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Biomedical subjects

L C Lee

Publications and source records attributed to L C Lee.

At least 37 records · Page 2Linked to original sources
PubMed1997

Diminished vasomotor component of systemic arterial pressure signals and baroreflex in brain death.

We compared the cardiovascular autonomic regulatory mechanisms between patients with brain death or under a persistent vegetative state and healthy volunteers, based on auto- and cross-spectral analysis of systolic blood pressure (SBP) and interpulse interval (PPI) signals. Brain-dead patients exhibited a significant reduction in the absolute and relative power of the low-frequency (LF; 0.04-0.15 Hz) component in both SBP and PPI spectra, along with appreciable decrease in the very low frequency (VLF; 0.004-0.04 Hz), LF, and high-frequency (HF; 0.15-0.4 Hz) power of the PPI signals. Patients in a persistent vegetative state exhibited a power of the VLF and LF component in the SBP spectrum that was comparable to that in healthy subjects, although a discernible reduction in the VLF, LF, and HF power of the PPI spectrum was manifested by the former group. Assessments with the magnitude of SBP-PPI transfer function and linear regression analysis of beat-to-beat fluctuations in SBP and PPI revealed a progressive decline in spontaneous baroreflex sensitivity from healthy subjects to patients in a persistent vegetative state or with brain death. We conclude that the vasomotor component of systemic arterial pressure signals and spontaneous baroreflex are highly correlated with the functional integrity of the brain stem.

Adult↗
PubMed1996

Evidence for alpha-helical conformation of an essential N-terminal region in the human Bcl2 protein.

A region occupying approximately 24 amino acids near the N terminus of human Bcl2 is essential for this cytoplasmic membrane protein's ability to inhibit apoptosis. Systematic mutagenesis of this N-terminal region indicates that only five hydrophobic and aromatic residues within it are specifically required for function. Computerized secondary structure prediction, together with circular dichroism spectroscopy of synthetic peptides, indicates that the region encompassing these five residues has the propensity to take on an alpha-helical conformation in the presence of SDS micelles, which presumably mimic the hydrophobic surfaces of cellular membranes or polypeptides. The five critical residues are predicted to be clustered on one face of this putative helix, where they might serve to mediate protein-protein contacts involved in the multimerization of Bcl2 or in the interaction of Bcl2 with other, as yet unidentified components of the apoptotic pathway. Apparent structural homologues of this helical motif are also present in at least some other anti-apoptotic proteins from the Bcl2 family but not in those family members that tend to potentiate, rather than inhibit, apoptosis.

Amino Acid Sequence↗
PubMed1996

In vitro and in vivo studies of benzisoquinoline ligands for the brain synaptic vesicle monoamine transporter.

Tetrabenazine is a high-affinity inhibitor of the vesicular monoamine transporter in mammalian brain. As part of a program to develop in vivo imaging agents for these transporters in human brain, a series of 2-alkylated dihydrotetrabenazine ligands was synthesized and evaluated in vitro and in vivo for binding to the brain vesicular monoamine transporter. Additions of organometallic reagents to tetrabenazine produced 2-methyl, 2-ethyl, 2-n-propyl, 2-isopropyl, and 2-isobutyl derivatives of dihydrotetrabenazine. The stereochemistry and conformation of the addition products were thoroughly verified by two-dimensional NMR techniques. All of these alkyl derivatives displayed in vitro affinity for the vesicular monoamine transporter binding site in rat brain using competitive assays with the radioligand [3H]methoxytetrabenazine. Except for the isopropyl derivative, all compounds when tested at 10 mg/kg iv showed an ability to inhibit in vivo accumulation of the radioligand [11C]methoxytetrabenazine in the mouse brain striatum. Derivatives with small alkyl groups (methyl, ethyl) were more effective than those with large groups (propyl, isobutyl). These studies suggest that large groups in the 2-position of the benzisoquinoline structure will significantly diminish both in vitro and in vivo binding of these compounds to the vesicular monoamine transporter.

Adrenergic Uptake Inhibitors↗
PubMed1996

Decreased striatal monoaminergic terminals in olivopontocerebellar atrophy and multiple system atrophy demonstrated with positron emission tomography.

We used [11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter (VMAT2), with positron emission tomography to study striatal monoaminergic presynaptic terminals in 4 patients with multiple system atrophy, 8 with sporadic olivopontocerebellar atrophy, and 9 normal control subjects. Specific binding in the striatum was significantly reduced in the multiple system atrophy patients as compared with the normal control group, with average reductions of 61% in the caudate nucleus (p = 0.002) and 58% in the putamen (p = 0.009). Smaller reductions were found in the sporadic olivopontocerebellar atrophy group, averaging 26% in the caudate nucleus (p = 0.05) and 24% in the putamen (p = 0.11). Mean blood-to-brain [11C]dihydrotetrabenazine transport (K1) was significantly different between groups only in the cerebellum, with values for the sporadic olivopontocerebellar atrophy group diminished compared with the normal control group. Cerebellar K1 was not significantly decreased in the multiple system atrophy group. The finding of reduced striatal VMAT2 in sporadic olivopontocerebellar atrophy patients suggests nigrostriatal pathology, indicating that some may later develop symptomatic extrapyramidal disease.

Adult↗
PubMed1996

Kinetic evaluation of [11C]dihydrotetrabenazine by dynamic PET: measurement of vesicular monoamine transporter.

(+)-alpha-[11C]Dihydrotetrabenazine (DTBZ) binds to the vesicular monoamine transporter (VMAT2) located in presynaptic vesicles. The purpose of this work was to evaluate various model configurations for analysis of [11C]DTBZ with the aim of providing the optimal measure of monoamine vesicular transporter density obtainable from a single dynamic PET study. PET studies on seven young normal volunteer subjects, ages 20-35, were performed following i.v. injection of 666 +/- 37 MBq (18 +/- 1 mCi) of (+)-alpha-[11C]DTBZ. Dynamic acquisition consisted of a 15-frame sequence over 1 h. Analysis methods included both creation of pixel-by-pixel functional images of transport (K1) and binding (DVtot) and nonlinear least-squares analysis of volume-of-interest data. Pixel-by-pixel calculations were performed for both two-compartment weighted integral calculations and slope-intercept estimations from Logan plots. Nonlinear least-squares analysis was performed applying model configurations with both two-compartments, estimating K1 and DVtot and three compartments, estimating K1-k4. For the more complex configuration, we examined the stability of various binding-related parameters including k3 (konBmax'), k3/k4 (Bmax'/Kd), DVsp[(K1/k2)(k3/k4)], and DVtot [K1/k2(1 + k3/k4)]. The three-compartment model provided significantly improved goodness-of-fit compared to the two-compartment model, yet did not increase the uncertainty in the estimate of the DVtot. Without constraining parameters in the three-compartment model fits, DVtot was found to provide a more stable estimate of binding density than either k3, k3/k4, or DVsp. The two-compartment least-squares analysis yielded approximately 10% underestimations of the total distribution. However, this bias was found to be very consistent from region to region as well as across subjects as indicated by the correlation between two- and three-compartment DVtot estimates of 0.997. We conclude that (+)-alpha-[11C]DTBZ and PET can provide excellent measures of VMAT2 density in the human brain.

Adult↗
PubMed1996

Detection of an IS2-encoded 46-kilodalton protein capable of binding terminal repeats of IS2.

The genome of the transposable element IS2 contains five open reading frames that are capable of encoding proteins greater than 50 amino acids; however, only one IS2 protein of 14 kDa had been detected. By replacing the major IS2 promoter located in the right terminal repeat of IS2 with the T7 promoter to express IS2 genes, we have detected another IS2 protein of 46 kDa. This 46-kDa protein was designated InsAB'. Analyses of the InsAB' sequence revealed motifs that are characteristic of transposases of other transposable elements. InsAB' has the ability to bind both terminal repeat sequences of IS2. It was shown to bind a 27-bp sequence (5'-GTTAAGTGATAACAGATGTCTGGAAAT-3', positions 1316 to 1290 by our numbering system [16 to 42 by the previous numbering system]) located at the inner end of the right terminal repeat and a 31-bp sequence (5'-TTATTTAAGTGATATTGGTTGTCTGGAGATT-3', positions 46 to 16 [1286 to 1316]), including the last 27 bp of the inner end and the adjacent 4 bp of the left terminal repeat of IS2. This result suggests that InsAB' is a transposase of IS2. Since there is no open reading frame capable of encoding a 46-kDa protein in the entire IS2 genome, this 46-kDa protein is probably produced by a translational frameshifting mechanism.

Amino Acid Sequence↗
PubMed1994

Functional analysis of the 14 kDa protein of insertion sequence 2.

The IS2 sequence encodes five open reading frames (ORF1 to ORF5) that are greater than 150 nucleotides each. Only one protein of 14 kDa was detected when the expression of IS2 genes was examined in minicells. This 14 kDa protein was referred to as InsA in this study and was determined to be encoded by ORF1. A sixfold decrease in IS2 transposition frequency was observed when insA was overexpressed. DNA footprinting results indicated that InsA binds to the sequence 5'-TAAATAA-3' located at IS2 nucleotide numbers 1286 to 1292. (The IS2 right terminal repeat spans nucleotides 1290 to 1331.) This InsA binding sequence is situated 4 bp upstream from the putative "-10" sequence of the insA promoter that overlaps the right terminal repeat of IS2. The presence of a promoter located in this region was demonstrated by the ability of a DNA fragment containing the right terminal repeat to drive the expression of a promoterless lacZ gene. The transcription of insA was determined to start at the A residue located at nucleotide number 1268. With the same insA promoter-lacZ fusion construct, overexpression of insA in the same cell was found to decrease the beta-galactosidase activity. The results of this study suggest that InsA affects IS2 transposition by regulating the transcription of IS2 genes.

Bacterial Proteins↗
PubMed1993

Evaluation of transesophageal echocardiography before cardioversion of atrial fibrillation and flutter in nonanticoagulated patients.

This study prospectively evaluated the role of transesophageal echocardiography (TEE) in screening for atrial thrombi before electrical cardioversion in 40 nonanticoagulated patients with nonvalvular atrial fibrillation (n = 33) or atrial flutter (n = 7). Transthoracic echocardiography did not detect atrial thrombus in any patient. TEE detected left atrial appendage thrombi in five patients (12%, p = 0.03), significantly associated with left ventricular systolic dysfunction (p = 0.02) and left atrial spontaneous echo contrast (p = 0.04). Cardioversion was cancelled in the five patients with thrombi and in two patients with spontaneous reversion before planned cardioversion. Cardioversion was successful in 25 (76%) of the 33 remaining patients. Cerebral embolism occurred 24 hours after successful cardioversion in one patient with atrial fibrillation and left ventricular dysfunction, who had left atrial spontaneous echo contrast, but no thrombus was detected by TEE before cardioversion. Repeat TEE after embolism showed a fresh left atrial appendage thrombus and increased left atrial spontaneous echo contrast. These results indicate that TEE improves the detection of left atrial appendage thrombi in candidates for cardioversion, in whom the procedure may be deferred. However, the exclusion by TEE of preexisting atrial thrombi before cardioversion does not eliminate the risk of embolism after cardioversion because of persistent atrial stasis and de novo thrombosis.

Anticoagulants↗
PubMed1993

Hematologic correlates of left atrial spontaneous echo contrast and thromboembolism in nonvalvular atrial fibrillation.

OBJECTIVES: This study examined the relation between left atrial spontaneous echo contrast, hematologic variables and thrombo-embolism in patients with nonvalvular atrial fibrillation. BACKGROUND: Left atrial spontaneous echo contrast is associated with left atrial stasis and thromboembolism in patients with nonvalvular atrial fibrillation. However, its hematologic determinants in patients with nonvalvular atrial fibrillation are unknown. METHODS: Clinical, hematologic and echocardiographic variables were prospectively measured in 135 consecutive patients with nonvalvular atrial fibrillation undergoing transesophageal echocardiography. RESULTS: Patients with left atrial spontaneous echo contrast (n = 74, 55%) had an increased fibrinogen concentration (p = 0.029), platelet count (p = 0.045), hematocrit (p = NS) and left atrial dimension (p = 0.005). Multivariate analysis showed that left atrial spontaneous echo contrast was independently related to hematocrit (odds ratio = 2.24, p = 0.002), fibrinogen concentration (odds ratio = 2.08, p = 0.008) and left atrial dimension (odds ratio = 1.90, p = 0.004) but not platelet count. It was also associated with left atrial thrombus (n = 15, p = 0.001) and with recent embolism (n = 40, p < 0.001). In 40 clinically stable outpatients without previous embolism, left atrial spontaneous echo contrast was significantly related to hematocrit (p = 0.005), fibrinogen concentration (p = 0.035) and left atrial dimension (p = 0.029) but not to coagulation factor VII, D-dimer, erythrocyte sedimentation rate, platelet count, plasma beta-thromboglobulin, plasma glycocalicin or glycocalicin index. CONCLUSIONS: Left atrial spontaneous echo contrast in patients with nonvalvular atrial fibrillation is independently related to hematocrit, fibrinogen concentration and left atrial dimension, indicating a relatively hypercoagulable state in addition to stasis. These findings support the hypothesis that left atrial spontaneous echo contrast is due to erythrocyte aggregation. Hematologic factors may contribute to its association with thromboembolism.

Aged↗
PubMed1992

Transoesophageal echocardiography in heart disease--old technologies, new tricks.

Cardiac ultrasound and upper gastrointestinal endoscopy are relatively old technologies. With the introduction of new ultrasound probes and by incorporating ultrasound technology into conventional endoscopes, 'new tricks' in cardiac imaging were discovered. Posterior structures of the heart are now able to be imaged clearly by the ultrasound probe from the oesophagus. Consequently, better resolution of cardiac anatomy allows more accurate diagnosis of cardiac pathologies which is not possible using conventional transthoracic (TT) approach. Over a period of two years, 1200 cases of transoesophageal echocardiography (TOE) were undertaken in our institution. The major indications were diseases of the aorta (10%), source of cardioembolism (28%), assessment of native and prosthetic valve function (20%), suspected endocarditis and its complication (17%), pre and post percutaneous transluminal mitral valvotomy (PTMV [13%], congenital heart disease (2%) and others (10%). The greatest impact with TOE is in the diagnosis of aortic dissection and transection. TOE is superior to conventional TT approach in detecting potential source of embolism, valvular vegetations and its complication, native and prosthetic valve dysfunction and LA thrombus prior to PTMV. Observations by TOE such as spontaneous echo contrast (SEC) in the left atrium open new challenges for further research in its role in the pathogenesis of LA thrombus and its association with cardioembolic event. Other areas of interest include; reclassification of distal aortic dissection and the use of TOE in intra-operative work.

Aortic Diseases↗
PubMed1991

Left atrial spontaneous echo contrast: a clinical and echocardiographic analysis.

The clinical and echocardiographic variables related to left atrial spontaneous echo contrast were prospectively evaluated in a consecutive series of 400 patients undergoing transesophageal echocardiography with a 5-MHz single plane transducer. Left atrial spontaneous echo contrast was found in 75 patients (19%) and was significantly associated with atrial fibrillation, mitral stenosis, absence of mitral regurgitation, increased left atrial dimension and a history of suspected embolism. Seventy-one (95%) of the patients with spontaneous echo contrast had atrial fibrillation or mitral stenosis. Anticoagulant therapy had no significant association with spontaneous echo contrast. Multivariate analysis in 89 patients with mitral stenosis or mitral valve replacement showed that spontaneous echo contrast was the only independent predictor (p = 0.03) of left atrial thrombus or suspected embolism, or both. In 60 patients with atrial fibrillation of nonvalvular origin, spontaneous echo contrast (p = 0.01) and age (p = 0.03) were the only independent predictors of left atrial thrombus or suspected embolism, or both. It is concluded that left atrial spontaneous echo contrast is 1) a common finding in patients undergoing transesophageal echocardiography, 2) associated with conditions favoring stasis of left atrial blood, and 3) a marker of previous thromboembolism in patients with nonvalvular atrial fibrillation and those with mitral stenosis or mitral valve replacement.

Atrial Fibrillation↗
PubMed1991

Role of transoesophageal echocardiography in evaluation of cardiogenic embolism.

OBJECTIVE: To determine the value of transoesophageal echocardiography in the assessment of selected patients at risk of cardiogenic embolism or after it. DESIGN: Prospective comparison of the results of transoesophageal and transthoracic echocardiography. Transoesophageal echocardiography was performed with a 5 MHz single plane phased array transducer. SETTING: University teaching hospital. PATIENTS: 100 patients referred for transoesophageal echocardiography after a cerebral ischaemic event or peripheral arterial embolism (n = 63), before percutaneous balloon dilatation of the mitral valve (n = 23), or before electrical cardioversion of atrial fibrillation (n = 14). RESULTS: Transthoracic echocardiography showed potential sources of embolism in four patients including left ventricular thrombus in two patients (with one false positive), left atrial appendage thrombus (n = 1), and patent foramen ovale (n = 1). Transoesophageal echocardiography showed 59 potential embolic sources in 45 patients including left atrial spontaneous echo contrast (n = 33), left atrial appendage thrombus (n = 13), left ventricular thrombus (n = 5), patent foramen ovale (n = 3), left ventricular spontaneous echo contrast (n = 2), mitral valve prosthesis thrombus (n = 1), mitral valve prolapse (n = 1), and pronounced aortic atheroma (n = 1). Transoesophagal echocardiography showed potential embolic sources in 36/53 (68%) patients with atrial fibrillation compared with 9/47 (19%) patients in sinus rhythm. Percutaneous balloon dilatation of the mitral valve was performed without embolic complications in 18 patients without left atrial thrombi and in three patients with small fixed thrombi in the left atrial appendage. It was cancelled in two patients with large thrombi in the left atrial appendage. Cardioversion was performed without embolic complications in 14 patients without left atrial thrombi. CONCLUSIONS: Transoesophageal echocardiography detects potential sources of embolism better than transthoracic echocardiography in selected patients at risk of cardiogenic embolism or after it.

Adult↗
PubMed1989

Pulse reflection sites and effective length of the arterial system.

The concept of effective length (L) of the arterial system implies that it may be represented by a single viscoelastic tube terminated by an impedance, creating a single reflection site. Although the concept is straightforward, investigators for years have been unable to agree on the value of L. Proposed values range from a few millimeters to a few meters, confounding the identification of arterial reflection sites. This report shows analytically and illustrates with experimental data that the determination of the effective length leaves room for an infinite number of exact solutions for L and the corresponding terminal impedance if the input impedance of the tube is to match the measured input impedance of an arterial system. None of the possible values of L needs to bear any relationship to actual reflection sites.

Animals↗
PubMed1988

Central attenuation of baroreflex by angiotensin II in normotensive and spontaneously hypertensive rats.

To determine whether angiotensin II (A II) can modify baroreflex centrally and contribute to the central resetting of baroreflex in spontaneously hypertensive rats (SHRs), the aortic depressor nerve (ADN) was electrically stimulated following intracerebroventricular (ICV) administration of A II and/or A II analog in urethane-anesthetized normotensive Wistar rats (WKYs) and SHRs. Electric stimulation of the ADN elicited frequency-dependent depressor, bradycardic, and sympatho-inhibitory responses. Angiotensin II, administered ICV, dose-dependently attenuated these responses induced by ADN stimulation in normotensive rats. We found, however, these attenuations could be abolished by ICV pretreatment with A II analog. Vasopressin (ICV) did not change any responses to ADN stimulation. The vasopressor and sympatho-inhibitory responses to ADN stimulation were significantly less in SHRs when compared with those in WKYs: In SHRs, A II analog completely cancelled the A II-attenuated responses to ADN stimulation. These findings suggest that A II can centrally attenuate baroreflex, which might be independent from vasopressin, and in the brain A II can contribute to the central resetting of baroreflex in SHRs.

Angiotensin II↗
PubMed1988

Central attenuation of baroreflex precedes the development of hypertension in DOCA-salt-treated rats.

To determine whether baroreflex is changed centrally before the development of hypertension in DOCA-salt treated rats, aortic depressor nerve was stimulated electrically 5 days after DOCA-salt treatment in urethane-anesthetized rats: compared with those of sham-operated control rats, blood pressure was not elevated in either awake or anesthetized rats. Aortic depressor nerve (ADN) stimulation elicited frequency-dependent vasodepressor, bradycardiac, and sympatho-inhibitory responses in both DOCA-salt-treated and control rats. However, the responses to ADN stimulation were significantly smaller in DOCA-salt-treated rats. These findings suggest that baroreflex is attenuated centrally before the development of hypertension and this attenuation may contribute to the pathogenesis of DOCA-salt hypertension.

Animals↗