Mechanomyographic and electromyographic amplitude and frequency responses from the superficial quadriceps femoris muscles during maximal,eccentric isokinetic muscle actions

The purposes of this study were to examine the effects of gender and muscle (vastus lateralis = VL, rectus femoris = RF, and vastus medialis = VM) on the velocity-related patterns for peak torque (PT), mean power output (MP), mechanomyographic (MMG) amplitude, electromyographic (EMG) amplitude, MMG mean power frequency (MPF), and EMG MPF during maximal, eccentric isokinetic muscle actions. Thirteen females (mean +/- SD age = 21 +/- 1 years) and eleven males (mean +/- SD age = 21 +/- 2 years) volunteered for this investigation. PT and MP were measured on a calibrated Cybex 6000 dynamometer at randomly ordered velocities of 60, 120, and 180 degrees.s-1, while MMG and EMG signals were recorded simultaneously from the VL, RF, and VM muscles. The results indicated no gender-related differences for the patterns of PT, MP, MMG amplitude, EMG amplitude, MMG MPF, or EMG MPF. Furthermore, no muscle-related differences were found for the patterns of MMG amplitude, EMG amplitude, or MMG MPF. The normalized values for MP and MMG amplitude increased from 60 to 180 degrees.s-1 (60 degrees.s-1 < 120 degrees.s-1 < 180 degrees.s-1). PT and EMG MPF remained unchanged across velocity, while EMG amplitude remained unchanged from 60 to 120 degrees.s-1, but decreased (approximately 10%) from 120 to 180 degrees.s-1. The findings indicated a close association between the patterns for MP and MMG amplitude, and a similarity between the patterns for PT, EMG amplitude, and EMG MPF across velocity. Therefore, the present findings suggested that motor unit recruitment (EMG amplitude), firing rate (MMG MPF), and muscle fiber action potential conduction velocity (EMG MPF) exhibited velocity-related patterns that were similar to PT production, while MMG amplitude was more closely associated with MP.     

Microcomputer Automated System for Measuring Systolic Time Intervals in Response to Exercise and a Psychophysiological Task

A microcomputer automated system for measuring systolic time intervals is described. Electrocardiogram, phonocardiogram, and carotid pulse tracings were measured in 38 healthy male subjects during baseline conditions and during either exercise on a bicycle ergometer or a video-game task. These measurements were recorded on both a traditional 3-channel ECG recorder and the computerized system. Both methods of recording systolic time intervals were independently scored by two different experimenters. In this way, interrater reliability of hand-scoring, intermethod reliability between hand-scoring versus computer-scoring, and interrater reliability of computer-scoring could be assessed. The interrater reliabilities of hand-scored systolic time intervals were generally above .90, ranging from .73 for left ventricular ejection time to .99 for R-R intervals of the ECG, with a mean of .92. The intermethod reliability of the computer versus hand-scored systolic time intervals also proved to be generally above .90, ranging from .76 for S1-S2 components of the phonocardiogram to .99 for R-R, with a mean of .94. The interrater reliabilities of the computer-scored systolic time intervals were all above .90, ranging from .93 for S1-S2 to .99 for R-R, with a mean of .98. These data indicate that the computerized method of scoring systolic time intervals is at least as reliable as the more traditional scoring of paper tracing.     

Dynamic responses of oxygen uptake at the onset and end of moderate and heavy exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in VO2 are found in the literature. Therefore the purpose of this study was to examine VO2 on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (VT) intensities. VO2 kinetics in exercise and recovery were better described by a single exponential model (VT). For moderate exercise, we found a symmetry of VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (VT). Our results do not support a dynamically linear system model of VO2 during cycling exercise in the heavy-intensity domain.     

Expression of VE-cadherin in zebrafish embryos: a new tool to evaluate vascular development.

We have identified the zebrafish homologue of VE-cadherin and documented its expression in the developing vascular system. The zebrafish VE-cadherin gene is specifically expressed in the vascular endothelial cell lineage beginning with the differentiation and migration of angioblasts and persists throughout vasculogenesis, angiogenesis, and endocardium development. Staining zebrafish embryos by whole-mount in situ hybridization with the VE-cadherin probe provides a method to screen embryos for vascular defects. To illustrate this utility, we used VE-cadherin expression to demonstrate a conservation of vascular endothelial growth factor-A (VEGF-A) function. The morpholino antisense oligonucleotide knockdown of VEGF-A function in zebrafish embryos results in a loss of angiogenic blood vessels, as indicated by the lack of VE-cadherin expression in the intersegmental vasculature. This loss can be restored in embryos supplemented with either zebrafish or human VEGF-A, the latter indicating that genes crucial to angiogenesis have highly conserved functional activities in vertebrates.     

Pathobiology of familial hypercholesterolemic atherosclerosis

Many factors play a role in the development of atherosclerotic lesions. One of the leading risk factors for development of atherosclerosis is familial hypercholesterolemia (FH). FH is a genetic disease characterized by a deficiency, and/or mutation, of receptors for low density lipoprotein (LDL) on the plasmalemma of endothelial cells (EC), a high level of low density lipoprotein in the plasma, and early, spontaneous development of atherosclerosis and skin xanthoma. In this review we describe Watanabe heritable hyperlipidemic (WHHL) rabbits, which represent such an animal model for human FH. This strain of the rabbits is characterized by a genetic deficiency or mutation of functional LDL receptors and develops severe atherosclerosis, which is pathologically similar to familial homozygous hyperlipidemic patients. The most completely characterized animal model is the Watanabe rabbit, a model of homozygous and heterozygous type IIa hypercholesterolemia related to an LDL receptor deficiency. Additional manipulation such as aortic injury in this rabbit model induces the development of atherosclerotic lesions that are structurally similar to those found in humans. Thus, this model of hypercholesterolemia fulfils the above criteria set, i.e. it is able to provide new insights for a better understanding of the pathogenesis of atherosclerosis and for testing new treatment strategies.     

Trypanosoma cruzi antigen that interacts with the beta1-adrenergic receptor and modifies myocardial contractile activity

Previously, we have demonstrated that plasma membranes from the parasite Trypanosoma cruzi (T. cruzi) recognize and adhere to host cells through parasite surface attachment molecules that have affinity for beta(1)-adrenergic receptors (beta(1)-ARs) on target organs. In this report we identify a parasite protein that not only interacts with beta(1)-ARs, but also displays beta-agonist-like activity. We demonstrate that a recombinant maltose binding protein fusion of Tc13 Tul (MBP-Tc13 Tul), a member of the T. cruzi antigen 13 family of surface antigen proteins, competes for binding sites with the beta-adrenergic receptor antagonist [125I]-CYP on membranes purified both from CHO cells expressing human beta(1)-ARs and from rat atria. The competition is prevented by pre-treating MBP-Tc13 Tul with antibodies directed against the EPKSA repeat domain of Tc13 Tul, implicating this portion of the molecule in binding to the beta(1)-AR. Furthermore, MBP-Tc13 Tul activates rat myocardial beta(1)-ARs, resulting in synthesis of cyclic adenosine monophosphate (cAMP) and an increase in cardiac contractility. These biological effects are selectively suppressed by the beta(1)-AR antagonist atenolol, by a synthetic peptide corresponding to the second extracellular loop of the human beta(1)-AR, and by the anti-EPKSA repeat antibodies. These results imply that the Tc13 Tul cell-surface antigen of T. cruzi plays a central role in misregulating the beta(1)-AR following parasite infection, and may be a causative factor of dysautonomic syndrome described in Chagas' disease.     

A quantitative approach to the design of antitumor drug dosage schedule via cell cycle kinetics and systems theory

A discrete-time kinetic model for chemotherapy was developed to deal with the effects of antitumor drugs on the cell cycle and proliferation kinetics of experimental tumor cell populations in which cell kinetic responses of chemotherapy are represented in terms of perturbation of cell kinetic parameters—cell age, cell size and DNA content distributions. The time-course behavior of these cell kinetic parameters was predicted by solving the discrete-time state equations which characterize the dynamics of tumor-drug interactions. The amount of antitumor drug administered was expressed to be the control function of the state equations and the transition matrix representing two modes of drug action, namely, cell kill and progression delay or accumulation of cells due to drug, was derived. The performance of the model, assessed by examining the effects of cell cycle stage-specific agents such as cytosine arabinoside on spontaneous AKR leukemia, compared favorably with experimental data. Utilizing an optimization scheme in engineering systems studies, an analytical method is described for optimizing the regimen of drug administration so as to maximize the effectiveness of drug dosage schedules and minimize the use of toxic amounts of the drug. The superiority of the schedule designed by an optimization scheme was evident at the termination of therapy, although the schedule designed by experimental trials reduced the number of surviving tumor cells more effectively than the one designed by an optimization scheme during the earlier therapy period. In the model, the proposed schedule will function more effectively for the entire therapy period when additional parameters of drug characteristics, such as the toxicity to the host and drug resistance, are encompassed.     

Coxsackievirus infection of the pancreas: evaluation of receptor expression, pathogenesis, and immunopathology

Coxsackievirus type B (CVB) infection of the pancreas induces a massive cellular infiltrate composed of natural killer cells, T cells, and macrophages and leads to the destruction of exocrine tissue. The physiological manifestations of pancreatic CVB infection are correlated with viral tropism; the virus infects acinar cells but spares the islets of Langerhans. Here we evaluate the mechanisms underlying pancreatic inflammation and destruction and identify the determinants of viral tropism. T-cell-mediated immunopathology has been invoked, along with direct virus-mediated cytopathicity, to explain certain aspects of CVB-induced pancreatic disease. However, we show here that in the pancreas, the extent of inflammation and tissue destruction appears unaltered in the absence of the cytolytic protein perforin; these findings exclude any requirement for perforin-mediated lysis by natural killer cells or cytotoxic T cells in CVB3-induced pancreatic damage. Furthermore, perforin-mediated cytotoxic T-cell activity does not contribute to the control of CVB infection in this organ. In addition, we demonstrate that the recently identified coxsackie-adenovirus receptor is expressed at high levels in acinar cells but is barely detectable in islets, which is consistent with its being a major determinant of virus tropism and, therefore, of disease. However, further studies using various cell lines of pancreatic origin reveal secondary determinants of virus tropism.