Search PubMed⌕ Search

Biomedical subjects

R T Lee

Publications and source records attributed to R T Lee.

At least 163 records · Page 9Linked to original sources
PubMed1990

Defined geometry of binding between triantennary glycopeptide and the asialoglycoprotein receptor of rat heptocytes.

Three derivatives of a triantennary glycopeptide, each containing a single uniquely located 6-amino-galactose residue at either position 6', 6, or 8, were modified at the 6-amino group by attachment of a photolyzable reagent and radiolabeled by iodination of tyrosine. These were allowed to bind to the asialoglycoprotein receptor of isolated rat hepatocytes and photolyzed for affinity labeling. (formula; see text) Each probe specifically labeled either the major (RHL1) or minor (RHL2/3) subunits which comprise the receptor. A photolyzable group attached to galactose residue 6 6' specifically radiolabeled RHL1, whereas a photolyzable group attached to galactose 8 specifically labeled RHL2/3. Photoaffinity labeling of a soluble rat hepatic lectin preparation demonstrated that the minor subunits (RHL2/3) were no longer labeled by the triantennary probe with a photolyzable group at galactose 8. The inhibitory potency of a variety of complex glycopeptides against radiolabeled ligand binding to both rat hepatocytes and soluble lectin are in agreement with photoaffinity results that galactose 8 of triantennary glycopeptide is of unique importance by binding solely to the minor subunits (RHL2/3) of the asialoglycoprotein receptor on hepatocytes. Conversely, galactose residues 6 and 6' bind specifically to the major subunit (RHL1), indicating a precise binding geometry between the trivalent ligand and lectin.

Affinity Labels↗
PubMed1990

Clinical, echocardiographic and Doppler correlates of clinical instability with onset of atrial fibrillation.

To identify clinical and Doppler echocardiographic correlates of instability with the onset of atrial fibrillation (AF), 87 consecutive patients with new-onset AF who had echocardiograms recorded during that hospital admission while in sinus rhythm were studied. Reviewers who were blinded to echocardiographic and Doppler data classified 51 patients (59%) as unstable because of the development of angina, congestive heart failure, syncope or hypotension with the onset of AF. Echocardiographic and Doppler data on transmitral blood flow velocity were analyzed by a single reviewer who was blinded to other clinical data. Multiple logistic regression analysis identified 3 variables as independent predictors of clinical instability with the onset of AF: (1) history of prior myocardial infarction (p less than 0.02); (2) echocardiographic evidence of left ventricular dysfunction (p less than 0.03); and (3) Doppler evidence of increased atrial filling fraction (p less than 0.0001). An atrial filling fraction threshold of 0.40 had a sensitivity for predicting clinical instability of 80% and a specificity of 72%. These data are consistent with the hypothesis that patients who are more dependent on the atrial contribution to ventricular filling are at increased risk of instability with AF due to the loss of atrial systole.

Aged↗
PubMed1990

Binding characteristics of galactoside-binding lectin (galaptin) from human spleen.

Binding characteristics of human spleen soluble galactoside-binding protein (galaptin) were studied using simple galactosides, galactose-terminated disaccharides, cluster glycosides containing up to 6 terminal lactosyl residues, bovine serum albumin derivatives containing 7 to 40 lactosyl residues, desialylated serum glycoproteins, and glycopeptides derived thereof as inhibitors in a newly developed binding assay. In this assay, aminohexyl lactoside was attached to divinyl sulfone-activated Sepharose, which was then used to bind 125I-galaptin. Similarly derivatized Sepharose containing mannoside served as a control. The assay is sensitive, maintains linearity in the concentration range of 125I-galaptin tested, and has very low nonspecific binding. The following new findings were made. 1) All the alpha-D-galactopyranosides with non-sugar aglycon were better inhibitors than the corresponding beta-D-galactopyranoside. 2) The S-galactosides were better inhibitors than the corresponding O-galactosides, regardless of the anomeric configuration. 3) Many Gal beta 1-4- and Gal beta 1-3-linked disaccharides were tested. Although the galaptin did not appear to recognize N-acetylglucosamine as a monosaccharide, the presence of this sugar penultimate to galactose increased the binding affinity by as much as 500-fold, as was the case for N-acetyllactosamine. Of a particular importance is the presence of an equatorial 3-OH group on this sugar. We synthesized the 3-deoxy derivative of N-acetyllactosamine and found that it had 50-fold lower binding affinity compared to N-acetyllactosamine. 4) The binding sites of this lectin do not seem to be operating in a cooperative fashion, since synthetic lactose-containing divalent ligands with various inter-galactose distances did not increase the binding affinity significantly.

Binding Sites↗
PubMed1990

Synthesis of N-acetylglucosamine derivatives as probes for specificity of chicken hepatic lectin.

Syntheses of the following compounds are described: 6-(Trifluoroacetylamino)hexyl 2-acetamido-2,6-dideoxy-beta-D-glucopyranoside and 2-acetamido-2-deoxy-alpha-D-xylopyranoside, two allyl 2-acetamido-2-deoxy-alpha-D-glucopyranosiduronic acid derivatives, and several allyl 2-acylamido-2-deoxy-beta-D-glucopyranosides having different acyl groups. These and other compounds were used as inhibitors in the binding assay for the chicken hepatic lectin specific for N-acetylglucosamine. We found that: 1) The inhibitory potency of N-acylglucosamine derivatives decreased progressively with increase in the size of acyl group, 2) absence of either 3- or 4-OH group of N-acetylglucosamine lowered the binding affinity more than 100-fold, and 3) the presence of a negatively charged group (carboxylic acid) at the C-6 position did not lower the affinity. The first two items are similar to the mammalian hepatic galactose/N-acetylgalactosamine lectins, but the last item is in a strong contrast to the mammalian lectins.

Acetylglucosamine↗
PubMed1990

Effects of nifedipine on transmitral Doppler blood flow velocity profile in patients with concentric left ventricular hypertrophy.

To examine the effects of calcium channel blockade on left ventricular diastolic function, transmitral blood flow was evaluated by Doppler echocardiography following administration of sublingual nitroglycerin and nifedipine in 10 younger normal subjects and in 10 subjects with concentric left ventricular hypertrophy (LVH) and abnormal Doppler transmitral flow patterns. Nitroglycerin decreased peak early filling velocity (E velocity) in both normal (p less than 0.01) and LVH subjects (p less than 0.05) but did not significantly alter peak late filling velocity (A velocity), early filling velocity time integral (VTI E), or late velocity time integral (VTI A). In normal subjects, nifedipine decreased E velocity (p less than 0.01) but did not significantly change A velocity, VTI E, or VTI A. In LVH subjects nifedipine increased E velocity (p less than 0.05) as well as VTI E (p less than 0.05) and the ratio of VTI E/VTI A (p less than 0.05). Thus nifedipine, unlike nitroglycerin, improves the transmitral Doppler flow profile in patients with concentric LVH.

Adult↗
PubMed1990

On the meaning of Maslach's three dimensions of burnout.

The dimensionality of Maslach's (1982) 3 aspects of job burnout--emotional exhaustion, depersonalization, and personal accomplishment--was examined among a sample of supervisors and managers in the human services. A series of confirmatory factor analyses supported the 3-factor model, with the first 2 aspects highly correlated. The 3 aspects were found to be differentially related to other variables reflecting aspects of strain, stress coping, and self-efficacy in predictable and meaningful ways. Implications for better understanding the burnout process are discussed.

Achievement↗
PubMed1990

In vivo expression and survival of gene-modified T lymphocytes in rhesus monkeys.

Lymphocytes can be readily transduced with retroviral vectors and the gene-modified lymphocytes will stably express the inserted genes in vitro for long periods. As a prelude to studies in humans, we evaluated the survival of gene-modified T lymphocytes and the expression of the introduced genes in nonhuman primate T lymphocytes both in vitro and in vivo to determine if lymphocytes could be a potential cellular gene therapy vehicle. Rhesus peripheral blood T-lymphocytes and/or lymph node lymphocytes were transduced with a retroviral vector that contained a bacterial neomycin resistance (NeoR) gene or both NeoR and the human adenosine deaminase (hADA) genes. The cells were then selected for NeoR expression by growth in the neomycin analogue G418 and the autologous gene-modified T cells were reintroduced into the donor animals. T lymphocytes were periodically regrown from the blood and selected in G418. Gene-modified cells persisted in 1 animal for 727 days as detected by analysis for vector DNA by polymerase chain reaction (PCR). Evidence for expression of the human ADA or NeoR genes has also been detected up to 727 days after cell infusion. These findings suggest that gene-modified T lymphocytes can survive and circulate for long periods in vivo and can continue to express the introduced genes.

Adenosine Deaminase↗
PubMed1990

Diagnosis and medical management of infective endocarditis: transthoracic and transesophageal echocardiography.

The use of echocardiography in the diagnosis of vegetative endocarditis has been a keystone in the diagnosis and treatment of this important clinical syndrome. In addition, with the use of transesophageal echo this modality has now made important advances in not only diagnosis but in evaluation of global cardiac function. A considerable amount of information has been gathered on the vegetation and these data will be discussed.

Echocardiography↗
PubMed1989

Prospective Doppler echocardiographic evaluation of pulmonary artery diastolic pressure in the medical intensive care unit.

To test the hypothesis that the noninvasive evaluation of pulmonary regurgitation can provide accurate estimates of pulmonary artery (PA) diastolic pressures and PA wedge pressures, Doppler echocardiographic studies were performed immediately before bedside PA catheterization in 29 medical intensive care unit patients. The characteristic color flow Doppler signal of pulmonary regurgitation was detected in 19 (66%) patients. In 17 of the 29 patients (59%), the gradient between the right ventricle and PA at end-diastole could be calculated from the pulsed-wave Doppler signal of pulmonary regurgitation using the simplified Bernoulli equation. Right atrial pressure was then estimated by examination of the jugular venous pulse or by electronic transduction of the pressure signal from a previously placed central venous catheter. A noninvasive estimate of PA diastolic pressure was made by adding the clinical estimate of right atrial pressure to the end-diastolic pressure gradient across the pulmonary valve. Pulmonary artery catheterization was then performed and stripchart recordings were interpreted by a physician who was unaware of the noninvasively-estimated PA diastolic pressure. The PA diastolic pressure estimated by Doppler echocardiography correlated closely with that found at catheterization (r = 0.94, mean absolute difference 3.3 mm Hg). The noninvasive estimate of PA diastolic pressure also correlated with the PA wedge pressure (r = 0.87, mean absolute difference 3.8 mm Hg). Therefore, in 59% of medical intensive care unit patients, Doppler echocardiographic evaluation of pulmonary regurgitation allowed accurate noninvasive estimation of PA diastolic pressure.

Aged↗
PubMed1989

Assessment of valvular heart disease with Doppler echocardiography.

The addition of Doppler principles to two-dimensional echocardiography has revolutionized the noninvasive evaluation of valvular heart disease. Doppler techniques allow precise measurements of blood flow velocity at different locations in the heart and great vessels, so that many aspects of hemodynamics can now be measured noninvasively. These techniques are particularly useful for the quantitative assessment of valvular stenosis; both valve areas and transvalvular gradients may be determined. Doppler echocardiography (particularly with color flow mapping) is also useful for the qualitative assessment of valvular regurgitation. By understanding the uses and limitations of Doppler echocardiography, physicians may now confidently follow up patients with mild or moderate valvular disease with serial noninvasive studies, avoiding the risks of cardiac catheterization in many patients.

Blood Flow Velocity↗
PubMed1989

Binding characteristics of N-acetylglucosamine-specific lectin of the isolated chicken hepatocytes: similarities to mammalian hepatic galactose/N-acetylgalactosamine-specific lectin.

Binding characteristics of N-acetylglucosamine- (GlcNAc) specific lectin on the chicken hepatocyte surface were probed by an inhibition assay using various sugars and glycosides as inhibitors. Results indicated that the binding area of the lectin is small, interacting only with GlcNAc residues whose 3- and 4-OH's are open. The combining site is probably of trough-type, since substitution with as large a group as monosaccharide is permitted on the C-6 side of GlcNAc, and on the C-1 side, the aglycon of GlcNAc can be very large (e.g., a glycoprotein). These binding characteristics are shared with the homologous mammalian lectin specific for galactose/N-acetylgalactosamine, suggesting that tertiary structure of the combining area of these two lectins is similar. This is understandable, since there is approximately 40% amino acid sequence identity in the carbohydrate recognition domain of these two lectins [Drickamer, K., Mannon, J. F., Binns, G., & Leung, J. O. (1984) J. Biol. Chem. 259, 770-778]. A series of glycosides, each containing two GlcNAc residues separated by different distances (from 0.8 to 4.7 nm), were synthesized. Inhibition assay with these and other cluster glycosides indicated that clustering of two or more GlcNAc residues increased the affinity toward the chicken lectin tremendously. Among the ligands containing two GlcNAc residues, the structure which allows a maximal inter-GlcNAc distance of 3.3 nm had the strongest affinity, its affinity increase over GlcNAc (monosaccharide) amounting to 100-fold. Longer distances slightly diminished the affinity, while shortening the distance caused substantial decrease in the affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylgalactosamine↗
PubMed1989

Subtype-specific increase in G-protein alpha-subunit mRNA by interleukin 1 beta.

The guanine nucleotide regulatory proteins (G-proteins) which are substrates for ADP-ribosylation by pertussis toxin (alpha i-1, alpha i-2, alpha i-3 and alpha o) transduce a variety of hormonal signals. Endothelial cells express mRNA for three alpha i subtypes although the level of alpha i-1 mRNA is very low. Interleukin 1 beta (IL 1 beta), a pleiotropic inflammatory mediator which stimulates a complex series of responses in human endothelial cells leading to increased coagulation and platelet adhesion, increases expression of one subtype of alpha i (alpha i-2) mRNA in human endothelial cells as determined by Northern blot analysis without affecting the level of mRNA for other alpha-subunits. These studies show that mRNA levels for alpha i subtypes are independently regulated, suggesting that there may be subtype specificity in the cell's requirements for the Gi class of signal-transducing proteins.

Adenosine Diphosphate Ribose↗
PubMed1989

Efficient coupling of glycopeptides to proteins with a heterobifunctional reagent.

A heterobifunctional linking reagent containing a masked aldehydo group and acyl hydrazide was synthesized for coupling of glycopeptides and other amino-containing compounds to proteins. After conversion to acyl azide, the reagent reacts with the amino group of a glycopeptide, and the modified glycopeptide is deacetalized with a weak acid to unmask the aldehydo group, which is then conjugated to bovine serum albumin (BSA) by reductive alkylation with pyridine-borane. The overall reaction scheme proceeds under relatively mild conditions. When the protein amino group was in a large excess (greater than 6-fold) of the aldehyde reagent, the efficiency of conjugation was as high as 88% even at submicromole levels. As a test case for application of this reagent, 6-aminohexyl beta-D-galactopyranoside (Gal-AH) was attached to the linking reagent and conjugated to BSA at various aldehyde-to-protein molar ratios ranging from 25 to 200. The level of O-galactosyl residue incorporated into BSA by this reagent far exceeded that observed in a similar reductive alkylation involving S-galactoside reagents [Lee, R. T., & Lee, Y. C. (1980) Biochemistry 19, 156-163]. By use of the present conjugating procedure, as many as 112 mol of Gal-AH residues were incorporated per mole of BSA, which represents near total modification of the amino groups. Some binding characteristics of the new BSA derivatives were studied in the mammalian hepatic galactose/N-acetylgalactosamine specific lectin system along with other types of BSA derivatives (containing S-galactosyl residues). In general, the behavior of the new derivatives was similar to that of other types. For instance, the affinity increased exponentially at low sugar substitution levels (up to 30 mol of galactosyl residues/mol of BSA), and the slope of exponential increase and affinity at a given sugar substitution level was similar to those of other types.

Amides↗
PubMed1989

Left ventricular tamponade: echocardiographic and hemodynamic manifestations.

A patient with progressive systemic sclerosis was evaluated for dyspnea. Echocardiography revealed enlarged right heart chambers, a moderate pericardial effusion, and diastolic collapse of the left ventricle. Hemodynamic studies before and after removal of pericardial fluid were consistent with compromise of left, but not right, heart filling by the pericardial fluid.

Cardiac Tamponade↗