Distributed moment histogram: a neurophysiology based method of agonist and antagonist trunk muscle activity prediction

A neurocortical-based technique of muscle recruitment is presented to solve the muscle indeterminacy problem for lumbar torso modeling. Cortical recordings from behaving primates have established motor cortex cells that respond to a wide range of task directions, but are tuned to a preferred direction. A characteristic activity pattern of these neurons seems to be associated with effort direction. It was hypothesized that a model which recruits muscles based on a similar distribution would predict antagonistic muscle activity with greater realism than a widely referenced optimization formulation. The predictions of the Distributed Moment Histogram (DMH) method were evaluated under common speed (< 30 degrees s-1) sagittal plane lifting conditions using five subjects. The predicted forces showed high correspondence with agonist and antagonist myoelectric patterns. The mean coefficient of determination for the erector spinae was r2 = 0.91, and 0.41 for the latissimus. For the antagonistic muscles, the rectus abdominus was found to be electrically silent (< 3% MVC) and no activity was predicted by the method. The external oblique muscle was observed to be minimally active (< 16% MVC), and the DMH method predicted its mostly constant activity with a mean standard error of 1.6% MVC. The realistic antagonistic predictions supported the hypothesis and justify this cortical based technique as an alternative for muscle tension estimation in biomechanical torso modeling. A primary advantage of this method is its computational simplicity and direct physiologic analog.     

Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish

The structure of the human glutaryl coenzyme A dehydrogenase (GCD) gene was determined to contain 11 exons and to span approximately 7 kb. Fibroblast DNA from 64 unrelated glutaric acidemia type I (GA1) patients was screened for mutations by PCR amplification and analysis of SSCP. Fragments with altered electrophoretic mobility were subcloned and sequenced to detect mutations that caused GA1. This report describes the structure of the GCD gene, as well as point mutations and polymorphisms found in 7 of its 11 exons. Several mutations were found in more than one patient, but no one prevalent mutation was detected in the general population. As expected from pedigree analysis, a single mutant allele causes GA1 in the Old Order Amish of Lancaster County, Pennsylvania. Several mutations have been expressed in Escherichia coli, and all produce diminished enzyme activity. Reduced activity in GCD encoded by the A421V mutation in the Amish may be due to impaired association of enzyme subunits.     

cDNA cloning of a chick homologue of human ATPase complex subunit 4, quantitative tissue distribution and tertiary structure comparison of the ATPase domain to RecA

The ocular lens consists of a single layer of epithelial cells on its anterior surface and underlying fiber cells, which are derived from the epithelial cells by differentiation and make up the bulk of the lens. Because lens cells are segregated by age and stage of differentiation, we are using this tissue to study the role of the proteasome in differentiation. The purpose of this study is to corroborate the ATPase function of chick subunit 4 (cS4) and assess the levels of the mRNA in the differentiating lens relative to other tissues. We have generated a computer model of the tertiary structure of the ATPase domain of the cS4 of the ATPase complex that regulates the 20S proteasome. The predicted polypeptide from the cloned cDNA of cS4 (440 residues) had a calculated molecular mass of 49,182 and is 98 and 73% identical to human and yeast S4 protein sequences, respectively. A computer search for comparison with known proteins in GenBank showed that the cS4 protein sequence has a conserved region of about 200 amino acid residues including an ATP/GTP binding site and a mitochondrial energy transfer proteins signature sequence. Based on secondary structure, the computer-generated model of the ATPase domain is comparable to that of RecA, with a root mean square deviation of 0.851 from the RecA triad. mRNA in the 14-day-old chick embryo lens is derived primarily (90%) from differentiating cells. The level of cS4 mRNA determined by quantitative RT/PCR in this differentiating tissue was comparable to the cS4 mRNA levels in chick liver, heart, and brain.     

Non-disjunction in human sperm: results of fluorescence in situ hybridization studies using two and three probes

Fluorescence in situ hybridization using two or three probes was utilized to estimate the incidence of diploidy, the incidence of disomy for the sex chromosomes and chromosomes 16 and 18, and the proportion of Y- and X-chromosome bearing sperm, in a series of normal males. Our results demonstrate the importance of using an approach capable of distinguishing disomy from diploidy, as most donors had levels of diploidy higher than the disomy levels of individual chromosomes. Our analyses suggest the existence of chromosome-specific mechanisms of paternal non-disjunction, as sex chromosome disomy was approximately 1.5 times as common as disomy 16, and over two times as common as disomy 18. In studies of gametic sex ratio, we found little evidence for marked deviation from an expected 1:1 ratio.     

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. III. Alterations in B-cell function and viability

The major goal of the study was to determine the effects of high and low levels of mercury on human B-cells. Following treatment of B-cells with HgCl2 (0-1000 ng) and MeHgCl2 (0-100 ng), their activation by mitogens was evaluated. Both forms of mercury caused a dose dependent reduction in B-cell proliferation in the presence or absence of monocytes. MeHgCl was approximately 10 times more potent than HgCl2. Mercury also inhibited the ability of these cells to synthesize IgM and IgG. Analysis of the expression of activation markers indicated that CD69, an early marker of cell activation, was not effected by mercury. In comparison, B-cell expression of the low affinity IgE receptor and the transferrin receptor were significantly reduced. Of particular interest, cells activated by mitogen for 48 hr became refractory to the immunotoxic effects of mercury. When exposed to high levels of HgCl2 (0.5-10 micrograms/ml) and MeHgCl (0.05-1 micrograms/ml), there was minimal reduction in B-cell viability at 1-4 hr, however, after exposure to mercury for 24 hr, cell death was apparent. MeHgCl was approximately 5-10 times more potent than HgCl2. Electron microscopic analysis revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation and condensation of nucleoplasm. Both forms of mercury caused a rapid and sustained elevation in the intracellular levels of Ca++. The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in B-cell function indicates that this metal is immunotoxic at very low exposure levels. Furthermore, the cytotoxic events are consistent with the notion that mercury initiates changes associated with programmed cell death.