Perioperative risk factors for development of protein-losing enteropathy following a Fontan procedure.
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Adolescent↗
Biomedical subjects
A J Powell
Publications and source records attributed to A J Powell.
Asymmetric interactions in the adenosine-binding pockets of the MS2 coat protein dimer.
BACKGROUND: The X-ray structure of the MS2 coat protein-operator RNA complex reveals the existence of quasi-synmetric interactions of adenosines -4 and -10 in pockets formed on different subunits of the coat protein dimer. Both pockets utilize the same five amino acid residues, namely Val29, Thr45, Ser47, Thr59, and Lys61. We call these sites the adenosine-binding pockets. RESULTS: We present here a heterodimer complementation analysis of the contributions of individual A-pocket amino acids to the binding of A-4 and A-10 in different halves of the dimer. Various substitutions of A-pocket residues were introduced into one half of single-chain coat protein heterodimers where they were tested for their abilities to complement Y85H or T91I substitutions (defects in the A-4 and A-10 half-sites, respectively) present in the other dimer half. CONCLUSIONS: These experiments provide functional tests of interactions predicted from structural analyses, demonstrating the importance of certain amino acid-nucleotide contacts observed in the crystal structure, and showing that others make little or no contribution to the stability of the complex. In summary, Val29 and Lys61 form important stabilizing interactions with both A-4 and A-10. Meanwhile, Ser47 and Thr59 interact primarily with A-10. The important interactions with Thr45 are restricted to A-4.
Journal Article↗
Allelic diversity at the het-c locus in Neurospora tetrasperma confirms outcrossing in nature and reveals an evolutionary dilemma for pseudohomothallic ascomycetes.
Vegetative cells of the filamentous ascomycete Neurospora tetrasperma are typically heterokaryotic, possessing haploid nuclei of both A and a mating types. As a consequence, N. tetrasperma is self-fertile. This life cycle, referred to as pseudohomothallism, clearly derives from true heterothallism of the type exhibited by related species such as N. crassa. Occasional homokaryotic, single-mating-type (heterothallic) isolates occur; in the laboratory, such strains can be outcrossed. The potential for outcrossing in N. tetrasperma raises the question of how this organism avoids heterokaryon incompatibility. Heterokaryon incompatability in vegetatively growing fungi is controlled by multiple loci. Two strains must be identical at each het locus (11 in N. crassa) to form a stable heterokaryon. Prior to the present survey, it seemed plausible that N. tetrasperma avoids heterokaryon incompatibility by maintaining compatible allele combinations through continual selfing. A survey of het-c variation among wild-type isolates in this study demonstrated that N. tetrasperma outcrosses in nature and that such matings can result in incompatible combinations of het-c alleles. Whereas individual wild-type isolates are invariably homoallelic for het-c, closely related strains may possess functionally different het-c alleles, which predate the origin of N. tetrasperma. Therefore, pseudohomothallic ascomycetes such as N. tetrasperma face an apparent evolutionary dilemma: the benefits of outcrossing must be balanced against the fact that matings can produce unstable heterokaryons and disrupt the pseudohomothallic life cycle.
Alleles↗
Outcome in infants with pulmonary atresia, intact ventricular septum, and right ventricle-dependent coronary circulation.
Management of all patients with pulmonary atresia, intact ventricular septum, and right ventricle-dependent coronary circulation (n = 12) with staged surgery directed toward a Fontan palliation resulted in an 83% 5-year actuarial survival. Both deaths in the study were presumably related to coronary ischemia and occurred in the first 4 months of life.
Abnormalities, Multiple↗
Recognition of structurally diverse substrates by type II 3-hydroxyacyl-CoA dehydrogenase (HADH II)/amyloid-beta binding alcohol dehydrogenase (ABAD).
Human type II hydroxyacyl-CoA dehydrogenase/amyloid-beta binding alcohol dehydrogenase (HADH II/ABAD) is an oxidoreductase whose salient features include broad substrate specificity, encompassing 3-hydroxyacyl-CoA derivatives, hydroxysteroids, alcohols and beta-hydroxybutyrate, and the capacity to bind amyloid-beta peptide, leading to propagation of amyloid-induced cell stress. In this study, we examine the structure and enzymatic activity of the homologous rat HADH II/ABAD enzyme. We report the crystal structure of rat HADH II/ABAD as a binary complex with its NADH cofactor to 2.0 A resolution, as a ternary complex with NAD(+) and 3-ketobutyrate (acetoacetate) to 1.4 A resolution, and as a ternary complex with NADH and 17 beta-estradiol to 1.7 A resolution. This first crystal structure of an HADH II confirms these enzymes are closely related to the short-chain hydroxysteroid dehydrogenases and differ substantially from the classic, type I 3-hydroxyacyl-CoA dehydrogenases. Binding of the ketobutyrate substrate is accompanied by closure of the active site specificity loop, whereas the steroid substrate does not appear to require closure for binding. Despite the different chemical nature of the two bound substrates, the presentation of chemical groups within the active site of each complex is remarkably similar, allowing a general mechanism for catalytic activity to be proposed. There is a characteristic extension to the active site that is likely to accommodate the CoA moiety of 3-hydroxyacyl-CoA substrates. Rat HADH II/ABAD also binds amyloid-beta (1-40) peptide with a K(D) of 21 nM, which is similar to the interaction exhibited between this peptide and human HADH II/ABAD. These studies provide the first structural insights into HADH II/ABAD interaction with its substrates, and indicate the relevance of the rodent enzyme and associated rodent models for analysis of HADH II/ABAD's physiologic and pathophysiologic properties.
3-Hydroxyacyl CoA Dehydrogenases↗
Distribution of voltage-gated sodium channel alpha-subunit and beta-subunit mRNAs in human hippocampal formation, cortex, and cerebellum.
The distribution of mRNAs encoding voltage-gated sodium channel alpha subunits (I, II, III, and VI) and beta subunits (beta1 and beta2) was studied in selected regions of the human brain by Northern blot and in situ hybridisation experiments. Northern blot analysis showed that all regions studied exhibited heterogenous expression of sodium channel transcripts. In situ hybridisation experiments confirmed these findings and revealed a predominantly neuronal distribution. In the parahippocampal gyrus, subtypes II and VI and the beta-subunit mRNAs exhibited robust expression in the granule cells of the dentate gyrus and pyramidal cell layer of the hippocampus. Subtypes I and III showed moderate expression in granule cells and low expression in the pyramidal cell layer. Distinct expression patterns were also observed in the cortical layers of the middle frontal gyrus and in the entorhinal cortex. In particular, all subtypes exhibited higher levels of expression in cortical layers III, V, and VI compared with layers I and II. All subtypes were expressed in the granular layer of the cerebellum, whereas specific expression of subtypes I, VI, beta1, and beta2 mRNAs was observed in Purkinje cells. Subtypes I, VI, and beta1 mRNAs were expressed, at varying levels, in the pyramidal cells of the deep cerebellar nuclei. These data indicate that, as in rat, human brain sodium channel mRNAs have a distinct regional distribution, with individual cell types expressing different compliments of sodium channels. The differential distribution of sodium channel subtypes suggest that they have distinct roles that are likely to be of paramount importance in maintaining the functional heterogeneity of central nervous system neurons.
Animals↗
3D-shaded surface rendering of gadolinium-enhanced MR angiography in congenital heart disease.
BACKGROUND: Gadolinium-enhanced three-dimensional (3D) MR angiography is a useful imaging technique for patients with congenital heart disease. OBJECTIVE: This study sought to determine the added value of creating 3D shaded surface displays compared to standard maximal intensity projection (MIP) and multiplanar reformatting (MPR) techniques when analyzing 3D MR angiography data. MATERIALS AND METHODS: Seventeen patients (range, 3 months to 51 years old) with a variety of congenital cardiovascular defects underwent gadolinium-enhanced 3D MR angiography of the thorax. Color-coded 3D shaded surface models were rendered from the image data using manual segmentation and computer-based algorithms. Models could be rotated, translocated, or zoomed interactively by the viewer. Information available from the 3D models was compared to analysis based on viewing standard MIP/ MPR displays. RESULTS: Median postprocessing time for the 3D models was 6 h (range, 3-25 h) compared to approximately 20 min for MIP/MPR viewing. No additional diagnostic information was gained from 3D model analysis. All major findings with MIP/MPR postprocessing were also apparent on the 3D models. Qualitatively, the 3D models were more easily interpreted and enabled adjacent vessels to be distinguished more readily. CONCLUSION: Routine use of 3D shaded surface reconstructions for visualization of contrast enhanced MR angiography in congenital heart disease cannot be recommended. 3D surface rendering may be more useful for presenting complex anatomy to an audience unfamiliar with congenital heart disease and as an educational tool.
Adolescent↗
Coronary echocardiography in tetralogy of fallot: diagnostic accuracy, resource utilization and surgical implications over 13 years.
OBJECTIVES: This study sought to determine the diagnostic accuracy and impact of the systematic use of coronary echocardiography in a large group of preoperative patients with tetralogy of Fallot (TOF). BACKGROUND: Accurate preoperative identification of an anomalous coronary artery crossing the right ventricular outflow tract (RVOT) in patients with TOF is important to prevent coronary injury during surgical repair. METHODS: A retrospective review identified 598 patients with TOF between 1983 to 1995 who underwent an echocardiogram at <2 years old before complete surgical repair. Associated diagnoses included pulmonary stenosis (n = 433), pulmonary atresia (n = 121), common atrioventricular canal (n = 17), absent pulmonary valve syndrome (n = 24) and aortopulmonary window (n = 3). RESULTS: Based on intraoperative findings, 32 patients (5.4%) were found to have a major coronary artery crossing the RVOT. The use and diagnostic performance of coronary echocardiography increased over time, while the number of patients undergoing preoperative cardiac catheterization declined. During the most recent study period (1991 to 1995, n = 274), 97% of patients underwent coronary echocardiography yielding a sensitivity of 82%, specificity of 99% and accuracy of 98.5%. Of the 18 patients with TOF and pulmonary stenosis who had abnormal coronary arteries during this period, only 6 (33%) required an extracardiac conduit as part of their complete repair. CONCLUSIONS: Coronary echocardiography is an accurate noninvasive tool to delineate coronary anatomy in infants with TOF before complete repair. Routine preoperative cardiac catheterization solely for diagnosis of coronary anatomy is not necessary. The use of an extracardiac conduit can be avoided in the majority of patients with TOF and pulmonary stenosis who have a major coronary artery crossing the RVOT.
Abnormalities, Multiple↗
Accuracy of MRI evaluation of pulmonary blood supply in patients with complex pulmonary stenosis or atresia.
Detailed imaging of pulmonary artery (PA) anatomy and significant aorto-pulmonary collaterals (APCs) is crucial for surgical planning and follow-up in patients with complex congenital heart disease (CHD) and pulmonary stenosis or atresia. Because examination by echocardiography is often technically limited and catheterization is invasive, this study evaluated the diagnostic accuracy of magnetic resonance imaging (MRI) as an alternate non-invasive tool. Thirteen patients (median age 28 years, range: 1-44 years) underwent both cardiac catheterization and MRI within a median of two months (range 0.1-8 months). Diagnoses included tetralogy of Fallot (TOF) with pulmonary atresia (n = 8), TOF with pulmonary stenosis (n = 2), single left ventricle with pulmonary stenosis (n = 2), and complex heterotaxy with pulmonary stenosis (n = 1). The MRI sequences used in this study were ECG-gated spin echo and gradient echo sequences acquired in multiple planes. Compared to catheterization, MRI had 100% sensitivity and specificity for the diagnosis of main PA (n = 6) and branch PA (n = 13) hypoplasia or stenosis, as well as discontinuous (n = 4) or absent (n = 10) branch PAs. There was complete agreement between catheterization and MRI identification of significant APCs (n = 18). Main PA atresia was noted by MRI in four patients but was not definitively seen by catheterization in any. MRI but not catheterization precisely defined the distance between discontinuous PAs and their relationship to other mediastinal structures. In conclusion, cardiac MRI is a reliable non-invasive imaging modality to define PA and APC anatomy in patients with complex pulmonary stenosis or atresia.
Adolescent↗
Different functions are required for initiation and maintenance of immortalization of rat embryo fibroblasts by SV40 large T antigen.
We have used two different, but complementary assays to characterize functions of SV40 T antigen that are necessary for its ability to immortalize rat embryo fibroblasts. In accordance with previous work, we found that several functions were required. These include activities that map to the p53 binding domain and the amino terminal 176 amino acids which contain the J domain as well as the CR1 and CR2 domain required for binding and sequestering the RB family of pocket proteins. Moreover, we found that even though activities dependent only upon the amino terminus were sufficient for immortalization they were unable to maintain it. This suggests that immortalization by these amino terminal functions requires either additional events or immortalization of a subset of cells within the heterogeneous rat embryo fibroblast population. We further found that an activity dependent upon amino acids 17 - 27 which remove a portion of the CR1 domain and the predicted alpha-1 helix of the J domain was not necessary to maintain growth but was required for direct immortalization suggesting that at least one of the functions required initially was not required to maintain the immortal state. This represents the first demonstration that some of the functions required for maintenance of the immortal state differ from those required for initiation of immortalization.
Animals↗
Evaluation of regional differences in right ventricular systolic function by acoustic quantification echocardiography and cine magnetic resonance imaging.
BACKGROUND: Accurate quantitative evaluation of right ventricular (RV) function has been limited by its complex structural geometry. Although embryological and anatomic observations suggest that the RV is composed of 2 distinct components, the RV sinus and infundibulum, most studies on RV dimensions and function viewed it as a single chamber. This study was designed to determine the volumes, relative contribution to global systolic function, and temporal course of contraction and relaxation of the RV sinus and infundibulum. METHODS AND RESULTS: Thirty-one individuals without heart disease (aged 1 month to 17 years, 16 boys and 15 girls) participated in this study. Instantaneous area over time, its derivatives, and the temporal course of contraction and relaxation were studied by acoustic quantification echocardiography and phonocardiography in 20 individuals. Global and regional RV volumes and ejection fraction were determined by cine MRI in 11 individuals. The RV sinus made up 81+/-6% of the combined RV end-diastolic volume and 87+/-4% of the combined stroke volume. The infundibulum accounted for the remaining 19+/-6% and 13+/-4%, respectively (P<0.0001). Compared with the infundibulum, the extent of RV sinus fiber shortening was significantly greater: for ejection fraction (56+/-11% versus 38+/-13%, P<0.001), fractional area change (42+/-14% versus 28+/-9%, P<0.0001), and dA/dt (27+/-17% versus 13+/-6%, P<0.0001). Analysis of temporal course of contraction and relaxation (expressed as percentage of the cardiac cycle to adjust for differences in heart rate) showed that the infundibulum follows the RV sinus: onset of contraction 53%+/-14 versus 19+/-11% of systole, time to peak systole 115+/-16% versus 97+/-19% (P< or =0.01), indicating a peristalsis-like pattern of contraction and relaxation. CONCLUSIONS: The results of this study demonstrate significant regional differences between the sinus and infundibulum components of the RV with regard to contribution to stroke volume, extent of fiber shortening, and sequence of mechanical activation. These data from normal individuals can be used in future research on RV function in pathological conditions.
Adolescent↗
Immortalization of rat embryo fibroblasts by a 3'-untranslated region.
We have exploited a cross-species expression screen to search for cellular immortalizing activities. A newt blastemal cDNA expression library was transfected into rat embryo fibroblasts and immortal cell lines were selected. This identified a 1-kb cDNA fragment which has a low representation in the cDNA library and is derived from the 3'-UTR of an alpha-glucosidase-related mRNA. Expression of this sequence in rat embryo fibroblasts has shown that it is active in promoting colony formation and immortalization. It is also able to cooperate with an immortalization-defective deletion mutant of SV40 T antigen, indicating that it can exert its growth-stimulatory activity in the pathway activated by a viral immortalizing oncogene. This is the first example of an immortalizing activity mediated by an RNA sequence, and further analysis of its mechanism should provide new insights into senescence and immortalization.
Animals↗
Rat embryo fibroblasts immortalized with simian virus 40 large T antigen undergo senescence upon its inactivation.
Introduction of simian virus 40 T antigen into rodent fibroblasts gives rise to cells that can proliferate indefinitely but are dependent upon it for maintenance of their growth once the normal mitotic life span has elapsed. Inactivation of T antigen in these immortalized cells causes rapid and irreversible cessation of growth. To determine whether this growth arrest is associated with entry into senescence, we have undertaken a genetic and biological analysis of conditionally immortal (tsa) cell lines derived by immortalizing rat embryo fibroblasts with the thermolabile tsA58 T antigen. This analysis has identified the following parallels between the tsa cells after inactivation of T antigen and senescent rat embryo fibroblasts: (i) growth arrest is irreversible; (ii) it occurs in G1 as well as G2; (iii) the G1 block can be partially overcome by stimulation with 20% fetal calf serum, but the G2 block cannot be overcome; (iv) 20% fetal calf serum induces c-fos, but c-myc is unaltered; and (v) fibronectin and p21(Waf1/Cip1/Sdi1) are upregulated upon growth arrest. These results suggest that T-antigen-immortalized fibroblasts are committed to undergo senescence but are prevented from undergoing this process by T antigen. Inactivation of T antigen removes this block and results in senescence of the cells. Thus, these cell lines may represent a powerful system for study of the molecular basis of entry into senescence.
Animals↗
Health risk appraisal and serum cholesterol nutrition education: an outcome study.
Records of 59 U.S. Army service members identified as at-risk for coronary heart disease were reviewed. Soldiers were divided into groups that completed and did not complete cholesterol nutrition education classes. Differences in the means of repeated cholesterol measures were compared within each group. Results showed statistically significant declines in total cholesterol, with t(35) = 2.94, p < 0.01 for the class completion group and t(22) = 2.18, p < 0.05 for the dropout group. Similar results were noted for low-density lipoprotein measures. However, cholesterol differences in the means between the two groups were not statistically significant. Results indicate that decreases in serum cholesterol may occur due to at-risk reactive behavior, but that full compliance with the current nutrition education program does not appear to further reduce cholesterol levels to any appreciable degree.
Adult↗
Prolongation of RV-PA conduit life span by percutaneous stent implantation. Intermediate-term results.
BACKGROUND: Right ventricle-to-pulmonary artery (RV-PA) homografts and bioprosthetic conduits are commonly used to palliate various types of complex congenital heart disease. These conduits frequently develop progressive obstruction and require surgical replacement. This report reviews our experience implanting balloon-expandable stents to relieve conduit obstruction and delay reoperation. METHODS AND RESULTS: A retrospective review identified 44 patients who underwent placement of 48 stents in obstructed RV-PA conduits. Median patient age was 6.9 years (range, 7 months to 30 years), and median follow-up time was 14.2 months (range, 0 to 48 months). Stent implantation initially decreased the RV-PA pressure gradient from 61.0 +/- 16.9 to 29.7 +/- 11.9 mm Hg (P < or = .001) and the right ventricular-to-systemic arterial pressure ratio from 0.92 +/- 0.17 to 0.63 +/- 0.20 (P < or = .001). The diameter of the stenotic region expanded from 9.3 +/- 3.5 to 12.3 +/- 3.3 mm in the anteroposterior view (P < or = .001) and from 6.6 +/- 2.9 to 10.9 +/- 2.5 mm in the lateral view (P < or = .001). During the follow-up period, 2 patients had their stents redilated, 7 had additional conduit stents deployed, and 14 underwent surgical replacement of their conduits. Actuarial freedom from conduit reoperation was 65% at 30 months postprocedure. Seven patients were found to have fractured stents on follow-up, suggesting an important role for external compressive forces in conduit failure. Recatheterization in 16 patients a median of 11.8 months (3 to 48 months) postprocedure demonstrated hemodynamic evidence of recurrent obstruction despite sustained enlargement at the previously stented sites. Complications included stent displacement (n = 1), bacterial endocarditis (n = 1), and false aneurysm formation (n = 1). One patient died awaiting conduit replacement surgery. CONCLUSIONS: Stent implantation in obstructed RV-PA conduits results in significant immediate hemodynamic and angiographic improvement. In a subgroup of patients, the procedure prolongs conduit life span by several years and increases the interval between conduit reoperations. Recurrent obstruction is caused by external compression and progressive stenosis outside the stented region.
Bioprosthesis↗
Toxicity of pesticides to earthworms in Kentucky bluegrass turf.
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Animals↗
A treadmill-mounted force platform.
Muscle, bone, and tendon forces; the movement of the center of mass, and the spring properties of the body during terrestrial locomotion can be measured using ground-mounted force platforms. These measurements have been extremely time consuming because of the difficulty in obtaining repeatable constant speed trials (particularly with animals). We have overcome this difficulty by mounting a force platform directly under the belt of a motorized treadmill. With this arrangement, vertical force can be recorded from an unlimited number of successive ground contacts in a much shorter time. With this treadmill-mounted force platform it is possible to accurately make the following measurements over the full range of steady speeds and under various perturbations of normal gait: 1) vertical ground reaction force over the course of the contact phase; 2) peak forces in bone, muscle, and tendon; 3) the vertical displacement of the center of mass; and 4) contact time for the limbs. In our treadmill-force platform design, belt forces and frictional forces cause no measurable cross-talk problem. Natural frequency (160 Hz), nonlinearity (less than 5%), and position independence (less than 2%) are all quite acceptable. Motor-caused vibrations are greater than 150 Hz and thus can be easily filtered.
Biomechanical Phenomena↗
Novel features of the plant cytoskeleton.
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Cell Membrane↗