Biomedical subjects

Lucy Trombley

Publications and source records attributed to Lucy Trombley.

3 recordsLinked to original sources

PubMed2007

Matrix metalloproteinase and tissue inhibitor expression in atherosclerotic and nonatherosclerotic thoracic aortic aneurysms.

OBJECTIVES: The altered expression of matrix metalloproteinases and their inhibitors influences the formation of atherosclerotic abdominal aortic aneurysms. Their association with thoracic aneurysms is less clear. This study describes the expression of metalloproteinases and their inhibitors in atherosclerotic and nonatherosclerotic thoracic aneurysms, and compares these with age-matched controls. METHODS: Matrix metalloproteinase-2 and 9 activity were measured by antibody capture, and tissue inhibitor-1 and 2 levels were measured by enzyme-linked immunosorbent assay in 24 patients with atherosclerotic aneurysms and in 63 patients with nonatherosclerotic aneurysms. Gene expression was assessed with reverse transcriptase polymerase chain reaction. The results were compared with 17 controls. RESULTS: Data are in nanograms per milligram of protein. Matrix metalloproteinase-2 activity was greater in controls than in the atherosclerotic and nonatherosclerotic groups (80 +/- 67 vs 49 +/- 50 and 35 +/- 44, P = .002). Matrix metalloproteinase-9 activity was greater in the atherosclerotic group than in the nonatherosclerotic group and controls (11.7 +/- 15.7 vs 2.5 +/- 2.2 and 1.7 +/- 1.9, P = .001). Tissue inhibitor-1 and 2 levels were greater in controls than in either aneurysm group (tissue inhibitor of metalloproteinase-1: 376 +/- 192 vs 234 +/- 233 and 174 +/- 148, P = .003; tissue inhibitor of metalloproteinase-2: 143 +/- 74 vs 14 +/- 13 and 27 +/- 43, P < .001). Atherosclerotic aneurysms expressed more matrix metalloproteinase mRNA than controls. CONCLUSIONS: The metalloproteinase/tissue inhibitor phenotype of atherosclerotic thoracic aneurysms is similar to that of abdominal aneurysms. The diminished expression of metalloproteinases and tissue inhibitors in nonatherosclerotic thoracic aneurysms relative to aged controls may represent a loss of smooth muscle cells.

Aged↗

PubMed2006

V(D)J recombinase-mediated processing of coding junctions at cryptic recombination signal sequences in peripheral T cells during human development.

V(D)J recombinase mediates rearrangements at immune loci and cryptic recombination signal sequences (cRSS), resulting in a variety of genomic rearrangements in normal lymphocytes and leukemic cells from children and adults. The frequency at which these rearrangements occur and their potential pathologic consequences are developmentally dependent. To gain insight into V(D)J recombinase-mediated events during human development, we investigated 265 coding junctions associated with cRSS sites at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus in peripheral T cells from 111 children during the late stages of fetal development through early adolescence. We observed a number of specific V(D)J recombinase processing features that were both age and gender dependent. In particular, TdT-mediated nucleotide insertions varied depending on age and gender, including percentage of coding junctions containing N-nucleotide inserts, predominance of GC nucleotides, and presence of inverted repeats (Pr-nucleotides) at processed coding ends. In addition, the extent of exonucleolytic processing of coding ends was inversely related to age. We also observed a coding-partner-dependent difference in exonucleolytic processing and an age-specific difference in the subtypes of V(D)J-mediated events. We investigated these age- and gender-specific differences with recombination signal information content analysis of the cRSS sites in the human HPRT locus to gain insight into the mechanisms mediating these developmentally specific V(D)J recombinase-mediated rearrangements in humans.

Adolescent↗

PubMed2004

Matrix metalloproteinase activity in thoracic aortic aneurysms associated with bicuspid and tricuspid aortic valves.

OBJECTIVE: Matrix metalloproteinases are endopeptidases that function in cell matrix turnover. Abnormal matrix metalloproteinase activity has been implicated in the formation of atherosclerotic abdominal aortic aneurysms. Recent studies suggest that abnormal matrix metalloproteinase activity may also be associated with the formation of atherosclerotic and nonatherosclerotic thoracic aortic aneurysms. Bicuspid aortic valves are associated with an intrinsic aortic pathology that predisposes to formation of proximal thoracic aneurysms while tricuspid aortic valves are not. The objective of this study was to compare the activities of matrix metalloproteinases and levels of their inhibitors in thoracic aneurysms of patients with bicuspid and tricuspid aortic valves. METHODS: Endogenous and total activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 were measured in proximal nonatherosclerotic thoracic aortic aneurysms of 16 patients with bicuspid aortic valves and 12 patients with tricuspid aortic valves. Levels of tissue inhibitor metalloproteinase-1 and -2 were also measured. Results were standardized to total protein (mg). RESULTS: Total matrix metalloproteinase-2 activity was greater in aneurysms associated with bicuspid valves when compared with those from tricuspid valves (43 +/- 11 ng/mg vs 14 +/- 2 ng/mg, P =.02). Total matrix metalloproteinase-9 activity was also greater in aneurysms associated with bicuspid aortic valves (4.0 +/- 0.9 vs 1.5 +/- 0.3, P =.02). There was no meaningful difference between groups in levels of tissue inhibitor-1 and -2. CONCLUSION: The increased activity of matrix metalloproteinases in the walls of aneurysms associated with bicuspid aortic valves may partly explain the predilection to aneurysm formation in these patients.

Aorta, Thoracic↗