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Biomedical subjects

R D Cox

Publications and source records attributed to R D Cox.

At least 55 records · Page 3Linked to original sources

Aggression and self-injurious behaviors in persons with autism--the TEACCH (Treatment and Education of Autistic and related Communications Handicapped Children) approach.

Aggression and self injurious behaviors are associated with some clients with autism and other forms of pervasive developmental disorder. These behaviors are not well understood, and treatment interventions are often ineffective. This article describes these behaviors in terms of the underlying deficits of autism, suggesting that interventions may be more effective if targeted at the underlying causes of the actions. The article presents behaviors and underlying causes within an "iceberg" conceptualization with visible behaviors depicted as occurring "above the water line" and hypothesized causes hidden "below the water line" of the iceberg. Examples of clinical cases are presented to illustrate the usefulness of the conceptualization.

Adolescent↗

Actin and myosin genes are transcriptionally regulated during mouse skeletal muscle development.

During primary and secondary myotube formation in utero and subsequent maturation of muscle fibers after birth there are complex changes in the pattern of contractile protein gene expression at the RNA and protein levels. In order to determine the degree of transcriptional regulation of actin and myosin genes we have carried out "nuclear run-on" experiments using nuclei prepared from the limb muscle of mice at 14.5, 15.5, 17.5, and 18.5 days in utero and at 10-12 and 12.5 days after birth. We show that transitions in the expression of these genes in vivo are regulated transcriptionally. Transcription of the sarcomeric alpha-actins changes from cardiac to predominantly skeletal actin over this time period; transcription of the beta-actin gene is repressed. The myosin heavy chain and myosin light chain genes also undergo transcriptional transitions during muscle development. Notably, transcription from the MLC3F promoter is activated after that of the MLC1F promoter, which is part of the same gene. These results are discussed in the context of published RNA data.

Actins↗

Three linked myosin heavy chain genes clustered within 370 kb of each other show independent transcriptional and post-transcriptional regulation during differentiation of a mouse muscle cell line.

We have examined myosin heavy chain gene transcription in the mouse muscle cell line C2/7 under different culture conditions. Gene-specific probes for embryonic (MHCemb), perinatal (MHCpn), and adult (MHCIIB) MHC sequences were used in nuclear run-on experiments, and transcriptional levels compared with cytoplasmic RNA accumulation of the transcripts during muscle cell differentiation. Transcripts are not detectable in myoblasts. These three MHC genes are physically linked within 370 kb of each other. However, they are not activated coordinately, but show independent transcriptional regulation as muscle cells differentiate into myotubes and as myotubes mature in culture. Post-transcriptional mechanisms also regulate cytoplasmic RNA accumulation of these MHC genes.

Animals↗

Interspersed repetitive element polymerase chain reaction product mapping using a mouse interspecific backcross.

We have developed a rapid method of generating and simultaneously mapping interrepeat polymerase chain reaction products using DNA from interspecific backcross animals derived from mating C57BL/6J and Mus spretus mice. This method is based on the high degree of B1, B2, and L1 dispersed repeat position polymorphism found between these two species of mouse. We have mapped 13 new loci to 9 different chromosomes and have found no evidence of clustering among these loci. The advantages of this approach are that no prior knowledge of sequence is required, a single PCR reaction generates many markers which can be mapped simultaneously, and only 50 ng of each backcross DNA (a finite resource) is required. We anticipate that many more markers remain to be characterized in this valuable new source of polymorphism.

Animals↗

Adaptation of the interspersed repetitive sequence polymerase chain reaction to the isolation of mouse DNA probes from somatic cell hybrids on a hamster background.

A strategy for the rapid isolation of DNA probes from radiation-fusion Chinese hamster cell hybrids containing overlapping portions of the murine X chromosome based on the interspersed repetitive sequence polymerase chain reaction (IRS-PCR) previously used with human somatic cell hybrids has been developed. This specific amplification of mouse DNA on a hamster background depends on the use of primers directed to the B2 short interspersed repeat element family and the R repeat, from the long interspersed repeat element family, L1. Two sets of amplification conditions, which gave specific amplification of mouse DNA from either a mouse X-monochromosomal hybrid or irradiation-fusion hybrids having reduced X content, were defined. The mouse X-only chromosome hybrid yielded approximately 20 discrete reproducible bands, while the irradiation-fusion hybrids yielded between 1 and 10 discrete products. Comparison of different irradiation-fusion hybrids has allowed the definition of both specific and shared products corresponding to different regions within the overlapping X-chromosome fragments present within these hybrids. Use of such hybrids and the IRS-PCR technique has allowed the isolation of probes corresponding to the central region of the mouse X chromosome that contains the X-inactivation center. The method should be widely applicable to the isolation of mouse DNA sequences from mouse hybrid cell lines on either human or Chinese hamster backgrounds.

Animals↗

Transcriptional regulation of actin and myosin genes during differentiation of a mouse muscle cell line.

During terminal differentiation of skeletal muscle cells in vitro there is a transition from a predominantly nonmuscle contractile protein phenotype to a sarcomeric contractile protein phenotype. In order to investigate whether this transition and subsequent changes in expression are primarily transcriptionally regulated, we have analysed the rate of transcription and level of corresponding RNA accumulation of actin and myosin light chain genes during differentiation of a mouse muscle cell line under different culture conditions (low-serum and serum-free). We have found by 'nuclear run-on' analysis, that the alpha-cardiac actin, alpha-skeletal actin, myosin light chain 1F/3F and embryonic myosin light chain genes are transcriptionally activated as myoblasts begin to fuse to form myotubes. In contrast the nonsarcomeric beta-actin gene is transcribed at high levels in myoblasts and is transcriptionally down-regulated during differentiation. There is a sequential transition in transcription and RNA accumulation from predominantly alpha-cardiac to predominantly alpha-skeletal actin during subsequent myotube maturation, which reflects the pattern of expression found during development in vivo. A similar transition from embryonic to adult patterns of myosin light chain expression does not occur. RNA accumulation of actin and myosin light chains is regulated at both transcriptional and post-transcriptional levels. In our culture system the expression of myosin light chains 1F and 3F, which are encoded by a single gene, is uncoupled, 3F predominating. These data are discussed in the context of gene regulation mechanisms.

Actins↗

Human muscle neural cell adhesion molecule (N-CAM): identification of a muscle-specific sequence in the extracellular domain.

cDNA clones encoding neural cell adhesion molecule (N-CAM) mRNAs of 6.7, 5.2, and 4.3 kb from human skeletal muscle cells were isolated. A 6.7 kb mRNA encodes a transmembrane N-CAM isoform, present predominantly in mononucleate myoblasts, that shows sequence homology with chick brain N-CAM-140 and is down-regulated during myotube formation. In contrast, the 5.2 and 4.3 kb mRNAs encode nontransmembrane N-CAM isoforms that greatly increase during myoblast fusion. Furthermore, a discrete muscle-specific sequence domain (MSD1) was detected in the extracellular coding regions of the 5.2 and 4.3 kb mRNAs. This encodes a unique run of 37 amino acids and is not expressed in 7.2 and 6.7 kb mRNAs from human or chick brain or in the corresponding 6.7 kb muscle transcript. The MSD1 is also absent from chick and mouse brain mRNAs of 4.0 and 2.9 kb. These results show that diversity in N-CAM primary structure can be found in the extracellular domain in a tissue-specific manner.

Amino Acid Sequence↗

Therapeutic model for experimental spinal cord injury in the rat: I. Mortality and motor deficit.

In the course of establishing a therapeutic model for experimental spinal cord injury in the rat, we determined the effects of trauma dose (20, 30, 40, 50, and 60 g-cm) on the mortality and motor deficit in the 4 weeks following injury. Mortality was dependent upon the trauma dose: 20 g-cm, 11%; 30 g-cm, 14%; 40 g-cm, 27%; 50 g-cm, 32%; 60 g-cm, 41%. Statistical analysis by linear regression is highly significant for increasing mortality with increasing trauma dose. The motor deficit determined by a modified Tarlov scale also was dependent upon trauma dose. A trauma dose-response curve based on this study indicates that a drug which reduces the motor deficit from that found at 40 g-cm to that at 30 g-cm may be detected at a significant level of 0.05 with a power of 0.8 if 30 rats are included in each of placebo and treated groups. The same sample size would detect a significant reduction of mortality from that of 40 g-cm to 30 g-cm.

Animals↗

Increased thromboxane level in experimental spinal cord injury.

An increased accumulation of tissue thromboxane A2 occurred shortly after spinal cord injury. Prostacyclin formation was not affected. The magnitude of the increase in thromboxane and the extent of post-traumatic vascular damage as determined by extravasation of 125I-labeled human serum albumin were both dependent on the degree of injury. These findings raise the possibility that activation of arachidonic acid metabolism with a preponderance in thromboxane formation may contribute to microvascular injury in experimental spinal cord contusion.

6-Ketoprostaglandin F1 alpha↗

Vascular permeability in experimental spinal cord injury.

Following spinal cord injury in rats there was a time-dependent change of vascular permeability as reflected by extravasation of 125I-labelled serum albumin. The change of vascular permeability correlated with tissue calcium and water accumulation suggesting that cord exposure to plasma calcium as a consequence of vascular injury may contribute to the progressive post-traumatic cord necrosis.

Animals↗

Analysis of oral suspensions containing sulfonamides in combination with erythromycin ethylsuccinate.

The sulfonamides and erythromycin ethylsuccinate in combination oral suspensions were determined by high-performance liquid chromatography and automated turbidimetry, respectively. The chromatographic procedure was rapid, specific, and stability-indicating for sulfisoxazole acetyl and the trisulfapyrimidines using a reversed-phase system with UV detection at 254 nm. Erythromycin ethylsuccinate did not interfere with the sulfonamide analysis and these compounds were assayed with relative standard deviations (RDS) ranging from +/- 2.1 to +/- 3.1%. Erythromycin ethylsuccinate was determined as erythromycin with RSD values of +/- 1.3 or 3.5% without interference by the sulfonamides present.

Chemical Phenomena↗

The ontogeny of hippocampal energy metabolism.

The postnatal functional development of the hippocampus has been studied with the use of the 2-deoxyglucose method. Metabolic changes occurred along three different axes with increasing age. High metabolic activity appeared first in the pyramidal cell layer and shifted to the molecular layer. Activity in the regio inferior preceded the regio superior at posterior and ventral levels. All of these changes occurred first in the dorsal hippocampus and progressed along the septal-temporal axis. The data suggest that maturational changes occur at different hippocampal regions and that critical periods in development may ultimately be specified with respect to different regions in the same structure.

Aging↗

The effect of dental amalgams on mercury levels in expired air.

The expired air of a group of 48 persons, 40 with and eight without dental amalgam restorations, was analyzed for its mercury content before and after chewing. Expired air samples were collected in polyethylene bags, and a known quantity of each was pumped into the mercury detector for measurement. The results showed that examined subjects with dental amalgams had higher pre-chewing mercury levels in their expired air than those without amalgams. After chewing, these levels were increased an average of 15.6-fold in the former and remained unchanged in the latter group. It was concluded that in situ dental amalgams can increase the level of mercury in expired air.

Dental Amalgam↗