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Biomedical subjects

T McCormack

Publications and source records attributed to T McCormack.

At least 19 recordsLinked to original sources
PubMed2005

Episodic temporal generalization: a developmental study.

Groups of 5-year-olds, 10-year-olds, and adults completed either an episodic temporal generalization task, in which no stimuli were repeated, or a repeated standard temporal generalization task, in which there was a fixed standard that was repeated on every trial. Significant developmental improvements were found on both tasks. In both tasks, gradients of performance over two different stimulus ranges superimposed well when plotted on the same relative scale. Performance was similar for the adults and 10-year-olds across tasks, but the 5-year-olds performed better on the repeated standard task. These findings suggest that perceptual processes are a source of scalar variability in timing, and that there are developmental changes in levels of such variability.

Adult↗
PubMed2003

Duration judgements in patients with schizophrenia.

BACKGROUND: The ability to encode time cues underlies many cognitive processes. In the light of schizophrenic patients' compromised cognitive abilities in a variety of domains, it is noteworthy that there are numerous reports of these patients displaying impaired timing abilities. However, the timing intervals that patients have been evaluated on in prior studies vary considerably in magnitude (e.g. 1 s, 1 min, 1 h etc.). METHOD: In order to obviate differences in abilities in chronometric counting and place minimal demands on cognitive processing, we chose tasks that involve making judgements about brief durations of time (< 1 s). RESULTS: On a temporal generalization task, patients were less accurate than controls at recognizing a standard duration. The performance of patients was also significantly different from controls on a temporal bisection task, in which participants categorized durations as short or long. Although time estimation may be closely intertwined with working memory, patients' working memory as measured by the digit span task did not correlate significantly with their performance on the duration judgement tasks. Moreover, lowered intelligence scores could not completely account for the findings. CONCLUSIONS: We take these results to suggest that patients with schizophrenia are less accurate at estimating brief time periods. These deficits may reflect dysfunction of biopsychological timing processes.

Adolescent↗
PubMed2000

Children's serial recall errors: implications for theories of short-term memory development.

Three experiments examined developmental changes in serial recall of lists of 6 letters, with errors classified as movements, omissions, intrusions, or repetitions. In Experiments 1 and 2, developmental differences between groups of children aged from 7 to 11 years and adults were found in the pattern of serial recall errors. The errors of older participants were more likely to be movements than were those of younger participants, who made more intrusions and omissions. The number of repetition errors did not change with age, and this finding is interpreted in terms of a developmentally invariant postoutput response inhibition process. This interpretation was supported by the findings of Experiment 3, which measured levels of response inhibition in 7-, 9-, and 11-year-olds by comparing recall of lists with and without repeated items. Response inhibition remained developmentally invariant, although older children showed greater response facilitation (improved correct recall of adjacent repeated items). Group differences in the patterns of other errors are accounted for in terms of developmental changes in levels of output forgetting and changes in the efficiency of temporal encoding processes.

Adolescent↗
PubMed1999

The effects of Shaker beta-subunits on the human lymphocyte K+ channel Kv1.3.

The activation of T-lymphocytes is dependent upon, and accompanied by, an increase in voltage-gated K+ conductance. Kv1.3, a Shaker family K+ channel protein, appears to play an essential role in the activation of peripheral human T cells. Although Kv1.3-mediated K+ currents increase markedly during the activation process in mice, and to a lesser degree in humans, Kv1.3 mRNA levels in these organisms do not, indicating post-transcriptional regulation. In other tissues Shaker K+ channel proteins physically associate with cytoplasmic beta-subunits (Kvbeta1-3). Recently it has been shown that Kvbeta1 and Kvbeta2 are expressed in mouse T cells and that they are up-regulated during mitogen-stimulated activation. In this study, we show that the human Kvbeta subunits substantially increase K+ current amplitudes when coexpressed with their Kv1.3 counterpart, and that unlike in mouse, protein levels of human Kvbeta2 remain constant upon activation. Differences in Kvbeta2 expression between mice and humans may explain the differential K+ conductance increases which accompany T-cell proliferation in these organisms.

Animals↗
PubMed1999

Molecular diversity of K+ channels.

K+ channel principal subunits are by far the largest and most diverse of the ion channels. This diversity originates partly from the large number of genes coding for K+ channel principal subunits, but also from other processes such as alternative splicing, generating multiple mRNA transcripts from a single gene, heteromeric assembly of different principal subunits, as well as possible RNA editing and posttranslational modifications. In this chapter, we attempt to give an overview (mostly in tabular format) of the different genes coding for K+ channel principal and accessory subunits and their genealogical relationships. We discuss the possible correlation of different principal subunits with native K+ channels, the biophysical and pharmacological properties of channels formed when principal subunits are expressed in heterologous expression systems, and their patterns of tissue expression. In addition, we devote a section to describing how diversity of K+ channels can be conferred by heteromultimer formation, accessory subunits, alternative splicing, RNA editing and posttranslational modifications. We trust that this collection of facts will be of use to those attempting to compare the properties of new subunits to the properties of others already known or to those interested in a comparison between native channels and cloned candidates.

Alternative Splicing↗
PubMed1999

Fetal syndromes and the charter: the Winnipeg glue-sniffing case.

The relationship between scientific knowledge and legal discourse is raised once again by a recent decision of the Supreme Court of Canada, a case involving a young Aboriginal woman who was pregnant and ordered by the court to remain in a drug treatment program at a health center until the baby was born. Her glue-sniffing habit was deemed dangerous to the normal development of the fetus. The Court held that her solvent-dependency did not justify the original court action, but both the Court and the various interveners disregarded the current state of our knowledge on the fetal syndromes. There is thus a continuing disconnect between the scientific understanding of fetal risk and the development of Constitutional law around women's reproductive rights. This paper reviews the case and follows it through the appellate process; we examine the research literature on fetal syndromes tracking the changes over time. Finally we comment on the interventions by the Winnipeg Child and Family Services, the Women's Health Rights Coalition, by The Canadian Civil Liberties Association, and both The Canadian Abortion Rights Action League and the Women's Legal Education and Action Fund.

Adult↗
PubMed1999

Developmental changes in time estimation: comparing childhood and old age.

Participants from ages 5 to 99 years completed 2 time estimation tasks: a temporal generalization task and a temporal bisection task. Developmental differences in overall levels of performance were found at both ends of the life span and were more marked on the generalization task than the bisection task. Older adults and children performed at lower levels than young adults, but there were also qualitative differences in the patterns of errors made by the older adults and the children. To capture these findings, the authors propose a new developmental model of temporal generalization and bisection. The model assumes developmental changes across the life span in the noisiness of initial perceptual encoding and across childhood in the extent to which long-term memory of time intervals is distorted.

Adolescent↗
PubMed1998

Role of the proteasome and NF-kappaB in streptococcal cell wall-induced polyarthritis.

The transcription factor NF-kappaB activates a number of genes whose protein products are proinflammatory. In quiescent cells, NF-kappaB exists in a latent form and is activated via a signal-dependent proteolytic mechanism in which the inhibitory protein IkappaB is degraded by the ubiquitin-proteasome pathway. Consequently, inhibition of the proteasome suppresses activation of NF-kappaB. This suppression should therefore decrease transcription of many genes encoding proinflammatory proteins and should ultimately have an anti-inflammatory effect. To this end, a series of peptide boronic acid inhibitors of the proteasome, exemplified herein by PS-341, were developed. The proteasome is the large multimeric protease that catalyzes the final proteolytic step of the ubiquitin-proteasome pathway. PS-341, a potent, competitive inhibitor of the proteasome, readily entered cells and inhibited the activation of NF-kappaB and the subsequent transcription of genes that are regulated by NF-kappaB. Significantly, PS-341 displayed similar effects in vivo. Oral administration of PS-341 had anti-inflammatory effects in a model of Streptococcal cell wall-induced polyarthritis and liver inflammation in rats. The attenuation of inflammation in this model was associated with an inhibition of IkappaBalpha degradation and NF-kappaB-dependent gene expression. These experiments clearly demonstrate that the ubiquitin-proteasome pathway and NF-kappaB play important roles in regulating chronic inflammation and that, as predicted, proteasome inhibition has an anti-inflammatory effect.

Animals↗
PubMed1998

Reduction in tensile strength of cartilage precedes surface damage under repeated compressive loading in vitro.

An experimental protocol for the fatiguing and tensile testing of articular cartilage has been established. Samples were taken from the interpatellar groove of bovine femurs collected post-slaughter, split into two test groups and subjected to a cyclically varying compressive load of approximately 65 N for 64,800 cycles or 97,200 cycles. The cartilage was then removed from the underlying bone and two specimens, one from the indented region and one from an unindented region - the control, were taken from it and prepared for subsequent tensile testing using notched specimens. From data collected during tensile testing, a value of maximum tensile stress was calculated for each sample. The underlying bone was examined for evidence of microdamage using the basic fuchsin method. A decrease in values of maximum tensile stress (p < 0.05) for the indented sample of each paired group of samples loaded for 97,200 cycles was found. In contrast, those fatigued for only 64,800 cycles showed no such difference. Examination of the underlying bone of these specimens revealed no evidence of trabecular failure and crack formation beneath both the indented and control regions. It is postulated that the fatiguing process used in this experiment induces trauma in the cartilage causing a weakening of the interfibril connections which link collagen fibrils in the matrix, leading to a reduction in tensile strength. This weakening occurs, however, without the appearance of fibrillation on the cartilage surface or any evidence of failure in the bony structure which supports it.

Animals↗
PubMed1995

Alternative splicing of the human Shaker K+ channel beta 1 gene and functional expression of the beta 2 gene product.

Mammalian voltage-activated Shaker K+ channels associate with at least three cytoplasmic proteins: Kv beta 1, Kv beta 2 and Kv beta 3. These beta subunits contain variable N-termini, which can modulate the inactivation of Shaker alpha subunits, but are homologous throughout an aldo-keto reductase core. Human and ferret beta 3 proteins are identical with rat beta 1 throughout the core while beta 2 proteins are not; beta 2 also contains a shorter N-terminus and has no reported physiological role. We report that human beta 1 and beta 3 are derived from the same gene and that beta 2 modulates the inactivation properties of Kv1.4 alpha subunits.

Alternative Splicing↗
PubMed1994

The load sharing classification of spine fractures.

STUDY DESIGN: A 3 to 4 year follow-up was performed on a consecutive series of 28 patients who had three-column spinal fractures surgically stabilized by short-segment instrumentation with first generation VSP (Steffee) screws and plates and autograft fusion. The follow-up revealed 10 patients with broken screws. BACKGROUND DATA: Retrospective examination of preoperative radiographs and computed tomographic axial and sagittal reconstruction images clearly demonstrated that the screw fractures all occurred in patients with a disproportionately greater amount of injury to the vertebral body. RESULTS: A point system (the load sharing classification) was developed that grades: 1) the amount of damaged vertebral body, 2) the spread of the fragments in the fracture site, and 3) the amount of corrected traumatic kyphosis. CONCLUSIONS: This point system can be used preoperatively to: 1) predict screw breakage when short segment, posteriorly placed pedicle screw implants are being used, 2) describe any spinal injury for retrospective studies, or 3) select spinal fractures for anterior reconstruction with strut graft, short-segment-type reconstruction.

Adult↗
PubMed1994

Surgical management of radiated scalp in patients with recurrent glioma.

Patients with malignant brain tumors requiring multiple craniotomies and external beam radiotherapy are at risk of scalp wound breakdown secondary to fibrosis and radiation damage. We present three cases to illustrate the nature of the problem and the surgical approaches to scalp repair. When a bicoronal incision has been used for the initial craniotomy, the plastic repair can be performed with a bipedicle visor scalp flap and split-thickness skin graft to cover the pericranium at the donor site. When a curvilinear (U-shaped or horseshoe) flap has been used for the initial craniotomy, a single-pedicle flap may be rotated to achieve closure without tension. In anticipation of the risk of scalp wound breakdown in patients with malignant brain tumors, the planning of the operative incision for the first craniotomy needs to take into account the long-term viability of the scalp. We recommend linear scalp incisions parallel to the arterial distribution instead of the traditional curvilinear (U-shaped or horseshoe) flaps; linear incisions are less likely to break down, and in the event of breakdown, linear wounds offer better therapeutic surgical options for plastic repair.

Adult↗
PubMed1991

A role for hydrophobic residues in the voltage-dependent gating of Shaker K+ channels.

A leucine heptad repeat is well conserved in voltage-dependent ion channels. Herein we examine the role of the repeat region in Shaker K+ channels through substitution of the leucines in the repeat and through coexpression of normal and truncated products. In contrast to leucine-zipper DNA-binding proteins, we find that the subunit assembly of Shaker does not depend on the leucine heptad repeat. Instead, we report that substitutions of the leucines in the repeat produce large effects on the observed voltage dependence of conductance voltage and prepulse inactivation curves. Our results suggest that the leucines mediate interactions that play an important role in the transduction of charge movement into channel opening and closing.

Amino Acid Sequence↗