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Michael Detmar - One of the best experts on this subject based on the ideXlab platform.
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prominent Lymphatic Vessel hyperplasia with progressive dysfunction and distinct immune cell infiltration in lymphedema
American Journal of Pathology, 2016Co-Authors: Epameinondas Gousopoulos, Steven T Proulx, Jeannette Scholl, Maja Uecker, Michael DetmarAbstract:Lymphedema is a common complication that occurs after breast cancer treatment in up to 30% of the patients undergoing surgical lymph node excision. It is associated with tissue swelling, fibrosis, increased risk of infection, and impaired wound healing. Despite the pronounced clinical manifestations of the disease, little is known about the morphological and functional characteristics of the Lymphatic vasculature during the course of lymphedema progression. We used an experimental murine tail lymphedema model where sustained fluid stasis was generated on disruption of Lymphatic flow, resulting in chronic edema formation with fibrosis and adipose tissue deposition. Morphological analysis of the Lymphatic Vessels revealed a dramatic expansion during the course of the disease, with active proliferation of Lymphatic endothelial cells at the early stages of lymphedema. The Lymphatic capillaries exhibited progressively impaired tracer filling and retrograde flow near the surgery site, whereas the collecting Lymphatic Vessels showed a gradually decreasing contraction amplitude with unchanged contraction frequency, leading to Lymphatic contraction arrest at the later stages of the disease. Lymphedema onset was associated with pronounced infiltration by immune cells, predominantly Ly6G(+) and CD4(+) cells, which have been linked to impaired Lymphatic Vessel function.
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in vivo visualization and quantification of collecting Lymphatic Vessel contractility using near infrared imaging
Scientific Reports, 2016Co-Authors: Chloe Chong, Michael Detmar, Felix Scholkmann, Samia B Bachmann, Paola Luciani, Jeanchristophe Leroux, Steven T ProulxAbstract:Techniques to image Lymphatic Vessel function in either animal models or in the clinic are limited. In particular, imaging methods that can provide robust outcome measures for collecting Lymphatic Vessel function are sorely needed. In this study, we aimed to develop a method to visualize and quantify collecting Lymphatic Vessel function in mice, and to establish an in vivo system for evaluation of contractile agonists and antagonists using near-infrared fluorescence imaging. The flank collecting Lymphatic Vessel in mice was exposed using a surgical technique and a near-infrared tracer was infused into the inguinal lymph node. Collecting Lymphatic Vessel contractility and valve function could be easily visualized after the infusion. A diameter tracking method was established and the diameter of the Vessel was found to closely correlate to near-infrared fluorescence signal. Phasic contractility measures of frequency and amplitude were established using an automated algorithm. The methods were validated by tracking the Vessel response to topical application of a contractile agonist, prostaglandin F2α, and by demonstrating the potential of the technique for non-invasive evaluation of modifiers of Lymphatic function. These new methods will enable high-resolution imaging and quantification of collecting Lymphatic Vessel function in animal models and may have future clinical applications.
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Decline of Lymphatic Vessel density and function in murine skin during aging
Angiogenesis, 2015Co-Authors: Sinem Karaman, Michael Detmar, Paola Luciani, Jeanchristophe Leroux, Dorina Buschle, Steven T ProulxAbstract: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.
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a transgenic prox1 cre tdtomato reporter mouse for Lymphatic Vessel research
PLOS ONE, 2015Co-Authors: Roberta Bianchi, Steven T Proulx, Taija Makinen, Alvaro Teijeira, Ailsa J Christiansen, Catharina D Seidel, Thomas Rulicke, Rene Hagerling, Cornelia Halin, Michael DetmarAbstract:The Lymphatic vascular system plays an active role in immune cell trafficking, inflammation and cancer spread. In order to provide an in vivo tool to improve our understanding of Lymphatic Vessel function in physiological and pathological conditions, we generated and characterized a tdTomato reporter mouse and crossed it with a mouse line expressing Cre recombinase under the control of the Lymphatic specific promoter Prox1 in an inducible fashion. We found that the tdTomato fluorescent signal recapitulates the expression pattern of Prox1 in Lymphatic Vessels and other known Prox1-expressing organs. Importantly, tdTomato co-localized with the Lymphatic markers Prox1, LYVE-1 and podoplanin as assessed by whole-mount immunofluorescence and FACS analysis. The tdTomato reporter was brighter than a previously established red fluorescent reporter line. We confirmed the applicability of this animal model to intravital microscopy of dendritic cell migration into and within Lymphatic Vessels, and to fluorescence-activated single cell analysis of Lymphatic endothelial cells. Additionally, we were able to describe the early morphological changes of the Lymphatic vasculature upon induction of skin inflammation. The Prox1-Cre-tdTomato reporter mouse thus shows great potential for Lymphatic research.
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chronic high fat diet impairs collecting Lymphatic Vessel function in mice
PLOS ONE, 2014Co-Authors: Katrin S Blum, Paola Luciani, Jeanchristophe Leroux, Steven T Proulx, Sinem Karaman, Alexandra M Ochsenbein, Christian Wolfrum, Michael DetmarAbstract: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.
Steven T Proulx - One of the best experts on this subject based on the ideXlab platform.
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prominent Lymphatic Vessel hyperplasia with progressive dysfunction and distinct immune cell infiltration in lymphedema
American Journal of Pathology, 2016Co-Authors: Epameinondas Gousopoulos, Steven T Proulx, Jeannette Scholl, Maja Uecker, Michael DetmarAbstract:Lymphedema is a common complication that occurs after breast cancer treatment in up to 30% of the patients undergoing surgical lymph node excision. It is associated with tissue swelling, fibrosis, increased risk of infection, and impaired wound healing. Despite the pronounced clinical manifestations of the disease, little is known about the morphological and functional characteristics of the Lymphatic vasculature during the course of lymphedema progression. We used an experimental murine tail lymphedema model where sustained fluid stasis was generated on disruption of Lymphatic flow, resulting in chronic edema formation with fibrosis and adipose tissue deposition. Morphological analysis of the Lymphatic Vessels revealed a dramatic expansion during the course of the disease, with active proliferation of Lymphatic endothelial cells at the early stages of lymphedema. The Lymphatic capillaries exhibited progressively impaired tracer filling and retrograde flow near the surgery site, whereas the collecting Lymphatic Vessels showed a gradually decreasing contraction amplitude with unchanged contraction frequency, leading to Lymphatic contraction arrest at the later stages of the disease. Lymphedema onset was associated with pronounced infiltration by immune cells, predominantly Ly6G(+) and CD4(+) cells, which have been linked to impaired Lymphatic Vessel function.
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in vivo visualization and quantification of collecting Lymphatic Vessel contractility using near infrared imaging
Scientific Reports, 2016Co-Authors: Chloe Chong, Michael Detmar, Felix Scholkmann, Samia B Bachmann, Paola Luciani, Jeanchristophe Leroux, Steven T ProulxAbstract:Techniques to image Lymphatic Vessel function in either animal models or in the clinic are limited. In particular, imaging methods that can provide robust outcome measures for collecting Lymphatic Vessel function are sorely needed. In this study, we aimed to develop a method to visualize and quantify collecting Lymphatic Vessel function in mice, and to establish an in vivo system for evaluation of contractile agonists and antagonists using near-infrared fluorescence imaging. The flank collecting Lymphatic Vessel in mice was exposed using a surgical technique and a near-infrared tracer was infused into the inguinal lymph node. Collecting Lymphatic Vessel contractility and valve function could be easily visualized after the infusion. A diameter tracking method was established and the diameter of the Vessel was found to closely correlate to near-infrared fluorescence signal. Phasic contractility measures of frequency and amplitude were established using an automated algorithm. The methods were validated by tracking the Vessel response to topical application of a contractile agonist, prostaglandin F2α, and by demonstrating the potential of the technique for non-invasive evaluation of modifiers of Lymphatic function. These new methods will enable high-resolution imaging and quantification of collecting Lymphatic Vessel function in animal models and may have future clinical applications.
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Decline of Lymphatic Vessel density and function in murine skin during aging
Angiogenesis, 2015Co-Authors: Sinem Karaman, Michael Detmar, Paola Luciani, Jeanchristophe Leroux, Dorina Buschle, Steven T ProulxAbstract: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.
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a transgenic prox1 cre tdtomato reporter mouse for Lymphatic Vessel research
PLOS ONE, 2015Co-Authors: Roberta Bianchi, Steven T Proulx, Taija Makinen, Alvaro Teijeira, Ailsa J Christiansen, Catharina D Seidel, Thomas Rulicke, Rene Hagerling, Cornelia Halin, Michael DetmarAbstract:The Lymphatic vascular system plays an active role in immune cell trafficking, inflammation and cancer spread. In order to provide an in vivo tool to improve our understanding of Lymphatic Vessel function in physiological and pathological conditions, we generated and characterized a tdTomato reporter mouse and crossed it with a mouse line expressing Cre recombinase under the control of the Lymphatic specific promoter Prox1 in an inducible fashion. We found that the tdTomato fluorescent signal recapitulates the expression pattern of Prox1 in Lymphatic Vessels and other known Prox1-expressing organs. Importantly, tdTomato co-localized with the Lymphatic markers Prox1, LYVE-1 and podoplanin as assessed by whole-mount immunofluorescence and FACS analysis. The tdTomato reporter was brighter than a previously established red fluorescent reporter line. We confirmed the applicability of this animal model to intravital microscopy of dendritic cell migration into and within Lymphatic Vessels, and to fluorescence-activated single cell analysis of Lymphatic endothelial cells. Additionally, we were able to describe the early morphological changes of the Lymphatic vasculature upon induction of skin inflammation. The Prox1-Cre-tdTomato reporter mouse thus shows great potential for Lymphatic research.
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chronic high fat diet impairs collecting Lymphatic Vessel function in mice
PLOS ONE, 2014Co-Authors: Katrin S Blum, Paola Luciani, Jeanchristophe Leroux, Steven T Proulx, Sinem Karaman, Alexandra M Ochsenbein, Christian Wolfrum, Michael DetmarAbstract: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.
Heikki Joensuu - One of the best experts on this subject based on the ideXlab platform.
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Lymphatic Vessel density in vocal cord carcinomas assessed with lyve 1 receptor expression
Radiotherapy and Oncology, 2005Co-Authors: Walter J Koskinen, Petri Bono, Ilmo Leivo, Antti Vaheri, Leenamaija Aaltonen, Heikki JoensuuAbstract:Abstract Background and purpose Early stage vocal cord carcinomas are usually cured by radiation therapy despite the use of portals that exclude the cervical lymph nodes. We investigated whether the Lymphatic Vessel density (LVD) of vocal cord carcinomas differs from that of other head and neck carcinomas. Patients and methods Deparaffinized tissue from tumors of 60 patients diagnosed with head and neck squamous cell carcinoma (HNSCC) were immunostained for LYVE-1, a novel Lymphatic Vessel marker. Twenty-two had vocal cord carcinoma. Tumor blood Vessel density (BVD) was assessed using immunostaining for CD31. Results Tumor overall LVD, including both intra- and peritumoral lymph Vessels, was 10-fold lower than the BVD (5counts/mm 2 vs. 52mm −2 , respectively). A high LVD was associated with a high BVD ( P =.002), but neither was associated with the tumor size. Both tumor LVD and BVD were lower in vocal cord carcinomas than in HNSCCs arising at other sites (median, 0 vs. 7mm −2 , P =.016; and median, 36 vs. 52mm −2 , P =.006, respectively). Only one vocal cord carcinoma was associated with a regional metastasis at the time of the diagnosis. Among the rest of the cases tumor size was a better predictor for the presence of regional metastases than tumor BVD or LVD in a logistic regression model (odds ratio 2.2, 95% CI 1.1–4.5). Conclusion Vocal cord carcinomas have a low lymph Vessel density as compared with HNSCCs arising at other sites.
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high lyve 1 positive Lymphatic Vessel numbers are associated with axillary lymph node metastases and poor outcome in breast cancer
Journal of Clinical Oncology, 2004Co-Authors: Petri Bono, David G Jackson, Velimatti Wasenius, Johan Lundin, Heikki JoensuuAbstract:9518 Background: The clinical significance of intratumoral or peritumoral lymph Vessel density is not known. LYVE-1, a Lymphatic endothelium specific hyaluronan receptor, is a novel Lymphatic Vessel marker which is expressed on lymph Vessel endothelial cells of both normal and neoplastic tissues. Methods: We investigated expression of LYVE-1 by means of immunhistoochemistry in a series of 180 unilateral, invasive ductal breast carcinomas, in order to assess the correlation between the density of lymph Vessels, the incidence of lymph node metastases and clinical outcome. Results: A minority (12%) of breast carcinomas had intratumoral lymph Vessels, whereas peritumoral lymph Vessels were identified in almost all cases (94%). No significant association was found between the number of LYVE-1 positive Vessels and the number of CD31 or VEGFR-3 (vascular endothelial growth factor receptor-3) positive Vessels. The number of metastatic axillary lymph nodes increased in parallel with increasing lymph Vessel counts ...
Giorgia Jurisic - One of the best experts on this subject based on the ideXlab platform.
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s1p s1pr1 activity controls vegf a signaling during Lymphatic Vessel development
bioRxiv, 2019Co-Authors: A M Goldingochsenbein, Solange Vidal, Wilmering B Wetter, C Guibourdenche, C Beerli, L Chang, S Leonhard, N Holway, Klaus Seuwen, Giorgia JurisicAbstract:Sphingosine-1-phosphate (S1P), a lipid signaling molecule produced by endothelial cells, is required for development and homeostasis of blood Vessels. However, its role during Lymphatic Vessel development is unclear. We show in murine newborns that pharmacologically enhanced S1P signaling increases VEGF-A-dependent LEC proliferation. In contrast, S1PR1 inhibition, mediated by the antagonist NIBR0213 or LEC-specific genetic deletion of S1pr1, promotes filopodia formation and Vessel branching, independent of VEGF-A. To investigate the S1P and VEGF-A signaling crosstalk observed in vivo, we used LECs cultured in vitro. We demonstrate that S1P activates endogenous S1PR1 in a constitutive, autocrine manner. Importantly, S1P-S1PR1 activity was required for VEGF-A-induced LEC proliferation and strongly supported ERK1/2 activation and VEGFR-2 trafficking to the perinuclear area. In conclusion, S1P-S1PR1 signaling promotes VEGF-A-dependent LEC proliferation and limits migratory and filopodia-forming responses. Hence, S1P-S1PR1 signaling is required for balanced growth factor-induced lymphangiogenesis and correctly patterned Lymphatic Vessels during postnatal development.
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blockade of vegf receptor 3 aggravates inflammatory bowel disease and Lymphatic Vessel enlargement
Inflammatory Bowel Diseases, 2013Co-Authors: Giorgia Jurisic, John P. Sundberg, Michael DetmarAbstract:BACKGROUND In contrast to the prominent function of the blood vasculature in promoting tissue inflammation, the role of Lymphatic Vessels in inflammation has been scarcely studied in vivo. To investigate whether modulating Lymphatic Vessel function might affect the course of chronic inflammation, the major lymphangiogenic receptor, vascular growth factor receptor 3 (VEGFR-3, FLT4), was blocked in an established model of inflammatory bowel disease. METHODS Interleukin 10 (IL10)-deficient mice that spontaneously develop inflammatory bowel disease were treated with a blocking antibody to VEGFR-3 for 18 days, and the inflammatory changes in colon tissue and the blood and Lymphatic vascularization were quantitatively analyzed. RESULTS We found a significant increase in the severity of colon inflammation in anti-VEGFR-3-treated mice. This was accompanied by an increased number of enlarged and tortuous Lymphatic Vessels and edema in colon submucosa, indicating impaired Lymphatic function. In contrast, no major effects of the treatment on the blood vasculature were observed. CONCLUSIONS These results indicate that therapies aimed at promoting Lymphatic function, e.g., with prolymphangiogenic factors, such as VEGF-C, might provide a novel strategy for the treatment of inflammatory conditions, such as inflammatory bowel disease.
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an unexpected role of semaphorin3a neuropilin 1 signaling in Lymphatic Vessel maturation and valve formation
Circulation Research, 2012Co-Authors: Giorgia Jurisic, Annamari Alitalo, Shoib S Siddiqui, Helene Mabyel Hajjami, Sinem Karaman, Alexandra M Ochsenbein, Carlos Ochoa Pereira, Tatiana V Petrova, Michael DetmarAbstract:Rationale: Lymphatic vasculature plays important roles in tissue fluid homeostasis maintenance and in the pathology of human diseases. Yet, the molecular mechanisms that control Lymphatic Vessel maturation remain largely unknown. Objective: We analyzed the gene expression profiles of ex vivo isolated Lymphatic endothelial cells to identify novel Lymphatic Vessel expressed genes and we investigated the role of semaphorin 3A (Sema3A) and neuropilin-1 (Nrp-1) in Lymphatic Vessel maturation and function. Methods and Results: Lymphatic and blood vascular endothelial cells from mouse intestine were isolated using fluorescence-activated cell sorting, and transcriptional profiling was performed. We found that the axonal guidance molecules Sema3A and Sema3D were highly expressed by Lymphatic Vessels. Importantly, we found that the semaphorin receptor Nrp-1 is expressed on the perivascular cells of the collecting Lymphatic Vessels. Treatment of mice in utero (E12.5-E16.5) with an antibody that blocks Sema3A binding to Nrp-1 but not with an antibody that blocks VEGF-A binding to Nrp-1 resulted in a complex phenotype of impaired Lymphatic Vessel function, enhanced perivascular cell coverage, and abnormal Lymphatic Vessel and valve morphology. Conclusions: Together, these results reveal an unanticipated role of Sema3A–Nrp-1 signaling in the maturation of the Lymphatic vascular network likely via regulating the perivascular cell coverage of the Vessels thus affecting Lymphatic Vessel function and Lymphatic valve development.
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Quantitative Lymphatic Vessel trait analysis suggests Vcam1 as candidate modifier gene of inflammatory bowel disease.
Genes and immunity, 2010Co-Authors: Giorgia Jurisic, Dietmar Vestweber, John P. Sundberg, André Bleich, Edward H. Leiter, Karl W. Broman, G Buechler, L Alley, Michael DetmarAbstract:Inflammatory bowel disease (IBD) is a chronic debilitating disease resulting from a complex interaction of multiple genetic factors with the environment. To identify modifier genes of IBD, we used an F2 intercross of IBD-resistant C57BL/6J-Il10(-/-) mice and IBD-susceptible C3H/HeJBir-Il10(-/-) (C3Bir-Il10(-/-)) mice. We found a prominent involvement of Lymphatic Vessels in IBD and applied a scoring system to quantify Lymphatic vascular changes. Quantitative trait locus (QTL) analyses revealed a large-effect QTL on chromosome 3, mapping to an interval of 43.6 Mbp. This candidate interval was narrowed by fine mapping to 22 Mbp, and candidate genes were analyzed by a systems genetics approach that included quantitative gene expression profiling, search for functional polymorphisms, and haplotype block analysis. We identified vascular adhesion molecule 1 (Vcam1) as a candidate modifier gene in the interleukin 10-deficient mouse model of IBD. Importantly, VCAM1 protein levels were increased in susceptible C3H/HeJ mice, compared with C57BL/6J mice; systemic blockade of VCAM1 in C3Bir-Il10(-/-) mice reduced their inflammatory Lymphatic Vessel changes. These results indicate that genetically determined expression differences of VCAM1 are associated with susceptibility to colon inflammation, which is accompanied by extensive Lymphatic Vessel changes. VCAM1 is, therefore, a promising therapeutic target for IBD.
Isao Koshima - One of the best experts on this subject based on the ideXlab platform.
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optimal sites for supermicrosurgical Lymphaticovenular anastomosis an analysis of Lymphatic Vessel detection rates on 840 surgical fields in lower extremity lymphedema patients
Plastic and Reconstructive Surgery, 2018Co-Authors: Takumi Yamamoto, Mitsunaga Narushima, Nana Yamamoto, Yuma Fuse, Isao KoshimaAbstract:Background:Supermicrosurgical Lymphaticovenular anastomosis is becoming a useful treatment option for progressive lower extremity lymphedema because of its minimal invasiveness. Finding a Lymphatic Vessel is a minimum requirement for Lymphaticovenular anastomosis surgery, but no study has reported c
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Lymphatic Vessel diameter in female pelvic cancer related lower extremity lymphedematous limbs
Journal of Surgical Oncology, 2018Co-Authors: Takumi Yamamoto, Mitsunaga Narushima, Isao KoshimaAbstract:BACKGROUND Lymphaticovenular anastomosis (LVA) has become one of the useful surgical treatments for compression-refractory lower extremity lymphedema (LEL). It is important to anastomose larger Lymphatic Vessels with abundant lymph flows in LVA surgery. This study aimed to clarify factors associated with Lymphatic Vessel diameter. METHODS One hundred thirty-four LEL patients who underwent pre-operative indocyanine green (ICG) lymphography and LVA from June 2009 to August 2014 in a single institution were included in this retrospective observational study. Clinical, ICG lymphography, and intraoperative findings were collected from medical charts. A Lymphatic Vessel with external diameters of 0.5 mm or larger was defined as a large Lymphatic Vessel (LLV). Independent factors associated with LLV were identified using logistic regression analysis. RESULTS Nine hundred sixty-two Lymphatic Vessels were identified, among which 438 (45.5%) were LLVs. Independent factors associated with LLV were older age (odds ration [OR], 1.408; 95% confidence interval [CI], 1.026-1.931; P = 0.034), positive history of radiation (OR, 1.634; 95%CI 1.228-2.173; P = 0.001), incision site in the thigh/lower leg compared with in the groin (OR, 1.617/1.685; 95%CI 1.076-2.432/1.148-2.473; P = 0.021/0.008). Inverse associations were observed in S-region/D-region on ICG lymphography compared with L-region (OR, 0.537/0.048; 95%CI, 0.397-0.726/0.006-0.371; P < 0.001/0.004). CONCLUSIONS D-region on ICG lymphography had the lowest OR to find LLV, representing that Lymphatic Vessels found in D-region on ICG lymphography would be significantly smaller than those in L-region. In LVA surgery, D-region should be avoided.
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supermicrosurgical deep Lymphatic Vessel to venous anastomosis for a breast cancer related arm lymphedema with severe sclerosis of superficial Lymphatic Vessels
Microsurgery, 2017Co-Authors: Takumi Yamamoto, Nana Yamamoto, Akitatsu Hayashi, Isao KoshimaAbstract: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.
