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R T Lee

Publications and source records attributed to R T Lee.

At least 91 records · Page 5Linked to original sources
PubMed1997

Early versus delayed angiotensin-converting enzyme inhibition therapy in acute myocardial infarction. The healing and early afterload reducing therapy trial.

BACKGROUND: Although ACE inhibitor therapy has been shown to reduce mortality in patients with acute myocardial infarction (MI), the optimal dose and the timing of its initiation have not been determined. METHODS AND RESULTS: In a double-blind trial of 352 patients with anterior MI, we compared the safety and effectiveness of early (day 1) versus delayed (day 14) initiation of the ACE inhibitor ramipril (10 mg) on echocardiographic measures of left ventricular (LV) area and ejection fraction (EF). An early, low-dose ramipril (0.625 mg) arm was also evaluated. Clinical events did not differ. During the first 14 days, the risk of manifesting a systolic arterial pressure of < or = 90 mm Hg was increased in both ramipril groups. LVEF increased in all groups during this period, but the early, full-dose ramipril group had the greatest improvement in EF (increase: full, 4.9 +/- 10.0; low, 3.9 +/- 8.2%; delayed, 2.4 +/- 8.8%; P for trend < .05) and was the only group that did not demonstrate a significant increase in LV diastolic area. CONCLUSIONS: The results of the present study demonstrated that in patients with anterior MI, the early use of ramipril (titrated to 10 mg) attenuated LV remodeling and was associated with a prompter recovery of LVEF. The use of low-dose regimen did not prevent hypotension and had only intermediate benefits on LV size and function. The more favorable effects on LV topography of the early use of full-dose ramipril support the results of the major clinical trials, which have demonstrated an early survival benefit of ACE inhibition.

Aged↗
PubMed1997

Efficient immobilization of proteins by modification of plate surface with polystyrene derivatives.

Immobilization of proteins on microplate wells by simple adsorption (e.g., for ELISA) is convenient, but it can be inefficient, especially if proteins are hydrophilic or small in size. This problem was alleviated by the use of polyvinylbenzyl lactonoylamide (PVLA). PVLA is strongly adsorbed to the hydrophobic well surface, and its lactonamide part can be oxidized with periodate to generate aldehydo groups. Proteins are then immobilized covalently to the aldehydo groups by reductive amination under mild conditions. Using this method, henceforth termed the PVLA method, alkaline phosphatase (AP) was immobilized to microplates six- to sevenfold greater than by simple adsorption (as measured by activity). Similarly, the activity of immobilized mannose-binding protein A (MBP-A) was 4- to 8-fold higher by the PVLA method than by simple adsorption. The PVLA-coated plates needed as little as 200 ng of MBP-A per well to have a sufficient amount of MBP-A immobilized for the measurement of binding of 125I-labeled mannosylated bovine serum albumin (125I-Man-BSA), but unmodified plates required as much as 20 micrograms/well MBP-A to obtain the same response. Recommended conditions for the PVLA method are 40 microliters of 2 mg/ml of PVLA for coating, 1 mM NaIO4 for the generation of the aldehydo groups, and a 2-h reductive amination at 37 degrees C between pH 8 and 9 for the protein ligation.

Adsorption↗
PubMed1997

Difference in the binding mode of two mannose-binding proteins: demonstration of a selective minicluster effect.

Serum-type and liver-type mannose-binding proteins (MBP) are both present in higher animals and both are composed of a carbohydrate-recognition domain (CRD) and a collagenous domain. Although known as mannose-binding proteins, these proteins bind N-acetylglucosamine and other related sugars quite well. An earlier specificity study using cloned CRD portions of both types of MBP from rat [Childs, R. A., Feizi, T., Yuen, C.-T., Drickamer, K., & Quesenberry, M. (1990) J. Biol. Chem. 265, 20770-20777] revealed that the liver MBP CRD binds the trimannosyl core structure of N-glycosides, whereas the serum MBP CRD does not. We studied the substrate preferences of these CRDs using both solid and solution phase assays, testing monosaccharides, glycoproteins, and synthetic cluster ligands. While there was no significant difference in the monosaccharide binding specificities of the two CRDs, they displayed very different affinities for natural glycoproteins and mannose-containing cluster glycosides. Most interestingly, synthetic cluster ligands with two terminal GlcNAc moieties have affinity equal to monovalent GlcNAc ligands toward both CRDs, whereas a series of structurally similar Man-terminated divalent ligand displays about 20-fold enhanced affinity toward liver CRD only. A plausible explanation is that the liver MBP CRD has two sugar binding sites per subunit, one of which binds only mannose, and the other, both mannose and N-acetylglucosamine. In contrast, the serum MBP CRD has only one site of the latter type. Results of isothermal titration calorimetry support this hypothesis.

Binding Sites↗
PubMed1997

Echocardiographic prediction of complications in patients with chest pain.

The optimal role of Doppler echocardiography in the evaluation of patients with acute chest pain syndromes is unclear. We prospectively studied a cohort of 466 patients admitted with acute chest pain syndromes to clarify the relation between echocardiographic data and the risk of serious predischarge complications, and to determine if echocardiographic data can provide incremental prognostic information beyond clinical and electrocardiographic variables. Doppler echocardiograms, performed an average of 21 hours after presentation, were independently analyzed by 2 echocardiographers for information on global left and right ventricular function and valvular disease. Regional function was assessed by a wall motion index (WMI). A composite complications end point was positive if significant recurrent myocardial ischemia, heart failure, or arrhythmia developed after the echocardiogram. In univariate analysis, left (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.6, 5.1) and right (OR 2.7, 95% CI 1.2, 6.2) ventricular function, left ventricular end-diastolic (OR 1.6/cm, 95% CI 1.1, 2.3) and end-systolic (OR 1.4/cm, 95% CI 1.1, 1.9) dimensions, and WMI (OR 3.0, 95% CI 1.8, 4.8) predicted complications that developed after the echocardiogram. In multivariate analysis, WMI remained an incremental predictor of risk with an OR of 2.2/unit (95% CI 1.2, 3.9) scaled from 1 to 4. Even in the subset of 403 patients without acute myocardial infarction, WMI was associated with an OR of 1.9 (95% CI 1.0, 3.7). We conclude that early echocardiography provides incremental prognostic information concerning risk of subsequent complications in patients hospitalized with chest pain.

Adult↗
PubMed1997

Difference in binding-site architecture of the serum-type and liver-type mannose-binding proteins.

The carbohydrate-recognition domains (CRDs) of the serum-type and the liver-type mannose-binding proteins (MBPs) from rat display different binding characteristics toward mannose-rich oligosaccharides derived from N-glycosides, despite the overall similarity in their binding site architecture, oligomeric status and actual binding specificity at the monosaccharide level. We found that the liver-type MBP CRD of rat (MBP-C) bound methyl glycosides of certain mannobioses and -trioses, which are part of the mannose-rich N-glycoside, more tightly than methyl alpha-mannopyranoside. In contrast, the serum-type MBP CRD of rat (MBP-A) bound all the methyl glycosides of manno-oligosaccharide and methyl alpha-mannopyranoside with similar affinities. The mannobiose and -triose most strongly bound to MBP-C CRD were Man alpha (1-2)Man alpha-OMe and Man alpha (1-2)Man alpha (1-6)Man alpha-OMe, respectively. From these and other data, we postulate that the binding site of MBP-C has an extended area of interaction, probably the size of a mannotriose, while MBP-A interacts essentially with one mannose residue.

Animals↗
PubMed1997

Clinical and echocardiographic correlates of health status in patients with acute chest pain.

OBJECTIVE: To assess the ability of echocardiographic data to predict important functional status outcomes in patients with chest pain. DESIGN: Prospective cohort study. SETTING: A large, urban teaching hospital. PATIENTS: Three hundred thirty-three patients admitted from the Emergency Department for evaluation of chest pain. MEASUREMENTS AND MAIN RESULTS: Patients underwent two-dimensional and Doppler echocardiography as well as a face-to-face interview during their initial hospitalization and a telephone interview 1 year thereafter. The interview included the Medical Outcomes Study 36-Item Short Form (SF-36) health inventory, a generic health status instrument with a physical function subscale. The relation between clinical and echocardiographic factors and functional status was explored by univariable and multivariable linear regression and logistic regression analyses. Multiple clinical and echocardiographic factors correlated significantly with functional status measures at 1 year. For the SF-36 score at 1 year, age, male gender, white race, the presence of rales, and a comorbidity score were independently predictors in multivariate analysis; echocardiographic findings of severe left ventricular dysfunction (parameter estimate [PE] -27.6; 95% confidence interval [CI] -43.1, -12.2) and aortic insufficiency (PE -16.7; 95% CI -26.4, -7.0) added independent predictive information. Explanatory power (r2) for models using clinical and demographic variables was .27 and increased after inclusion of echocardiographic data to an r2 of .35. Results in the subset of patients (n = 148) with acute coronary syndromes such as unstable angina or myocardial infarction were qualitatively similar. Selected factors (rales on examination, electrocardiographic changes suggestive of ischemia, and moderate to severe mitral regurgitation) also predicted which patients would die or have a decline in their functional status. In multivariate analysis, only rales remained an independent predictor of poor outcome (odds ratio 2.4; 95% CI 1.2, 4.5). CONCLUSIONS: Echocardiographic data are correlated with measures of functional status in patients with chest pain, but the ability to predict future functional status from clinical or echocardiographic information is limited. Because functional status cannot be predicted adequately from either patients' characteristics or echocardiographic testing, it must be assessed directly.

Aged↗
PubMed1997

Mechanical strain tightly controls fibroblast growth factor-2 release from cultured human vascular smooth muscle cells.

Although fibroblast growth factor-2 (FGF-2) participates in the response to vascular injury, the role of cellular deformation in FGF-2 release is incompletely understood. To test the hypothesis that mechanical strain tightly controls FGF-2 release, a novel device was used to impose homogeneous and uniform biaxial strain to human vascular smooth muscle cells. Release of FGF-2 increased with the number of cycles of strain (14%, 1 Hz); 1, 9, and 90 cycles of strain, respectively, released 0.55 +/- 0.06%, 2.9 +/- 0.3%, and 5.5 +/- 1.3% of the total cellular FGF-2 (versus 0.00 +/- 0.40% for control, P < .05), but release was not further increased for strain of 90 to 90,000 cycles. Mechanical release of FGF-2 depended on both the frequency and amplitude of deformation. For example, strain (90 cycles, 1 Hz) at 4% amplitude released only 0.1 +/- 0.1% of the total FGF-2, but strain at 14% and 33% amplitudes, respectively, released 5.7 +/- 0.5% and 19.0 +/- 3.0% of the FGF-2 cellular pool (P < .05), suggesting a strain amplitude threshold for FGF-2 release. Injury to a subpopulation of cells increased with the frequency and amplitude of strain, but cells were not injured by strains below 10% amplitude. Strain following pretreatment with heparin released 12.6 +/- 1.6% of the total FGF-2 (versus 15.8 +/- 0.9% for strain alone, P < .05), indicating that most FGF-2 was liberated from the nuclear or cytoplasmic pools and not from low-affinity extracellular receptors. Conversely, strain in the presence of heparin released 25.2 +/- 3.5% of the total FGF-2 (versus 15.6 +/- 2.6% for strain alone, P < .05). Thus, cellular strain closely modulates the release of intracellular FGF-2 from human vascular smooth muscle cells, but FGF-2 release is negligible in response to the smaller strains that occur in the normal artery. In addition, larger mechanical strains lead to transfer of intracellular FGF-2 to the extracellular low-affinity receptors, where FGF-2 may be displaced by heparin. These observations provide insight into the mechanisms by which deforming vascular injury, such as that produced by arterial interventions, may elicit a proliferative response.

Cells, Cultured↗
PubMed1996

Pathogenic mechanisms of atherosclerosis: effect of lipid lowering on the biology of atherosclerosis.

Numerous trials have demonstrated that cholesterol-lowering therapy leads to marked reductions in cardiovascular and overall mortality and in the need for coronary revascularization. Angiographic regression trials have shown that cholesterol lowering can reduce progression and, in some instances, achieve regression of coronary atherosclerotic lesions. However, recent studies have contradicted the traditional view that the clinical course of coronary artery disease is closely linked to the severity of coronary artery stenosis. It is now apparent that stenoses responsible for myocardial infarction or unstable angina are typically mild rather than severe. These observations suggest that regression may not be the principal mechanism by which cholesterol lowering affects cardiovascular risk. Two mechanisms---plaque stabilization and improved endothelial function-have been examined in this regard. Basic studies suggest that cholesterol lowering favorably alters those features of atherosclerosis that promote plaque stability. Recent clinical studies have clearly established that aggressive lipid-lowering therapy improves endothelial function and reduces myocardial ischemia in patients with hypercholesterolemia.

Acetylcholine↗
PubMed1996

Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism.

This study analyzed the regional pattern of right ventricular (RV) dysfunction on transthoracic echocardiograms in patients with and without acute pulmonary embolism. Quantitative (centerline) and qualitative (wall motion score) analyses of segmental RV free wall motion were performed on a "training" cohort of 41 patients (group 1), including 14 patients with acute pulmonary embolism, 9 patients with primary pulmonary hypertension, and 18 normal subjects. Patients with acute pulmonary embolism had a distinct regional pattern of RV dysfunction, with akinesia of the mid-free wall (centerline excursion: -0.2 +/- 0.8 mm, p = 0.0001 vs normal) but normal motion at the apex (centerline excursion: 5.7 +/- 0.8 mm, p = NS vs normal). In contrast, patients with primary pulmonary hypertension had abnormal wall motion in all regions (p <0.03 vs normal). This echocardiographic finding of normal wall motion at the apex and abnormal wall motion in the mid-free wall in acute pulmonary embolism was then tested in a "validation" cohort of 85 patients (group 2), consisting of hospitalized patients with RV dysfunction from any cause, including 13 patients with acute pulmonary embolism. The finding had a 77% sensitivity and a 94% specificity for the diagnosis of acute pulmonary embolism, with a positive predictive value of 71% and a negative predictive value of 96%. Thus, a distinct echocardiographic pattern of regional RV dysfunction, in which the apex is spared occurs in acute pulmonary embolism. This finding should raise the level of clinical suspicion for the diagnosis of acute pulmonary embolism.

Acute Disease↗
PubMed1996

Induction of DNA synthesis by a single transient mechanical stimulus of human vascular smooth muscle cells. Role of fibroblast growth factor-2.

BACKGROUND: Although mechanical vascular injury leads to smooth muscle cell proliferation that contributes to restenosis after balloon angioplasty, the role of the single transient mechanical stimulation of smooth muscle cells in this process is unknown. METHODS AND RESULTS: To test the hypothesis that a single transient mechanical stimulus can increase DNA synthesis, human vascular smooth muscle cells cultured in a three-dimensional collagen gel system were subjected to transient compression. Transient compression (5-minute duration) of smooth muscle cell-collagen gel cultures in defined serum-free conditions led to delayed increases in [3H]thymidine incorporation. At 12 to 24 hours after compression, there was a 3.3 +/- 0.5-fold (P<.001 versus control) and 3.0 +/- 0.6-fold (P<.002 versus control) increase for 60% and 80% strain, respectively; at 24 to 36 hours after compression, there was a 1.8 +/- 0.5-fold (P<.05 versus control) and 4.3 +/- 0.8-fold (P<.001 versus control) increase. Also, serum-free media conditioned by transiently compressed gel cultures induced DNA synthesis in control, unstimulated smooth muscle cell cultures, suggesting the release of growth factors by transient compression. Although neutralizing antibodies against platelet-derived growth factor did not affect the mechanical induction of DNA synthesis, a neutralizing monoclonal antibody against fibroblast growth factor-2 (FGF-2) decreased this induction by 89% and completely blocked the increase in DNA synthesis caused by media conditioned by transiently compressed gels. Media conditioned by transient compression contained elevated levels of FGF-2 (17 +/- 5 versus 2 +/- 2 pg/mL for control, P<.005) with no increase in lactate dehydrogenase activity, suggesting release of FGF-2 with sublethal cellular injury. CONCLUSIONS: A single transient mechanical stimulus increases DNA synthesis in human vascular smooth muscle cells, in part by autocrine or paracrine FGF-2 release.

Cells, Cultured↗
PubMed1996

Echocardiographic predictors of survival after surgery for mitral regurgitation in the age of valve repair.

The objective of this study was to identify echocardiographic and clinical predictors of survival after mitral valve surgery when mitral repair is an option. In 132 patients undergoing mitral valve repair or replacement for the diagnosis of mitral regurgitation, preoperative echocardiograms were analyzed quantitatively and reviewed by two independent observers for structural abnormalities of the mitral valve. In Cox regression analysis, clinical factors such as age (mortality rate ratio [MRR] 1.7/decade, 95% confidence intervals [CI] 1.1, 2.4), and New York Heart Association class IV (MRR 3.1, 95% CI 1.4, 6.7) and echocardiographic factors including morphologic evidence of endocarditis or myxomatous disease (MRR 0.3, 95% CI 0.1, 0.7) were significant predictors of overall survival, although valve repair itself was not. End-systolic dimensions and volumes were not, likely related to the small number of patients with markedly increased end-systolic dimensions or volumes (5 patients [4%] with end-systolic dimension > 5.5 cm, 12 patients [9%] with end-systolic volume index > 60 ml/m2). New York Heart Association class IV (MRR 2.9, 95% CI 1.3, 6.4), age (MRR 1.7/decade, 95% CI 1.2, 2.6), and the presence of calcification (MRR 4.6, 95% CI 1.3, 16.2) were independent predictors of survival in multivariate analysis. In this contemporary cohort of patients undergoing repair or replacement for mitral regurgitation, factors such as echocardiographically determined cause of disease and presence of calcification predicted survival; traditional measurements such as end-systolic dimensions and volumes were less predictive, most likely because patients underwent surgery before their ventricles became markedly enlarged. Clinical factors such as age and functional status remained the most potent predictors of survival after surgery for mitral regurgitation.

Age Factors↗
PubMed1996

Clinical and microbiologic evaluation of a resin modified glass ionomer cement for orthodontic bonding.

This study evaluated the clinical performance of a new resin modified glass ionomer cement, Geristore (Den-Mat Corp., Santa Maria, Calif.), for the bonding of orthodontic brackets and its effect on certain caries-associated microorganisms. This cement has been shown to possess increased mechanical properties and long-term fluoride release. There were 716 brackets bonded in 40 patients (17 males and 23 females), with a split-mouth technique and a composite resin, Phase II (Reliance, Itasca, III.), as a control. Bond failures were recorded up to 1 year. Plaque scores and plaque samples were taken from the area of the bonding adhesive in 20 patients, before, at 1 week, and 5 months after the placement of brackets. The plaque samples were investigated for the presence of Streptococcus mutans and lactobacilli. The overall bond failure rate was found to be 8.9% for Geristore and 3.1% for Phase II (p < 0.05). Labially, there was no significant difference (p > 0.05) in bond failure rate: 3.8% for Geristore and 1.7% for Phase II. The proportions of S. mutans and lactobacilli in plaque taken from around Geristore cement were reduced at 1 week and 5 months, when compared with Phase II resin, and this reduction was statistically significant (p < 0.05) at 1 week. Results of this study suggest that Geristore may be of use in the labial segments, especially in caries prone patients, in whom demineralization at debond may present an esthetic and restorative problem several years after treatment.

Adolescent↗
PubMed1996

A meta-analytic examination of the correlates of the three dimensions of job burnout.

This meta-analysis examined how demand and resource correlates and behavioral and attitudinal correlates were related to each of the 3 dimensions of job burnout. Both the demand and resource correlates were more strongly related to emotional exhaustion than to either depersonalization or personal accomplishment. Consistent with the conservation of resources theory of stress, emotional exhaustion was more strongly related to the demand correlates than to the resource correlates, suggesting that workers might have been sensitive to the possibility of resource loss. The 3 burnout dimensions were differentially related to turnover intentions, organizational commitment, and control coping. Implications for research and the amelioration of burnout are discussed.

Achievement↗
PubMed1996

Macrophages and atherosclerotic plaque stability.

Physical disruption of atheroma frequently causes coronary thrombosis. Ruptured plaques usually have thin fibrous caps overlying a large thrombogenic lipid core rich in lipid-laden macrophages. The biology of plaque monocyte-derived macrophages thus assumes critical importance in understanding plaque instability. Monocyte recruitment involves binding to leukocyte adhesion receptors on the endothelial surface such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Once adherent to the endothelial surface, monocytes enter the intima at sites of lesion predilection. This process probably requires directed migration of the mononuclear cells. A number of chemoattractant molecules, such as the monocyte chemoattractant molecule-1, may participate in signaling this entry of adherent monocytes into the artery wall. Once resident in the arterial intima, monocytes accumulate lipid, via increasingly well characterized receptor-mediated uptake, and transform into macrophage foam cells. These lesional macrophages also acquire other functional properties including production of the potent procoagulant, tissue factor, apolipoprotein E, and an increasing list of cytokines (protein mediators of information and immunity) that may participate importantly in autocrine and paracrine signaling among leukocytes and vascular endothelial and smooth muscle cells. Fatty streaks seldom cause clinical events but may evolve into complicated atheromatous plaques characterized by an accumulation of smooth muscle cells and extracellular matrix and formation of a central core containing extracellular lipid. Death of macrophages, including programmed cell death or apoptosis, probably promotes formation of this thrombogenic lipid pool whose size correlates with plaque instability. Lesion complication often culminates in rupture of the fibrous cap overlying this lipid core. The integrity of the fibrous cap, and thus its resistance to rupture, depends critically on the collagenous extracellular matrix of the plaque's fibrous cap. This aspect of plaque structure in turn depends upon the balance between synthesis and degradation of the macromolecules that comprise the extracellular matrix of the cap, principally interstitial forms of collagen derived from arterial smooth muscle cells. Collagen breakdown, however, appears to depend critically on macrophages. Plaque macrophages express a variety of matrix-degrading enzymes that can contribute to the weakening of the fibrous cap. In this way, macrophages can critically influence aspects of the biology of human atheroma related to lesion stability. We hypothesize that lipid-lowering reduces clinical events, as shown in recent trials, by stabilizing lesions in part by reversing some of the maladaptive functions of macrophages described above.

Arteriosclerosis↗