Mesenteric cysts,lymphatic leak,and cerebral cavernous malformation in a proband with KRIT1-related disease

Cerebral cavernous malformations (CCMs) of the central nervous system arise sporadically or secondary to genomic variation. Established genetic etiologies include deleterious variants in KRIT1 (CCM1), malcavernin (CCM2), and PDCD10 (CCM3). KRIT1-related disease has not been described in conjunction with lymphatic defects, although lymphatic defects with abnormal endothelial cell junctions have been observed in mice deficient in HEG1-KRIT1 signaling. We report a proband with CCMs, multiple chylous mesenteric cysts, and chylous ascites with leaky lymphatic vasculature. Clinical short-read exome sequencing detected a disease-associated KRIT1 variant (NM_194456.1:c.[1927C>T];[=], p.(Gln643*)). We postulate an expansion of KRIT1-related disease to include lymphatic malformations and lymphatic endothelial dysfunction.     

Role of COX-2 in lymphangiogenesis and restoration of lymphatic flow in secondary lymphedema

The pathophysiology of secondary lymphedema remains poorly understood. To clarify the roles of cyclooxygenase (COX)-2 in enhancement of lymphangiogenesis during secondary lymphedema, we tested a mouse tail model and evaluated the recurrence of lymph flow. To induce lymphedema, a circumferential incision was made in the tail of anesthetized mice to sever the dermal lymphatic vessels. The maximum diameters of the tails were measured weekly. We found that the diameters of the tails around the wounds were markedly increased after surgery, and reached maximum size 2 weeks after wounding in mice without a COX-2 inhibitor, celecoxib (Celecoxib-). Expression of COX-2 in wound granulation tissues was markedly increased 1 week after surgery compared with unwounded naive control mice. In Celecoxib-, recurrence of lymphatic flow in the wound granulation tissues was detected 3 weeks after surgical treatment. In contrast, lymphatic flow was markedly suppressed in mice treated with celecoxib (Celecoxib+). Newly formed lymphatic structures were identified in the granulation tissues formed at wounded lesions in Celecoxib-, whereas those were markedly suppressed in Celecoxib+. Interstitial tissue pressures in the distal areas of the tail wounds were markedly increased in Celecoxib+ with reduced expression of vascular endothelial cell growth factor (VEGF)-C. F4/80-positive cells were accumulated to the wound granulation tissues in Celecoxib-, and the accumulation of these cells was suppressed in Celecoxib+. Prostaglandin E(2) (PGE(2)) upregulated the expressions of VEGF-A and VEGF-C in cultured macrophages, but not human lymphatic microvascular endothelial cells. The present study therefore suggests that lymphangiogenesis, together with recurrence of lymph flow after surgical induction of lymphedema, is upregulated by COX-2 possibly via generation of PGs.     

99Tcm-右旋糖酐淋巴显像诊断以淋巴水肿为发症状的淋巴结恶性肿瘤

目的 探讨下肢淋巴显像对淋巴水肿为首发症状的淋巴结恶性肿瘤的诊断价值.方法 回顾性分析21例以下肢淋巴水肿为首发症状的淋巴结恶性肿瘤患者的淋巴显像结果.显像方法：于患者双足第1、2趾间皮下缓慢注射99Tcm-右旋糖酐（99TcmO4-DX）,注射后10min和1h、3h、6h分别行从足到头的全身动态显像,重点观察淋巴回流中断部位及淋巴结显影特征.结果 21例患者均经淋巴结穿刺活检或淋巴结切除术,病理证实不显影的淋巴结均出现不同程度的恶性肿瘤浸润,转移癌18例,非霍奇金淋巴瘤3例.淋巴动态显像主要表现：下肢主淋巴管显影增宽,可伴有侧枝淋巴管显影;下肢、腰臀部、盆腹壁、会阴部不同程度的皮下淋巴返流;腹股沟、髂、腰不同部位的淋巴管显影中断,相应部位淋巴结不显影.结论 99TcmO4-DX淋巴显像能准确发现下肢淋巴回流情况和病变淋巴结部位,对以下肢淋巴水肿为首发症状的淋巴结恶性肿瘤患者病因诊断有重要意义.     

Murine Notch1 is required for lymphatic vascular morphogenesis during development

BACKGROUND: The transmembrane receptor Notch1 is a critical regulator of arterial differentiation and blood vessel sprouting. Recent evidence shows that functional blockade of Notch1 and its ligand, Dll4, leads to postnatal lymphatic defects in mice. However, the precise role of the Notch signaling pathway in lymphatic vessel development has yet to be defined. Here we show the developmental role of Notch1 in lymphatic vascular morphogenesis by analyzing lymphatic endothelial cell (LEC)‐specific conditional Notch1 knockout mice crossed with an inducible Prox1CreER^T2 driver. RESULTS: LEC‐specific Notch1 mutant embryos exhibited enlarged lymphatic vessels. The phenotype of lymphatic overgrowth accords with increased LEC sprouting from the lymph sacs and increased filopodia formation. Furthermore, cell death was significantly reduced in Notch1‐mutant LECs, whereas proliferation was increased. RNA‐seq analysis revealed that expression of cytokine/chemokine signaling molecules was upregulated in Notch1‐mutant LECs isolated from E15.5 dorsal skin, whereas VEGFR3, VEGFR2, VEGFC, and Gja4 (Connexin 37) were downregulated. CONCLUSIONS: The lymphatic phenotype of LEC‐specific conditional Notch1 mouse mutants indicates that Notch activity in LECs controls lymphatic sprouting and growth during development. These results provide evidence that similar to postnatal and pathological lymphatic vessel formation, the Notch signaling pathway plays a role in inhibiting developmental lymphangiogenesis. Developmental Dynamics 243:957–964, 2014. © 2014 Wiley Periodicals, Inc.     

Lymph vessel defects in patients with ovarian dysgenesis

Lymphangiography of the lower extremities was performed in 21 patients with ovarian dysgenesis. Seventeen subjects turned out to have hypoplastic superficial lymph vessels of the lower limbs. Aplasia of the lymphatics of the legs occurred in four instances. Hypoplastic lymph pathways were also observed in the pelvis and in the retroperitoneal space. Although the impairment of the lymphatic channels occurred in all cases of ovarian dysgenesis, it appears that it is more severe in patients with streak gonads. There was no correlation between the lymphatic defect and the karyotype. Patients with and without lymphedema had similar lymphatic defects. Our findings suggest that hypoplasia of the superficial lymph vessels of the lower limbs is a common abnormality in patients with ovarian dysgenesis irrespective of their chromosomal complements. The hypothesis that lymphedema in ovarian dysgenesis is mainly attributable to hypoplasia of the lymphatic channels is supported by this study. However, it appears that other factor(s) may also play a role in the pathogenesis of the lymphedema, since, despite lymphatic hypoplasia, lymphedema does not develop in all instances.     

Dermal Collagen and Lipid Deposition Correlate with Tissue Swelling and Hydraulic Conductivity in Murine Primary Lymphedema

Primary lymphedema is a congenital pathology of dysfunctional lymphatic drainage characterized by swelling of the limbs, thickening of the dermis, and fluid and lipid accumulation in the underlying tissue. Two mouse models of primary lymphedema, the Chy mouse and the K14-VEGFR-3-Ig mouse, both lack dermal lymphatic capillaries and exhibit a lymphedematous phenotype attributable to disrupted VEGFR-3 signaling. Here we show that the differences in edematous tissue composition between these two models correlated with drastic differences in hydraulic conductivity. The skin of Chy mice possessed significantly higher levels of collagen and fat, whereas K14-VEGFR-3-Ig mouse skin composition was relatively normal, as compared with their respective wild-type controls. Functionally, this resulted in a greatly increased dermal hydraulic conductivity in K14-VEGFR3-Ig, but not Chy, mice. Our data suggest that lymphedema associated with increased collagen and lipid accumulation counteracts an increased hydraulic conductivity associated with dermal swelling, which in turn further limits interstitial transport and swelling. Without lipid and collagen accumulation, hydraulic conductivity is increased and overall swelling is minimized. These opposing tissue responses to primary lymphedema imply that tissue remodeling—predominantly collagen and fat deposition—may dictate tissue swelling and govern interstitial transport in lymphedema.Primary or congenital lymphedema is a pathological condition in which excess fluid accumulates in the limb because of dysfunctional lymphatic drainage.^1,2 In humans, primary lymphedema has been linked to mutations in lymphatic endothelial cell genes that result in malformations in lymphatic valve and mural structure or insufficient organization of lymphatic capillaries.^3–8 As a chronic pathology, lymphedema results in characteristic morphological changes including remodeling of the skin and subcutaneous extracellular matrix (ECM) and accumulation of lipids.^9–12 Lymphatic function is tightly controlled by the mechanical properties of the tissue via anchoring filaments that attach lymphatic endothelium to the surrounding ECM,^13,14 such that structural changes can further retard interstitial fluid clearance.^11,15 No treatment to date can truly restore tissue fluid balance or improve lymphatic function, but there has been success using compression sleeves, massage, and surgical removal of tissue in limiting the pathology.¹⁶ These successes further underscore lymphedema as not simply a disease of lymphatic transport, but a pathology governed by the ECM.To recreate the pathology of primary lymphedema in mouse models, lymphatic genes have been targeted to disrupt proper formation of lymphatic vessels during development, but many of these are lethal, including the deletion of Foxc2,^3,7 VEGFR-3,^3,7 VEGF-C,¹⁷ or Prox-1.¹⁸ Heterozygote mutations or deletions of these genes, however, are sometimes viable and may present poorly formed lymphatic vessels, an edematous phenotype in adulthood, or failed responses to interstitial challenge.^3,7,17–19 Although the lymphedema exhibited in such models never entirely recapitulates the extent of swelling of whole limbs or pathological asymmetry found in humans, such models provide an excellent platform for studying the consequential dermal pathology of lymphedema and potential treatments.The Chy mouse and the K14-VEGFR-3-Ig mouse are two such models previously developed targeting VEGFR-3 signaling.^20,21 The Chy mouse possesses a heterozygous VEGFR-3 mutation in the tyrosine kinase domain, preventing phosphorylation and resulting in early developmental deficiencies in some lymphatic vessels and chylous ascites as newborns.²⁰ Adult Chy mice lack dermal lymphatics.^20,22 In contrast, the K14-VEGFR-3-Ig mouse secretes a soluble variant of VEGFR-3, formed by the fusion of the extracellular ligand-binding domain of VEGFR-3 and an IgG Fc domain, in the epidermis under the keratin-14 (K14) promoter.²¹ The secreted VEGFR-3 appropriates VEGF-C, preventing lymphatic capillary development in the skin.²¹ No abnormal blood vascular phenotypes have been reported in these mice resulting from these mutations. Both mouse models exhibit lymphedema, particularly in the lower limbs, tail, and snout, and tissue histology shows dermal remodeling and fluid accumulation in the hypodermis.^20,21 Symptomatically, these models represent features of the human disease arising from VEGFR-3 and VEGF-C mutations⁸ and provide a platform for dermal transport consequences in lymphedema.Interstitial fluid pressure (IFP) provides the driving force for flow through tissues while the hydraulic conductivity (K) of the tissue determines its resistance to flow. Fluid moves more freely through tissues with a higher K, potentially limiting the swelling load on the ECM. Factors influencing tissue hydraulic conductivity include tissue hydration,^23,24 matrix composition,^25,26 and IFP.²⁷ Small changes in matrix composition or IFP can result in large changes to hydraulic conductivity.²⁸ We therefore hypothesized that tissue composition changes associated with dysfunctional local lymphatic drainage likely alter tissue hydraulic conductivity and interstitial fluid transport that would dictate the functional manifestation of lymphedema. Tissue collagen, lipid, and water content were measured to determine tissue compositional changes in these mice, and interstitial transport was measured by applying a quantitative in situ model of tissue hydraulic conductivity. Despite both models lacking dermal lymphatics, we found that the tissue compositional changes were quite different between the two models, resulting in large differences in interstitial transport properties. This demonstrates that lymphatic transport deficiencies alone do not determine the extent of lymphedema, but rather that tissue composition plays a critical and potentially compounding influence.     

腹股沟区淋巴的应用研究

为治疗阴囊和下肢淋巴水肿，选择较满意的淋巴管静脉吻合手术部位提供解剖学依据。方法：在２９具胎儿和６具新生儿新鲜尸体上，采用间接淋巴管注射法，分别从外生殖器和下肢趾噗行间接淋巴管注射。结果；腹股沟浅淋巴结有６－２６个，来自外生殖器的输入管有４－２４条，直径为０．４－０．９ｍｍ；来自一肢的有６－１５条，直径为０．５－１００ｍｍ。     

Blockade of transforming growth factor-beta1 accelerates lymphatic regeneration during wound repair

Lymphedema is a complication of cancer treatment occurring in approximately 50% of patients who undergo lymph node resection. Despite its prevalence, the etiology of this disorder remains unknown. In this study, we determined the effect of soft tissue fibrosis on lymphatic function and the role of transforming growth factor (TGF)-β1 in the regulation of this response. We determined TGF-β expression patterns in matched biopsy specimens collected from lymphedematous and normal limbs of patients with secondary lymphedema. To determine the role of TGF-β in regulating tissue fibrosis, we used a mouse model of lymphedema and inhibited TGF-β function either systemically with a monoclonal antibody or locally by using a soluble, defective TGF-β receptor. Lymphedematous tissue demonstrated a nearly threefold increase in the number of cells that stained for TGF-β1. TGF-β inhibition markedly decreased tissue fibrosis, increased lymphangiogenesis, and improved lymphatic function compared with controls. In addition, inhibition of TGF-β not only decreased TGF-β expression in lymphedematous tissues, but also diminished inflammation, migration of T-helper type 2 (Th2) cells, and expression of profibrotic Th2 cytokines. Similarly, systemic depletion of T-cells markedly decreased TGF-β expression in tail tissues. Inhibition of TGF-β function promoted lymphatic regeneration, decreased tissue fibrosis, decreased chronic inflammation and Th2 cell migration, and improved lymphatic function. The use of these strategies may represent a novel means of preventing lymphedema after lymph node resection.     

Evaluation using a combination of lymphatic invasion on D2-40 immunostain and depth of dermal invasion is a strong predictor for nodal metastasis in extramammary Paget's disease

In extramammary Paget's disease (EPD), lymph node metastasis occasionally occurs and nodal metastasis influences prognosis. Therefore, in the present study a predictor of nodal metastasis in EPD was examined. Surgical specimens from 54 cases of EPD in the external genitalia were examined on D2-40 immunostain. In 23 cases, dissection of the inguinal lymph nodes was performed. Dermal invasion occurred in 24 patients (44.4%). Nodal metastasis was found in seven patients who had dermal invasion >1 mm. In non-metastatic patients, three had dermal invasion <0.5 mm in depth. Lymphatic invasion was well detected on D2-40 immunostain, and invasion was found in five patients. All four patients with lymphatic invasion, in whom lymph node dissection was performed, had nodal metastasis. However, three patients with dermal invasion, who did not have lymphatic invasion, did have nodal metastasis, and the depth of invasion was >1 mm. Dermal invasion ( P  < 0.001) and lymphatic invasion according to D2-40 immunostain ( P  = 0.001) had a positive correlation with nodal metastasis. In conclusion, evaluation using a combination of lymphatic invasion according to D2-40 immunostain and depth of dermal invasion is a strong predictor of nodal metastasis in EPD.     

Therapeutic lymphangiogenesis using stem cell and VEGF-C hydrogel

Lymphedema is a manifestation of lymphatic system insufficiency. It arises from primary lymphatic dysplasia or secondary obliteration after lymph node dissection or irradiation. Although improvement of swelling can be achieved by comprehensive non-operative therapy, treatment of this condition requires lifelong care and good compliance. Recently molecular-based treatments using VEGF-C have been investigated by several researchers. We designed the present study to determine whether the therapeutic efficacy of implanted human adipose-derived stem cells (hADSCs) could be improved by applying a gelatin hydrogel containing VEGF-C (VEGF-C hydrogel) to the site of tissue injury in a lymphedema mouse model. Four weeks after the operation, we evaluated edema and determined lymphatic vessel density at various post-operative time points. Mice treated with hADSCs and VEGF-C hydrogel showed a significantly decreased dermal edema depth compared to the groups of mice that received hADSCs only or VEGF-C hydrogel only. Immunohistochemical analysis also revealed that the hADSC/VEGF-C hydrogel group showed significantly greater lymphatic vessel regeneration than all the other groups. hADSCs were detected in the implantation sites of all mice in the hADSC/VEGF-C group, and exhibited a lymphatic endothelial differentiation phenotype as determined by co-staining PKH-labeled hADSCs for the lymphatic marker LYVE-1. Our results suggest that co-administration of hADSCs and VEGF-C hydrogel has a substantial positive effect on lymphangiogenesis.     

PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature

The transmembrane ligand ephrinB2 and its cognate Eph receptor tyrosine kinases are important regulators of embryonic blood vascular morphogenesis. However, the molecular mechanisms required for ephrinB2 transduced cellular signaling in vivo have not been characterized. To address this question, we generated two sets of knock-in mice: ephrinB2DeltaV mice expressed ephrinB2 lacking the C-terminal PDZ interaction site, and ephrinB2(5F) mice expressed ephrinB2 in which the five conserved tyrosine residues were replaced by phenylalanine to disrupt phosphotyrosine-dependent signaling events. Our analysis revealed that the homozygous mutant mice survived the requirement of ephrinB2 in embryonic blood vascular remodeling. However, ephrinB2DeltaV/DeltaV mice exhibited major lymphatic defects, including a failure to remodel their primary lymphatic capillary plexus into a hierarchical vessel network, hyperplasia, and lack of luminal valve formation. Unexpectedly, ephrinB2(5F/5F) mice displayed only a mild lymphatic phenotype. Our studies define ephrinB2 as an essential regulator of lymphatic development and indicate that interactions with PDZ domain effectors are required to mediate its functions.     

Lymphangiogenesis and expression of specific molecules as lymphatic endothelial cell markers

In recent years, several functional molecules specifically expressed and localized in lymphatic endothelial cells, such as 5'-nucleotidase, lymphatic vessel endothelial receptor-1, vascular endothelial growth factor receptor-3, podoplanin and Prox-1, have been identified. The discovery of the lymphatic endothelial cell markers facilitated detailed analysis of the nature and structural organization of the lymphatic vessels and their growth (lymphangiogenesis). As a result, over the past few years, advances have been made in understanding the cellular and molecular aspects of physiological lymphangiogenesis and tumor-induced lymphangiogenesis. The biology of lymphangiogenesis, particularly the mechanism of its regulation, is very important in understanding the formation of the lymphatic system as a biological regulation system transporting tissue fluid and wandering cells, including lymphocytes, and disease involving lymphangiogenesis. The understanding of the molecular mechanism of lymphangiogenesis and the elucidation of the development of normal and pathological tissues are expected to lead to the development of therapy for intractable diseases, such as malignant tumors and lymphedema.     

Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins

Lymphatic vessels are essential for immune surveillance, tissue fluid homeostasis and fat absorption. Defects in lymphatic vessel formation or function cause lymphedema. Here we show that the vascular endothelial growth factor C (VEGF-C) is required for the initial steps in lymphatic development. In Vegfc-/- mice, endothelial cells commit to the lymphatic lineage but do not sprout to form lymph vessels. Sprouting was rescued by VEGF-C and VEGF-D but not by VEGF, indicating VEGF receptor 3 specificity. The lack of lymphatic vessels resulted in prenatal death due to fluid accumulation in tissues, and Vegfc+/- mice developed cutaneous lymphatic hypoplasia and lymphedema. Our results indicate that VEGF-C is the paracrine factor essential for lymphangiogenesis, and show that both Vegfc alleles are required for normal lymphatic development.     

Transgenic induction of vascular endothelial growth factor-C is strongly angiogenic in mouse embryos but leads to persistent lymphatic hyperplasia in adult tissues

Vascular endothelial growth factor-C (VEGF-C) is the quintessential lymphangiogenic growth factor that is required for the development of the lymphatic system and is capable of stimulating lymphangiogenesis in adults by activating its receptor, VEGFR-3. Although VEGF-C is a major candidate molecule for the development of prolymphangiogenic therapy for defective lymphatic vessels in lymphedema, the stability of lymph vessels generated by exogenous VEGF-C administration is not currently known. We studied VEGF-C-stimulated lymphangiogenesis in inducible transgenic mouse models in which growth factor expression can be spatially and temporally controlled without side effects, such as inflammation. VEGF-C induction in adult mouse skin for 1 to 2 weeks caused robust lymphatic hyperplasia that persisted for at least 6 months. VEGF-C induced lymphangiogenesis in numerous tissues and organs when expressed in the vascular endothelium in either neonates or adult mice. Very few or no effects were observed in either blood vessels or collecting lymph vessels. Additionally, VEGF-C stimulated lymphangiogenesis in embryos after the onset of lymphatic vessel development. Strikingly, a strong angiogenic effect was observed after VEGF-C induction in vascular endothelium at any point before embryonic day 16.5. Our results indicate that blood vessels can undergo VEGF-C-induced angiogenesis even after down-regulation of VEGFR-3 in embryos; however, transient VEGF-C expression in adults can induce long-lasting lymphatic hyperplasia with no obvious side effects on the blood vasculature.     

二参泽术汤对腹膜淋巴孔的影响及腹水转归机理的研究

目的:研究二参泽术汤对腹膜淋巴孔的调控作用和治疗腹水的意义,并应用NO供体 (硝普钠)和一氧化氮合酶 (NOS)抑制剂 (N^G-单甲基-L-精氨酸),观察NO的淋巴孔舒张作用和对腹水转归影响,探讨二参泽术汤对腹膜淋巴孔的调控机制。方法:应用CCl4 法建立小鼠肝纤维化模型;用扫描电镜观察,并使用计算机与扫描电镜联机的图像处理系统测定腹膜淋巴孔的变化;用全自动生化分析仪测定尿离子浓度。结果:①二参泽术汤可明显促进腹膜淋巴孔开放面积增大,周长和分布密度增加 (P <0.01),尿中Na⁺ 、K⁺ 、Cl^-排出增多 (P <0.05或P <0.01);②二参泽术汤对腹膜淋巴孔的调控和对腹水转归的作用可以被NO供体和NOS抑制剂增强或抑制。结论:①二参泽术汤能调控腹膜淋巴孔,促进腹膜腔内液体转归,使尿中Na⁺ 、K⁺ 、Cl^-排出增加,减轻水钠潴留,具有良好的消腹水作用;②二参泽术汤调控腹膜淋巴孔,促腹水转归机制,可能与内源性NO的变化存在着密切的关系.     

Tumour necrosis factor superfamily member 15 (Tnfsf15) facilitates lymphangiogenesis via up‐regulation of Vegfr3 gene expression in lymphatic endothelial cells

Lymphangiogenesis is essential in embryonic development but is rare in adults. It occurs, however, in many disease conditions including cancers. Vascular endothelial growth factor‐C/D (VEGF‐C/D) and VEGF receptor‐3 (Vegfr3) play a critical role in the regulation of lymphangiogenesis. We investigated how the VEGF‐C/Vegfr3 signalling system is regulated by tumour necrosis factor superfamily member 15 (Tnfsf15), an endothelium‐derived cytokine. We report here that Tnfsf15, which is known to induce apoptosis in vascular endothelial cells, can promote lymphatic endothelial cell (LEC) growth and migration, stimulate lymphangiogenesis, and facilitate lymphatic circulation. Treatment of mouse LECs with Tnfsf15 results in up‐regulation of Vegfr3 expression; this can be inhibited by gene silencing of death domain‐containing receptor‐3 (DR3; Tnfrsf25), a cell surface receptor for Tnfsf15, with siRNA, or by blocking Tnfsf15–DR3 interaction with a Tnfsf15 neutralizing antibody, 4‐3H. Additionally, Tnfsf15/DR3 signalling pathways in LECs include activation of NF‐κB. Tnfsf15‐overexpressing transgenic mice exhibit a marked enhancement of lymph drainage; this is confirmed by treatment of wild‐type mice with intraperitoneal injection of recombinant Tnfsf15. Moreover, systemic treatment of pregnant Tnfsf15 transgenic mice with 4‐3H leads to inhibition of embryonic lymphangiogenesis. Our data indicate that Tnfsf15, a cytokine produced largely by endothelial cells, facilitates lymphangiogenesis by up‐regulating Vegfr3 gene expression in LECs, contributing to the maintenance of the homeostasis of the circulatory system. This finding also suggests that Tnfsf15 may be of potential value as a therapeutic tool for the treatment of lymphoedema. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

小鼠胰腺淋巴管的分布及其与胰岛的关系

目的:探讨小鼠胰腺淋巴管的形态分布及其结构特点。方法:对小鼠胰组织切片进行HE染色,5核苷酸酶(5-Nase)和碱性磷酸酶(ALP)双重染色,光镜、透射电镜、扫描电镜二次电子和背散射电子图像(SEI/BEI)观察。结果:小鼠胰腺的淋巴管结构较典型,在胰腺的小叶间结缔组织内,较大淋巴管与血管和导管相互伴行;毛细淋巴管起自胰腺腺泡周围,并且均匀地分布于整个小叶内;小叶内有单独走行的集合淋巴管,亦存在与血管并行情况;在胰岛内部未发现毛细淋巴管,但胰岛周围可见丰富的毛细淋巴管。结论:小鼠胰腺小叶间和小叶内结缔组织中,均有淋巴管分布;胰岛内部虽无淋巴管,但胰岛与周围毛细淋巴管的关系较密切。     

Primary lymphedema and other lymphatic anomalies are associated with 22q11.2 deletion syndrome

Background

Lymphedema is an abnormal accumulation of interstitial fluid within the tissues. Primary lymphedema is caused by aberrant lymphangiogenesis and it has been historically classified based on age at presentation. Although most cases are sporadic, primary lymphedema may be familial or present in association with chromosomal abnormalities and syndromic disorders. To the best of our knowledge, primary lymphedema has never been described in patients with 22q11.2 deletion syndrome.