Publications (46) View all
-
Article: Lymphedema: How Do We Diagnose and Reduce the Risk of This Dreaded Complication of Breast Cancer Treatment?
[show abstract] [hide abstract]
ABSTRACT: Lymphedema is an under-recognized, progressive, life-long condition estimated to impact 2-3 million people in the United States. The incidence of breast cancer related lymphedema varies greatly in the literature largely due to different measurement techniques, competing thresholds for defining lymphedema, and variation in length of follow-up. Multiple imaging techniques have become useful for diagnosis. Lymphoscintigraphy is one of the most commonly used, as it can identify pathways of lymphatic drainage, quantify extent of dermal backflow, and help determine functional and morphologic changes in the lymphatic system. Early detection and intervention hold the greatest promise of reducing the incidence of lymphedema. Health care providers involved with cancer patients need to become more educated about lymphedema, aware of current risk-reduction practices, and familiar with methods of diagnosis and assessment, so that patients with early swelling can be referred to lymphedema treatment specialists at a time when treatment is more effective. KeywordsLymphedema-Breast cancerCurrent Breast Cancer Reports 04/2012; 2(1):53-58. -
Article: Dysmorphogenesis of lymph nodes in Foxc2 haploinsufficient mice.
[show abstract] [hide abstract]
ABSTRACT: Dysmorphogenesis of lymph nodes displayed in a fork head transcription factor Foxc2 haploinsufficient mice--a model for lymphedema-distichiasis syndrome--was studied by immunohistochemistry and electron microscopy. The Foxc2 heterozygous mice manifested lymph node hyperplasia composed of conspicuous proliferation of endothelial cells forming the lymphatic sinus and α-smooth muscle actin (SMA)-immunopositive fibroblast-like cells in the lymphatic pulp, particularly around the sinus. The hyperplastic sinus endothelial cells and the SMA-positive cells demonstrated distinct immunolocalization of platelet-derived growth factor (PDGF)-B, a crucial chemoattractant for vascular mural cell recruitment, and its receptor, PDGFR-β, respectively. The observations suggest that the sinus endothelial cells elicit abnormal recruitment of the fibroblast-like cells as a type of vascular mural cells via PDGF-B/PDGFR-β signaling in lymph nodes of the Foxc2 heterozygotes. Furthermore, in Foxc2 heterozygous lymph nodes, recruited SMA-positive cells displayed an intense immunoreaction for vascular endothelial growth factor (VEGF)-C, a highly specific lymphangiogenic factor, and its receptor, VEGFR-3, was preferentially distributed in the lymphatic sinus endothelial cells. These findings suggest that an interactive cycle between lymphatic sinus endothelial cells and the fibroblast-like cells, which involves PDGF-B/PDGFR-β and VEGF-C/VEGFR-3 signaling, is essential for aberrant hyperplasia of the lymphatic sinus and the fibroblast-like cells in Foxc2 haploinsufficiency.Histochemie 06/2011; 135(6):603-13. · 2.59 Impact Factor -
Article: Establishment of primary cultures of human brain microvascular endothelial cells to provide an in vitro cellular model of the blood-brain barrier.
[show abstract] [hide abstract]
ABSTRACT: We describe a method for generating primary cultures of human brain microvascular endothelial cells (HBMVECs). HBMVECs are derived from microvessels isolated from temporal tissue removed during operative treatment of epilepsy. The tissue is mechanically fragmented and size filtered using polyester meshes. The resulting microvessel fragments are placed onto type I collagen-coated flasks to allow HBMVECs to migrate and proliferate. The overall process takes less than 3 h and does not require specialized equipment or enzymatic processes. HBMVECs are typically cultured for approximately 1 month until confluent. Cultures are highly pure ( approximately 97% endothelial cells; approximately 3% pericytes), are reproducible, and show characteristic brain endothelial markers (von Willebrand factor, glucose transporter-1) and robust expression of tight and adherens junction proteins as well as caveolin-1 and efflux protein P-glycoprotein. Monolayers of HBMVECs show characteristically high transendothelial electric resistance and have proven useful in multiple functional studies for in vitro modeling of the human blood-brain barrier.Nature Protocol 07/2010; 5(7):1265-72. · 8.36 Impact Factor -
Article: Elevated levels of bilirubin and long-term exposure impair human brain microvascular endothelial cell integrity.
[show abstract] [hide abstract]
ABSTRACT: The pathogenesis of encephalopathy by unconjugated bilirubin (UCB) seems to involve the passage of high levels of the pigment across the blood-brain barrier (BBB) and the consequent damage of neuronal cells. However, it remains to be clarified if and how the disruption of BBB occurs by UCB. We used confluent monolayers of human brain microvascular endothelial cells (HBMEC) to explore the sequence of events produced by UCB. A cell line and primary cultures of HBMEC were exposed to 50 or 100 µM UCB, in the presence of 100 µM human serum albumin, to mimic moderate and severe jaundice, for 1-72 h. UCB caused loss of cell viability in a concentration-dependent manner. UCB inhibited the secretion of interleukin-6, interleukin-8, monocyte chemoattractant protein-1 and vascular endothelial growth factor at early time points, but enhanced their secretion at later time points. Upregulation of mRNA expression, particularly by 100 µM UCB, preceded cytokine secretion. Other early events include the disruption of glutathione homeostasis and the increase in endothelial nitric oxide synthase expression followed by nitrite production. Prolonged exposure to UCB upregulated the expression of β-catenin and caveolin-1. In conclusion, elevated concentrations of UCB affect the integrity of HBMEC monolayers mediated by oxidative stress and cytokine release. UCB also induced increased expression of caveolin-1, which has been associated with BBB breakdown, and β-catenin, probably as an attempt to circumvent that impairment. These findings provide a basis for target-directed therapy against brain endothelial injury caused by UCB.Current neurovascular research 04/2011; 8(2):153-69. · 3.23 Impact Factor -
Article: Novel discovery of LYVE-1 expression in the hyaloid vascular system.
[show abstract] [hide abstract]
ABSTRACT: The hyaloid vascular system (HVS) is a transient network nourishing developing eyes and has been widely used as a natural model to study blood vessel regression. Failure of its regression in humans leads to several blinding diseases. Lymphatic vessel endothelial hyaluronic acid receptor (LYVE-1) is a recently defined lymphatic marker that is also expressed by a subpopulation of macrophages. To date, there is no report on its expression in the HVS. This study was conducted to investigate whether LYVE-1 is expressed in the HVS and how it is associated with the vascular structure and macrophage phenotype. Normal C57BL/6 mouse eyeballs were sampled from embryonic day (E) 10.5 to postnatal (P) and adult stages for immunofluorescent microscopic studies with antibodies against LYVE-1, CD31 (panendothelial cell marker), and F4/80 (macrophage marker). Additionally, Angiopoietin-2 (Ang-2) knockout mice with abnormally persistent HVS were examined. The LYVE-1 expression was detected on normal HVS between E12.5 and P14. The LYVE-1(+) cells were F4/80(+) but CD31(-), indicating a macrophage lineage. Additionally, LYVE-1(+) cells bud on CD31(+) vessels and constitute an integral part of the network in both normal developing and Ang-2 knockout mice. This study provides the first evidence that the HVS contains a LYVE-1(+) cellular component in both physiological and pathologic conditions. This novel finding not only provides a new concept in defining the embryogenesis and pathogenesis of the HVS, it also leads to a completely natural model in which to study the functions of the LYVE-1 pathway, an important topic for lymphatic research as well.Investigative ophthalmology & visual science 12/2010; 51(12):6157-61. · 3.43 Impact Factor
