidity prevalence.

    PubMed

    Mathieu, Els; Amann, Josef; Eigege, Abel; Richards, Frank; Sodahlon, Yao

    2008-01-01

    The lymphatic filariasis elimination program aims not only to stop transmission, but also to alleviate morbidity. Although geographically limited morbidity projects exist, few have been implemented nationally. For advocacy and planning, the program coordinators need prevalence estimates that are currently rarely available. This article compares several approaches to estimate morbidity prevalence: (1) data routinely collected during mapping or sentinel site activities; (2) data collected during drug coverage surveys; and (3) alternative surveys. Data were collected in Plateau and Nasarawa States in Nigeria and in 6 districts in Togo. In both settings, we found that questionnaires seem to underestimate the morbidity prevalence compared with existing information collected through clinical examination. We suggest that program managers use the latter for advocacy and planning, but if not available, questionnaires to estimate morbidity prevalence can be added to existing surveys. Even though such data will most likely underestimate the real burden of disease, they can be useful in resource-limited settings.

  8. Smooth muscle–endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation

    PubMed Central

    Lutter, Sophie; Xie, Sherry; Tatin, Florence

    2012-01-01

    Active lymph transport relies on smooth muscle cell (SMC) contractions around collecting lymphatic vessels, yet regulation of lymphatic vessel wall assembly and lymphatic pumping are poorly understood. Here, we identify Reelin, an extracellular matrix glycoprotein previously implicated in central nervous system development, as an important regulator of lymphatic vascular development. Reelin-deficient mice showed abnormal collecting lymphatic vessels, characterized by a reduced number of SMCs, abnormal expression of lymphatic capillary marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and impaired function. Furthermore, we show that SMC recruitment to lymphatic vessels stimulated release and proteolytic processing of endothelium-derived Reelin. Lymphatic endothelial cells in turn responded to Reelin by up-regulating monocyte chemotactic protein 1 (MCP1) expression, which suggests an autocrine mechanism for Reelin-mediated control of endothelial factor expression upstream of SMC recruitment. These results uncover a mechanism by which Reelin signaling is activated by communication between the two cell types of the collecting lymphatic vessels—smooth muscle and endothelial cells—and highlight a hitherto unrecognized and important function for SMCs in lymphatic vessel morphogenesis and function. PMID:22665518

  9. Molecular and functional analyses of the contractile apparatus in lymphatic muscle

    NASA Technical Reports Server (NTRS)

    Muthuchamy, Mariappan; Gashev, Anatoliy; Boswell, Niven; Dawson, Nancy; Zawieja, David; Delp, Z. (Principal Investigator)

    2003-01-01

    Lymphatics are necessary for the generation and regulation of lymph flow. Lymphatics use phasic contractions and extrinsic compressions to generate flow; tonic contractions alter resistance. Lymphatic muscle exhibits important differences from typical vascular smooth muscle. In this study, the thoracic duct exhibited significant functional differences from mesenteric lymphatics. To understand the molecular basis for these differences, we examined the profiles of contractile proteins and their messages in mesenteric lymphatics, thoracic duct, and arterioles. Results demonstrated that mesenteric lymphatics express only SMB smooth muscle myosin heavy chain (SM-MHC), whereas thoracic duct and arterioles expressed both SMA and SMB isoforms. Both SM1 and SM2 isoforms of SM-MHC were detected in arterioles and mesenteric and thoracic lymphatics. In addition, the fetal cardiac/skeletal slow-twitch muscle-specific beta-MHC message was detected only in mesenteric lymphatics. All four actin messages, cardiac alpha-actin, vascular alpha-actin, enteric gamma-actin, and skeletal alpha-actin, were present in both mesenteric lymphatics and arterioles. However, in thoracic duct, predominantly cardiac alpha-actin and vascular alpha-actin were found. Western blot and immunohistochemical analyses corroborated the mRNA studies. However, in arterioles only vascular alpha-actin protein was detected. These data indicate that lymphatics display genotypic and phenotypic characteristics of vascular, cardiac, and visceral myocytes, which are needed to fulfill the unique roles of the lymphatic system.

  10. Decline of lymphatic vessel density and function in murine skin during aging.

    PubMed

    Karaman, Sinem; Buschle, Dorina; Luciani, Paola; Leroux, Jean-Christophe; Detmar, Michael; Proulx, Steven T

    2015-10-01

    Lymphatic vessels play important roles in the pathogenesis of many conditions that have an increased prevalence in the elderly population. However, the effects of the aging process on the lymphatic system are still relatively unknown. We have applied non-invasive imaging and whole-mount staining techniques to assess the lymphatic vessel function and morphology in three different age groups of mice: 2 months (young), 7 months (middle-aged), and 18 months (aged). We first developed and validated a new method to quantify lymphatic clearance from mouse ear skin, using a lymphatic-specific near-infrared tracer. Using this method, we found that there is a prominent decrease in lymphatic vessel function during aging since the lymphatic clearance was significantly delayed in aged mice. This loss of function correlated with a decreased lymphatic vessel density and a reduced lymphatic network complexity in the skin of aged mice as compared to younger controls. The blood vascular leakage in the skin was slightly increased in the aged mice, indicating that the decreased lymphatic function was not caused by a reduced capillary filtration in aged skin. The decreased function of lymphatic vessels with aging might have implications for the pathogenesis of a number of aging-related diseases.

  11. Primary and Secondary Lymphatic Valve Development: Molecular, Functional and Mechanical Insights

    PubMed Central

    Bazigou, Eleni; Wilson, John T.; Moore, James E.

    2015-01-01

    Fluid homeostasis in vertebrates critically relies on the lymphatic system forming a hierarchical network of lymphatic capillaries and collecting lymphatics, for the efficient drainage and transport of extravasated fluid back to the cardiovascular system. Blind–ended lymphatic capillaries employ specialized junctions and anchoring filaments to encourage a unidirectional flow of the interstitial fluid into the initial lymphatic vessels, whereas collecting lymphatics are responsible for the active propulsion of the lymph to the venous circulation via the combined action of lymphatic muscle cells and intraluminal valves. Here we describe recent findings on molecular and physical factors regulating the development and maturation of these two types of valves and examine their role in tissue-fluid homeostasis. PMID:25086182

  12. Defining error in anatomic pathology.

    PubMed

    Sirota, Ronald L

    2006-05-01

    Although much has been said and written about medical error and about error in pathology since the publication of the Institute of Medicine's report on medical error in 1999, precise definitions of what constitutes error in anatomic pathology do not exist for the specialty. Without better definitions, it is impossible to accurately judge errors in pathology. The lack of standardized definitions has implications for patient care and for the legal judgment of malpractice. To review the goals of anatomic pathology, to discuss the problems inherent in applying these goals to the judgment of error in pathology, to offer definitions of major and minor errors in pathology, and to discuss error in anatomic pathology in relation to the classic laboratory test cycle. Existing literature. Definitions for major and minor error in anatomic pathology are proffered, and anatomic pathology error is characterized in the classic test cycle.

  13. Efficient Assessment of Developmental, Surgical and Pathological Lymphangiogenesis Using a Lymphatic Reporter Mouse and Its Embryonic Stem Cells

    PubMed Central

    Jung, Wonhyuek; Seong, Young Jin; Park, Eunkyung; Bramos, Athanasios; Kim, Kyu Eui; Lee, Sunju; Daghlian, George; Seo, Jung In; Choi, Inho; Choi, In-Seon; Koh, Chester J.; Kobielak, Agnieszka; Ying, Qi-Long; Johnson, Maxwell; Gardner, Daniel; Wong, Alex K.; Choi, Dongwon; Hong, Young-Kwon

    2016-01-01

    Several lymphatic reporter mouse lines have recently been developed to significantly improve imaging of lymphatic vessels. Nonetheless, the usage of direct visualization of lymphatic vessels has not been fully explored and documented. Here, we characterized a new Prox1-tdTomato transgenic lymphatic reporter mouse line, and demonstrated how this animal tool enables the researchers to efficiently assess developmental, surgical and pathological lymphangiogenesis by direct visualization of lymphatic vessels. Moreover, we have derived embryonic stem cells from this reporter line, and successfully differentiated them into lymphatic vessels in vivo. In conclusion, these experimental tools and techniques will help advance lymphatic research. PMID:27280889

  14. The complexity of anatomical systems

    PubMed Central

    Grizzi, Fabio; Chiriva-Internati, Maurizio

    2005-01-01

    Background The conception of anatomical entities as a hierarchy of infinitely graduated forms and the increase in the number of observed anatomical sub-entities and structural variables has generated a growing complexity, thus highlighting new properties of organised biological matter. Results (1) Complexity is so pervasive in the anatomical world that it has come to be considered as a primary characteristic of anatomical systems. (2) Anatomical entities, when viewed at microscopic as well as macroscopic level of observation, show a different degree of complexity. (3) Complexity can reside in the structure of the anatomical system (having many diverse parts with varying interactions or an intricate architecture) or in its behaviour. Often complexity in structure and behaviour go together. (4) Complex systems admit many descriptions (ways of looking at the system) each of which is only partially true. Each way of looking at a complex system requires its own description, its own mode of analysis and its own breaking down of the system in different parts; (5) Almost all the anatomical entities display hierarchical forms: their component structures at different spatial scales or their process at different time scales are related to each other. Conclusion The need to find a new way of observing and measuring anatomical entities, and objectively quantifying their different structural changes, prompted us to investigate the non-Euclidean geometries and the theories of complexity, and to apply their concepts to human anatomy. This attempt has led us to reflect upon the complex significance of the shape of an observed anatomical entity. Its changes have been defined in relation to variations in its status: from a normal (i.e. natural) to a pathological or altered state introducing the concepts of kinematics and dynamics of anatomical forms, speed of their changes, and that of scale of their observation. PMID:16029490

  15. Esophageal cancer: anatomic particularities, staging, and imaging techniques.

    PubMed

    Encinas de la Iglesia, J; Corral de la Calle, M A; Fernández Pérez, G C; Ruano Pérez, R; Álvarez Delgado, A

    2016-01-01

    Cancer of the esophagus is a tumor with aggressive behavior that is usually diagnosed in advanced stages. The absence of serosa allows it to spread quickly to neighboring mediastinal structures, and an extensive lymphatic drainage network facilitates tumor spread even in early stages. The current TNM classification, harmonized with the classification for gastric cancer, provides new definitions for the anatomic classification, adds non-anatomic characteristics of the tumor, and includes tumors of the gastroesophageal junction. Combining endoscopic ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging provides greater accuracy in determining the initial clinical stage, and these imaging techniques play an essential role in the selection, planning, and evaluation of treatment. In this article, we review some particularities that explain the behavior of this tumor and we describe the current TNM staging system; furthermore, we discuss the different imaging tests available for its evaluation and include a diagnostic algorithm. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Tracking in anatomic pathology.

    PubMed

    Pantanowitz, Liron; Mackinnon, Alexander C; Sinard, John H

    2013-12-01

    Bar code-based tracking solutions, long present in clinical pathology laboratories, have recently made an appearance in anatomic pathology (AP) laboratories. Tracking of AP "assets" (specimens, blocks, slides) can enhance laboratory efficiency, promote patient safety, and improve patient care. Routing of excess clinical material into research laboratories and biorepositories are other avenues that can benefit from tracking of AP assets. Implementing tracking is not as simple as installing software and turning it on. Not all tracking solutions are alike. Careful analysis of laboratory workflow is needed before implementing tracking to assure that this solution will meet the needs of the laboratory. Such analysis will likely uncover practices that may need to be modified before a tracking system can be deployed. Costs that go beyond simply that of purchasing software will be incurred and need to be considered in the budgeting process. Finally, people, not technology, are the key to assuring quality. Tracking will require significant changes in workflow and an overall change in the culture of the laboratory. Preparation, training, buy-in, and accountability of the people involved are crucial to the success of this process. This article reviews the benefits, available technology, underlying principles, and implementation of tracking solutions for the AP and research laboratory.

  17. Vascular Endothelial Growth Factor Receptor-2 Promotes the Development of the Lymphatic Vasculature

    PubMed Central

    Dellinger, Michael T.; Meadows, Stryder M.; Wynne, Katherine; Cleaver, Ondine; Brekken, Rolf A.

    2013-01-01

    Vascular endothelial growth factor receptor 2 (VEGFR2) is highly expressed by lymphatic endothelial cells and has been shown to stimulate lymphangiogenesis in adult mice. However, the role VEGFR2 serves in the development of the lymphatic vascular system has not been defined. Here we use the Cre-lox system to show that the proper development of the lymphatic vasculature requires VEGFR2 expression by lymphatic endothelium. We show that Lyve-1wt/Cre;Vegfr2flox/flox mice possess significantly fewer dermal lymphatic vessels than Vegfr2flox/flox mice. Although Lyve-1wt/Cre;Vegfr2flox/flox mice exhibit lymphatic hypoplasia, the lymphatic network is functional and contains all of the key features of a normal lymphatic network (initial lymphatic vessels and valved collecting vessels surrounded by smooth muscle cells (SMCs)). We also show that Lyve-1Cre mice display robust Cre activity in macrophages and in blood vessels in the yolk sac, liver and lung. This activity dramatically impairs the development of blood vessels in these tissues in Lyve-1wt/Cre;Vegfr2flox/flox embryos, most of which die after embryonic day14.5. Lastly, we show that inactivation of Vegfr2 in the myeloid lineage does not affect the development of the lymphatic vasculature. Therefore, the abnormal lymphatic phenotype of Lyve-1wt/Cre;Vegfr2flox/flox mice is due to the deletion of Vegfr2 in the lymphatic vasculature not macrophages. Together, this work demonstrates that VEGFR2 directly promotes the expansion of the lymphatic network and further defines the molecular mechanisms controlling the development of the lymphatic vascular system. PMID:24023956

  18. Vascular endothelial growth factor receptor-2 promotes the development of the lymphatic vasculature.

    PubMed

    Dellinger, Michael T; Meadows, Stryder M; Wynne, Katherine; Cleaver, Ondine; Brekken, Rolf A

    2013-01-01

    Vascular endothelial growth factor receptor 2 (VEGFR2) is highly expressed by lymphatic endothelial cells and has been shown to stimulate lymphangiogenesis in adult mice. However, the role VEGFR2 serves in the development of the lymphatic vascular system has not been defined. Here we use the Cre-lox system to show that the proper development of the lymphatic vasculature requires VEGFR2 expression by lymphatic endothelium. We show that Lyve-1(wt/Cre);Vegfr2(flox/flox) mice possess significantly fewer dermal lymphatic vessels than Vegfr2(flox/flox) mice. Although Lyve-1(wt/Cre);Vegfr2(flox/flox) mice exhibit lymphatic hypoplasia, the lymphatic network is functional and contains all of the key features of a normal lymphatic network (initial lymphatic vessels and valved collecting vessels surrounded by smooth muscle cells (SMCs)). We also show that Lyve-1(Cre) mice display robust Cre activity in macrophages and in blood vessels in the yolk sac, liver and lung. This activity dramatically impairs the development of blood vessels in these tissues in Lyve-1(wt/Cre);Vegfr2(flox/flox) embryos, most of which die after embryonic day14.5. Lastly, we show that inactivation of Vegfr2 in the myeloid lineage does not affect the development of the lymphatic vasculature. Therefore, the abnormal lymphatic phenotype of Lyve-1(wt/Cre);Vegfr2(flox/flox) mice is due to the deletion of Vegfr2 in the lymphatic vasculature not macrophages. Together, this work demonstrates that VEGFR2 directly promotes the expansion of the lymphatic network and further defines the molecular mechanisms controlling the development of the lymphatic vascular system.

  19. Efficacy of B cell Depletion Therapy on Joint Flare is Associated with Increased Lymphatic Flow

    PubMed Central

    Li, Jie; Ju, Yawen; Bouta, Echoe M.; Xing, Lianping; Wood, Ronald W.; Kuzin, Igor; Bottaro, Andrea; Ritchlin, Christopher T.; Schwarz, Edward M.

    2012-01-01

    Objective B cell depletion therapy (BCDT) ameliorates rheumatoid arthritis by mechanisms that are incompletely understood. Arthritic flare in tumor necrosis factor transgenic (TNF-Tg) mice is associated with efferent lymph node (LN) “collapse,” triggered by B cell translocation into lymphatic spaces and decreased lymphatic drainage. We examined whether BCDT efficacy is associated with restoration of lymphatic drainage due to removal of obstructing nodal B cells. Methods We developed contrast-enhancement (CE) MRI imaging, near-infrared indocyanine green (NIR-ICG) imaging, and intravital immunofluorescent imaging to longitudinally assess synovitis, lymphatic flow, and cell migration in lymphatic vessels in TNF-Tg mice. We tested to see if BCDT efficacy is associated with restoration of lymphatic draining and cell egress from arthritic joints. Results Unlike active lymphatics to normal and pre-arthritic knees, afferent lymphatic vessels to collapsed LNs in inflamed knees do not pulse. Intravital immunofluorescent imaging demonstrated that CD11b+ monocytes/macrophages in lymphatic vessels afferent to expanding LN travel at high velocity (186 ± 37 micrometer/sec), while these cells are stationary in lymphatic vessels afferent to collapsed PLN. BCDT of flaring TNF-Tg mice significantly decreased knee synovial volume by 50% from the baseline level, and significantly increased lymphatic clearance versus placebo (p<0.05). This increased lymphatic drainage restored macrophages egress from inflamed joints without recovery of the lymphatic pulse. Conclusion These results support a novel mechanism in which BCDT of flaring joints lessens inflammation by increasing lymphatic drainage and subsequent migration of cells and cytokines from the synovial space. PMID:23002006

  20. [Functional assessment of the lymphatic bed of patients in the late clinical classes of chronic venous insufficiency according to the international GEAP classification].

    PubMed

    Chepelenko, G V

    2006-01-01

    The author revises the contents and limits of the anatomic CEAP classification. For this purpose 84 patients with different types of trophic disorders of the lower limbs were examined with the aid of the author's technique of functional lymphography and lymphoscintigraphy. Impairment of drainage and transport function of the lymphatic capillaries was established from the ulcer edge at the level of the outgoing (from skin to collector) and collecting (from foot to regional nodes) capillaries. A close relationship was discovered between secondary changes in the lymphatic bed and the severity of trophic disorders. In groups with dilated and stenosed vessels, there were subgroups of patients with preserved function of lympangions. The data obtained evidence that lymphovenous insufficiency beyond the area of trophic disorders is more pronounced than in the focus itself. This may play a decisive role in the choice of the treatment modality as dependent on the condition of the drainage pathways. To refine the diagnosis in patients showing disease progression, with failed treatment of trophic ulcers including ulcerous defects, the author suggests that A category may be divided into two subgroups: Av for characterization of different veins and Al for lymphatic vessels of varying levels: S (skin), (Tissue) and Lnd (lymph nodes). The use of additional criteria for the diagnosis substantially improves the characteristics of the international CAAP classification.

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

    PubMed

    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.

  2. Supermicrosurgical deep lymphatic vessel-to-venous anastomosis for a breast cancer-related arm lymphedema with severe sclerosis of superficial lymphatic vessels.

    PubMed

    Yamamoto, Takumi; Yamamoto, Nana; Hayashi, Akitatsu; Koshima, Isao

    2017-02-01

    Lymphatic supermicrosurgery or supermicrosurgical lymphaticovenular anastomosis (LVA) is becoming popular for the treatment of compression-refractory upper extremity lymphedema (UEL) with its effectiveness and minimally invasiveness. In conventional LVA, superficial lymphatic vessels are used for anastomosis, but its treatment efficacy would be minimum when superficial lymphatic vessels are severely sclerotic. Theoretically, deep lymphatic vessels can be used for LVA, but no clinical case has been reported regarding deep lymphatic vessel-to-venous anastomosis (D-LVA). We report a breast cancer-related UEL case treated with D-LVA, in which a less-sclerotic deep lymphatic vessel was useful for anastomosis but superficial lymphatic vessels were not due to severe sclerosis. A 62-year-old female suffered from an 18-year history of compression-refractory right UEL after right breast cancer treatments, and underwent LVA under local infiltration anesthesia. Because superficial lymphatic vessels found in surgical fields were all severely sclerotic, a deep lymphatic vessel was dissected at the cubital fossa. A 0.50-mm deep lymphatic vessel running along the brachial artery was supermicrosurgically anastomosed to a nearby 0.40-mm vein. At postoperative 12 months, her right UEL index decreased from 134 to 118, and she could reduce compression frequency from every day to 1-2 days per week to maintain the reduced lymphedematous volume. D-LVA may be a useful option for the treatment of compression-refractory UEL, when superficial lymphatic vessels are severely sclerotic. © 2015 Wiley Periodicals, Inc. Microsurgery 37:156-159, 2017. © 2015 Wiley Periodicals, Inc.

  3. Anatomical adaptations of aquatic mammals.

    PubMed

    Reidenberg, Joy S

    2007-06-01

    This special issue of the Anatomical Record explores many of the anatomical adaptations exhibited by aquatic mammals that enable life in the water. Anatomical observations on a range of fossil and living marine and freshwater mammals are presented, including sirenians (manatees and dugongs), cetaceans (both baleen whales and toothed whales, including dolphins and porpoises), pinnipeds (seals, sea lions, and walruses), the sea otter, and the pygmy hippopotamus. A range of anatomical systems are covered in this issue, including the external form (integument, tail shape), nervous system (eye, ear, brain), musculoskeletal systems (cranium, mandible, hyoid, vertebral column, flipper/forelimb), digestive tract (teeth/tusks/baleen, tongue, stomach), and respiratory tract (larynx). Emphasis is placed on exploring anatomical function in the context of aquatic life. The following topics are addressed: evolution, sound production, sound reception, feeding, locomotion, buoyancy control, thermoregulation, cognition, and behavior. A variety of approaches and techniques are used to examine and characterize these adaptations, ranging from dissection, to histology, to electron microscopy, to two-dimensional (2D) and 3D computerized tomography, to experimental field tests of function. The articles in this issue are a blend of literature review and new, hypothesis-driven anatomical research, which highlight the special nature of anatomical form and function in aquatic mammals that enables their exquisite adaptation for life in such a challenging environment. 2007 Wiley-Liss, Inc.

  4. Absence of lymphatic vessels in the developing human sclera.

    PubMed

    Schlereth, Simona L; Neuser, Barbara; Herwig, Martina C; Müller, Annette M; Koch, Konrad R; Reitsamer, Herbert A; Schrödl, Falk; Cursiefen, Claus; Heindl, Ludwig M

    2014-08-01

    The adult sclera is free of lymphatic vessels, but contains a net of blood vessels. Whether and when this selectively lymphangiogenic privilege is achieved during embryologic development is not known yet. Therefore, we investigated the developing human sclera for blood- and lymphatic vessels in 34 abortions/stillborns (12-38 weeks of gestation). The probes were subdivided into three groups (group 1: 12-18 weeks of gestation, n = 10; group 2: 19-23 weeks of gestation, n = 13; group 3: 24-38 weeks of gestation, n = 11), and prepared for paraffin sections followed by immunohistochemistry against CD31 to detect blood vessels, and against lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1)/podoplanin to detect lymphatic vessels. We could show, that in the human episclera distinct CD31 + blood vessels are present as early as week of gestation 13. Their amount increased during pregnancy, whereas stromal CD31 + blood vessels were elevated in early pregnancy and regressed with ongoing pregnancy. In the lamina fusca CD31 + blood vessels were absent at any time point investigated. Single LYVE1 + cells were identified primarily in the episclera; their amount decreased significantly with increasing gestational ages (group 1 compared to group 3: p < 0.01). However, LYVE1+/podoplanin + lymphatic vessels were not detectable in the sclera at any gestational ages analyzed. In contrast to the conjunctiva where LYVE1+/podoplanin + lymphatic vessels were detectable as early as week 17, the amount of LYVE1 + cells in the sclera was highest in early pregnancy (group 1), with a significant decrease during continuing pregnancy (p < 0.001). These findings are the first evidence for a fetal lymphangiogenic privilege of the sclera and show, that the fetal human sclera contains CD31 + blood vessels, but is primarily alymphatic. Our findings suggest a strong expression of selectively antilymphangiogenic factors, making the developing sclera a potential model to

  5. Progressive loss of lymphatic vessels in skin of patients with systemic sclerosis.

    PubMed

    Manetti, Mirko; Milia, Anna Franca; Guiducci, Serena; Romano, Eloisa; Matucci-Cerinic, Marco; Ibba-Manneschi, Lidia

    2011-02-01

    Systemic sclerosis (SSc) is a connective tissue disorder characterized by microvascular and fibrotic changes in the skin and internal organs. The role of blood vessel dysfunction in the pathogenesis of SSc has been extensively investigated, but few studies have addressed the involvement of the lymphatic vascular system. Our aim was to evaluate dermal lymphatic vessels in patients with SSc according to different phases of skin involvement. Skin biopsies were obtained from the forearm of 25 SSc patients (10 early/15 late-stage disease) and 13 healthy controls. Skin sections were immunostained for podoplanin (D2-40), which is selectively expressed in lymphatic endothelial cells, and examined by confocal laser scanning microscopy. Lymphatic vessels were counted in the papillary and reticular dermis. Data were analyzed using Student's t test. The number of lymphatic vessels was significantly reduced in the papillary and reticular dermis of SSc patients compared with controls. In early SSc, lymphatic vessel counts were not different from controls in the papillary dermis, and showed a trend toward a reduction in the reticular dermis. In late SSc, a significant reduction in lymphatic vessels compared with controls was found in both the papillary and reticular dermis. The number of lymphatic vessels in the papillary dermis of late SSc was significantly lower than in early SSc. In SSc, lymphatic microangiopathy is linked to the progression of skin involvement. The progressive disappearance of lymphatic vessels may have a critical pathogenetic role in the progression of SSc from an early edematous phase to overt fibrosis.

  6. Blockade of FLT4 suppresses metastasis of melanoma cells by impaired lymphatic vessels.

    PubMed

    Lee, Ji Yoon; Hong, Seok-Ho; Shin, Minsang; Heo, Hye-Ryeon; Jang, In Ho

    2016-09-16

    The metastatic spread of tumor cells via lymphatic vessels affects the relapse of tumor patients. New lymphatic vessel formation, including lymphangiogenesis, is promoted in the tumor environment. The lymphangiogenic factor VEGF-C can mediate lymphatic vessel formation and induce tumor metastasis by binding with FLT4. In melanoma, metastasis via lymphatics such as lymph nodes is one of the main predictors of poor outcome. Thus, we investigated whether blockade of FLT4 can reduce metastasis via the suppression of lymphatic capillaries. Proliferative lymphatic capillaries in melanoma were estimated by immunohistochemistry using FLT4 antibody after the injection of the FLT4 antagonist MAZ51. The numbers of tumor modules in metastasised lungs were calculated by gross examination and lymphatic related factors were examined by qRT-PCR. MAZ51 injection resulted in the suppression of tumor size and module number and the inhibition of proliferative lymphatic vessels in the intratumoral region in the lung and proliferating melanoma cells in the lung compared to those of untreated groups. Additionally, high FLT4 and TNF-alpha were detected in melanoma-induced tissue, while lymphatic markers such as VEGF-C, FLT4 and Prox-1 were significantly decreased in MAZ51 treated groups, implying that anti-lymphangiogenesis by MAZ51 may provide a potential strategy to prevent tumor metastasis in melanoma and high number of lymphatic capillaries could be used diagnosis for severe metastasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. LyP-1-conjugated doxorubicin-loaded liposomes suppress lymphatic metastasis by inhibiting lymph node metastases and destroying tumor lymphatics

    NASA Astrophysics Data System (ADS)

    Yan, Zhiqiang; Zhan, Changyou; Wen, Ziyi; Feng, Linglin; Wang, Fei; Liu, Yu; Yang, Xiangkun; Dong, Qing; Liu, Min; Lu, Weiyue

    2011-10-01

    Lymphatic metastasis can be greatly promoted by metastases growth and lymphangiogenesis in lymph nodes (LNs). LyP-1, a cyclic peptide, is able to specifically bind with tumor cells and tumor lymphatics in metastatic LNs. This work aimed to use LyP-1-conjugated liposomes (L-LS) loaded with doxorubicin (DOX) (L-LS/DOX) to suppress lymphatic metastasis by inhibiting both metastases and tumor lymphatics in LNs. L-LS were prepared and exhibited sizes around 90 nm and spherical morphology as characterized by transmission electron microscopy. The in vitro cellular studies showed that LyP-1 modification obviously increased liposome uptake by MDA-MB-435 tumor cells and enhanced the cytotoxicity of liposomal DOX. A popliteal and iliac LN metastases model was successfully established by subcutaneous inoculation of tumor cells to nude mice. The immunofluorescence staining analysis indicated that LyP-1 modification enabled specific binding of liposome with tumor lymphatics and enhanced the destroying effect of liposomal DOX on tumor lymphatics. The in vivo fluorescence imaging and pharmacodynamic studies showed that LyP-1 modification increased liposome uptake by metastatic LNs and that L-LS/DOX significantly decreased metastatic LN growth and LN metastasis rate. These results suggested that L-LS/DOX were an effective delivery system for suppressing lymphatic metastasis by simultaneously inhibiting LN metastases and tumor lymphatics.

  8. Rapid assessment of the geographical distribution of lymphatic filariasis in Uganda, by screening of schoolchildren for circulating filarial antigens.

    PubMed

    Onapa, A W; Simonsen, P E; Baehr, I; Pedersen, E M

    2005-03-01

    To permit improvements in the targeting of control activities, the geographical distribution of lymphatic filariasis in Uganda was assessed by using a rapid immunochromatographic card test to check school-aged children for Wuchereria bancrofti-specific circulating filarial antigens (CFA). Survey sites were selected to represent the various ecological and topographical diversities in the country. Overall, 17,533 children from 76 sites were examined. CFA-positive cases were detected at 31 of the sites, with prevalences ranging from 0.4% to 30.7%. There appeared to be strikingly more lymphatic filariasis in the north of the country than in the south. The main focus was north of the Victoria Nile, where 27 (66%) of 41 sites had CFA-positive cases, often at high prevalences. Only four (11.4%) of the 35 sites south of the Victoria Nile had CFA-positive cases, and all four were along the western rift valley and had relatively low CFA prevalences. Geostatistical interpolation was used to create a map showing the geographical distribution of CFA prevalences in Uganda (by ordinary kriging), and to assess the population exposed to W. bancrofti transmission. Estimates based on population data from 2002 indicated that approximately 8.7 million people (35.3% of the national population) lived in areas where > 1% of the school-aged children were CFA-positive. CFA prevalences generally decreased with increasing altitude, and no CFA-positive cases were found at sites that were > 1300 m above sea level. Although it gives an under-estimate of the overall community prevalence (a fact that should be taken into account when interpreting the present results and comparing them with the results of other surveys), the screening of schoolchildren for CFA was found to be a simple and useful approach for mapping the geographical distribution of lymphatic filariasis.

  9. Quantitative study of the topographic distribution of conjunctival lymphatic vessels in the monkey.

    PubMed

    Guo, Wenyi; Zhu, Yuanfang; Yu, Paula K; Yu, Xiaobo; Sun, Xinghuai; Cringle, Stephen J; Su, Er-Ning; Yu, Dao-Yi

    2012-01-01

    The purpose of this study was to quantify the topographic distribution of bulbar conjunctival microlymphatic vessels in the monkey. Sixteen eyes from 8 rhesus monkeys were used. Full thickness pieces of globe wall were excised from each quadrant. Cryosections were stained for 5'-nucleotidase, an enzyme histochemical staining for lymphatic vessels, or vascular endothelial growth factor receptor-3, an immunohistochemical marker for the identification of lymphatic endothelial cells, and then counterstained by hematoxylin. The remaining bulbar conjunctiva was dissected and flat mounted. The tissue was then processed with 5'-nucleotidase and alkaline phosphatase, an enzyme histochemical stain with higher activity in blood vessels. Microscope images were further analysed by image processing. The density of lymphatics, diameter of lymphatic vessels, and the size of the drainage zone of each blind end of the initial lymphatics were studied. Conjunctival lymphatics consisted of initial lymphatics and pre-collectors. The initial lymphatics with blind ends were predominately distributed just under the epithelium. The density of these lymphatics (∼50%) and the drainage zone area (∼0.81 mm(2)) was similar in each quadrant, with no difference in the limbus and fornix regions. The average diameter of lymphatic vessels in each quadrant ranged from 82 to 111 μm, and was greater in the superior and nasal regions. Larger calibre pre-collectors with valve-like structures were mostly located sub Tenon's membrane and predominantly located in the region mid-way between the limbus and fornix. There was a marked depth difference in initial lymphatic distribution, with the initial lymphatics mostly confined to the region between Tenon's membrane and the conjunctival epithelium. Detailed knowledge of the topographic distribution of conjunctival lymphatics have significant relevance to a better understanding of immunology, drug delivery, glaucoma filtration surgery, and tumour

  10. Lymphoscintigraphic studies of lymphatic drainage from the testes

    SciTech Connect

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

    1986-12-01

    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.

  11. Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration

    PubMed Central

    Brinkman, C. Colin; Iwami, Daiki; Hritzo, Molly K.; Xiong, Yanbao; Ahmad, Sarwat; Simon, Thomas; Hippen, Keli L.; Blazar, Bruce R.; Bromberg, Jonathan S.

    2016-01-01

    Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LTαβ rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NFκB signalling via LTβR. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression. PMID:27323847

  12. Imaging blood vessels and lymphatic vessels in the zebrafish.

    PubMed

    Jung, H M; Isogai, S; Kamei, M; Castranova, D; Gore, A V; Weinstein, B M

    2016-01-01

    Blood vessels supply tissues and organs with oxygen, nutrients, cellular, and humoral factors, while lymphatic vessels regulate tissue fluid homeostasis, immune trafficking, and dietary fat absorption. Understanding the mechanisms of vascular morphogenesis has become a subject of intense clinical interest because of the close association of both types of vessels with pathogenesis of a broad spectrum of human diseases. The zebrafish provides a powerful animal model to study vascular morphogenesis because of their small, accessible, and transparent embryos. These unique features of zebrafish embryos permit sophisticated high-resolution live imaging of even deeply localized vessels during embryonic development and even in adult tissues. In this chapter, we summarize various methods for blood and lymphatic vessel imaging in zebrafish, including nonvital resin injection-based or dye injection-based vessel visualization, and alkaline phosphatase staining. We also provide protocols for vital imaging of vessels using microangiography or transgenic fluorescent reporter zebrafish lines. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Current treatment paradigms in the management of lymphatic malformations.

    PubMed

    Renton, John P; Smith, Richard J H

    2011-01-01

    Lymphatic malformations (LMs) are benign abnormalities of the lymphatic system that can be significantly infiltrative and intimately involve critical structures of the head and neck, making their management difficult. Historically, LMs have been managed by surgical excision, but this treatment approach results in significant morbidity and a high recurrence rate secondary to subtotal resection. As an alternative to surgery a variety of drugs have been used as intralesional sclerosants and immunotherapeutics. These agents offer improved outcomes with lower morbidity as compared to surgery when targeted to macrocystic LMs. However intralesional therapy is not effective in the treatment of microcystic LMs. The development of treatments that are effective for all types of LMs will require further understanding of lymphangiogenesis and the pathogenesis of LMs.

  14. Pediatric lymphatic malformations: evolving understanding and therapeutic options.

    PubMed

    Defnet, Ann M; Bagrodia, Naina; Hernandez, Sonia L; Gwilliam, Natalie; Kandel, Jessica J

    2016-05-01

    Multimodal treatment of lymphatic malformations continues to expand as new information about the biology and genetics of these lesions is discovered, along with knowledge gained from clinical practice. A patient-centered approach, ideally provided by a multidisciplinary medical and surgical team, should guide timing and modality of treatment. Current treatment options include observation, surgery, sclerotherapy, radiofrequency ablation, and laser therapy. New medical and surgical therapies are emerging, and include sildenafil, propranolol, sirolimus, and vascularized lymph node transfer. The primary focus of management is to support and optimize these patients' quality of life. Researchers continue to study lymphatic malformations with the goal of increasing therapeutic options and developing effective clinical pathways for these complicated lesions.

  15. Core content for training in venous and lymphatic medicine

    PubMed Central

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

    2014-01-01

    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. PMID:25059735

  16. Lymphatic Vessel Abnormalities Arising from Disorders of Ras Signal Transduction

    PubMed Central

    Sevick-Muraca, Eva M.; King, Philip D.

    2013-01-01

    A number of genetic diseases in man have been described in which abnormalities in the development and function of the lymphatic vascular (LV) system are prominent features. The genes that are mutated in these diseases are varied and include genes that encode lymphatic endothelial cell (LEC) growth factor receptors and their ligands and transcription factors that control LEC fate and function. In addition, an increasing number of genes have been identified that encode components of the Ras signal transduction pathway that conveys signals from cell surface receptors to regulate cell growth, proliferation and differentiation. Gene targeting studies performed in mice have confirmed that the LV system is particularly susceptible to perturbations in the Ras pathway. PMID:24183794

  17. Lymphatic filariasis in India: epidemiology and control measures.

    PubMed

    Raju, Khk; Jambulingam, P; Sabesan, S; Vanamail, P

    2010-01-01

    Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is an important public health problem in India. Both parasites produce essentially similar clinical presentations in man, related mainly to the pathology of the lymphatic system. Filariasis is endemic in 17 States and six Union Territories, with about 553 million people at risk of infection. The Government of India has accorded a high priority for elimination of this infection through mass chemotherapy programme (annual, single dose of Diethylcarbamazine citrate, i.e. DEC - 6 mg/kg of bodyweight, plus Albendazole repeated four to six times). This campaign has become a part of the National Vector-Borne Disease Control Programme in 2003 under the National Health Policy 2002 and aims to eliminate filariasis by 2015. We discuss here the epidemiology and current control strategy for filariasis; highlighting key issues, challenges and options in the implementation of the programme, and suggesting measures for mid-course corrections in the elimination strategy.

  18. Developmental Dyslexia: Current Anatomical Research.

    ERIC Educational Resources Information Center

    Galaburda, Albert

    1983-01-01

    Findings from anatomical research are highlighted in a discussion of the role of anomalous lateralization and asymmetry in the dyslexic brain. Studies of animal asymmetry are cited along with studies of humans. (CL)

  19. The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: A Proposed Lymph Node Map for Thymic Epithelial Tumors in the Forthcoming 8th Edition of the TNM Classification of Malignant Tumors.

    PubMed

    Bhora, Faiz Y; Chen, David J; Detterbeck, Frank C; Asamura, Hisao; Falkson, Conrad; Filosso, Pier Luigi; Giaccone, Giuseppe; Huang, James; Kim, Jhingook; Kondo, Kazuya; Lucchi, Marco; Marino, Mirella; Marom, Edith M; Nicholson, Andrew G; Okumura, Meinoshin; Ruffini, Enrico; Van Schil, Paul

    2014-09-01

    Although the presence of nodal disease is prognostic in thymic malignancy, the significance of the extent of nodal disease has yet to be defined. Lymph node dissection has not been routinely performed, and there is currently no node map defined for thymic malignancy. To establish a universal language for reporting as well as characterize the staging of this disease more accurately, an empiric node map is proposed here. This was developed using prior classification systems, series reporting specifics of nodal involvement, anatomical studies of lymphatic drainage, and preexisting node maps of the chest as defined by the International Association for the Study of Lung Cancer and the neck as defined by the American Academy of Otolaryngology-Head and Neck Surgery and the American Society for Head and Neck Surgery. The development of this node map was a joint effort by the International Thymic Malignancy Interest Group and the Thymic Domain of the IASLC Staging and Prognostic Factors Committee. It was reviewed and subsequently approved by the members of ITMIG. This map will be used as an adjunct to define node staging as part of a universal stage classification for thymic malignancy. As more data are gathered using definitions set forth by this node map, a revision may be undertaken in the future.

  20. Imported lymphatic filariasis in an Indian immigrant to iran.

    PubMed

    Kia, Eshrat Beigom; Sharifdini, Meysam; Hajjaran, Homa; Shahbazi, Ali Ehsan; Sayyad Talaie, Zahra

    2014-03-01

    Lymphatic filariasis (LF), a nematode disease transmitted by arthropod vectors, is repeatedly reported in immigrant population. This disease is not endemic in Iran; however, different species of mosquitoes, capable of transmission of parasite microfilaria, are distributed in the country. Hereby, incidental detection of an imported case of LF due to Wuchereria bancrofti in an Indian worker in Iran is reported. Identification of the case was performed based on morphological and morphometrical characteristics of microfilaria and PCR sequencing.

  1. Studies of lymphatic drainage from testes by lymphoscintigraphy

    SciTech Connect

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

    1985-05-01

    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.

  2. [Clinical analysis of two cases with diffuse pulmonary lymphatic disease].