Learning disabilities and language function in epilepsy.
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Achievement↗
Biomedical subjects
A Woodard
Publications and source records attributed to A Woodard.
Evidence for mitogen-associated protein kinase activation and transduction of mitogenic signals by platelet-derived growth factor in human meningioma cells.
OBJECT: Coexpression of platelet-derived growth factor (PDGF)-BB and activated PDGF-beta receptor in meningioma cells indicates that this cytokine may act as an autocrine or paracrine stimulant of meningioma growth. The intracellular events transducing signals from PDGF-beta receptor tyrosine kinases are unknown. In this study the authors evaluated whether or not mitogen-activated protein kinases (MAPKs) are expressed in meningiomas, regulate their growth, and transduce mitogenic signals of PDGF-BB. METHODS: Ten human meningioma tumors as well as cells cultured from two normal leptomeninges and 10 additional human meningiomas were evaluated using Western blot analysis to determine the presence of MAPK and phosphorylated (activated) MAPK. The effects of PD098059, a selective inhibitor of MAPK phosphorylation/activation, on proliferation of meningioma cells stimulated with 10% fetal bovine serum was also evaluated. Last, the authors evaluated whether PDGF-BB stimulation of meningioma cells was associated with activation of MAPK. Western blots of lysates from meningiomas and from cultured leptomeningeal and meningioma cells demonstrated MAPK and phosphorylated MAPK. Treatment with PD098059 produced a 52 to 84% (x = 69.8) loss in [3H]thymidine incorporation, which was associated with a partial or complete loss of phosphorylated MAPK after 3 days of treatment. The PDGF-BB produced a significant increase in [3H]thymidine incorporation and phosphorylation of MAPK at 1 and 3 days. Coadministration of PD098059 completely blocked PDGF-BB's stimulation of [3H]thymidine incorporation and cell proliferation concomitant with reduced MAPK phosphorylation. CONCLUSIONS: The findings indicate that MAPK is constitutively expressed in leptomeningeal and meningioma cells and transduces mitogenic signals of PDGF, contributing to the growth of human meningiomas.
Adolescent↗
Comorbid psychiatric symptoms in temporal lobe epilepsy: association with chronicity of epilepsy and impact on quality of life.
Purpose. The goals of this work were to determine: (1) the nature and extent of differences in self-reported psychiatric symptoms between patients with temporal lobe epilepsy and matched healthy controls, (2) the relationship between chronicity (duration) of temporal lobe epilepsy and comorbid interictal psychiatric symptoms, and (3) the impact of comorbid psychiatric symptoms on self-reported health-related quality of life. Methods. Patients with temporal lobe epilepsy (n = 54) and healthy controls (n = 38) were administered the Symptom Checklist-90-Revised (SCL-90-R) to assess the nature and severity of psychiatric symptomatology and epilepsy patients completed the Quality of Life in Epilepsy-89 (QOLIE-89) to define health-related quality of life. Among epilepsy patients the SCL-90-R scales were examined in relation to chronicity of temporal lobe epilepsy as well as the impact of comorbid emotional-behavioral distress on health-related quality of life. Results. Compared with healthy controls, patients with epilepsy exhibited significantly higher (worse) scores across all but one of the 12 SCL-90-R scales. Among patients with epilepsy, increasing chronicity was associated with significantly higher (worse) scores across all SCL-90-R scales and increased emotional-behavioral distress was associated with lower (worse) scores across all 17 QOLIE-89 scales. Conclusion. Comorbid interictal psychiatric symptoms are elevated among patients with temporal lobe epilepsy compared with healthy controls and appear to be modestly associated with increasing chronicity (duration) of epilepsy. This comorbid emotional-behavioral distress is specifically associated with a significantly poorer health-related quality of life, and suggests that quality-of-life research should devote greater attention to the potential impact of comorbid psychiatric distress.
Journal Article↗
Pediatric epilepsy surgery: neuroimaging, neuropsychology, and anticonvulsants.
Neuroimaging and the neuropsychological evaluation are important components of the presurgical evaluation for epilepsy surgery. Advances in neuroimaging over the last decade, to a large part, underlie improvements in pediatric epilepsy surgery outcomes. The neuropsychological evaluation plays an important role in the evaluation of the older child and adolescent, particularly in the evaluation of mesial temporal sclerosis. However, its role in the young child being considered for surgery remains to be defined. This section reviews the definition of medical intractability, issues related to medication withdrawal during video-EEG monitoring, recent neuroimaging advances, and the neuropsychological evaluation.
Adolescent↗
Neuropsychological and behavioral status of children with complex partial seizures.
Neuropsychological and behavioral status were examined in 57 children aged 7 to 16 years with complex partial seizures (CPS) and compared with 27 sibling control children of the same age. Epilepsy had a significant effect on both cognitive and behavioral adjustment measures. Children with CPS had significant impairment across all seven cognitive domains assessed, reflective of a profile of relatively diffuse and generalized cognitive dysfunction. Age at onset of recurrent seizures was the strongest and most consistent predictor of adequacy of cognitive functioning; earlier age at onset was associated with poorer cognitive status. Children with CPS also had more problems compared with sibling control children on measures of social and school competence and internalizing behavior problems, but not externalizing behaviors. Further, frequency of seizure activity in the past year, rather than age at seizure onset, emerged as the strongest predictor of these behavioral difficulties. These findings are discussed in the context of understanding the impact of CPS on cognition and behavioral adjustment, and identifying the contribution of various aspects of the neurodevelopmental course of CPS to these issues.
Achievement↗
Co-morbid psychiatric disorder in chronic epilepsy: recognition and etiology of depression.
This article briefly presents one approach to conceptualizing known and suspected risk factors for co-morbid psychiatric disorder in epilepsy. The utility of this model is then reviewed by examining selected neurobiologic, psychosocial, and iatrogenic risk factors for a common co-morbid psychiatric disorder, interictal depression. Finally, data are presented concerning the rates of current and lifetime mood disorders among a sample of 76 patients with chronic complex partial seizures, the degree to which co-morbid depression has been recognized and treated in chronic epilepsy, and the health-related quality of life status associated with current and past mood disorders. Finally, these findings are related to the larger literature concerned with the recognition and treatment of depression.
Adult↗
Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells.
Naive CD4+ T cells can differentiate into cells predominantly involved in humoral immunity, known as T helper type 2 cells (Th2), or cells involved in cell-mediated immunity, known as Th1 cells. In this report, we show that priming of CD4+ T cells bearing a transgene-encoded T cell receptor can lead to differentiation into Th1-like cells producing abundant interferon gamma when the cells are exposed to high antigen doses, while low doses of the same peptide induce cells with the same T cell receptor to differentiate into Th2-like cells producing abundant interleukin 4. Thus antigen dose is one factor that can control the differentiation fate of a naive CD4+ T cell.
Animals↗
Deficits in radial arm maze performance in kindled rats: evidence for long-lasting memory dysfunction induced by repeated brief seizures.
Repeated activation of neural pathways by kindling induces brief seizures, permanent increases in seizure susceptibility, neuronal loss in the hippocampus, and mossy fiber sprouting in the dentate gyrus. Because kindling induces permanent cellular alterations in hippocampal pathways that have been implicated in memory, it was of interest to determine if kindling also induces long-lasting impairments in a spatial memory task in rats. In this study, the effects of kindling on memory were investigated by assessing kindled rats in a radial arm maze behavior that is impaired by hippocampal damage. Kindled rats studied at 1 month after the last of 30-134 evoked generalized tonic-clonic seizures acquired competence in the performance of the radial arm maze task at a rate that was indistinguishable from age-matched normal controls, but demonstrated a deficit in the ability to repeat the task on consecutive days. The repetition deficit was not observed in rats that experienced three afterdischarges or three generalized tonic-clonic seizures, and the severity of the deficit varied directly with the number of evoked kindled seizures. Repeated brief seizures evoked by kindling induced a long-lasting deficit in a radial arm maze task that is a rodent model of memory. The observation of a long-lasting deficit in radial arm maze performance in kindled rats suggests that the cellular alterations induced in the hippocampus by seizures could contribute to the memory dysfunction in human epilepsy.
Animals↗
Cloning and characterization of the recA genes from Mycoplasma pulmonis and M. mycoides subsp. mycoides.
The RecA protein has a central role in DNA repair and is essential for homologous recombination in most eubacteria. Little is known about these critical processes in mycoplasmas. By using standard and inverse polymerase chain reactions (PCR) coupled with conventional cloning techniques, a series of overlapping fragments comprising the entire recA genes of Mycoplasma mycoides subsp. mycoides (Mm) and Mycoplasma pulmonis (Mp) were generated. Each gene was sequenced in its entirety. The recA genes of Mm and Mp would encode proteins of 345 amino acids (aa) and 339 aa, respectively. The mycoplasmal RecA proteins revealed strong conservation when compared with RecA sequences from other bacterial species.
Amino Acid Sequence↗
Mycoplasma corogypsi sp. nov., a new species from the footpad abscess of a black vulture, Coragyps atratus.
Strain BV1 was isolated from the exudate of the footpad abscess of a black vulture (Coragyps atratus). The colonies had a "fried-egg" appearance consistent with that of mycoplasmal species. Electron microscopic examination of the cells revealed irregular elongated or elliptical forms and smaller circular budding processes. Profuse growth was observed in Frey medium supplemented with 20% swine serum at 37 degrees C in a humidified atmosphere of 10% CO2 and air. Typical of mycoplasma, strain BV1 required sterol for growth and catabolized glucose but did not hydrolyze arginine or urea. The guanine-plus-cytosine content of the DNA was 28 mol%. The organism demonstrated the ability to hemolyze, absorb onto, and agglutinate the erythrocytes from several animal species. Strain BV1 was serologically unrelated by the growth inhibition test to previously established Mycoplasma, Acholeplasma, Entomoplasma, and Mesoplasma species, as well as to strains belonging to these genera but not identified to species level. Moreover, BV1 had a 16S rRNA gene with a nucleotide sequence distinct from reported sequences of other mycoplasmas. This organism represents a new species for which the name Mycoplasma corogypsi is proposed. Strain BV1 (ATCC 51148T) is the type strain of Mycoplasma corogypsi sp. nov.
Abscess↗
Construction of recA mutants of Acholeplasma laidlawii by insertional inactivation with a homologous DNA fragment.
Mycoplasmas (class Mollicutes) are wall-less prokaryotes phylogenetically related to gram-positive bacteria. This study describes the construction of recA mutants of the mycoplasma Acholeplasma laidlawii. An internal fragment of the recA gene from A. laidlawii was cloned into a plasmid that does not replicate in this organism. When this plasmid construct was used to transform A. laidlawii, it inserted into the chromosome, disrupting the recA gene. The phenotype of the resulting recA mutant was compared to that of wild-type cells and to that of a strain that has a naturally occurring ochre mutation in its recA gene. As found in other bacterial systems, loss of RecA activity resulted in cells deficient in DNA repair.
Acholeplasma laidlawii↗
Cloning and DNA sequence of a mycoplasmal recA gene.
Mycoplasmas are wall-less prokaryotes phylogenetically related to gram-positive bacteria. In order to investigate DNA recombination in these organisms, we have cloned the recA gene from the mycoplasma Acholeplasma laidlawii. DNA sequence data indicate extensive homology between the A. laidlawii recA gene and recA genes from other bacteria, particularly Bacillus subtilis. The recA sequences from three A. laidlawii strains (strains JA1, K2, and 8195) were compared, and surprisingly, the gene from A. laidlawii 8195 was found to contain a nonsense mutation that results in truncation of 36 amino acids from the carboxyl terminus of the RecA protein. By using sensitivity to UV irradiation as a measure of DNA repair, strain 8195 had an apparent RecA- phenotype. When carried on a multicopy plasmid, the wild-type A. laidlawii recA gene was detrimental to growth of Escherichia coli, perhaps because of improper regulation of the RecA protein.
Acholeplasma laidlawii↗
Degenerate oligonucleotide primers for enzymatic amplification of recA sequences from gram-positive bacteria and mycoplasmas.
RecA protein in gram-negative bacteria, especially in Escherichia coli, has been extensively studied, but little is known about this key enzyme in other procaryotes. Described here are degenerate oligonucleotide primers that have been used to amplify by the polymerase chain reaction (PCR) recA sequences from several gram-positive bacteria and mycoplasmas. The DNA sequences of recA PCR products from Streptococcus pyogenes, Streptococcus mutans, Enterococcus faecalis, and Mycoplasma pulmonis were determined and compared. These data indicate that the M. pulmonis recA gene has diverged significantly from recA genes of other eubacteria. It should be possible to use cloned recA PCR products to construct recA mutants, thereby providing the means of elucidating homologous genetic recombination and DNA repair activities in these organisms.
Amino Acid Sequence↗