Biomedical subjects

L Mureebe

Publications and source records attributed to L Mureebe.

8 recordsLinked to original sources

PubMed2001

Calciphylaxis: a poor prognostic indicator for limb salvage.

INTRODUCTION: Calciphylaxis (calcific uremic arteriolopathy) is a rare complication of end-stage renal disease in patients with secondary hyperparathyroidism. Subcutaneous skin nodules and extensive tissue necrosis with vascular calcification characterize this process. DESIGN AND SETTING: The design of the study included case series and literature review. The study was set in a tertiary care hospital. PATIENTS: Four patients presented over an 8-month period with extensive tissue loss and the subsequent diagnosis of calciphylaxis. Two of these patients were revascularized. One underwent primary amputation, and the final patient died before revascularization. The mortality rate for this group was 75%. All patients had significant vascular complications outside the area of initial presentation. CONCLUSIONS: These individuals represent a subset of patients who may not benefit from revascularization or may require extensive regulation of divalent metabolism before consideration for revascularization.

Aged↗

PubMed1998

Smooth muscle cell migration and proliferation are mediated by distinct phases of activation of the intracellular messenger mitogen-activated protein kinase.

PURPOSE: Mitogen-activated protein kinase (MAPK) is a ubiquitous signaling protein that has been associated with cellular proliferation; however, its role in cellular migration has not been established. In this study, we investigate the role of MAPK in platelet-derived growth factor (PDGF)-induced migration and proliferation of human vascular smooth muscle cells (SMCs). METHODS: SMC migration was measured using a microchemotaxis assay (4 hours), and proliferation was assessed using 3H-thymidine uptake and cell counts. PD098059 was used as a specific noncompetitive inhibitor of MAPK activation. RESULTS: Coincubation of SMCs with PD098059 resulted in significant inhibition of PDGF-BB (5 ng/ml)-induced SMC chemotaxis and proliferation. The IC50 for both processes was approximately 10 mumol/L with complete inhibition at 50 mumol/L. Stimulation of SMCs with PDGF produced an early peak in MAPK activity followed by a plateau of activity that persisted for 24 hours. We hypothesized that variations in the temporal activation of MAPK might explain the action of this enzyme on these two disparate cellular events. By adding PD098059 at intervals after stimulation of SMCs with PDGF, we demonstrated an association between MAPK activity within the first 15 minutes and SMC migration, whereas MAPK activity between 1 and 4 hours was associated with SMC proliferation. CONCLUSIONS: MAPK activity is essential for both SMC migration and proliferation, and distinct phases of enzyme activation are required to stimulate these two discrete cellular events. Inhibition of this signaling protein may prove to be a useful method for preventing intimal hyperplasia.

Becaplermin↗

PubMed1998

Wound infection: a physician's perspective.

Infection in a wound represents a colony count of 10(5) or greater. Contamination is the presence of many surface organisms. Moist wound healing, not dehydration, protects and prepares the wound for coverage and closure. Relief of pain is a critical factor in achieving healing: a biological or pharmaceutical device can achieve protection and facilitate healing.

Debridement↗

PubMed1998

Epidemiology, risk factors, and management of peripheral vascular disease.

Peripheral vascular occlusive disease is initiated with a genetic risk factor component compounded by patient-controlled contributions including obesity, diabetes, hypertension, and smoking. Medical management of these factors may delay or obviate surgical intervention. Angiography may be used to perform angioplasty (+/- stents) or to guide various interventional procedures. The major contribution to pre- and post-operative assessment is the noninvasive laboratory.

Angioplasty↗

PubMed1997

Activation of pp60c-src is necessary for human vascular smooth muscle cell migration.

BACKGROUND: The most widely distributed nonreceptor tyrosine kinase is pp60c-src (src), yet the role of this intracellular signaling protein in cell migration has not been defined. Given that smooth muscle cell (SMC) migration is essential for the development of intimal hyperplasia, we investigated the importance of src in locomotion of human vascular SMC. METHODS: SMC migration was evaluated using a microchemotaxis chamber assay and videomicroscopy. Src kinase activity was determined by measuring phosphorylation of a synthetic derivative of p34cdc2, a specific substrate for src. Blocking antibodies to src were introduced using a cytoplasmic microinjection technique. RESULTS: Stimulation of SMC with platelet-derived growth factor (PDGF)-BB and AB resulted in an increase in src activation, whereas PDGF-AA did not consistently enhance src activity. These findings correlated with the ability of the PDGF isotypes to stimulate SMC chemotaxis; PDGF-BB and AB produced 7.4 +/- 0.3- and 5.3 +/- 0.5-fold increases in SMC chemotaxis, whereas PDGF-AA inhibited chemotaxis. SMC migration in response to PDGF-BB and serum was significantly inhibited by intracellular injection of a blocking antibody. CONCLUSIONS: Our findings reveal an association between agonist-induced src activation and chemotaxis. Moreover, an antibody that inhibits src activation dramatically inhibits migration of individual SMC. We conclude that activation of src is necessary for SMC migration. Because of its importance in SMC migration, either molecular or pharmacologic inhibitors of src may be useful in the control of intimal hyperplasia.

Becaplermin↗

PubMed1997

The role of integrins in saphenous vein vascular smooth muscle cell migration.

PURPOSE: Smooth muscle cell (SMC) migration is an essential feature of the intimal hyperplastic process that so frequently limits the patency of vascular reconstructions. The purpose of this investigation was to evaluate the effect of a series of integrins, or cell surface receptors that mediate cellular attachment, on platelet-derived growth factor (PDGF) and extracellular matrix (ECM) protein-induced migration of human SMCs. METHODS: Immunofluorescence staining was used to search for various integrins and subunits on the surface of SMCs derived from human saphenous vein. Chemotaxis and haptotaxis of SMCs to various matrix proteins and PDGF were assayed using a 48-well microchemotaxis chamber in the presence or absence of antibodies that blocked the function of these integrins. RESULTS: Several subunits (beta 1, alpha 2, alpha 5) and one integrin (alpha v beta 3) were identified in saphenous vein SMCs. The beta 1 integrin antibody inhibited chemotaxis to collagen I and IV, laminin, and PDGF. The alpha 2 integrin antibody inhibited collagen I and IV, and laminin-induced chemotaxis. The alpha 5 integrin antibody had no effect on SMC migration. The alpha v beta 3 integrin antibody inhibited chemotaxis to PDGF but not to the ECM proteins. CONCLUSIONS: Integrins are necessary for SMC migration induced by PDGF and ECM proteins. The integrin or subunits responsible for facilitating migration varies with the stimulant. Agonists designed to inhibit integrin function might be used to suppress SMC migration and suppress the formation of intimal hyperplasia.

Cell Movement↗

PubMed1996

Differential effects of platelet-derived growth factor isotypes on human smooth muscle cell proliferation and migration are mediated by distinct signaling pathways.

BACKGROUND: Platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant for vascular smooth muscle cells (SMCs). Three isotypes of PDGF (BB, AB, and AA) have been identified; each of these isotypes may have differing effects on the behaviour of vascular SMCs. In this study we evaluated the influence of PDGF isotypes on proliferation and migration of human venous SMCs and explored the signaling pathways through which these effects are mediated. METHODS: Proliferation was measured by a 72-hour assay of cell number, and migration was evaluated by a 4-hour microchemotaxis assay. The effects of PDGF isotypes on the activities of the signaling proteins mitogen-activated protein kinase (MAP-K), p 125 focal adhesion kinase (p125FAK), and tensin were measured by immunoprecipitation of these proteins and subsequent phosphorylation on myelin basic protein (in MAP-K) and Western blotting with antiphosphotyrosine (in tensin and p125FAK). RESULTS: All three isotypes stimulated SMC proliferation (PDGF-BB > AB > AA). PDGF-BB and -AB, but not -AA, stimulated chemotaxis. All three isotypes activated MAP-K with an intensity that corresponded to their proliferative effects. PDGF-BB and -AB tyrosine phosphorylated tensin and p125FAK, whereas PDGF-AA had no effect on either of these proteins. CONCLUSIONS: For human vascular SMCs the physiologic effects and the signaling pathways that mediate these effects are specific for each of the three PDGF isotypes. These data also suggest an association between MAP-K and SMC proliferation and between the proteins, p125FAK and tensin, and migration.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1996

Popliteal artery injury after total knee arthroplasty.

Total knee arthroplasty (TKA) is a commonly performed orthopedic procedure. The incidence of vascular complications after TKA is low. However, these complications may be debilitating, limb-threatening, and potentially avoidable. Our first patient, who had no preexisting vascular occlusive disease, developed an ischemic extremity after TKA. The second patient underwent TKA and was diagnosed with a severely ischemic limb 48 hours postoperatively. Both patients underwent above-knee to below-knee popliteal artery saphenous vein bypass grafting. Although limb salvage was obtained in both cases, one had a significantly neuropathic foot. In conclusion, long-term morbidity can be avoided by early identification and treatment of ischemia by bypass grafting.

Aged↗