Biomedical subjects

John Semple

Publications and source records attributed to John Semple.

3 recordsLinked to original sources

PubMed2006

Lymphangiogenesis following obstruction of large postnodal lymphatics in sheep.

We examined the impact of lymph flow obstruction in large post-nodal lymphatic vessels in sheep. A silk ligature was placed 2 cm downstream from the prescapular or popliteal lymph node and tightened to interrupt flow. At 6, 12 and 16 weeks after lymph flow blockage, a network of small interconnecting lymphatics (approximately 10-40 microm in diameter) could be observed in the vicinity of the ligature. These were identified using antibodies to the lymphatic endothelial markers LYVE-1 or VEGFR-3 or unequivocally, with the upstream intraluminal injection of the non-specific cell dye CFDA-SE. The observed lymphangiogenesis coincided with increased levels of Prox1, Tie2 (Y992) phosphorylation, MAPK activation, and decreased Akt activition. In the popliteal preparations, saline was infused into the prenodal ducts upstream of the regeneration site. The slopes of the inflow pressure versus flow relationships were 17.3+/-3.6, immediately after vessel obstruction, 36.2+/-9.6 at 6 weeks and 15.0+/-5.3 at 12-16 weeks. For comparison, the average slope in a completely intact popliteal system was 3.1+/-0.3 (from a previous publication). The resistance to flow remained high up to 12-16 weeks after flow obstruction suggesting that normal flow parameters had not been achieved over this time. The lymph node appeared to have some role in limiting the impact of post-nodal lymph obstruction, a function that appeared to be compromised by lymph stasis.

Animals↗

PubMed2005

Carnitine/xenobiotics transporters in the human mammary gland epithelia, MCF12A.

The barrier function of the human mammary gland collapses if challenged with cationic drugs, causing their accumulation in milk. However, underlying molecular mechanisms are not well understood. To gain insight into the mechanism, we characterized transport of organic cations in the MCF12A human mammary gland epithelial cells, using carnitine and tetraethylammonium (TEA) as representative nutrient and xenobiotics probes, respectively. Our results show that the mammary gland cells express mRNA and proteins of human (h) novel organic cation transporters (OCTN) 1 and hOCTN2 (a Na+-dependent carnitine carrier with Na+-independent xenobiotics transport function), which belong to the solute carrier superfamily (SLC) of transporters. Other SLC OCTs such as hOCT1 and extraneuronal monoamine transporter (EMT)/hOCT3 are also expressed at mRNA levels, but hOCT2 was undetectable. We further showed mRNA expression of ATB0+ (an amino acid transporter with a Na+/Cl(-)-dependent carnitine transport activity), and Fly-like putative transporter 2/OCT6 (a splice variant of carnitine transporter 2: a testis-specific Na+-dependent carnitine transporter). TEA uptake was pH dependent. Carnitine uptake was dependent on Na+, and partly on Cl-, compatible with hOCTN2 and ATB0+ function. Modeling analyses predicted multiplicity of the uptake mechanisms with the high-affinity systems characterized by K(m) of 5.1 microM for carnitine and 1.6 mM for TEA, apparently similar to the reported hOCTN2 parameter for carnitine, and that of EMT/hOCT3 for TEA. Verapamil, cimetidine, carbamazepine, quinidine, and desipramine inhibited the carnitine uptake but required supratherapeutic concentrations, suggesting robustness of the carnitine uptake systems against xenobiotic challenge. Our findings suggest functional roles of a network of multiple SLC organic cation/nutrient transporters in human mammary gland drug transfer.

Carnitine↗

PubMed2002

Prophylactic bilateral mastectomy: patterns of practice.

BACKGROUND: Many women who are at an elevated risk of developing breast carcinoma choose prophylactic mastectomy to decrease their risk. We conducted a population-based study to review the indications for, and patterns of practice of prophylactic mastectomy in Ontario, Canada, since 1991. METHODS: A medical chart review was conducted at 33 hospitals that were identified as having conducted at least one prophylactic mastectomy. All bilateral mastectomy patients with no diagnosis of invasive or in situ breast carcinoma were eligible. RESULTS: The number of prophylactic bilateral mastectomies performed varied from 6 to 19. The mean age of women undergoing prophylactic mastectomy was 43.5 years. Eighty percent of the women had prophylactic mastectomy performed because of a family history of breast carcinoma (89 of 99) or because of a known BRCA1 or BRCA2 mutation (10 of 99). Twenty percent of the women had no family history, but had the surgery for other benign breast conditions. Women with a family history of breast carcinoma were much more likely to have a total mastectomy (89%) than a subcutaneous mastectomy (11%). Sixty percent of the women had reconstructive surgery following mastectomy. CONCLUSIONS: Prophylactic mastectomy is not performed on a large scale. The introduction of genetic testing for BRCA1 and BRCA2 has the potential to change the patterns of practice for prophylactic mastectomy.

Adult↗