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Biomedical subjects

John W Moore

Publications and source records attributed to John W Moore.

25 records · Page 2Linked to original sources
PubMed2002

A mycobacterial iron chelator, desferri-exochelin, induces hypoxia-inducible factors 1 and 2, NIP3, and vascular endothelial growth factor in cancer cell lines.

Hypoxia is a key phenomenon in tumor behavior, selecting for resistance to apoptosis, conferring resistance to radiotherapy and chemotherapy, and also inducing angiogenic factors such as vascular endothelial growth factor (VEGF). Exochelins are naturally evolved iron chelators produced by Mycobacterium tuberculosis. Because iron chelation has been reported to activate the hypoxia-inducible factor (HIF), we investigated the effects of an exochelin [desferri-exochelin (DFE) 772SM] on this hypoxia-inducible pathway and downstream target genes. DFE induced HIF-1alpha and HIF-2alpha transcription factors regulating the hypoxic response in the breast tumor cell line MDA468. DFE was 10 times more potent and more rapid in onset of effect than the clinically used iron chelator deferoxamine. The expression of downstream hypoxia-responsive target genes VEGF and the proapoptotic protein NIP3 was activated by transcription. MDA468 proliferation was inhibited via HIF-independent pathways, related to other effects of iron chelation. DFE inhibited effects of VEGF on endothelial cell proliferation. DFE potentially could be useful in cancer therapy by inducing apoptosis via NIP3 in conjunction with other non-HIF-related growth inhibitory pathways and blocking endothelial proliferation despite the presence of VEGF.

Adenocarcinoma↗
PubMed2002

Trisomy 18 in a 20-year-old woman.

A 20-year-old female with trisomy 18 is described. Survival past infancy is rare in this disorder. Little is known concerning the factors that contribute to prolonged survival with this syndrome. This case provides an opportunity to review the management of older children and young adults with trisomy 18.

Abnormalities, Multiple↗
PubMed2002

Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation.

The von Hippel-Lindau tumor suppressor protein acts as the substrate recognition component of a ubiquitin E3 ligase that targets hypoxia-inducible factor (HIF)-alpha subunits for proteolysis. Stabilization of HIF-alpha subunits has been described in VHL-defective cell lines, leading to HIF activation and up-regulation of hypoxia-inducible mRNAs. Mutations of the von Hippel-Lindau tumor suppressor protein are found in most clear cell renal cell carcinomas (CC-RCCs) but not other renal tumors, raising a question about the importance of activation of the HIF pathway in CC-RCC development. To address this question, we have examined the expression of HIF-alpha subunits in 45 primary renal tumors and related this to tumor subtype, the presence of VHL mutations, and measures of angiogenesis. We show that HIF-alpha is up-regulated in the majority of CC-RCCs, and that the pattern of expression is biased toward the HIF-2alpha isoform. Expression of HIF-alpha proteins was associated significantly with up-regulation of VEGF mRNA and protein and increased microvessel density. Up-regulation of HIF-alpha in CC-RCC was found to involve increased mRNA as well as protein expression, suggesting that both VHL-dependent and VHL-independent mechanisms are involved. These results suggest that activation of the HIF pathway is functionally important in CC-RCC development and might provide a new therapeutic target.

Adenocarcinoma, Clear Cell↗
PubMed2002

Fontan's operation: is aspirin enough? Is coumadin too much?

BACKGROUND: Thromboembolism after Fontan's operation is attributed to low flow states, stasis in venous pathways, right to left shunts, blind cul-de-sacs, prosthetic materials, atrial arrhythmias, and hypercoagulable states. We assessed the efficacy of a strategy to reduce thromboembolic events including aspirin anticoagulation. METHODS: From January 1996 through December 2000, 72 patients underwent Fontan procedures. Management included (1) avoidance of direct caval cannulation and central venous lines, (2) inotropic support for 48 to 72 hours to optimize cardiac output, (3) aortopulmonary anastomosis or suture closure of patent pulmonary valves, and (4) administration of aspirin (81 mg per day) beginning on postoperative day one. No other anticoagulation strategies were used. Surveillance included intraoperative and postoperative transesophageal echo, transthoracic echo at discharge, at first reevaluation, and at 6 month intervals, and catheterization 1 year after surgery. RESULTS: There were no early or late deaths. Follow-up was completed with 2,882 patient-months and a mean of 40 months. There were no documented thromboembolic events; however, all suspicious occurrences were investigated by echo and brain imaging. There were no hemorrhagic events or aspirin-related complications. CONCLUSIONS: Low dose aspirin can be used safely in young patients with Fontan connections. At intermediate follow-up, the strategies described appear effective in preventing thromboembolic complications. Routine use of more aggressive anticoagulation regimens seems unwarranted.

Adolescent↗
PubMedDate not supplied

Use of a covered stent modification to produce a transcatheter valve: laboratory and animal testing.

Stent-based transcatheter valves continue to require large sheaths inappropriate for deployment in children. Low-profile covered stent valves (CSVs) were constructed by removing triangular sections from two sides of partially expanded Palmaz P308 stents before covering the stents with 0.1 mm polytetrafluoroethylene. Valves were carefully crimped onto balloon catheters and deployed in a pulsatile flow loop. With fixed afterload and pump output, flow, degree of stenosis, effect on pulse pressure, and ease of deployment were determined for each valve. In vivo transcatheter feasibility studies were then performed by disabling the aortic valve of two 25-kg pigs, and deploying transcatheter CSVs into their descending aorta. All transcatheter valves deployed consistently via sheaths three French sizes larger than the recommended sheath for their balloon and none created significant obstruction. With the bicuspid and supravalvar CSVs, the flow was 64% and 79% (respectively) of a commercially available valve. Angiograms revealed excellent acute CSV function after deployment with only mild regurgitation and without significant obstruction to systolic flow. Although long-term testing is required, a modified CSV design may have utility in low-profile pediatric transcatheter valve replacement.

Adult↗