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Biomedical subjects

R T Lee

Publications and source records attributed to R T Lee.

At least 19 recordsLinked to original sources
PubMed1992

Microcalorimetric study of wheat germ agglutinin binding to N-acetylglucosamine and its oligomers.

The energetics of association of wheat germ agglutinin (WGA) with N-acetylglucosamine (GlcNAc) and its beta(1,4) oligomers have been measured using isothermal titration calorimetry. Association constants of 0.4, 5.3, 11.1, 12.3, and 19.1 mM-1 and enthalpies of binding of -6.1, -15.6, -19.4, -19.3, and -18.2 kcal mol-1 were obtained at 26 degrees C for the titration of WGA with GlcNAc, (GlcNAc)2, (GlcNAc)3, (GlcNAc)4, and (GlcNAc)5, respectively. The term T delta S was always of negative value, indicating that the binding process is enthalpically driven. Titrations of WGA performed at pH 4.5 did not differ significantly from those performed at pH 7.0, suggesting that no groups with a pKa in this range are directly involved in the binding event. Also, performing the titration in a buffer system with a higher enthalpy of protonation did not change the enthalpy of binding confirming that there is no net protonation or deprotonation when WGA binds GlcNAc residues at pH 7. A model of four independent binding sites was found to adequately describe the binding curves, except in the case of (GlcNAc)4 which exhibited positive cooperativity. The energetic values are discussed within the context of the structure of the WGA-(GlcNAc)2 complex.

Acetylglucosamine↗
PubMed1992

Ligand binding characteristics of the major mistletoe lectin.

Carbohydrate binding specificity of the galactose-specific, major lectin of mistletoe extract (ML-1) was studied by an inhibition assay using monosaccharides, monosaccharide derivatives, disaccharides, and compounds containing multiple galactosyl terminals. The results indicate that 1) both alpha- and beta-galactosyl residues are recognized equally well; 2) each of the hydroxyl groups of galactose contributes to varying degrees to the binding process, the 4-OH being the most important and the 6-OH the least important hydroxyl group; 3) disaccharide sequences of Gal beta 2Gal and Gal beta 3Gal have much higher affinity than galactose, whereas affinity of all other Gal-disaccharides is only slightly better than galactose; 4) macromolecular ligands having 10 or more terminal galactosyl residues have 500-fold higher affinity than Gal; and 5) a group on ML-1 with pK alpha of 4.8 appears to be involved in the binding of ligand.

Binding Sites↗
PubMed1992

Multivalent ligand binding by serum mannose-binding protein.

The serum-type mannose-binding protein (MBP) is a defense molecule that has carbohydrate-dependent bactericidal effects. It shares with mammalian and chicken hepatic lectins similarity in the primary structure of the carbohydrate-recognition domain, as well as the ligand-binding mode: a high affinity (KD approximately nM) is generated by clustering of approximately 30 terminal target sugar residues on a macromolecule, such as bovine serum albumin, although the individual monosaccharides have low affinity (KD 0.1-1 mM). On the other hand, MBP does not manifest any significant affinity enhancement toward small, di- and trivalent ligands, in contrast to the hepatic lectins whose affinity toward divalent ligands of comparable structures increased from 100- to 1000-fold. Such differences may be explained on the basis of different subunit organization between the hepatic lectins and MBP.

Acute-Phase Proteins↗
PubMed1992

Cloning of a human galactokinase gene (GK2) on chromosome 15 by complementation in yeast.

A human cDNA encoding a galactokinase (EC 2.7.1.6) was isolated by complementation of a galactokinase-deficient (gal1-) strain of Saccharomyces cerevisiae. This cDNA encodes a predicted protein of 458 amino acids with 29% identity to galactokinase of Saccharomyces carlsbergensis. Previous studies have mapped a human galactokinase gene (GK1) to chromosome 17q23-25, closely linked to thymidine kinase. The galactokinase gene that we have isolated (GK2) is located on chromosome 15. The relationship between the disease locus for galactokinase deficiency galactosemia, which is responsible for cataracts in newborns and possibly presenile cataracts in adults, and the two galactokinase loci is unknown.

Amino Acid Sequence↗
PubMed1992

Relation between Doppler color flow variables and invasively determined jet variables in patients with aortic regurgitation.

OBJECTIVES: The purpose of this study was to test the hypothesis that invasively derived jet variables including regurgitant orifice area and momentum determine the characteristics of Doppler color flow jets in patients with aortic regurgitation. BACKGROUND: In vitro studies have demonstrated that the velocity distribution of a regurgitant jet is best characterized by the momentum of the jet, which incorporates orifice area and velocity of flow through the orifice. METHODS: Peak jet momentum, peak flow rate and regurgitant orifice area were determined with intraaortic Doppler catheter and cardiac catheterization techniques in 22 patients with chronic aortic regurgitation. These invasively derived variables were compared with apical and parasternal long-axis Doppler color echocardiographic variables obtained in the catheterization laboratory. RESULTS: Jet momentum increased significantly with the angiographic grade of regurgitation. The apical color jet area of aortic regurgitation increased linearly with jet momentum and regurgitant orifice area in vivo, but the correlations were only moderately good (r = 0.63 and 0.65, respectively). Color jet length also increased linearly with jet momentum and with regurgitant orifice area. There was only a trend for Doppler color jet width to increase with all invasively derived jet variables. CONCLUSIONS: Whereas jet area by Doppler color flow imaging is directly related to both orifice area and jet momentum in vivo, Doppler color variables measured in planes normal to the orifice do not correlate well enough with either jet momentum or regurgitant orifice area to predict jet flow variables in patients with aortic regurgitation. It is likely that the important influence of adjacent boundaries will limit the use of the velocity distribution of aortic regurgitant jets for determining the severity of disease.

Aortic Valve Insufficiency↗
PubMed1992

Serial assessment of left ventricular function and mass after orthotopic heart transplantation: a 4-year longitudinal study.

Long-term changes in left ventricular performance and geometry in the transplanted human heart have been incompletely described. Therefore, two-dimensional echocardiograms were performed on 22 recipients of an orthotopic heart transplant at 1 month (32 +/- 20 days), 1 year (11 +/- 3 months) and 4 years (54 +/- 9 months) after transplantation. All studies were performed at a time when the patient had no pathologic evidence of rejection. Ten healthy men served as a normal control group. Over 4 years of follow-up, mean systolic blood pressure in the study patients increased from 121 +/- 12 (p = NS vs. values in the control group) to 139 +/- 11 mm Hg (p less than 0.05 vs. both control values and values at 1 month); mean diastolic blood pressure increased from 72 +/- 7 (p = NS vs. normal values in the control group) to 93 +/- 8 mm Hg (p less than 0.05 vs. both control values and values at 1 month). Left ventricular end-systolic volume increased from 42 +/- 10 (p = NS vs. control values) to 51 +/- 14 ml (p less than 0.05 vs. both control values and values at 1 month) and end-diastolic volume increased from 103 +/- 28 (p = NS vs. control values) to 112 +/- 27 ml (p less than 0.05 vs. control values) over 4 years. Left ventricular mass and ejection fraction did not change significantly within the patient cohort and remained similar to that found in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1992

Prediction of mechanical properties of human atherosclerotic tissue by high-frequency intravascular ultrasound imaging. An in vitro study.

Intravascular ultrasound may be useful for studying the natural history of atherosclerotic lesions of different morphologies and for guiding interventional strategies. This study was designed to test the hypothesis that tissue appearance by intravascular ultrasound is related to the biomechanical properties of atheroma components. Forty-three atheroma caps were obtained from the abdominal aortas of 22 patients at autopsy and studied with an ultrasensitive, servo-controlled spectrometer. By measuring the static strain caused by increasing levels of compressive stress from 30 to 90 mm Hg, the uniaxial unconfined compression stiffness (ratio of stress to strain) was determined. After mechanical testing, specimens were imaged with a 6F, 20-MHz intravascular ultrasound transducer, and images were interpreted by an investigator who was unaware of the mechanical measurements. Specimens were classified as nonfibrous (n = 14), fibrous (n = 18), or calcified (n = 11) based on intravascular ultrasound appearance. The static stiffnesses of the nonfibrous, fibrous, and calcified ultrasound classes were 41.2 +/- 18.8 kPa, 81.7 +/- 33.2 kPa, and 354.5 +/- 245.4 kPa, respectively (p = 0.0002 by analysis of variance). The times to reach static equilibrium (creep time) for the nonfibrous, fibrous, and calcified classes were 79.6 +/- 26.5 minutes, 50.2 +/- 20.0 minutes, and 19.4 +/- 8.1 minutes, respectively (p = 0.0007). Intravascular ultrasound appearance was most significantly related to biomechanical behavior when calcium deposits were noted; the differences in biomechanical behavior between nonfibrous and fibrous tissue appearances were less apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta, Abdominal↗
PubMed1992

Influence of aortic pressure on effective regurgitant orifice area in aortic regurgitation.

BACKGROUND: The regurgitant volume in aortic regurgitation is determined by the diastolic filling period, the pressure gradient between the left ventricle and aorta, and the hemodynamic size of the regurgitant orifice area. METHODS AND RESULTS: To test the hypothesis that the aortic regurgitant orifice area is related to aortic pressure and aortic root size, 16 fresh calf heart and aorta specimens were studied in vitro using a continuous-flow system over a range of aortic pressures. Regurgitant orifice areas were calculated as the ratio of flow divided by peak velocity through the valve measured by image-guided continuous-wave Doppler, and aortic root areas were measured by two-dimensional echocardiography. When the defect was created at the edge of the noncoronary leaflet (n = 10), regurgitant orifice area gradually increased 51 +/- 33% when aortic pressure was increased from approximately 40 to 152 cm of water (29.6 to 112.5 mm Hg) (p less than 0.0001). Similarly, the aortic root size increased 82 +/- 29% when the defect was created at the leaflet edge (p less than 0.0001). In contrast, when defects were created at the center of the noncoronary leaflet (n = 6), only a small increase in regurgitant orifice area (9 +/- 7%) was observed with increasing pressure (p = 0.043). The aortic root area remained strongly pressure dependent in specimens with defects at leaflet centers (p less than 0.0001). CONCLUSIONS: The aortic regurgitant orifice area is dependent on both aortic pressure and the nature of the defect in the valve. Because not all regurgitant aortic valves are alike, further study of the nature of the regurgitant orifice area in humans may allow identification of patients who would benefit most from aggressive pharmacological therapy.

Animals↗
PubMed1992

Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels.

It is likely that factors other than stenosis severity predispose some atherosclerotic plaques to rupture. Because focal increases in circumferential stress may be an important mechanism of plaque rupture, we examined peak circumferential stress of atherosclerotic lesions by using finite element analysis based on idealized two-dimensional cross sections of diseased vessels similar to intravascular ultrasound images. The study was designed to test the hypothesis that subintimal plaque structural features such as thickness of the fibrous cap are more important factors in the distribution of stress in the plaque than stenosis severity. The analysis incorporated equilibrium biomechanical parameters from normal and diseased vessels and determined the stress distribution within the plaque at a mean luminal internal pressure of 110 mm Hg. With a constant luminal area reduction of 70%, maximum circumferential stress (sigma max) normalized to luminal pressure (sigma max/P) increased from 6.0 to 24.8 as the thickness of the lipid pool was increased from 38% to 54% of the plaque thickness because of the thinner fibrous cap over the lipid pool. When the lipid pool thickness was constant, increasing the stenosis severity from 70% to 91% by increasing the fibrous cap thickness decreased sigma max/P from 24.8 to 4.7. When no lipid pool was present and the stenosis severity was increased from 70% to 99%, sigma max/P decreased from 5.3 to 4.7. Thus, reducing the fibrous cap thickness dramatically increases peak circumferential stress in the plaque, whereas increasing the stenosis severity actually decreases peak stress in the plaque.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1991

Doppler echocardiographic estimation of mitral valve area during changing hemodynamic conditions.

Patients with mitral stenosis often present during periods of hemodynamic stress such as pregnancy or infections. The Doppler pressure half-time method of mitral valve area (MVA) determination is dependent on the net atrioventricular compliance as well as the peak transmitral gradient. The continuity equation method of MVA determination is based on conservation of mass and may be less sensitive to changes in the hemodynamic state. To test this hypothesis, 17 patients admitted for catheterization with symptomatic mitral stenosis and no more than mild regurgitation underwent Doppler echocardiography at rest and during supine bicycle exercise targeted to an increase in heart rate by 20 to 30 beats/minute. Net atrioventricular compliance was also estimated noninvasively. Cardiac output and transmitral gradient increased significantly during exercise (p less than 0.001), while net atrioventricular compliance decreased (p less than 0.001). MVA by the pressure half-time method increased significantly during exercise from 1.0 +/- 0.2 to 1.4 +/- 0.4 cm2 (p less than 0.001). There was no significant difference in MVA estimation using the continuity equation comparing rest to exercise, with the mean area remaining constant at 0.8 +/- 0.3 cm2 (p = 0.83). Thus, during conditions of changing hemodynamics, the continuity equation method for estimating MVA may be preferable to the pressure half-time method.

Adult↗
PubMed1991

Prediction of major cardiac events after peripheral vascular surgery using dipyridamole echocardiography.

Patients undergoing peripheral vascular surgery are at increased risk of postoperative cardiac complications. To evaluate the role of dipyridamole echocardiography in predicting major cardiac events, 109 unselected patients undergoing elective peripheral vascular surgery were prospectively studied. Preoperative dipyridamole echocardiograms were interpreted by an echocardiographer unaware of all clinical data. Patients were followed up until hospital discharge by research physicians without knowledge of dipyridamole echocardiography results. Outcomes were classified using strict predefined criteria by reviewers unaware of other clinical and echocardiographic data. Of the 109 patients, 9 (8%) had positive studies defined as development of new regional wall motion abnormalities or worsening of preexistent wall motion abnormalities. Of these 9 patients, 7 had postoperative events, including 3 cardiac deaths, 1 nonfatal myocardial infarction, 2 with unstable angina, and 1 with pulmonary edema. Only 1 event occurred among the 100 patients with negative studies. The sensitivity and specificity of dipyridamole echocardiography for predicting cardiac events after vascular surgery were 88 and 98%, respectively; the positive and negative predictive values were 78 and 99%. The relative risk of having a cardiac event if dipyridamole echocardiography was abnormal was 78 (95% confidence interval, 11 to 564; p less than 0.0001). If these results are extended and confirmed by other investigators, preoperative dipyridamole echocardiography may be an important screening test for patients undergoing elective peripheral vascular surgery.

Aged↗
PubMed1991

Doppler echocardiographic study of porcine bioprosthetic heart valves in the aortic valve position in patients without evidence of cardiac dysfunction.

To study the natural history of the hemodynamic performance of bioprosthetic heart valves, Doppler echocardiograms were recorded in a group of clinically stable patients at 2 and 5 years after replacement of native aortic valves with bioprosthetic valves. Eighteen patients completed a 2-year and 26 patients a 5-year follow-up examination. The effective orifice areas of identical models of bioprosthetic valves (Hancock II) were determined in vitro in a left-sided heart pulse duplicator system. In vivo Doppler-derived effective orifice areas were compared with the in vitro measurements for the same valve size. At both the 2- and 5-year follow-up examinations, the Doppler-derived effective orifice area was significantly less than the in vitro area (p less than 0.0001 at each interval). Ten of 16 valves evaluated serially decreased greater than 0.20 cm2 in the Doppler-derived effective orifice area between studies. The mean decrease in effective orifice area in valves evaluated serially was 0.25 +/- 0.29 cm2 (p less than 0.005). The peak transaortic gradient increased from 21 +/- 6 to 27 +/- 8 mm Hg (p less than 0.01). The mean transaortic gradient increased from 12 +/- 4 to 15 +/- 7 mm Hg (p less than 0.05). It is concluded that serial Doppler echocardiographic studies demonstrate a deterioration in the hemodynamic performance of bioprosthetic valves over time in patients with no symptoms or signs of valvular dysfunction and that Doppler echocardiography may be useful for identifying subclinical bioprosthetic valvular dysfunction.

Adult↗
PubMed1991

Ligand-binding characteristics of rat serum-type mannose-binding protein (MBP-A). Homology of binding site architecture with mammalian and chicken hepatic lectins.

Sugar-binding characteristics of rat serum mannose-binding protein (MBP) were studied using the carbohydrate-recognition domain of this protein expressed from a cloned cDNA. To assess the binding affinity of various test compounds, they were added as inhibitors in a binding assay in which 125I-MBP was incubated with yeast cells and the extent of binding was estimated from the radioactivity associated with the pelleted cells. The results of such inhibition assays suggest that MBP has a small binding site which is probably of the trough-type. The 3- and 4-OH of the target sugar are indispensable, while the 6-OH is not required. These characteristics are shared by the rat hepatic lectin and chicken hepatic lectin, both of which are C-type lectins containing carbohydrate-recognition domains highly homologous to that of MBP. Apparently, the related primary structures of these lectins give rise to similar gross architecture of their binding sites, despite the fact that each exhibits different sugar binding specificities.

Animals↗
PubMed1991

Doppler echocardiographic comparison of the Carpentier and Duran anuloplasty rings versus no ring after mitral valve repair for mitral regurgitation.

To compare the hemodynamic results of different anuloplasty techniques of primary valve repair for mitral regurgitation, 122 patients were prospectively studied with Doppler echocardiograms 5 to 10 days after operation. Seventy-seven patients had mitral valve prolapse, 27 had coronary artery disease, 13 patients had rheumatic mitral valve lesions and 5 patients had infective endocarditis. Forty-eight patients received the flexible Duran ring, 46 received the more rigid Carpentier ring and 28 patients received no ring. Doppler echocardiography demonstrated a significant decrease in mitral valve area estimated by the pressure half-time method in patients who received either a Carpentier (2.6 +/- 0.8 cm2) or Duran ring (2.8 +/- 0.8 cm2) when compared with patients who received no ring (3.2 +/- 0.7 cm2) (p = 0.01). No significant differences were observed for peak transmitral diastolic velocity, peak transmitral diastolic gradient, or the grade of mitral regurgitation by color flow Doppler mapping between patients with and without rings. The etiology of mitral disease and concomitant surgical procedures accompanying mitral valve repair did not significantly influence mitral valve area, peak velocity or peak gradient. These data suggest that Carpentier and Duran rings decrease the hemodynamic mitral valve area; however, the decrease in valve area is small and not associated with a clinically important increase in transvalvular gradient.

Echocardiography, Doppler↗
PubMed1991

Load dependence of the effective regurgitant orifice area in a sheep model of aortic regurgitation.

Treatment of patients with aortic regurgitation with vasodilators reduces regurgitant volume, ventricular dilation and left ventricular mass. Although these effects are presumably due to afterload reduction, it is also possible that the aortic regurgitant orifice area is not constant. To test the latter hypothesis, aortic regurgitation was created in 10 open chest sheep by partial resection of the noncoronary leaflet under direct visualization. Regurgitant flow was measured with an aortic supravalvular electromagnetic probe; aortic and left ventricular pressures were measured with catheter-tipped micromanometer pressure transducers. The effective regurgitant orifice area was calculated by a modification of the continuity equation in a manner similar to the Gorlin equation. The regurgitant orifice area was measured three times: after aortic regurgitation was created, after mean arterial pressure was increased by 15 to 25 mm Hg with intravenous dopamine and after mean arterial pressure was reduced by 15 to 25 mm Hg with intravenous sodium nitroprusside. Comparison of regurgitant volumes and areas obtained after creation of aortic regurgitation and at the conclusion of the experiment in the absence of dopamine or sodium nitroprusside demonstrated no significant change over time. Dopamine administration was associated with an 86 +/- 81% increase in regurgitant volume (p less than 0.01) and a 38 +/- 44% increase in regurgitant orifice area (p less than 0.01). Sodium nitroprusside administration resulted in a 51 +/- 14% decrease in regurgitant volume (p less than 0.001) and a 28 +/- 21% reduction in regurgitant orifice area (p = 0.007). In this model of acute aortic regurgitation, the effective regurgitant orifice area was altered by increasing or decreasing the aortic transvalvular pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effective aortic regurgitant orifice area: description of a method based on the conservation of mass.

The natural history of aortic regurgitation is incompletely understood in part because of the lack of a simple method to estimate the defect size. A method of determining the effective regurgitant orifice area that combines Doppler catheter and Doppler echocardiographic techniques and is based on the principle of conservation of mass (the continuity equation) is described. To validate the application of the Doppler catheter system for measuring regurgitant supravalvular diastolic flow, an in vitro model of retrograde aortic flow was used. These studies indicated that measurements of supravalvular retrograde velocity with the Doppler catheter accurately reflect retrograde diastolic velocity when the aorta is less than 4.8 cm in diameter. Twenty-three patients undergoing cardiac catheterization were studied; 20 of these patients had aortic regurgitation. Retrograde supravalvular diastolic velocity was determined from a Doppler catheter positioned above the aortic valve. The effective regurgitant orifice area was calculated with use of the Doppler catheter-derived regurgitant volume and mean transvalvular diastolic velocity as determined by either catheterization or continuous wave Doppler echocardiography. The catheterization-derived regurgitant orifice area increased with the angiographic grade of as follows: 1+ (0.04 to 0.10 cm2), 2+ (0.15 to 0.49 cm2), 3+ (0.29 to 1.11 cm2) and 4+ (1.24 to 1.33 cm2). By combining Doppler catheter, echocardiographic and cardiac catheterization techniques, the effective aortic regurgitant orifice area may be estimated; this hydrodynamic area correlates with grading by supravalvular aortography. Calculation of this area provides a quantitative alternative to aortography for estimating the severity of aortic regurgitation but should be used with caution in patients with a markedly dilated aorta.

Aortic Valve Insufficiency↗
PubMed1991

A splint for immediate surgical orthognathic fixation and release during orthodontic treatment.

A splint has been designed for surgical use during the course of orthodontic treatment. The two-piece splint is ligated directly to the orthodontic arch wires. Surgically, the splint has the advantage of saving operative time, of ensuring precise location rapidly in all three planes, and allowing immediate release and replacement. Orthodontically, the splints allow a shorter preoperative phase of orthodontics, with the orthodontic treatment being completed postoperatively to ensure precise tooth positions and functional occlusion.

Dental Occlusion↗