Biomedical subjects

David G Jackson

Publications and source records attributed to David G Jackson.

40 records · Page 3Linked to original sources

PubMed2002

Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer.

How tumors access and spread via the lymphatics is not understood. Although it is clear that dissemination via the blood system involves hemangiogenesis, it is uncertain whether tumors also induce lymphangiogenesis or simply invade existing peritumoral vessels. To address the issue we quantitated tumor lymph vessels in archival specimens of head and neck cancer by immunostaining for the recently described lymphatic endothelial marker LYVE-1, the vascular endothelial marker CD34, and the pKi67 proliferation marker, correlating lymph vessel density and proliferation index with clinical and pathological variables. Discrete "hotspots" of intratumoral small proliferating lymphatics were observed in all carcinomas, and a high intratumoral lymph vessel density was associated with neck node metastases (n = 23; P = 0.027) and an infiltrating margin of tumor invasion (P = 0.046) in the oropharyngeal subgroup. Quantitation of the lymphangiogenic growth factor vascular endothelial growth factor C by real-time PCR and immunohistochemistry revealed higher levels of mRNA in tumor tissue than in normal samples (n = 8; P = 0.017), but no obvious correlation with intratumoral lymphatics. Our results provide new evidence that proliferating lymphatics can occur in human cancers and may in some cases contribute to lymph node metastasis.

Adolescent↗

PubMed2002

Hepatic expression of secondary lymphoid chemokine (CCL21) promotes the development of portal-associated lymphoid tissue in chronic inflammatory liver disease.

The chronic inflammatory liver disease primary sclerosing cholangitis (PSC) is associated with portal inflammation and the development of neolymphoid tissue in the liver. More than 70% of patients with PSC have a history of inflammatory bowel disease and we have previously reported that mucosal addressin cell adhesion molecule-1 is induced on dendritic cells and portal vascular endothelium in PSC. We now show that the lymph node-associated chemokine, CCL21 or secondary lymphoid chemokine, is also strongly up-regulated on CD34(+) vascular endothelium in portal associated lymphoid tissue in PSC. In contrast, CCL21 is absent from LYVE-1(+) lymphatic vessel endothelium. Intrahepatic lymphocytes in PSC include a population of CCR7(+) T cells only half of which express CD45RA and which respond to CCL21 in migration assays. The expression of CCL21 in association with mucosal addressin cell adhesion molecule-1 in portal tracts in PSC may promote the recruitment and retention of CCR7(+) mucosal lymphocytes leading to the establishment of chronic portal inflammation and the expanded portal-associated lymphoid tissue. This study provides further evidence for the existence of portal-associated lymphoid tissue and is the first evidence that ectopic CCL21 is associated with lymphoid neogenesis in human inflammatory disease.

Blood Cells↗

PubMed2002

Increased nuchal translucency is associated with jugular lymphatic distension.

BACKGROUND: Measurement of nuchal translucency (NT) is a widely used method of screening for chromosomal abnormalities. Increased NT is seen in a diversity of fetal malformations. The mechanism explaining the abnormal fluid accumulation and the transient nature of NT remains unexplained. METHODS: The nuchal regions of normal and trisomy 16 mouse embryos were examined for (lympho)vascular abnormalities using immunohistochemical markers against lymphatic vessels (LYVE-1) and smooth muscle (1A4) and endothelial (CD34) cells. Additionally, an ultrasonographic study was carried out on 17 human fetuses with an increased NT. Two of these fetuses were examined morphologically. RESULTS: In both abnormal human and mouse specimens, we found a mesenchyme lined cavity within the posterior nuchal region as well as bilaterally enlarged jugular LYVE-1 positive lymphatic sacs. The persistence of jugular lymphatic sacs was also confirmed by ultrasound in 14 human fetuses with increased NT. CONCLUSION: Our findings identify the cause of increased NT as mesenchymal oedema in the presence of distended jugular lymphatic sacs, detected by the hyaluronan receptor LYVE-1. The delayed organization and connection of these lymphatic sacs to the venous circulation might explain the transient nature of NT. Disturbance in timing of endothelial differentiation might be a common denominator in the origin of NT, linking cardiovascular and haemodynamic abnormalities.

Animals↗

PubMedDate not supplied

Biology of the lymphatic marker LYVE-1 and applications in research into lymphatic trafficking and lymphangiogenesis.

The pace of research into the lymphatic system continues to accelerate with the availability of new molecular markers. One such marker, LYVE-1, the lymphatic receptor for the extracellular matrix mucopolysaccharide hyaluronan, has been a key component of many important studies on embryonic and tumour-induced lymphangiogenesis, and continues to be used for the detection and isolation of lymphatic endothelial cells. However, LYVE-1 is interesting in its own right. Being a member of the Link protein family whose only other major hyaluronan receptor is directly involved in leukocyte migration and tumour metastasis, LYVE-1 is already implicated in the trafficking of cells within lymphatic vessels and lymph nodes. The current challenge is to determine the precise roles played by LYVE-1 and other scavenger type receptors in the immune functions of the lymphatics as well as to use LYVE-1 and other markers to investigate the way in which tumours exploit lymphatic vessels for metastasis.

Amino Acid Sequence↗