Inflammatory Manifestations of Experimental Lymphatic Insufficiency
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{"title"=>"Inflammatory manifestations of experimental lymphatic insufficiency", "type"=>"journal", "authors"=>[{"first_name"=>"Raymond", "last_name"=>"Tabibiazar", "scopus_author_id"=>"6602618594"}, {"first_name"=>"Lauren", "last_name"=>"Cheung", "scopus_author_id"=>"8252005700"}, {"first_name"=>"Jennifer", "last_name"=>"Han", "scopus_author_id"=>"56170949300"}, {"first_name"=>"Jeffrey", "last_name"=>"Swanson", "scopus_author_id"=>"55423096800"}, {"first_name"=>"Andreas", "last_name"=>"Beilhack", "scopus_author_id"=>"8587426300"}, {"first_name"=>"Andrew", "last_name"=>"An", "scopus_author_id"=>"6701725455"}, {"first_name"=>"Soheil S.", "last_name"=>"Dadras", "scopus_author_id"=>"26639216300"}, {"first_name"=>"Ned", "last_name"=>"Rockson", "scopus_author_id"=>"6505663871"}, {"first_name"=>"Smita", "last_name"=>"Joshi", "scopus_author_id"=>"55466300000"}, {"first_name"=>"Roger", "last_name"=>"Wagner", "scopus_author_id"=>"7404292272"}, {"first_name"=>"Stanley G.", "last_name"=>"Rockson", "scopus_author_id"=>"7005902777"}], "year"=>2006, "source"=>"PLoS Medicine", "identifiers"=>{"scopus"=>"2-s2.0-33746464968", "sgr"=>"33746464968", "issn"=>"15491277", "doi"=>"10.1371/journal.pmed.0030254", "pmid"=>"16834456", "isbn"=>"1549-1676 (Electronic)\\r1549-1277 (Linking)", "pui"=>"44125997"}, "id"=>"5794bae3-3bf8-3374-b7ea-c2ea07d9221f", "abstract"=>"BACKGROUND: Sustained lymph stagnation engenders a pathological response that is complex and not well characterized. Tissue inflammation in lymphedema may reflect either an active or passive consequence of impaired immune traffic.\\n\\nMETHODS AND FINDINGS: We studied an experimental model of acute post-surgical lymphedema in the tails of female hairless, immunocompetent SKH-1 mice. We performed in vivo imaging of impaired immune traffic in experimental, murine acquired lymphatic insufficiency. We demonstrated impaired mobilization of immunocompetent cells from the lymphedematous region. These findings correlated with histopathological alterations and large-scale transcriptional profiling results. We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response.\\n\\nCONCLUSIONS: We have characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging and histopathological correlation. The model closely simulates the volume response, histopathology, and lymphoscintigraphic characteristics of human acquired lymphedema, and the response is accompanied by an increase in the number and size of microlymphatic structures in the lymphedematous cutaneous tissues. Molecular characterization through clustering of genes with known functions provides insights into processes and signaling pathways that compose the acute tissue response to lymph stagnation. Further study of genes identified through this effort will continue to elucidate the molecular mechanisms and lead to potential therapeutic strategies for lymphatic vascular insufficiency.", "link"=>"http://www.mendeley.com/research/inflammatory-manifestations-experimental-lymphatic-insufficiency", "reader_count"=>50, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Researcher"=>7, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>4, "Student > Master"=>9, "Other"=>5, "Student > Bachelor"=>5, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Researcher"=>7, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>4, "Student > Master"=>9, "Other"=>5, "Student > Bachelor"=>5, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Nursing and Health Professions"=>1, "Medicine and Dentistry"=>21, "Agricultural and Biological Sciences"=>20, "Veterinary Science and Veterinary Medicine"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>21}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>20}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"South Korea"=>1, "United States"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/958211"], "description"=>"<p>Tail Volume Changes at Post-Surgical Day 7 and at Day 14</p>", "links"=>[], "tags"=>["post-surgical"], "article_id"=>628244, "categories"=>["Cancer", "Cell Biology"], "users"=>["Raymond Tabibiazar", "Lauren Cheung", "Jennifer Han", "Jeffrey Swanson", "Andreas Beilhack", "Andrew An", "Soheil S Dadras", "Ned Rockson", "Smita Joshi", "Roger Wagner", "Stanley G Rockson"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030254.g001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tail_Volume_Changes_at_Post_Surgical_Day_7_and_at_Day_14_/628244", "title"=>"Tail Volume Changes at Post-Surgical Day 7 and at Day 14", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:33:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/958671"], "description"=>"<div><p>(A) In vivo bioluminescence imaging of immune traffic. Bioluminescence imaging was performed at defined time points following the introduction of \n\t\t\t\t\t\t\t<i>luc<sup>+</sup></i> cells. This figure contains a representative series of imaging experiments for paired normal control (A) and lymphedema (B) mice. Photon densities range from red (high) to blue (low). In general, clearance of bioluminescent immunocytes from the lymphedematous tails was delayed, but remained unimpaired in the surgical sham controls. The left panel shows a perceptible increase in photon densities in lymphedema on day 3 post-injection (post-operative day 10). Within several days, the disparity in cellular clearance is even more evident (middle panel); as late as day 17 post-injection, there is still visible bioluminescence in the lymphedematous tail, while all activity has cleared from the normal tail (right panel). The original surgical site is depicted by the white arrows. The black marks on the tail denote 8-mm vertical distances; splenocyte injection was performed 24 mm below the surgical site.\n\t\t\t\t\t\t</p>\n <p>(B) Quantitative assessment of in vivo bioluminescence imaging of immune traffic. Relative photon density, expressed as a percent of the observed value on day 1, was significantly greater in lymphedema than in normal controls, both at day 3 and at day 7 post-injection (*, \n\t\t\t\t\t\t\t<i>p <</i> 0.05; §, \n\t\t\t\t\t\t\t<i>p <</i> 0.02).\n\t\t\t\t\t\t</p></div>", "links"=>[], "tags"=>["imaging"], "article_id"=>628702, "categories"=>["Cancer", "Cell Biology"], "users"=>["Raymond Tabibiazar", "Lauren Cheung", "Jennifer Han", "Jeffrey Swanson", "Andreas Beilhack", "Andrew An", "Soheil S Dadras", "Ned Rockson", "Smita Joshi", "Roger Wagner", "Stanley G Rockson"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030254.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dynamic_Imaging_of_Immune_Traffic_in_Experimental_Lymphedema_/628702", "title"=>"Dynamic Imaging of Immune Traffic in Experimental Lymphedema", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:37:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/958527"], "description"=>"<p>Immunohistochemical staining for LYVE-1 is depicted in surgical sham controls (A) and in lymphedema (B) (black arrows). The lymphedema response is characterized by the presence of numerous dilated microlymphatic structures in the dermis and subdermis. Lymphedema produces a statistically significant increase in average cross-sectional vessel area.</p>", "links"=>[], "tags"=>["immunohistochemical"], "article_id"=>628554, "categories"=>["Cancer", "Cell Biology"], "users"=>["Raymond Tabibiazar", "Lauren Cheung", "Jennifer Han", "Jeffrey Swanson", "Andreas Beilhack", "Andrew An", "Soheil S Dadras", "Ned Rockson", "Smita Joshi", "Roger Wagner", "Stanley G Rockson"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030254.g003", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LYVE_1_Immunohistochemical_Staining_/628554", "title"=>"LYVE-1 Immunohistochemical Staining", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:36:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/958349"], "description"=>"<div><p>Lymphedema was characterized by the presence of marked acute inflammatory changes, both adjacent to the surgical site and within distal regions of the tail, remote from the site of surgical ablation.</p>\n <p>(A) Normal tail skin harvested 16 mm from the base of the tail is characterized by the presence of a thin dermis and epidermis, with a normal epidermal/dermal junction. Surgical sham controls were indistinguishable from normals, with no increased cellularity in dermis or epidermis, and no enlarged nuclei or hyperkeratosis.</p>\n <p>(B) Lymphedematous skin harvested immediately distal to the site of prior surgical lymphatic ablation is characterized by the presence of marked acute inflammatory changes, absent in the tissue derived from the normal tails. There is a notable increase in cellularity, with an increase in the number of observed fibroblasts and histiocytes, as well as a large infiltration of neutrophils. There is hyperkeratosis and spongiosis and edema of the epidermis, with irregularity of the epidermal/dermal junction, elongation of the dermal papillae, and a 2- to 3-fold expansion of tissue between the bone and the epidermis. There are numerous dilated lymphatic microvessels in the dermis and subdermis (black arrows). In contrast, normal tail sections were devoid of these dilated structures.</p>\n <p>(C) Normal skin derived from the distal tail. No inflammation, hypercellularity, or lymphatic dilatation is observed.</p>\n <p>(D) Distal skin in lymphedema. Spongiosis and lymphatic microvascular dilatation (black arrows) are once again detectable.</p></div>", "links"=>[], "tags"=>["lymphedema", "murine"], "article_id"=>628382, "categories"=>["Cancer", "Cell Biology"], "users"=>["Raymond Tabibiazar", "Lauren Cheung", "Jennifer Han", "Jeffrey Swanson", "Andreas Beilhack", "Andrew An", "Soheil S Dadras", "Ned Rockson", "Smita Joshi", "Roger Wagner", "Stanley G Rockson"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030254.g002", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histopathology_of_Experimental_Lymphedema_in_the_Murine_Tail_/628382", "title"=>"Histopathology of Experimental Lymphedema in the Murine Tail", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:34:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/958882"], "description"=>"<p>The graph represents fold-changes of expression in lymphedema, relative to normal controls, for each of eight representative genes, by microarray hybridization and qRT-PCR. For \n\t\t\t\t\t\t\t<i>MYD88</i> by microarray and \n\t\t\t\t\t\t\t<i>HADH2</i> by qRT-PCR, the log (gene expression) equaled zero. \n\t\t\t\t\t\t\t<i>HADH2, hydroxysteroid (17-beta) dehydrogenase; 2MMP, matrix metalloproteinase; MYD88, myeloid differentiation primary response gene 88.</i></p>", "links"=>[], "tags"=>["confirmation", "microarray"], "article_id"=>628909, "categories"=>["Cancer", "Cell Biology"], "users"=>["Raymond Tabibiazar", "Lauren Cheung", "Jennifer Han", "Jeffrey Swanson", "Andreas Beilhack", "Andrew An", "Soheil S Dadras", "Ned Rockson", "Smita Joshi", "Roger Wagner", "Stanley G Rockson"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030254.g006", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_qRT_PCR_Confirmation_of_the_Results_of_Microarray_Hybridization_/628909", "title"=>"qRT-PCR Confirmation of the Results of Microarray Hybridization", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:38:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/475127"], "description"=>"<div><h3>Background</h3><p>Sustained lymph stagnation engenders a pathological response that is complex and not well characterized. Tissue inflammation in lymphedema may reflect either an active or passive consequence of impaired immune traffic.</p> <h3>Methods and Findings</h3><p>We studied an experimental model of acute post-surgical lymphedema in the tails of female hairless, immunocompetent SKH-1 mice. We performed in vivo imaging of impaired immune traffic in experimental, murine acquired lymphatic insufficiency. We demonstrated impaired mobilization of immunocompetent cells from the lymphedematous region. These findings correlated with histopathological alterations and large-scale transcriptional profiling results. We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response.</p> <h3>Conclusions</h3><p>We have characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging and histopathological correlation. The model closely simulates the volume response, histopathology, and lymphoscintigraphic characteristics of human acquired lymphedema, and the response is accompanied by an increase in the number and size of microlymphatic structures in the lymphedematous cutaneous tissues. Molecular characterization through clustering of genes with known functions provides insights into processes and signaling pathways that compose the acute tissue response to lymph stagnation. Further study of genes identified through this effort will continue to elucidate the molecular mechanisms and lead to potential therapeutic strategies for lymphatic vascular insufficiency.</p> </div>", "links"=>[], "tags"=>["inflammatory", "manifestations", "lymphatic", "insufficiency"], "article_id"=>153614, "categories"=>["Cancer", "Cell Biology"], "users"=>["Raymond Tabibiazar", "Lauren Cheung", "Jennifer Han", "Jeffrey Swanson", "Andreas Beilhack", "Andrew An", "Soheil S Dadras", "Ned Rockson", "Smita Joshi", "Roger Wagner", "Stanley G Rockson"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030254", "stats"=>{"downloads"=>3, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Inflammatory_Manifestations_of_Experimental_Lymphatic_Insufficiency/153614", "title"=>"Inflammatory Manifestations of Experimental Lymphatic Insufficiency", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2006-07-18 01:00:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/958793"], "description"=>"<p>At an FDR of 5%, SAM analysis identified 429 upregulated genes in the lymphedema state versus 183 downregulated genes. There were no statistically significant differences between normal mice and surgical control animals (SAM, FDR < 25%). Enrichment analysis with the Fisher's exact test (EASE software) demonstrated several statistically significant ontologies.</p>", "links"=>[], "tags"=>["microarray"], "article_id"=>628821, "categories"=>["Cancer", "Cell Biology"], "users"=>["Raymond Tabibiazar", "Lauren Cheung", "Jennifer Han", "Jeffrey Swanson", "Andreas Beilhack", "Andrew An", "Soheil S Dadras", "Ned Rockson", "Smita Joshi", "Roger Wagner", "Stanley G Rockson"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030254.g005", "stats"=>{"downloads"=>3, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SAM_Analysis_of_Microarray_Data_/628821", "title"=>"SAM Analysis of Microarray Data", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:38:08"}

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Relative Metric

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