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G A Stouffer

Publications and source records attributed to G A Stouffer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Vascular expression of integrin-associated protein and thrombospondin increase after mechanical injury.

BACKGROUND: Integrin-associated protein (IAP) is a thrombospondin (TSP)-binding, Gi protein-coupled cell surface receptor. The vascular function of IAP has not been defined, and it is not known whether TSP and IAP are expressed at the same time in injured arteries. METHODS: Left brachial arteries of baboons were injured using balloon withdrawal technique. Arteries were harvested 1 week after injury, and immunohistochemistry and in situ hybridization were performed using standard techniques. Uninjured right brachial arteries served as a control. Proliferation studies were performed using cultured human aortic smooth muscle cells (SMC). RESULTS: We found significant IAP expression in the media and neointima 7 days after injury using BRIC-126, an immunoglobulin (Ig) G2b monoclonal antibody that recognizes IAP with high specificity. In contrast, IAP staining in the uninjured vessel was only observed in the endothelium. Concurrent with IAP expression, TSP mRNA and protein expression in the neointima and media was enhanced 1 week after injury. In cultured SMC, activation of IAP was sufficient to elicit a proliferative response. TSP-induced proliferation was inhibited by antibodies that block TSP binding to IAP and mimicked by 4N1K, a 10-amino acid peptide derived from the IAP binding site within the carboxyl terminus of TSP. CONCLUSIONS: Vascular expression of IAP and TSP increased after mechanical injury and activation of IAP elicited a proliferative response in cultured SMC. These findings support the hypothesis that IAP participates in vascular healing responses.

Animals↗
PubMed2000

Left main coronary artery disease in adults younger than 50 years: a comparison with older patients.

Left main coronary artery (LMCA) disease is a potentially lethal disease that can be effectively treated if it is recognized expeditiously. To determine whether clinical signs and symptoms vary with age, we examined data from 100 patients with angiographically significant LMCA disease (> or =50% stenosis). The majority of patients had myocardial infarction (32%) or Braunwald class I unstable angina (46%). There were no differences in initial symptoms, electrocardiographic findings (normal or only nonspecific changes in 52% of patients), or left ventricular function (normal or only mildly impaired in 76% of patients) between younger patients (< 50 yr; n = 29) and older patients (n = 71). Severe atherosclerosis was common in both groups. Risk factor profiles were different, however, in that diabetes mellitus (10% vs. 34%; P = 0.028) and hypertension (38% vs. 73%; P = 0.002) were less common and tobacco use was more common (79% vs. 39%; P <0.001) in younger patients. In summary, age influenced the risk factors associated with but not the clinical signs and symptoms of LMCAD.

Adult↗
PubMed2000

Focal elastic obstruction of the inferior vena cava.

Obstruction of the supra-hepatic inferior vena cava (IVC) is a common cause of hepatic venous hypertension and the most common cause of Budd-Chiari Syndrome. Because most cases of IVC obstruction go undiagnosed until Budd-Chiari Syndrome develops, the natural history of IVC obstruction is not well defined. We report a case of a focal, elastic, non-membranous obstruction of the IVC causing hepatic venous hypertension and elevated serum transaminases in a 36-year-old man. The obstruction was successfully treated with placement of a self-expanding metallic stent with normalization of hepatic transaminases.

Adult↗
PubMed2000

A prospective evaluation of angiography-guided coronary stent implantation with high versus very high balloon inflation pressure.

BACKGROUND: High inflation pressure (HP) after coronary stent deployment has become a standard approach because it has been associated with a decreased subacute stent thrombosis (SAT) rate. However, the impact of HP on long-term outcomes is still unclear. We compared the long-term results of a strategy of increasing HP (>/=12 atm) until the achievement of angiographic success (<20% residual stenosis) with a prespecified very high inflation pressure (VHP) strategy of 20 atm without intermediate inflations. METHODS AND RESULTS: We conducted a parallel-group, nonrandomized study to evaluate the short- and long-term results in 136 consecutive eligible patients who underwent successful single Palmaz-Schatz stent implantation in vessels >/=3 mm. Major adverse cardiac events (MACE), that is, death, myocardial infarction, and target lesion revascularization (TLR), were monitored for a minimum of 6 months. No significant differences were observed between the two strategies in terms of final minimal lumen diameter (HP, 3.0 +/- 0.5 vs VHP, 3. 1 +/- 0.5 mm) and acute gain (HP, 2.1 +/- 0.7 vs VHP, 2.2 +/- 0.6). The overall rate of subacute stent thrombosis was 0.7%. During a 405 +/- 148-day follow-up, 21 (28.8%) patients in the VHP group and 6 (9. 5%) in the HP group (P =.005) had MACE, with a TLR rate of 27.4% versus 7.9% (P =.009), respectively. By multivariate analysis, the use of VHP increased the odds of long-term MACE by a factor of 3.48 (P =.009). Among patients undergoing TLR, those treated with VHP had a greater lumen loss (HP, 1.83 +/- 0.57 vs VHP, 2.15 +/- 0.36 mm, P =.02) and a more frequent pattern of diffuse restenosis (71% vs 16%, P =.06). CONCLUSIONS: In our study, the two strategies had similar acute and short-term results, but VHP was associated with a poorer long-term outcome. These data provide a rationale for a less aggressive strategy for stent deployment by optimizing rather than attempting to maximize inflation pressure and stent expansion.

Aged↗
PubMed2000

Morphological patterns of death by myocytes in arrhythmogenic right ventricular dysplasia.

There are two forms of nuclear loss from eukaryotic cells: biochemical DNA degradation in apoptosis and nuclear extrusion from the cell body as seen in mammalian erythroblasts. In biopsies of right ventricular myocardium from 8 patients with arrhythmogenic right ventricular dysplasia (ARVD), we found not only a terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick-end labeling (TUNEL)-positive nucleus in mononuclear myocytes, but also 1 or 2 TUNEL-positive nuclei in multinuclear myocytes. With electron microscopy, we found a nuclear dislocation to the cell periphery, followed by its extrusion into the extracellular space. Both the migration and extrusion of the nuclei of myocytes resemble the morphogenesis of human erythroblasts. Nuclear extrusion from myocytes may be another form of programmed cell death. In support of this possibility, we also found evidence of cytoplasmic degradation in right ventricular myocytes from our ARVD cases, a process similar to one often seen in developmental programmed cell death and differing from typical nuclear apoptosis. In our ARVD cases, we thus found several different patterns of cell death, all associated with initial preservation of the plasmalemma and avoidance of local inflammation. All these features may be different responses to common signals for selective non-necrotic (apoptotic) death of right ventricular myocytes.

Adult↗
PubMed2000

Autocrine thrombospondin partially mediates TGF-beta1- induced proliferation of vascular smooth muscle cells.

Transforming growth factor (TGF)-beta1 has been implicated in vascular healing responses after mechanical injury. Using cultured rat aortic smooth muscle cells (RASMC), we examined the hypothesis that production and secretion of thrombospondin (TSP) contributes to TGF-beta1-induced proliferation. We found that TGF-beta1 enhanced production and secretion of TSP, with peak levels of secreted TSP observed 24 h after treatment. RASMC treated with TGF-beta1 secreted a mitogenic activity that was transferable in conditioned media and partially inhibited by C6.7, a monoclonal anti-TSP antibody. Exogenous TSP stimulated a proliferative response, with maximal [(3)H]thymidine incorporation occurring 24 h earlier than maximal [(3)H]thymidine incorporation in response to TGF-beta1-treatment. Pretreatment with C6.7 or polyclonal anti-TSP neutralizing antibodies inhibited TGF-beta1-induced proliferation of RASMC. Proliferative responses to TGF-beta1 were also inhibited by pretreatment with an anti-beta(3) integrin monoclonal blocking antibody (F11), RGD peptides, and the anti-alpha(v)beta(3) disintegrin echistatin. Treatment with TSP and TGF-beta1 increased c-Jun NH(2)-terminal kinase (JNK)1 activity, with peak effects observed at 15 min and 4 h, respectively. Treatment with C6.7 or F11 inhibited TGF-beta-induced activation of JNK1. In summary, these studies support the hypothesis that TGF-beta-induced JNK1 activation and proliferation of RASMC require secretion of TSP and ligation of alpha(v)beta(3)-integrins.

Animals↗
PubMed2000

Protein complexes involving alpha v beta 3 integrins, nonmuscle myosin heavy chain-A, and focal adhesion kinase from in thrombospondin-treated smooth muscle cells.

alpha v beta 3 integrins have been implicated in regulating vascular healing in animal models of arterial injury. Because the specific cellular events mediated by alpha v beta 3 integrins are not completely understood, we examined alpha v beta 3 integrin-dependent cytoplasmic events in cultured human smooth muscle cells (SMC) following treatment with thrombospondin-1 (TSP), a glycoprotein concentrated at sites of blood vessel injury. TSP treatment elicited a time-dependent association of nonmuscle myosin heavy chain-A (NMHC-A) with alpha v beta 3 integrins. NMHC-A also associated with focal adhesion kinase (FAK) in TSP-treated SMC. FAK, a nonreceptor kinase implicated in integrin-mediated signaling, was phosphorylated on tyrosine in growth-arrested SMC, but levels of tyrosine phosphorylation increased following treatment with TSP. To test whether NMHC-A was regulated by vascular injury, we examined expression in baboon brachial arteries. In uninjured arteries, NMHC-A staining was present in the media. In arteries injured by balloon withdrawal, medial NMHC-A expression was increased with intense staining at specific sites. In summary, heteromeric protein complexes involving alpha v beta 3 integrins, NMHC-A, and FAK form following treatment of human SMC with TSP. These results suggest that the formation of protein signaling complexes is one mechanism whereby alpha v beta 3 integrins influence intracellular signaling pathways.

Animals↗
PubMed1999

Queuing for coronary angiography during severe supply-demand mismatch in a US public hospital: analysis of a waiting list registry.

CONTEXT: Adverse cardiac events have been reported in patients waiting for either coronary surgery or angioplasty. However, data on the risk of adverse events while awaiting coronary angiography are limited, and none are available from a US population. OBJECTIVE: To quantify cardiac outcomes in patients waiting for elective coronary angiography. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 381 adult outpatients (mean [SD] age, 55 [12] years; 64% male; 61% white) on a waiting list for coronary angiography at a US tertiary care public teaching hospital during 1993-1994. MAIN OUTCOME MEASURES: Rates of cardiac death, nonfatal myocardial infarction, and hospitalizations for unstable angina or heart failure as a function of amount of time spent on a waiting list. RESULTS: Sixty-six patients were dropped from the waiting list but were included in the study analysis. During a mean (SD) follow-up of 8.4 (6.5) months, cardiac death, myocardial infarction, and hospitalization occurred in 6 (1.6%), 4 (1.0%), and 26 (6.8%) patients, respectively. The probability of events was minimal in the first 2 weeks and increased steadily between 3 and 13 weeks. By Cox multivariate analysis, 2 variables independently identified an increased risk of adverse events: a strongly positive treadmill exercise electrocardiogram or positive stress imaging result at referral (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.22-4.16; P=.01) and the use of 2 to 3 anti-ischemic medications (OR, 1.98; 95% CI, 1.19-3.96; P=.04). Among 311 patients who ultimately underwent angiography, those with adverse events had a higher prevalence of coronary disease (96% vs 60%; P<.001), more frequently required revascularization (93% vs 53%; P<.001), and had longer hospital stays (mean [SD], 6.2 [4.3] vs 1.3 [0.7] days; P=.001). CONCLUSION: Our data suggest that in a cohort referred for coronary angiography, delaying the procedure places some patients at risk for death, myocardial infarction, unplanned hospitalization, a longer hospital stay, and, potentially, a poorer prognosis. Waits longer than 2 weeks should be avoided, and patients with strongly positive stress test results and those who require 2 to 3 anti-ischemic medications should be prioritized for early intervention.

Aged↗
PubMed1999

Interesting cases from the University of Texas Medical Branch.

This article discusses the cases for four patients with unstable angina. The first case is an example of the "high-risk" patient with widespread ECG changes, heart failure, and enzymatic elevations during an episode of chest pain. The second patient illustrates an unusual cause of unstable angina in a young women. The third patient had a large thrombus visible on angiography and management strategies for dealing with intracoronary thrombus are discussed. The final patient had an extensive past cardiac history with two prior coronary artery bypass operations and we discuss the recent advances made in the treatment of degenerative vein graft disease.

Abciximab↗
PubMed1999

Use of glycoprotein IIb/IIIa inhibitors in patients with coronary artery disease.

GP IIb/IIIa inhibitors are one of the most exciting pharmacological advances in the treatment of coronary artery disease to be developed this decade. They have proven benefit in the treatment of patients undergoing high-risk percutaneous interventions and in patients with unstable angina or non-Q-wave myocardial infarction. In all of these patients, they should be used in conjunction with aspirin and heparin. Although bleeding complications are high in initial studies, they are much less common with increased clinical experience and careful attention to heparin dosing. Important questions that will be answered in the next several years include whether there are significant differences between the available agents and whether oral formulations will be safe and effective.

Abciximab↗
PubMed1998

Beta3 integrins are upregulated after vascular injury and modulate thrombospondin- and thrombin-induced proliferation of cultured smooth muscle cells.

BACKGROUND: Treatment with an antibody that binds beta3 integrins (abciximab; c7E3 Fab) at the time of coronary angioplasty decreases the need for repeat revascularization. Two potential mechanisms have been proposed to explain this effect: (1) inhibition of platelet aggregation or (2) interruption of ligand binding to beta3 integrins on the smooth muscle cell (SMC) surface. We examined the latter hypothesis by determining (1) if beta3 integrin expression is upregulated after vascular injury in the baboon, (2) if 7E3 binds beta3 integrins on cultured SMC, and (3) if beta3 integrin activation plays a role in proliferation of cultured SMC. METHODS AND RESULTS: Results demonstrated that immunostaining for beta3 integrins was present in the neointima 1 week after balloon withdrawal injury of baboon brachial arteries and that beta3 integrin expression colocalized with alpha-actin-positive cells. In contrast, staining for beta3 integrins was undetectable in contralateral uninjured brachial arteries. 7E3 bound to cultured human aortic SMC with an affinity (KD=3.3 nmol/L) similar to 7E3 binding to endothelial cells or platelets. Cotreatment with 7E3 partially inhibited thrombospondin-induced or alpha-thrombin-induced proliferation but not PDGF-induced or serum-induced proliferation. CONCLUSIONS: In summary, these studies demonstrate that vascular cell beta3 integrin expression is increased after injury, that 7E3 binds to cultured SMC with high affinity, and that beta3 activation is important for thrombospondin-induced or alpha-thrombin-induced proliferation. These results support the hypothesis that beta3 integrins play a role in SMC growth responses after balloon injury.

Abciximab↗