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Biomedical subjects

J D Thomas

Publications and source records attributed to J D Thomas.

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

TatB and TatC form a functional and structural unit of the twin-arginine translocase from Escherichia coli.

In Escherichia coli, a subset of periplasmic proteins is exported via the twin-arginine translocation (Tat) pathway. In the present study, we have purified the Tat complex from E. coli, and we show that it contains only TatA, TatB, and TatC. Within the purified complex, TatB and TatC are present in a strict 1:1 ratio, suggesting a functional association. This has been confirmed by expression of a translational fusion between TatB and TatC. This Tat(BC) chimera supports efficient Tat-dependent export, indicating that TatB and TatC act as a unit in both structural and functional terms. The purified Tat complex contains varying levels of TatA, suggesting a gradual loss during isolation and a looser association. The molecular mass of the complex is approximately 600 kDa, demonstrating the presence of multiple copies of TatA, B, and C. Co-immunoprecipitation experiments show that TatC is required for the interaction of TatA with TatB, suggesting that TatA may interact with the complex via binding to TatC.

Base Sequence↗
PubMed2001

Hypotension, autonomic failure, and cardiac hypertrophy in transgenic mice overexpressing the alpha 1B-adrenergic receptor.

alpha(1)-Adrenergic receptors (alpha(1A), alpha(1B), and alpha(1D)) are regulators of systemic arterial blood pressure and blood flow. Whereas vasoconstrictory action of the alpha(1A) and alpha(1D) subtypes is thought to be mainly responsible for this activity, the role of the alpha(1B)-adrenergic receptor (alpha(1B)AR) in this process is controversial. We have generated transgenic mice that overexpress either wild type or constitutively active alpha(1B)ARs. Transgenic expression was under the control of the isogenic promoter, thus assuring appropriate developmental and tissue-specific expression. Cardiovascular phenotypes displayed by transgenic mice included myocardial hypertrophy and hypotension. Indicative of cardiac hypertrophy, transgenic mice displayed an increased heart to body weight ratio, which was confirmed by the echocardiographic finding of an increased thickness of the interventricular septum and posterior wall. Functional deficits included an increased isovolumetric relaxation time, a decreased heart rate, and cardiac output. Transgenic mice were hypotensive and exhibited a decreased pressor response. Vasoconstrictory regulation by alpha(1B)AR was absent as shown by the lack of phenylephrine-induced contractile differences between ex vivo mesenteric artery preparations. Plasma epinephrine, norepinephrine, and cortisol levels were also reduced in transgenic mice, suggesting a loss of sympathetic nerve activity. Reduced catecholamine levels together with basal hypotension, bradycardia, reproductive problems, and weight loss suggest autonomic failure, a phenotype that is consistent with the multiple system atrophy-like neurodegeneration that has been reported previously in these mice. These results also suggest that this receptor subtype is not involved in the classic vasoconstrictory action of alpha(1)ARs that is important in systemic regulation of blood pressure.

Animals↗
PubMed2001

Comparison of quantitative and semiquantitative methods for assessing mitral regurgitation by transesophageal echocardiography.

Semiquantitative grading of mitral regurgitation (MR) by transesophageal echocardiography (TEE) is widely used for clinical decision making. However, the relation between semiquantitative grading by biplane or multiplane TEE and quantitative measures remains undetermined. Biplane or multiplane TEE was performed in 113 patients in the operating room. MR severity was graded from 1 to 4+ by Doppler color flow mapping. MR was quantified using the thermodilution-Doppler method as mitral regurgitant stroke volume (RSV) derived from the difference between total mitral inflow measured by pulsed Doppler and forward flow measured by thermodilution. Mitral regurgitant orifice area (ROA) was calculated by RSV divided by mitral regurgitant velocity. RSV and ROA were also calculated using the proximal isovelocity surface area method. RSV and ROA significantly correlated with the semiquantitative grading either by TEE or angiogram in a nonlinear fashion, with the best fit being given by an exponential model with correlation coefficients from 0.73 to 0.87 (p <0.001). Substantially increased RSV and ROA were observed in MR grades of > or =3+. In the same grades of 3+ or 4+ MR, the largest RSV was 4 times larger than the smallest (190 to 220 vs 44 to 45 ml), and the largest ROA (1.82 to 2.0 vs 0.26 to 0.27 cm2) was sixfold larger than the smallest. Patients with 2 to 3+ MR had significantly variable RSV and ROA (range 21 to 91 ml and 0.12 to 0.65 cm2, respectively). Color flow mapping by biplane or multiplane TEE or angiography is able to categorize precisely mild (< or =2+) and severe (> or =3+) MR, but cannot accurately determine actual hemodynamic load of MR in more severe degrees of MR.

Echocardiography, Transesophageal↗
PubMed2001

Comparison of new Doppler echocardiographic methods to differentiate constrictive pericardial heart disease and restrictive cardiomyopathy.

This study assesses how the newer modalities of tissue Doppler echocardiography and color M-mode flow propagation compare with respiratory variation of Doppler flow in distinguishing between constrictive pericarditis and restrictive cardiomyopathy. We studied 30 patients referred for further evaluation of diastolic function who had a diagnosis of constrictive pericarditis or restrictive cardiomyopathy established by diagnostic tests, including clinical assessment, magnetic resonance imaging, cardiac catheterization, endomyocardial biopsy, and surgical findings. Nineteen patients had constrictive pericarditis and 11 had restrictive cardiomyopathy. We performed 2-dimensional transesophageal echocardiography combined with pulsed-wave Doppler of the pulmonary veins and mitral inflow with respiratory monitoring, tissue Doppler echocardiography of the lateral mitral annulus, and color M-mode flow propagation of left ventricular filling. Respiratory variation of the mitral inflow peak early (peak E) velocity of > or =10% predicted constrictive pericarditis with 84% sensitivity and 91% specificity and variation in the pulmonary venous peak diastolic (peak D) flow velocity of > or =18% distinguished constriction with 79% sensitivity and 91% specificity. Using tissue Doppler echocardiography, a peak early velocity of longitudinal expansion (peak Ea) of > or =8.0 cm/s differentiated patients with constriction from restriction with 89% sensitivity and 100% specificity. A slope of > or =100 cm/s for the first aliasing contour in color M-mode flow propagation predicted patients with constriction with 74% sensitivity and 91% specificity. Thus, the newer methods of tissue Doppler echocardiography and color M-mode flow propagation are equivalent and complimentary with Doppler respiratory variation in distinguishing between constrictive pericarditis and restrictive cardiomyopathy. The additive role of the new methods needs to be established in difficult cases of constrictive pericarditis where respiratory variation may be absent or decreased.

Adult↗
PubMed2001

Percutaneous transluminal alcohol septal myocardial ablation after aortic valve replacement.

When left ventricular outflow tract obstruction develops after aortic valve replacement, few treatment choices have been available until now. We present a patient with prior aortic valve replacement who developed left ventricle outflow tract obstruction that was successfully treated with a percutaneous transcoronary myocardial septal alcohol ablation. This technique is a useful tool for the treatment of obstructive hypertrophic cardiomyopathy, especially in those patients with prior heart surgery.

Angioplasty, Balloon, Coronary↗
PubMed2001

Short-term hemodynamic performance of the mitral Carpentier-Edwards PERIMOUNT pericardial valve. Carpentier-Edwards PERIMOUNT Investigators.

BACKGROUND: Although long-term durability data exist, little data are available concerning the hemodynamic performance of the Carpentier-Edwards PERIMOUNT pericardial valve in the mitral position. METHODS: Sixty-nine patients who were implanted with mitral PERIMOUNT valves at seven international centers between January 1996 and February 1997 consented to participate in a short-term echocardiography follow-up. Echocardiographs were collected at a mean of 600+/-133 days after implantation (range, 110 to 889 days); all underwent blinded core lab analysis. RESULTS: At follow-up, peak gradients were 9.09+/-3.43 mm Hg (mean, 4.36+/-1.79 mm Hg) and varied inversely with valve size (p < 0.05). The effective orifice areas were 2.5+/-0.6 cm2 and tended to increase with valve size (p = 0.08). Trace mitral regurgitation (MR) was common (n = 48), 9 patients had mild MR, 1 had moderate MR, none had severe MR. All MR was central (n = 55) or indeterminate (n = 3). No paravalvular leaks were observed. Mitral regurgitation flow areas were 3.4+/-2.8 cm2 and were without significant volumes. CONCLUSIONS: In this multicenter study, these mitral valves are associated with trace, although physiologically insignificant, central MR. Despite known echocardiographic limitations, the PERIMOUNT mitral valves exhibit similar hemodynamics to other prosthetic valves.

Aged↗
PubMed2001

Real-time three-dimensional color Doppler echocardiography for characterizing the spatial velocity distribution and quantifying the peak flow rate in the left ventricular outflow tract.

Quantification of flow with pulsed-wave Doppler assumes a "flat" velocity profile in the left ventricular outflow tract (LVOT), which observation refutes. Recent development of real-time, three-dimensional (3-D) color Doppler allows one to obtain an entire cross-sectional velocity distribution of the LVOT, which is not possible using conventional 2-D echo. In an animal experiment, the cross-sectional color Doppler images of the LVOT at peak systole were derived and digitally transferred to a computer to visualize and quantify spatial velocity distributions and peak flow rates. Markedly skewed profiles, with higher velocities toward the septum, were consistently observed. Reference peak flow rates by electromagnetic flow meter correlated well with 3-D peak flow rates (r = 0.94), but with an anticipated underestimation. Real-time 3-D color Doppler echocardiography was capable of determining cross-sectional velocity distributions and peak flow rates, demonstrating the utility of this new method for better understanding and quantifying blood flow phenomena.

Animals↗
PubMed2001

Interaliasing distance of the flow convergence surface for determining mitral regurgitant volume: a validation study in a chronic animal model.

OBJECTIVES: We aimed to validate a new flow convergence (FC) method that eliminated the need to locate the regurgitant orifice and that could be performed semiautomatedly. BACKGROUND: Complex and time-consuming features of previously validated color Doppler methods for determining mitral regurgitant volume (MRV) have prevented their widespread clinical use. METHODS: Thirty-nine different hemodynamic conditions in 12 sheep with surgically created flail leaflets inducing chronic mitral regurgitation were studied with two-dimensional (2D) echocardiography. Color Doppler M-mode images along the centerline of the accelerating flow towards the mitral regurgitation orifice were obtained. The distance between the two first aliasing boundaries (interaliasing distance [IAD]) was measured and the FC radius was mathematically derived according to the continuity equation (R(calc) = IAD/(1 - radicalv(1)/v(2)), v(1) and v(2) being the aliasing velocities). The conventional 2D FC radius was also measured (R(meas)). Mitral regurgitant volume was then calculated according to the FC method using both R(calc) and R(meas). Aortic and mitral electromagnetic (EM) flow probes and meters were balanced against each other to determine the reference standard MRV. RESULTS: Mitral regurgitant volume calculated from R(calc) and R(meas) correlated well with EM-MRV (y = 0.83x + 5.17, r = 0.90 and y = 1.04x + 0.91, r = 0.91, respectively, p < 0.001 for both). However, both methods resulted in slight overestimation of EM-MRV (Delta was 3.3 +/- 2.1 ml for R(calc) and 1.3 +/- 2.3 ml for R(meas)). CONCLUSIONS: Good correlation was observed between MRV derived from R(calc) (IAD method) and EM-MRV, similar to that observed with R(meas) (conventional FC method) and EM-MRV. The R(calc) using the IAD method has an advantage over conventional R(meas) in that it does not require spatial localization of the regurgitant orifice and can be performed semiautomatedly.

Animals↗
PubMed2001

Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery.

OBJECTIVES: This study was conducted to evaluate follow-up results in patients with hypertrophic obstructive cardiomyopathy (HOCM) who underwent either percutaneous transluminal septal myocardial ablation (PTSMA) or septal myectomy. BACKGROUND: Controversy exists with regard to these two forms of treatment for patients with HOCM. METHODS: Of 51 patients with HOCM treated, 25 were treated by PTSMA and 26 patients via myectomy. Two-dimensional echocardiograms were performed before both procedures, immediately afterwards and at a three-month follow-up. The New York Heart Association (NYHA) functional class was obtained before the procedures and at follow-up. RESULTS: Interventricular septal thickness was significantly reduced at follow-up in both groups (2.3 +/- 0.4 cm vs. 1.9 +/- 0.4 cm for septal ablation and 2.4 +/- 0.6 cm vs. 1.7 +/- 0.2 cm for myectomy, both p < 0.001). Estimated by continuous-wave Doppler, the resting pressure gradient (PG) across the left ventricular outflow tract (LVOT) significantly decreased immediately after the procedures in both groups (64 +/- 39 mm Hg vs. 28 +/- 29 mm Hg for PTSMA, 62 +/- 43 mm Hg vs. 7 +/- 7 mm Hg for myectomy, both p < 0.0001). At three-month follow-up, the resting PG remained lower in the PTSMA and myectomy groups (24 +/- 19 mm Hg and 11 +/- 6 mm Hg, respectively, vs. those before procedures, both p < 0.0001). The NYHA functional class was also significantly improved in both groups (3.5 +/- 0.5 vs. 1.9 +/- 0.7 for PTSMA, 3.3 +/- 0.5 vs. 1.5 +/- 0.7 for myectomy, both p < 0.0001). CONCLUSIONS: Both myectomy and PTSMA reduce LVOT obstruction and significantly improve NYHA functional class in patients with HOCM. However, there are benefits and drawbacks for each therapeutic method that must be counterbalanced when deciding on treatment for LVOT obstruction.

Adult↗
PubMed2001

Left ventricular endocardial surface detection based on real-time 3D echocardiographic data.

OBJECTIVE: A new computerized semi-automatic method for left ventricular (LV) chamber segmentation is presented. METHODS: The LV is imaged by real-time three-dimensional echocardiography (RT3DE). The surface detection model, based on level set techniques, is applied to RT3DE data for image analysis. The modified level set partial differential equation we use is solved by applying numerical methods for conservation laws. The initial conditions are manually established on some slices of the entire volume. The solution obtained for each slice is a contour line corresponding with the boundary between LV cavity and LV endocardium. RESULTS: The mathematical model has been applied to sequences of frames of human hearts (volume range: 34-109 ml) imaged by 2D and reconstructed off-line and RT3DE data. Volume estimation obtained by this new semi-automatic method shows an excellent correlation with those obtained by manual tracing (r = 0.992). Dynamic change of LV volume during the cardiac cycle is also obtained. CONCLUSION: The volume estimation method is accurate; edge based segmentation, image completion and volume reconstruction can be accomplished. The visualization technique also allows to navigate into the reconstructed volume and to display any section of the volume.

Echocardiography, Three-Dimensional↗
PubMed2001

Export of active green fluorescent protein to the periplasm by the twin-arginine translocase (Tat) pathway in Escherichia coli.

The twin-arginine translocation (Tat) system targets cofactor-containing proteins across the Escherichia coli cytoplasmic membrane via distinct signal peptides bearing a twin-arginine motif. In this study, we have analysed the mechanism and capabilities of the E. coli Tat system using green fluorescent protein (GFP) fused to the twin-arginine signal peptide of TMAO reductase (TorA). Fractionation studies and fluorescence measurements demonstrate that GFP is exported to the periplasm where it is fully active. Export is almost totally blocked in tat deletion mutants, indicating that the observed export in wild-type cells occurs predominantly, if not exclusively, by the Tat pathway. Imaging studies reveal a halo of fluorescence in wild-type cells corresponding to the exported periplasmic form; the GFP is distributed uniformly throughout the cytoplasm in a tat mutant. Because previous work has shown GFP to be incapable of folding in the periplasm, we propose that GFP is exported in a fully folded, active state. These data also show for the first time that heterologous proteins can be exported in an active form by the Tat pathway.

Amino Acid Sequence↗
PubMed2001

Localization of needle tip with color doppler during pericardiocentesis: In vitro validation and initial clinical application.

This study evaluates a new device that uses color Doppler ultrasonography to enable real-time image guidance of the aspirating needle, which has not been possible until now. The ColorMark device (EchoCath Inc, Princeton, NJ) induces high-frequency, low-amplitude vibrations in the needle to enable localization with color Doppler. We studied this technique in 25 consecutive patients undergoing pericardiocentesis, and in vitro, in a urethane phantom with which the accuracy of color Doppler localization of the needle tip was compared with that obtained by direct measurement. Tip localization was excellent in vitro; errors axial to the ultrasound beam (velocity Doppler -0.13 +/- 0.90 mm, power Doppler -0.05 +/- 1.7 mm) were less than lateral errors (velocity -0.36 +/- 1.8 mm, power -0.02 +/- 2.8 mm). In 18 of 25 patients, the needle was identified and guided into the pericardial space with the ColorMark technique, and it allowed successful, uncomplicated drainage of fluid. Initial failures were the result of incorrect settings on the echocardiographic machine and inappropriate combinations of the needle puncture site and imaging window. This study demonstrates a novel color Doppler technique that is highly accurate at localizing a needle tip. The technique is feasible for guiding pericardiocentesis. Further clinical validation of this technique is required.

Echocardiography↗
PubMed2001

Right atrial spontaneous echo contrast and thrombi in atrial fibrillation: a transesophageal echocardiography study.

BACKGROUND: Previous studies have reported the clinical and echocardiographic findings of patients with left atrial spontaneous echo contrast (SEC) and thrombi. We sought to study these characteristics in patients with right atrial SEC and thrombi. METHODS: We reviewed 580 consecutive patients from the ACUTE (Assessment of Cardioversion Using Transesophageal Echocardiography) Registry and found 79 patients (14%, aged 67 +/-13 years, 67 male) with transesophageal echocardiography (TEE) findings of right atrial SEC or thrombi (group 1). This group was compared with a control group of 75 consecutive patients (group 2) (aged 68 +/- 13 years, P = not significant; 49 male, P <.005) from the registry with no TEE findings of SEC or thrombi in the left or right atrium. RESULTS: Atrial fibrillation was present in 60 of 79 group 1 patients (76%). Five right atrial (6%) and 11 left atrial (14%) thrombi were identified. Both left ventricular ejection fraction (39% +/- 16% versus 47% +/- 14%; P =.0005) and presence of right ventricular dysfunction (n = 44 versus 18; P =.0001) differed significantly between groups 1 and 2, respectively. Right atrial area (24 +/- 6 cm(2) versus 22 +/- 6 cm(2); P = .02) was larger in patients in group 1. Left atrial SEC was present in 68 of 79 group 1 patients (86%). Patients with right atrial thrombi and right atrial SEC had a longer duration of arrhythmia (524 +/-812 days versus 147 +/-368 days, P <.05) than patients with right atrial SEC only. CONCLUSIONS: Right atrial SEC has a prevalence of 14% in patients with atrial arrhythmia who undergo TEE-guided cardioversion. Right atrial thrombi are a rare finding and were seen in fewer than 1% (5/580) of patients with atrial arrhythmia. Right atrial thrombi among patients on anticoagulation therapy were not associated with clinically significant pulmonary embolism.

Adult↗
PubMed2001

Calculation of mitral regurgitant orifice area with use of a simplified proximal convergence method: initial clinical application.

To validate a previously proposed simplified proximal flow convergence method for calculating mitral regurgitant orifice area (ROA), a prospective study was conducted in ambulatory patients and in patients undergoing open heart surgery. Assuming a pressure difference between the left ventricle and left atrium of approximately 100 mm Hg (jet velocity [v(p)] 500 cm/s) and setting the color aliasing velocity (v(a)) to 40 cm/s, we simplified the conventional proximal convergence method formula (ROA = 2pi(r2)v(a)/v(p)) to r2/2, where r is the radius of the proximal convergence isovelocity hemisphere. For 57 ambulatory patients with a wide range of mitral regurgitant severity (1 to 4+), ROA was calculated by the conventional (x) and simplified (y) methods, demonstrating excellent accuracy (r = 0.92; P <.001; DeltaROA [y - x] = 0.004 +/- 0.08 cm2). For 24 intraoperative patients, ROA calculated by the simplified formula (y) correlated well with the pulsed Doppler-thermodilution method (x) (r = 0.84; P <.01; DeltaROA [y - x] = -0.002 +/- 0.08cm2). This simplified proximal convergence formula yields an accurate assessment of ROA for a wide range of regurgitant severity, while the time required for this measurement is shortened by half (1.5 +/- 0.5 minutes versus 3.2 +/- 0.7 minutes). This may increase the frequency of calculating ROA in the clinical laboratory.

Aged↗
PubMed2001

Comparison of MPEG-1 digital videotape with digitized sVHS videotape for quantitative echocardiographic measurements.

Digital format is rapidly emerging as a preferred method for displaying and retrieving echocardiographic studies. The qualitative diagnostic accuracy of Moving Pictures Experts Group (MPEG-1) compressed digital echocardiographic studies has been previously reported. The goals of the present study were to compare quantitative measurements derived from MPEG-1 recordings with the super-VHS (sVHS) videotape clinical standard. Six reviewers performed blinded measurements from still-frame images selected from 20 echocardiographic studies that were simultaneously acquired in sVHS and MPEG-1 formats. Measurements were obtainable in 1401 (95%) of 1486 MPEG-1 variables compared with 1356 (91%) of 1486 sVHS variables (P <.001). Excellent agreement existed between MPEG-1 and sVHS 2-dimensional linear measurements (r = 0.97; MPEG-1 = 0.95[sVHS] + 1.1 mm; P <.001; Delta = 9% +/- 10%), 2-dimensional area measurements (r = 0.89), color jet areas (r = 0.87, p <.001), and Doppler velocities (r = 0.92, p <.001). Interobserver variability was similar for both sVHS and MPEG-1 readings. Our results indicate that quantitative off-line measurements from MPEG-1 digitized echocardiographic studies are feasible and comparable to those obtained from sVHS.

Echocardiography↗
PubMed2001

Chronic mitral regurgitation and Doppler estimation of left ventricular filling pressures in patients with heart failure.

Previous studies relating Doppler parameters and pulmonary capillary wedge pressures (PCWP) typically exclude patients with severe mitral regurgitation (MR). We evaluated the effects of varying degrees of chronic MR on the Doppler estimation of PCWP. PCWP and mitral Doppler profiles were obtained in 88 patients (mean age 55 +/- 8 years) with severe left ventricular (LV) dysfunction (mean ejection fraction 23% +/- 5%). Patients were classified by severity of MR. Patients with severe MR had greater left atrial areas, LV end-diastolic volumes, and mean PCWPs and lower ejection fractions (each P <.01). In patients with mild MR, multiple echocardiographic parameters correlated with PCWP; however, with worsening MR, only deceleration time strongly related to PCWP. From stepwise multivariate analysis, deceleration time was the best independent predictor of PCWP overall, and it was the only predictor in patients with moderate or severe MR. Doppler-derived early mitral deceleration time reliably predicts PCWP in patients with severe LV dysfunction irrespective of degree of MR.

Chronic Disease↗