Massive congenital bidirectional coronary arteriovenous malformation presenting with signs and symptoms of congestive heart failure in an adult: a case report and review of the literature.

Congenital anomalies of the coronary arteries are relatively rare. Mostly asymptomatic, however, some can cause problems, as heart failure, myocardial ischemia, and ventricular arrhythmia, and are associated with risk of complications, such as endocarditis and coronary rupture or sudden death. A case of a 69-year-old man with complaints of tiredness, dyspnea, and palpitation due to coronary artery fistula is presented with a review of the literature.

Left main stem disease in a patient with Takayasu's arteritis.

Takayasu's arteritis is a chronic vasculitis of unknown aetiology involving the aorta and its main branches, the pulmonary and coronary tree. Women are affected more often than men (80 to 90% of the cases) with an age onset between 10 and 40 years. This case report demonstrates the limitations of exercise testing and stress echocardiography in diagnosing the extent of coronary artery disease in patients with inflammatory disease in the left main stem coronary artery. (Neth Heart J 2007;15:260-2.).

Coexistence of a bradycardia- and tachycardia-dependent bundle branch block.

Aberrant ventricular conduction is a rare phenomenon as compared with the more frequently occurring antrioventricular conduction disturbances. It leads to widening of the QRS complex, which is either due to a complete or functional block in one of the bundle branches or a block within the intramyocardial conduction system itself. Mechanisms that are potentially involved in the genesis of aberrant ventricular conduction are sudden shortening of cycle length (tachycardia-dependent phase III), antegrade block with retrograde concealed conduction, or bradycardia-dependent block (enhanced phase IV). In this paper, we present a patient with aberrant ventricular conduction with the occurrence of a tachycardia-dependent, as well as a bradycardia-dependent bundle branch block, which is an even rarer phenomenon.

Arrhythmogenic right ventricular dysplasia as a possible cause of sudden cardiac death: a case report and clinical review.

Sudden cardiac death can be described as an unexplained natural death due to a cardiac cause. It occurs within a short period, one hour or less, after onset of symptoms in a person without any prior medical history. Among the many causes of unexplained sudden cardiac death, we would like to specifically discuss arrhythmogenic right ventricular dysplasia as a rare cause in otherwise healthy and usually young individuals.

Conformational analysis of a flexible oligosaccharide using residual dipolar couplings.

We present a new approach to the analysis of the conformational and the motional properties of an oligosaccharide, methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside. The approach relies on an order matrix analysis of residual dipolar couplings in the solution state. By combining a number of different types of couplings, (1)D(CH), (2)D(CH), and D(HH), an order matrix is solved for each ring of the trimannoside. The resulting order parameters indicate the internal motion at the alpha (1,3) linkage to be limited, while significant motion is suggested at the alpha (1,6) linkage. Two structures for the trimannoside were determined by aligning the order tensor principal axes obtained from two different orienting media, bicelles and phage. The very similar conformations at the alpha (1,3) linkage of these two structures confirm that the internal motion at the alpha (1,3) linkage is small and the conformation is a good representation of a single preferred structure. The different conformations at the alpha (1,6) linkage suggest that the motional amplitudes are large and the conformations must be viewed as virtual conformers. Compared with traditional NMR methods, data acquisition is easy and data analysis is straightforward.

Field- and phage-induced dipolar couplings in a homodimeric DNA quadruplex: relative orientation of G.(C-A) triad and G-tetrad motifs and direct determination of C2 symmetry axis orientation.

We present a new NMR procedure for determining the three-dimensional fold of C2-symmetric nucleic acid homodimers that relies on long-range orientational constraints derived from the measurement of two independent sets of residual dipolar couplings under two alignment conditions. The application is demonstrated on an (15)N/(13)C-enriched deoxyoligonucleotide sequence, d(G-G-G-T-T-C-A-G-G), shown previously to dimerize into a quadruplex in solution and form a pair of G.(C-A) triads and G-G-G-G tetrads (G-tetrad) motifs. One-bond (1)H-(15)N ((1)D(NH)) and (1)H-(13)C ((1)D(CH)) residual dipolar couplings have been measured between nuclei in the bases of these motifs using bacteriophage as an ordering medium, and under direct magnetic field alignment (800 MHz). By combining the two dipolar data sets in an order matrix analysis, the orientation of the G.(C-A) triad relative to the G-tetrad within a contiguous monomeric unit can directly be determined, even in the presence of interstrand/intrastrand NOE ambiguity. We further demonstrate that the orientation of the C2-axis of molecular symmetry in the homodimer relative to the G.(C-A) triad and G-tetrad motifs can unambiguously be determined using the two sets of independent dipolar coupling measurements. The three-dimensional fold of the homodimer determined using this procedure is very regular and in excellent agreement with a previously determined high-resolution NOE-based NMR structure, where interstrand/intrastrand NOEs were treated as ambiguous and where noncrystallographic symmetry constraints were implicitly imposed during the structure calculation.

Structural and dynamic analysis of residual dipolar coupling data for proteins.

The measurement of residual dipolar couplings in weakly aligned proteins can potentially provide unique information on their structure and dynamics in the solution state. The challenge is to extract the information of interest from the measurements, which normally reflect a convolution of the structural and dynamic properties. We discuss here a formalism which allows a first order separation of their effects, and thus, a simultaneous extraction of structural and motional parameters from residual dipolar coupling data. We introduce some terminology, namely a generalized degree of order, which is necessary for a meaningful discussion of the effects of motion on residual dipolar coupling measurements. We also illustrate this new methodology using an extensive set of residual dipolar coupling measurements made on (15)N,(13)C-labeled human ubiquitin solvated in a dilute bicelle solution. Our results support a solution structure of ubiquitin which on average agrees well with the X-ray structure (Vijay-Kumar, et al., J. Mol. Biol. 1987, 194, 531--544) for the protein core. However, the data are also consistent with a dynamic model of ubiquitin, exhibiting variable amplitudes, and anisotropy, of internal motions. This work suggests the possibility of primary use of residual dipolar couplings in characterizing both structure and anisotropic internal motions of proteins in the solution state.

Rapid determination of protein folds using residual dipolar couplings.

Over the next few years, various genome projects will sequence many new genes and yield many new gene products. Many of these products will have no known function and little, if any, sequence homology to existing proteins. There is reason to believe that a rapid determination of a protein fold, even at low resolution, can aid in the identification of function and expedite the determination of structure at higher resolution. Recently devised NMR methods of measuring residual dipolar couplings provide one route to the determination of a fold. They do this by allowing the alignment of previously identified secondary structural elements with respect to each other. When combined with constraints involving loops connecting elements or other short-range experimental distance information, a fold is produced. We illustrate this approach to protein fold determination on (15)N-labeled Eschericia coli acyl carrier protein using a limited set of (15)N-(1)H and (1)H-(1)H dipolar couplings. We also illustrate an approach using a more extended set of heteronuclear couplings on a related protein, (13)C, (15)N-labeled NodF protein from Rhizobium leguminosarum.

Variation of molecular alignment as a means of resolving orientational ambiguities in protein structures from dipolar couplings.

Residual dipolar couplings for pairs of proximate magnetic nuclei in macromolecules can easily be measured using high-resolution NMR methods when the molecules are dissolved in dilute liquid crystalline media. The resulting couplings can in principle be used to constrain the relative orientation of molecular fragments in macromolecular systems to build a complete structure. However, determination of relative fragment orientations based on a single set of residual dipolar couplings is inherently hindered by the multi-valued nature of the angular dependence of the dipolar interaction. Even with unlimited dipolar data, this gives rise to a fourfold degeneracy in fragment orientations. In this Communication, we demonstrate a procedure based on an order tensor analysis that completely removes this degeneracy by combining residual dipolar coupling measurements from two alignment media. Application is demonstrated on (15)N-(1)H residual dipolar coupling data acquired on the protein zinc rubredoxin from Clostridium pasteurianum dissolved in two different bicelle media.

Molecular symmetry as an aid to geometry determination in ligand protein complexes.

Dipole-dipole couplings between pairs of spin 12 nuclei, which can be measured from NMR spectra in field-ordered media, offer useful constraints on the orientation of various fragments in molecular systems. However, the orientation of fragments relative to a molecule fixed reference frame is often key to complete structure determination. Here, we demonstrate that the symmetry properties of molecular complexes can aid in the definition of a reference frame. It is shown that a threefold rotational symmetry axis dictates the direction and symmetry of the experimentally determined order tensor for alpha-methyl-mannose in fast exchange among the three symmetry-related binding sites of mannose binding protein. This approach facilitates studies of the geometry of the ligand in the protein-ligand complex and also may provide a novel route to structure determination of a homomultimeric protein.

Residual dipolar coupling derived orientational constraints on ligand geometry in a 53 kDa protein-ligand complex.

The geometric relationships between ligands and the functional groups that bind ligands in soluble ligand-protein complexes have traditionally been deduced from distance constraints between pairs of NMR active nuclei spanning the ligand-protein interface. Frequently, the steep inverse distance dependence of the nuclear Overhauser effect (NOE), from which the distance constraints are derived, makes identification of sufficient numbers of constraints difficult. In these cases the ability to supplement NOE-derived information with distance-independent angular information can be very important. Here, the observation of residual dipolar couplings from alpha-methyl mannose bound to mannose binding-protein in a dilute liquid crystalline medium has allowed the determination of a bound ligand's average orientation. The 3-fold rotational symmetry of mannose-binding protein defines its orientational tensor and obviates the need to determine experimentally the protein's average orientation. Through superimposition of ligand and protein orientational tensors we describe the binding geometry of alpha-methyl mannose bound to mannose-binding protein. This new method is of general applicability to the study of ligands bound to proteins, and it is of particular interest when neither X-ray crystallography nor NOE techniques can provide sufficient information to describe binding geometries.