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Biomedical subjects

A K Wong

Publications and source records attributed to A K Wong.

12 recordsLinked to original sources

A survey of multiple sequence comparison methods.

Multiple sequence comparison refers to the search for similarity in three or more sequences. This article presents a survey of the exhaustive (optimal) and heuristic (possibly sub-optimal) methods developed for the comparison of multiple macromolecular sequences. Emphasis is given to the different approaches of the heuristic methods. Four distance measures derived from information engineering and genetic studies are introduced for the comparison between two alignments of sequences. The use of entropy, which plays a central role in information theory as measures of information, choice and uncertainty, is proposed as a simple measure for the evaluation of the optimality of an alignment in the absence of any a priori knowledge about the structures of the sequences being compared. This article also gives two examples of comparison between alternative alignments of the same set of 5SRNAs as obtained by several different heuristic methods.

Algorithms

Structural remodeling of human myocardial tissue after infarction. Quantification with ultrasonic backscatter.

BACKGROUND: Remodeling of myocardial tissue after infarction may culminate in the development of either a well-healed scar or a thin, expanded heart wall segment that predisposes to ventricular aneurysm formation, congestive heart failure, or ventricular tachycardia. The three-dimensional architecture of mature human infarct tissue and the mechanisms that determine it have not been elucidated. We have previously shown that quantitative ultrasonic backscatter can be used to define the transmural organization of human myofibers in the normal ventricular wall by measuring the dependence of backscatter on the angle of insonification, or ultrasonic anisotropy. We propose that measurement of ultrasonic anisotropy of backscatter may permit quantitative characterization of the transmural architecture of tissue from areas of myocardial infarction and facilitate identification of fundamental mechanisms of remodeling of the ventricular wall. METHODS AND RESULTS: We measured integrated backscatter in 33 transmural sections from 12 cylindrical biopsy specimens (1.4-cm diameter) sampled from central regions of mature infarction in six explanted fixed human hearts. Tissue samples were insonified in two-degree steps around their entire circumference at successive transmural levels with a 5-MHz broad-band piezoelectric transducer. Backscatter radio frequency data were gated from the center of each specimen, and spectral analysis was performed on the gated radio frequency for the computation of integrated backscatter. Histological morphometric analysis was performed on each specimen for determination of the predominant fiber orientation and the percentage of tissue infarcted at consecutive transmural levels. The average percentage of tissue infarcted for all transmural levels was 49 +/- 3% (range, 13-80%). Histological attributes varied from patchy fibrosis to extensive confluent zones of scar tissue. The angle-averaged integrated backscatter for all transmural levels in infarct tissue was approximately 5 dB greater than that previously measured in normal tissue in our laboratory (-48.3 +/- 0.5 versus -53.4 +/- 0.4 dB, infarct versus normal). Marked anisotropy of backscatter was observed in tissue from areas of infarction and was characterized by a sinusoid-like dependence on the angle of insonification at each transmural level. Insonification perpendicular to infarct fibers yielded values for integrated backscatter 14.8 +/- 0.5 dB greater than those for insonification parallel to these fibers. Juxtaposition of the sinusoid-like anisotropy functions from all consecutive transmural levels demonstrated a progressive shift in the orientation of scar tissue elements from epicardial to endocardial levels of 14.6 +/- 1.5 degrees/mm of tissue. The transmural shift in fiber orientation per millimeter of tissue from the area of infarction exceeded that previously measured for normal tissue (9.2 +/- 0.7 degrees/mm) by 59%. This marked augmentation in angular shift per millimeter of tissue results from a generalized structural rearrangement (or reorientation) of fibers across the entire ventricular wall in the infarct zone that we hypothesize is determined in part by dynamic mechanical forces, imposed by the surrounding functional normal tissue, that tether the "infarcted" tissue. CONCLUSIONS: Myocardial tissue from areas of myocardial infarction manifests substantial anisotropy of ultrasonic scattering that may be useful for quantitative characterization of the alignment and overall three-dimensional anatomic organization of mature infarct scars.

Biopsy

Detection of unique transmural architecture of human idiopathic cardiomyopathy by ultrasonic tissue characterization.

BACKGROUND: Noninvasive approaches to the evaluation of idiopathic cardiomyopathy are limited. Recent work from our laboratory has used quantitative ultrasound to define the three-dimensional structure of normal human myocardium and the myocardial remodeling associated with infarction. Our goal was to define the role of ultrasonic tissue characterization for detection of specific alterations in the three-dimensional transmural architecture of idiopathic dilated cardiomyopathy. METHODS AND RESULTS: We measured frequency-dependent backscatter from 22 cylindrical biopsy specimens from nine explanted fixed hearts of patients who underwent heart transplantation for idiopathic cardiomyopathy, seven specimens from normal portions, and 12 specimens of infarcted tissue from six explanted fixed human hearts. Consecutive transmural levels from each specimen were insonified with a 5-MHz broadband transducer. The dependence of apparent (uncompensated for attenuation) backscatter, B(f), on frequency (f) was computed from radiofrequency (rf) data as: magnitude of B(f)2 = afn, where n is an index that reflects in part the size of the dominant scatterers in myocardial tissue. Myofiber diameter and percentage fibrosis were determined at each transmural level for each specimen. For cardiomyopathic tissue, the frequency dependence of backscatter (n) increased progressively from epicardial to endocardial (0.02 +/- 0.37 to 1.01 +/- 0.12, p less than 0.05) levels in conjunction with a progressive decrease in myofiber diameter (29.5 +/- 0.9 to 21.4 +/- 0.6 microns, p less than 0.0001). In contrast, in tissue from areas of infarction, the frequency dependence decreased progressively from epicardium to endocardium (0.91 +/- 0.20 to 0.23 +/- 0.21, p less than 0.05) in conjunction with a progressive increase in the percentage of fibrosis (23.5 +/- 9.4% to 54.5 +/- 4.9%, p less than 0.005). Normal tissue exhibited no significant transmural trend for frequency dependence, myofiber diameter, or percentage fibrosis. CONCLUSIONS: These data indicate the presence of a heterogenous transmural distribution of scattering structures associated with human idiopathic cardiomyopathy and myocardial infarction that may be detected by ultrasonic tissue characterization. The divergence of these transmural trends for frequency dependence of backscatter reflects distinct mechanisms of structural heterogeneity for different pathological processes that comprise a transmural gradation of cell size and fibrosis for idiopathic cardiomyopathy and infarction, respectively.

Cardiomyopathies

Identification of novel single-stranded d(TC)n binding proteins in several mammalian species.

A group of single-stranded d(TC)n specific binding proteins has been detected in the nuclear extracts of several mammalian species that included mouse, human, African green monkey, chimpanzee, and Chinese muntjac. Southwestern analysis of 500 mM KCI nuclear extracts has shown that these proteins cluster in a similar size range, 55.5 to 57 kD. An additional 54 kD band was present for the three primate species examined. The single-stranded d(TC)n binding activity was confirmed with bandshift assay. Specific double-stranded binding activity for duplex d(TC)n.d(GA)n or single-stranded d(GA)n was not detected. The conservation of size distribution and d(TC)n-binding activity across the species examined indicates that this class of single-stranded binding proteins may have an important biological function in vivo.

Animals

Isolated atrial infarction in a patients with single vessel disease of the sinus node artery.

Atrial infarction is found in approximately 17 percent of autopsy-proven cases of myocardial infarction, but is a frequently missed clinical diagnosis. The antemortem diagnosis of atrial infarction occurring in the absence of ventricular infarction has not been previously reported. We present a patient with ischemic chest discomfort associated with paroxysmal atrial fibrillation. Electrocardiographic and enzymatic changes were consistent with atrial infarction. Cardiac catheterization demonstrated single vessel critical stenosis at the origin of the sinus node artery. Combined atrial and ventricular infarction occurs frequently and should be considered in the setting of paroxysmal supraventricular arrhythmias occurring early in the course of ventricular myocardial infarction. Lone atrial infarction is a rare but distinct clinical entity. The tetrad of typical ischemic chest discomfort, paroxysmal supraventricular arrhythmia, P-Ta segment shifts, and elevated cardiac enzyme levels without evidence for ventricular infarction strongly suggests isolated atrial infarction.

Aged

Longer, healthier and happier lives.

In Singapore an effort is being made to keep elderly people physically and mentally fit for as long as possible so that they can maintain their normal daily activities and living arrangements. In order to care for the growing proportion of older people both humanely and in a manner that society can afford, measures are being taken to encourage the revival of the extended family system whereby the elderly reside with their younger relatives. The placing of older people in institutions is being kept to a minimum, partly because they prefer to live with their children and partly because special homes are very expensive.

Aged

Distribution of CT-rich tracts is conserved in vertebrate chromosomes.

The distribution of d(CT)-rich pyrimidine tracts in the karyotypes of a variety of vertebrates was studied by in situ hybridization. The probe for these studies was a 56bp homopyrimidine/homopurine sequence obtained from a mouse genomic library constructed with DNA prepared from a restriction enzyme digestion of metaphase chromosomes. Single-stranded DNA nuclease digestions and two-dimensional gel analysis of topoisomers of this sequence indicated that it is capable of adopting a triplex conformation in vitro. In situ hybridization with this probe to the karyotypes of ten different vertebrate species revealed a highly conserved chromosomal distribution of d(CT)-rich tracts. These tracts are found throughout the chromosomal arms and in some karyotypes they are clustered, producing a banding pattern. However, at the resolution of the light microscope these tracts appeared to be absent from the centromeric regions of all chromosomes examined except those of chicken. The non-random distribution of these tracts to the chromosomal arm regions implies an organizational or functional role for this repeat class. It is unlikely that the 56 bp sequence type contributed to the formation of the triplex DNA structure previously detected in centromeric domains of mouse.

Animals

Relationship between myocardial metabolites and contractile abnormalities during graded regional ischemia. Phosphorus-31 nuclear magnetic resonance studies of porcine myocardium in vivo.

The mechanisms responsible for changes in myocardial contractility during regional ischemia are unknown. Since changes in high-energy phosphates during ischemia are sensitive to reductions in myocardial blood flow, it was hypothesized that myocardial function under steady-state conditions of graded regional ischemia is closely related to changes in myocardial high-energy phosphates. Therefore, phosphorus-31 nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements of regional subendocardial blood flow, high-energy phosphates, pH, and myocardial segment shortening were made during various degrees of regional ischemia in which subendocardial blood flow was reduced by 16-94%. During mild reductions in myocardial blood flow (subendocardial blood flow = 83% of nonischemic myocardium), only the ratio of phosphocreatine to inorganic phosphate (PCr/Pi), Pi, and [H+] were significantly changed from control. PCr, ATP, and PCr/ATP were not significantly reduced from control with mild reductions in blood flow. Changes in myocardial segment shortening were most closely associated with changes in PCr/Pi (r = 0.94). Pi and [H+] were negatively correlated with segment shortening (r = -0.64 and -0.58, respectively) and increased over twofold when blood flow was reduced by 62%. Thus, these data demonstrate that PCr/Pi is sensitive to reductions in myocardial blood flow and closely correlates with changes in myocardial function. These data are also consistent with a role for Pi or H+ as inhibitors of myocardial contractility during ischemia.

Adenosine Triphosphate

Orthodontic elastic materials.

Latex elastics and synthetic elastomers have certain similarities and differences. In the fracture tests the latex elastics showed a greater amount of loss in strength than plastic elastomers when stretched over a 21 day period. There is a great variability, as much as 50%, in the tensile strength of the plastic materials taken from the same batch and stretched under the same conditions. The Ormco Power Chain was more resilient than the Unitek AlastiK chain. The Unitek AlastiKs had more force and stretched less. The force decay of synthetic elastomers, stretched over a specific length and time, exhibited a great loss in force. This loss could be as great as 73% during the first day. The decay of force continued at a slower rate during the rest of the 21 day period. Unitek AlastiK C2 double links, when stretched 17 millimeters, had a higher initial force averaging 641 grams (22.5 ounces) than the Ormco Power Chain which averages 342 grams (12.0 ounces). In one day the force was reduced to 171 grams (6.0 ounces) for both materials. The elastic materials within the same batch showed a great variation in the modulus of elasticity under different test conditions. The approximate force generated when stretched dry, within the elastic limit, was 22 grams per millimeter for 3/16 inches heavy latex elastics. The Unitek AlastiK C2 gave a force of 89 grams per millimeter, while the Ormco Power Chain had a value of 46 grams per millimeter. The modulus of elasticity of all of the materials was much lower after immersion in the water bath. The force decay under constant force application to latex, elastic, polymer chains, and tied loops showed that the greatest amount of force decay occurred during the first three hours in the water bath. The forces remained relatively the same throughout the rest of the test period. The elastic materials undergo permanent deformation in shape. The synthetic elastomers exhibited plastic deformation when the elastomers were stretched 17 millimeters for 21 days. In the dry condition the force decay was 63% for the Unitek chains and 42% for the Ormco Power Chain. The synthetic elastomers should be prestretched before being placed in the mouth. The elastomers should be used within their resilient ranges. Clinical treatment procedures should take into consideration the rapid initial force decay of elastic materials that occurs during the first day and the residual forces remaining.

Elasticity