Strain and model dependent differences in inflammatory cell recruitment in mice.

Objective And Design: The objective of this study was to determine genetic differences in inflammation in these distinct inbred mouse strains.

Methods: Peritoneal leukocyte recruitment, matrix metalloproteinases and cytokines were quantified in A/J, 129/svJ, C57BL/6J, using thioglycollate or biomaterial implants as inflammatory stimuli.

Results: In response to thioglycollate, A/J had significant decreases compared to C57BL/6J in both neutrophil (86 %) and macrophage (62 %) recruitment, and 129/svJ had a significant (43 %) decrease compared to C57BL/6J in macrophage recruitment.

In vivo comparison of the inflammatory response induced by different vascular biomaterials.

Biomaterial implants induce a local inflammatory response. A comparison of the inflammatory cell response was made between several biomaterials commonly used as vascular prostheses. Disks of polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), aluminum, titanium, copper, and stainless steel were surgically placed into the peritoneum of mice.

Support vector machines with profile-based kernels for remote protein homology detection.

Two new techniques for remote protein homology detection particulary suited for sparse data are introduced. These methods are based on position specific scoring matrices or profiles and use a support vector machine (SVM) for discrimination. The performance on standard benchmarks outperforms previous non-discriminative techniques and is comparable to that of other SVM-based methods while giving distinct advantages.

A central role for plasminogen in the inflammatory response to biomaterials.

The inflammatory response to implanted biomaterials severely limits their deployment in patients. Plasminogen has been shown to play a central role in cell migration, and therefore could regulate this inflammatory response. We sought to determine if plasminogen influences recruitment of inflammatory cells to a biomaterial implanted into plasminogen-deficient (Plg(-/-)) mice.

Leukocyte engagement of fibrin(ogen) via the integrin receptor alphaMbeta2/Mac-1 is critical for host inflammatory response in vivo.

The leukocyte integrin alpha(M)beta(2)/Mac-1 appears to support the inflammatory response through multiple ligands, but local engagement of fibrin(ogen) may be particularly important for leukocyte function. To define the biological significance of fibrin(ogen)-alpha(M)beta(2) interaction in vivo, gene-targeted mice were generated in which the alpha(M)beta(2)-binding motif within the fibrinogen gamma chain (N(390)RLSIGE(396)) was converted to a series of alanine residues. Mice carrying the Fibgamma(390-396A) allele maintained normal levels of fibrinogen, retained normal clotting function, supported platelet aggregation, and never developed spontaneous hemorrhagic events.

Immediate repair compared with surveillance of small abdominal aortic aneurysms.

Background: Whether elective surgical repair of small abdominal aortic aneurysms improves survival remains controversial.

Methods: We randomly assigned patients 50 to 79 years old with abdominal aortic aneurysms of 4.0 to 5.

Diagnosis and management of aortoenteric fistulas.

Development of an aortoenteric fistula (AEF) is a devastating and life-threatening condition, which is as difficult to diagnose as it is to treat. Fortunately, it is rare, most commonly seen as a delayed complication of aortic reconstruction. Two types are recognized: primary and secondary.

Inhibition of endothelial cell migration by cigarette smoke condensate.

Cigarette smoking is among the leading risk factors in the etiology of atherosclerotic vascular disease. The mechanism, however, that links cigarette smoking to an increased incidence of atherosclerosis is poorly understood. Endothelial cell (EC) integrity is critical in preventing vascular lesion formation, and after a loss of EC integrity reendothelialization must be rapid and complete.

Endoluminal arterial injury in plasminogen-deficient mice.

Background: Vascular remodeling following arterial injury is characterized by an initial inflammatory reaction. Prior experiments using peritoneal inflammatory models have shown that the plasminogen system plays a role in the intensity of the inflammatory response. This study was undertaken to test the hypothesis that an absence of plasminogen would lead to a decrease in vascular remodeling.

A role of plasminogen in atherosclerosis and restenosis models in mice.

In addition to its preeminent role in fibrinolysis, the plasminogen system is believed to play a key role in mediating cell migration. Leukocyte migration into the vessel wall is a key and early event in the development of the lesions of atherosclerosis and restenosis, pathologies which may be viewed as specific examples of vascular inflammatory responses. The development of mice in which the plasminogen gene has been inactivated affords an opportunity to test the contribution of plasminogen in leukocyte migration during in vivo.

Carotid duplex overestimation of stenosis due to severe contralateral disease.

Background: In the quest to use carotid duplex to assess carotid occlusive disease, it has been reported that the current velocity criteria to calculate stenosis tends to overestimate the severity when there is a contralateral highly stenotic or occluded carotid artery.

Methods: Patient records were reviewed for 592 consecutive carotid endarterectomies performed from 1987 to 1994. Preoperative and postoperative duplex scan results were compared in a subset of patients in whom duplex overestimated the degree of stenosis, as compared to preoperative angiography.

Antisense suppresssion of protein kinase C-alpha and -delta in vascular smooth muscle.

Understanding and being able to manipulate intracellular signaling pathways which control VSMC gene expression and proliferation will be important in efforts to control neointimal hyperplastic vascular diseases. Activation of the protein kinase C (PKC) family of enzymes is a central event in growth factor-stimulated cells. PKC activation results in the activation of downstream protein kinases including mitogen activated protein kinase (MAPK).

Spontaneous dissection of the abdominal aorta: experience with five patients.

Spontaneous dissection of the infradiaphragmatic abdominal aorta is a rare form of aortic dissection. Its natural history and management are not well defined. We have recently treated five patients with spontaneous aortic dissection.