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PubMed1995

Three-dimensional ultrasound in diagnosing phocomelia.

Deformations of the extremities with limb reduction are rare congenital defects which affect one in 1692 live babies. Three-dimensional ultrasound can be of value in the prenatal diagnosis of such deformities. We present a case of upper phocomelia and congenital thrombocytopenia (TAR syndrome). Visualization of the upper extremities was achieved by three-dimensional ultrasound after surface and volume rendering. This new technique allows imaging not only of surfaces like the fetal skin, but also of internal structures like the fetal skeleton.

Adult↗

PubMed1991

Mutational analysis of leucine 47 in human epidermal growth factor.

Seven site-specific mutants (including changes to other hydrophobic, charged, and heterocyclic amino acids) of leucine 47 of human epidermal growth factor (EGF) were generated by protein engineering and characterized for their activity in three assays: radioreceptor competition binding in membrane fractions, the stimulation of the EGF receptor's tyrosine kinase activity, and the stimulation of thymidine uptake in tissue culture cells. K1/2 (concentration required for half maximum response) values for each of the mutants are reported in the three assays. The results show that the native leucine residue is quite important for EGF activity. Substitutions are tolerated to different degrees, depending upon hydrophobicity and size of the side chain. Substitution with ionic residues led to the most drastic reduction in activity. One-dimensional nuclear magnetic resonance spectroscopy, at physiological pH, of several of the mutants did not detect any major structural perturbations which would account for the loss of activity. The results suggest that the side chain of leucine 47, because of its charge neutrality, size, and hydrophobicity, is highly important, although not absolutely essential for the interaction of EGF with its receptor. A striking finding was the lower (compared with wild type) Vmax values of the mutants in the tyrosine kinase reaction, but these low Vmax mutants, in cell culture experiments, were able to stimulate at high concentrations a growth response equivalent to wild type EGF.

Base Sequence↗

PubMed2005

Analysis and visualization of growth-related and treatment-induced craniofacial changes.

An analysis and visualization of craniofacial shape changes due to growth or orthodontic treatment is presented. The suggested method is based on an adapted Karhunen-Loève decomposition of time-discrete data based on landmarks in lateral X-rays of the skull. It allows for a reduction of the high-dimensional dynamic problem to a few spatial modes representing synchronous components of growth patterns with time-dependent mode coefficients. The growth-related shape changes as well as the orthodontic treatment effects are visualized by overdrawing the underlying shape changes. The results based on this technique give insight into the still controversially discussed question to which degree the craniofacial skeletal structures can be influenced by orthodontic appliances.

Child↗

PubMed2005

Small hippocampal size in cognitively normal subjects with coronary artery disease.

OBJECTIVE: Hippocampal size reduction detected by three-dimensional structural magnetic resonance imaging (3D-MRI) represents an important hallmark of Alzheimer's disease (AD). Recently, epidemiological and neuropathological studies have associated coronary artery disease (CAD) and cardiovascular risk factors with AD. The present study aimed to assess whether small hippocampal size is also a feature of CAD. METHODS: Hippocampal volumes were assessed in 20 men with CAD and 20 healthy matched control subjects by use of 3D-MRI. Subjects with a history of neurological or psychiatric disorder, or signs of cognitive impairment were rigorously excluded. RESULTS: Compared with controls, subjects with CAD had significantly smaller (-14%) hippocampal volumes. Cardiovascular risk factors were not related to hippocampal volumes of CAD subjects. CONCLUSIONS: Our results demonstrate small hippocampal size in CAD subjects without any cognitive impairment. Future studies should clarify whether the annual rate of hippocampal volume loss of persons with CAD is greater than that of healthy individuals and predicts later cognitive decline or dementia.

Causality↗

PubMed2003

A physical model of potassium channel activation: from energy landscape to gating kinetics.

We have developed a method for rapidly computing gating currents from a multiparticle ion channel model. Our approach is appropriate for energy landscapes that can be characterized by a network of well-defined activation pathways with barriers. To illustrate, we represented the gating apparatus of a channel subunit by an interacting pair of charged gating particles. Each particle underwent spatial diffusion along a bistable potential of mean force, with electrostatic forces coupling the two trajectories. After a step in membrane potential, relaxation of the smaller barrier charge led to a time-dependent reduction in the activation barrier of the principal gate charge. The resulting gating current exhibited a rising phase similar to that measured in voltage-dependent ion channels. Reduction of the two-dimensional diffusion landscape to a circular Markov model with four states accurately preserved the time course of gating currents on the slow timescale. A composite system containing four subunits leading to a concerted opening transition was used to fit a series of gating currents from the Shaker potassium channel. We end with a critique of the model with regard to current views on potassium channel structure.

Adaptation, Physiological↗

PubMed2003

Clinical performance of a highly cross-linked polyethylene at two years in total hip arthroplasty: a randomized prospective trial.

We report the 2-year results for a prospective randomized trial comparing highly cross-linked with standard polyethylene in total hip replacements. In our study, 46 hips were available for radiographic analysis at 2- and 3-year follow-up. Femoral bearings were 28-mm cobalt chrome with the polyethylene insert randomly selected at the time of implantation to be highly cross-linked polyethylene (Crossfire; Stryker Howmedica Osteonics, Allendale, NJ) or standard polyethylene (N(2)/Vac, Stryker Howmedica Osteonics). Polyethylene wear rates were measured based on anterior-posterior (AP) and lateral pelvis radiographs at 6 weeks and at yearly intervals using a validated computer-assisted edge-detection method. Wear rates between the 2 groups were compared using the nonparametric Mann-Whitney test at the 95% level. A significant reduction in 2- and 3-dimensional linear wear rates (42% and 50%) was found in the highly cross-linked group (P =.001 and P =.005).

Arthroplasty, Replacement, Hip↗

PubMed2005

Identification and characterization of deamidation sites in the conserved regions of human immunoglobulin gamma antibodies.

Deamidation of asparagine residues of biological pharmaceuticals is a major cause of chemical degradation if the compounds are not formulated and stored appropriately. The mechanism of this nonenzymatic chemical reaction has been studied in great detail; however, the identification of deamidation sites in a given protein remains a challenge. In this study, we identified and characterized all deamidation sites in the conserved region of a recombinant monoclonal antibody. The conserved region of this antibody is shared by all human IgGs with the exception of minor differences in the hinge region. Our high-performance liquid chromatography method could separate the succinimide, isoaspartic, and aspartic acid isoforms of peptide fragments generated using trypsin. Each of the isoforms was unambiguously identified using tandem mass spectrometry. Deamidation at the identified four sites was slow for the intact, folded antibody at accelerated degradation conditions (pH 7.5 and 37 degrees C). Deamidation was enhanced after reduction, alkylation, and tryptic digestion, indicating that the three-dimensional structure of the antibody reduced deamidation. Furthermore, after the reduction, alkylation, and tryptic digestion, only 4 of a possible 25 asparagine residues showed deamidation, demonstrating the effect of the primary amino acid sequence, especially the -1 and +1 amino acids flanking the deamidation site. For instance, the amino acid motifs SNG, ENN, LNG, and LNN were found to be more prone to deamidation, whereas the motifs GNT, TNY, YNP, WNS, SNF, CNV, SNT, WNS, FNW, HNA, FNS, SNK, GNV, HNH, SNY, LNW, SNL, NNF, DNA, GNS, and FNR showed no deamidation. Our findings should help predict deamidation sites in proteins and peptides and help develop deamidation-resistant biological therapeutics.

Amino Acid Sequence↗

PubMed1983

Laws of composition of Bäcklund transformations and the universal form of completely integrable systems in dimensions two and three.

Bäcklund transformations are defined as operations on solutions of a Riemann boundary value problem (vector bundles over P(1)) that add apparent singularities. For solutions of difference and differential linear spectral problems, Bäcklund transformations are presented in explicit form through the Christoffel formula and its generalizations. Identities satisfied by iterations of elementary Bäcklund transformations are represented in the form of the law of addition or as the three-dimensional difference equation of Hirota's type. Matrix two-dimensional isospectral deformation equations are imbedded into three-dimensional scalar systems of Kadomtzev-Petviashvili (law of addition) form. Two-dimensional matrix systems correspond to reductions of Kadomtzev-Petviashvili equations with pseudodifferential operators satisfying algebraic equations.

Journal Article↗

PubMedDate not supplied

Aqueous oxygen attenuation of reperfusion microvascular ischemia in a canine model of myocardial infarction.

Uncorrected microvascular ischemia may contribute to left ventricular impairment during reperfusion after prolonged coronary artery occlusion. Attenuation of such ischemia in microvessels with impaired erythrocyte flow may require delivery of oxygen at high levels in plasma. Intraarterial infusion of aqueous oxygen (AO) can be used in a site specific manner to achieve hyperoxemic levels of oxygenation in the perfusate. With this new approach, the hypothesis was tested that reperfusion microvascular ischemia can be attenuated. After a 90 min coronary balloon occlusion in a canine model, AO hyperoxemic intracoronary perfusion was performed for 90 min after a 30 min period of autoreperfusion. Control groups consisted of normoxemic reperfusion, both passive (autoreperfusion) and active (roller pump). A significant improvement in left ventricular ejection fraction (p < 0.05) at 2 hr of reperfusion was noted only in the AO hyperoxemia group (17 +/- 6% by two dimensional echo), without a significant reduction in the improvement 1 hr after termination of treatment. During AO hyperoxemic perfusion, ECG ST segment isoelectric deviation normalized, and frequency of ventricular premature contractions was significantly reduced, in contrast to the autoreperfusion control group (p < 0.05). Microvascular blood flow, measured as the ischemic/normal left ventricular segment ratio by radiolabeled microspheres immediately after AO hyperoxemic perfusion, was double the value of the autoreperfusion control group at 2 hr of reperfusion (p < 0.05). We conclude that reperfusion microvascular ischemia is attenuated by intracoronary AO hyperoxemic perfusion and acutely improves left ventricular function in this model.

Animals↗

PubMed2000

Ground state of trapped interacting bose-einstein condensates by an explicit imaginary-time algorithm

We show that an explicit time-marching method previously developed for the numerical study of the dynamics of Bose-Einstein condensates can be profitably adapted to the numerical determination of their ground state. After reduction to a one-dimensional model, we first reproduce and test known results on condensates in harmonic traps and then determine the ground state of a condensate in a harmonically bound optical lattice in the range of parameters which are relevant to existing experiments.

Journal Article↗

PubMed2005

Coupled dynamics of voltage and calcium in paced cardiac cells.

We investigate numerically and analytically the coupled dynamics of transmembrane voltage and intracellular calcium cycling in paced cardiac cells using a detailed physiological model, and its reduction to a three-dimensional discrete map. The results provide a theoretical framework to interpret various experimentally observed modes of instability ranging from electromechanically concordant and discordant alternans to quasiperiodic oscillations of voltage and calcium.

Action Potentials↗

PubMed2000

Novel longitudinal mode in the coupled quantum chain compound KCuF3

Inelastic neutron scattering measurements are reported that show a new longitudinal mode in the antiferromagnetically ordered phase of the spin- 1/2 quasi-one-dimensional antiferromagnet KCuF3. This mode signals the crossover from one-dimensional to three-dimensional behavior and indicates a reduction in the ordered spin moment of a spin- 1/2 antiferromagnet. The measurements are compared with recent quantum field theory calculations and are found to be in excellent agreement. A feature of the data not predicted by theory is a damping of the mode by decay processes to the transverse spin-wave branches.

Journal Article↗

PubMed1976

Attrition: possible mechanisms of compensation.

Attrition, or wear of the occlusal surfaces of the teeth, may not only be physiologically normal, but necessary for function. Since occlusal wear must lead to reduction in tooth length, significant dimensional changes in facial morphology are inevitable unless mechanisms exist to compensate for attrition. Secondary dentine formation, alveolar growth, and adaptive changes in the masticatory muscles can provide this compensation, and may be part of a complex system by which an effective level of masticatory function is maintained even when attrition is extreme.

Adult↗

PubMed1988

Identification of pemphigus vulgaris antigen extracted from normal human epidermis and comparison with pemphigus foliaceus antigen.

Immunoprecipitations of cultured keratinocyte extracts have shown that pemphigus vulgaris (PV) sera bind a polypeptide of 210,000 mol wt with disulfide-linked chains of 130,000 and 85,000 mol wt. To identify proteins in normal human skin recognized by PV antibodies, we performed immunoprecipitations of normal human epidermal extracts. All 22 PV sera tested immunoprecipitated a complex of polypeptides (PV complex) of 210,000, 130,000, and 85,000 mol wt, after reduction. One- and two-dimensional gel electrophoresis showed that the 130,000- and 85,000-mol-wt polypeptides of the PV antigen from both cultured keratinocytes and epidermis have identical charges and sizes. In addition to precipitating the PV complex, 14 of 22 PV sera also have antibodies to a calcium-sensitive epitope on a different complex of polypeptides (PF complex) which has previously been shown to be precipitated by all pemphigus foliaceus (PF) sera. The PF complex consists of polypeptides of 260,000, 160,000, 110,000, and 85,000 mol wt. Although the majority of PV sera also precipitate the PF complex, no PF sera precipitate the PV complex. Thus, PV and PF can be absolutely distinguished on a molecular level using the patients' autoantibodies. The PV and PF complexes, although distinct, have certain similarities. The 85,000-mol-wt polypeptide of each is identical. The 160,000-mol wt-peptide of the PF complex and the 130,000-mol-wt peptide of the PV complex have the same isoelectric point and both are capable of disulfide linkage to the 85,000-mol-wt polypeptide. The PV and PF complexes are closely related and may prove important in cell adhesion.

Autoantigens↗

PubMed2000

Congenital absence of a cervical pedicle: report of two cases and review of the literature.

OBJECTIVE AND IMPORTANCE: The congenital absence of a cervical pedicle is a rare clinical entity. Patients with this anomaly tend to present with cervical pain or after a traumatic incident. Initial evaluations with conventional radiography frequently lead to misinterpretation and misguided intervention. We report two cases of absent cervical pedicles and describe the presentation, diagnosis, and treatment of these patients. Moreover, we review the literature on this clinical entity. CLINICAL PRESENTATION: The first patient was a 4-year-old boy who presented with neck pain after falling off a trampoline. His neurological examination did not reveal any focal abnormalities, but radiographs were thought to be consistent with a right, C4-C5, unilateral, jumped facet. The second patient was a 27-year-old woman who presented with severe neck, back, and left upper extremity pain and paresthesias after an alleged incident of spousal abuse. Her neurological examination results were remarkable for left upper extremity weakness and hemibody sensory changes. Conventional radiographs were thought to reveal a left, C3-C4, unilateral, locked facet. INTERVENTION: For both patients, reduction attempts were made with Gardner-Wells tongs and traction. After failure to achieve adequate reduction, evaluations using two-dimensional computed tomography confirmed congenitally absent cervical pedicles. Both patients were ultimately treated conservatively and experienced resolution of their presenting symptoms. CONCLUSION: The congenital absence of a cervical pedicle is a rare entity that is frequently misdiagnosed. Diagnoses can be accurately confirmed with two-dimensional computed tomography. Conservative treatment resulted in successful management of this clinical entity.

Adult↗

PubMed1992

[Evaluation of evoked potential or event-related potential mapping].

Strategies for the evaluation of EP and ERP maps are discussed. Spatial interpolation is presented. The reference does not change the landscape but the wave shapes, the baselines change the landscape but not the wave shapes. Electric strength of the map is assessed using Global Field Power, whereby non-ambivalent component latencies can be established. Map landscapes are compared using Global Dissimilarity. Maps are classified using extracted landscape descriptors: locations of minimal and maximal potential, locations of the centroids of the positive and negative map area, reduction to a three-dimensional model dipole source. Adaptive segmentation into echoes of stable landscape (functional microstates) based on landscape descriptors is discussed. Diagnostic and physiological-functional interpretation of the results ought to be distinguished.

Brain Mapping↗

PubMed1990

[Effect of hemodialysis on hemodynamic assessment and cardiac flows determined by Doppler echocardiography].

25 patients with end-stage renal failure were studied by different echocardiographic techniques before and immediately after hemodialysis using M-mode, 2-dimensional and Doppler echocardiography. Preload reduction after dialysis was manifested by a decrease in body weight, in left atrial diameter and in the left ventricular end-diastolic dimension. Doppler flow patterns immediately after dialysis showed reduction in early diastolic velocities across the atrioventricular valves and increase in the flow velocities across the semilunar valves and the peripheral A-V fistula. The flow velocity integral, calculated by Doppler echocardiography, was lower after dialysis. Significant improvement in left ventricular myocardial function after dialysis was correlated with reduction in afterload and increase in myocardial contractility.

Blood Flow Velocity↗

PubMed1989

New frontiers in the treatment of the trauma victim with facial injuries.

Use of rigid fixation in facial skeletal reconstruction has had a resurgence in popularity. Miniplates and screws to rigidly fix fractures, control occlusal osteotomies, and even congenital craniofacial osteotomies, have revolutionized facial reconstructive surgery. In facial fractures, where restoration of preinjury facial appearance is the goal, rigid fixation has added a new treatment potential, providing immediate three-dimensional stability of the fracture reduction.

Bone Transplantation↗