Biomedical subjects

Campbell L Stewart

Publications and source records attributed to Campbell L Stewart.

3 recordsLinked to original sources

PubMed2004

Gene microarray analysis of human brain arteriovenous malformations.

OBJECTIVE: Human brain arteriovenous malformations (BAVMs) display abnormal expression of various angiogenesis-related genes and their products. We examined gene expression patterns in BAVMs by the gene microarray technique. METHODS: We analyzed BAVM and control brain samples obtained by temporal lobectomy for medically intractable seizure by Affymetrix Human Gene Set U95Av2 (Affymetrix, Inc., Santa Clara, CA). The gene microarray data were compared with new and previously published data that used conventional molecular biology techniques. RESULTS: We analyzed six BAVM and five control brain samples. From 12,625 gene probes assayed, 1781 gene probes showed differential expression between BAVMs and controls. BAVM samples had a gene expression pattern that was distinct from those of control brain samples. Increased messenger ribonucleic acid expression of vascular endothelial growth factor A was accompanied by increased expression of its protein product. A majority of the gene data was in agreement with previously published data. The gene microarray data generated a new testable hypothesis regarding integrin, and we found increased expression of integrin alphavbeta3 protein in BAVMs. CONCLUSION: The gene expression pattern of BAVMs was distinct from those of control brain samples. We verified the gene microarray data by demonstrating that increased gene expression levels for angiogenesis-related molecules were accompanied by increased levels of their protein product expression. The gene microarray technique may be a useful tool to study multiple pathways simultaneously in BAVM specimens.

Adolescent↗

PubMed2004

The transgenic arteriovenous fistula in the rat: an experimental model of gene therapy for brain arteriovenous malformations.

OBJECTIVE: To introduce the transgenic arteriovenous fistula model in the rat, constructed by interposing mouse aorta in a fistula between the common carotid artery and external jugular vein in a nude rat, and to describe the model's technical feasibility, long-term patency, and expression of reporter genes. METHODS: Carotid-jugular fistulae were surgically created in 112 rats. In 25 immunodeficient nude rats, wild-type mouse thoracic aorta (TAo) was interposed in the fistula; in 10 immunocompetent rats, TAo was interposed; in 19 nude rats, transgenic TAo with reporter genes for beta-galactosidase or green fluorescent protein was interposed; in 18 nude rats, wild-type mouse ascending aorta was interposed; and in 40 rats, a simple fistula was constructed without an interpositional graft. Host tolerance and graft viability were analyzed by histopathology and immunohistochemistry for CD31 (mouse endothelial cell marker), endothelial nitric oxide synthase, smooth muscle actin, fibronectin, beta-galactosidase, and green fluorescent protein. RESULTS: The transgenic arteriovenous fistula was technically feasible and immunologically tolerated in nude rats but not in immunocompetent rats. The overall angiographic patency rate was 41% with TAo grafts and 56% with ascending aorta grafts, both lower than the 98% patency rate in fistulae with a single anastomosis and no interpositional graft. Mouse endothelium survived on the graft for 3 months according to CD31 staining, but longer survival by transgenic smooth muscle cells resulted in continued expression of beta-galactosidase for 6 months and green fluorescent protein for 4 months. Endothelium and smooth muscle in the fistula were functional, with normal expression of endothelial nitric oxide synthase as well as smooth muscle actin and fibronectin, respectively. CONCLUSION: The transgenic arteriovenous fistula model enhances other carotid-jugular fistula models by integrating transgenic tissue, thereby creating an experimental system for investigating the molecular biology of and gene therapies for arteriovenous malformations.

Animals↗

PubMed2003

Locomotion, stereotypy, and dopamine D1 receptors after chronic "binge" cocaine in C57BL/6J and 129/J mice.

We have shown that C57BL/6J and 129/J mice differ in their behavioral response to "binge" pattern cocaine (three daily injections of 15 mg/kg separated by 1 h). To determine if these differences persist during chronic binge cocaine administration, we examined the effects of 14-day binge pattern cocaine on home cage behavior. Since the dopamine D(1) receptor may be an important mediator of cocaine-induced locomotor activity, we examined binding to the dopamine D(1) receptor. Locomotor activity was increased by chronic binge cocaine in C57BL/6J (P<.0001) but not in 129/J mice. C57BL/6J mice developed tolerance to the locomotor-activating effects of cocaine. Stereotypic responses were greater in C57BL/6J than in 129/J mice (P=.03), with neither tolerance nor sensitization in either strain. Dopamine D(1) receptor binding in the nucleus accumbens and olfactory tubercle did not differ between strains and was not affected by chronic binge cocaine. In the caudate putamen, subregion specific strain differences in dopamine D(1) receptor binding were observed; chronic binge cocaine increased dopamine D(1) receptor binding in the caudal (P<.05), but not rostral caudate putamen. There was no correlation between locomotor activity or stereotypy and dopamine D(1) receptor density. Thus, with chronic binge cocaine administration, behavioral differences persist between the C57BL/6J and 129/J mice, and cocaine-induced locomotor activity is not correlated with changes in dopamine D(1) receptor binding.

Animals↗