Biomedical subjects

M A Lawson

Publications and source records attributed to M A Lawson.

At least 19 recordsLinked to original sources

PubMed2000

Oriented endocytic recycling of alpha5beta1 in motile neutrophils.

During cell migration, integrin attachments to the substratum provide the means to generate the traction and force necessary to achieve locomotion. Once the cell has moved over these attachments, however, it is equally important that integrins detach from the substratum. The fate of integrins after detachment may include release from the cell, lateral diffusion across the cell surface, or endocytosis and redelivery to the cell surface. Polymorphonuclear neutrophils (PMNs) become stuck on the extracellular matrix proteins fibronectin and vitronectin when their intracellular free calcium concentration ([Ca(++)]i) is buffered. Taking advantage of this feature of PMN migration, we investigated the fate of integrins to differentiate among various models of migration. We demonstrate that alpha5beta1, one of the fibronectin-binding integrins, is responsible for immobilization of [Ca(++)](i)-buffered PMNs on fibronectin. We find that alpha5 and beta1 are in endocytic vesicles in PMNs and that alpha5 colocalizes with a marker for an endocytic recycling compartment. When [Ca(++)](i) is buffered, alpha5 and beta1 become concentrated in clusters in the rear of the adherent cells, suggesting that [Ca(++)](i) transients are required for alpha5beta1 detachment from the substratum. Inhibition of alpha5beta1 detachment by buffering [Ca(++)](i) results in the depletion of alpha5 from both endocytic vesicles and the recycling compartment, providing compelling evidence that integrins are normally recycled by way of endocytosis and intracellular trafficking during cell migration. This model is further refined by our demonstration that the endocytic recycling compartment reorients to retain its localization just behind the leading lamella as PMNs migrate, indicating that membrane recycling during neutrophil migration has directionality. (Blood. 2000;95:2471-2480)

Cell Compartmentation↗

PubMed2000

Epinephrine upregulates calpain activity in cultured C2C12 muscle cells.

C2C12 cells were grown to confluence at 37 degrees C under a continuous 5% CO(2) stream and myotube formation was stimulated. The cultures were then incubated with or without 2 microg/mL epinephrine for 18 h prior to harvesting and calpain extraction. Epinephrine treatment resulted in a three-fold increase in extractable mu-calpain activity (P < 0.05), a three-fold increase in extractable m-calpain activity (P < 0.05), a 36% increase in calpastatin activity (P < 0.001), and a 16% decrease (P < 0.05) in the total protein content in the C2C12 cell homogenate. These results suggest that calpains may play a role in protein metabolism and that the hormone epinephrine may be directly involved in the regulation of their cellular expression.

Animals↗

PubMed2000

Differentiation of myoblasts in serum-free media: effects of modified media are cell line-specific.

Myoblast cell lines are grown and differentiated readily in cell culture. Two cell lines typically used for investigating the growth and differentiation of muscle are the mouse cell line C2C12 and the rat cell line L6. The differentiation of these cells in vitro requires a switch from a serum-rich medium to a less rich medium after the cells have reached confluence. Since the components present in serum are not well characterized, the use of a better defined medium for these studies was investigated. C2C12 and L6 myoblasts were differentiated in both serum-containing and serum-free media. The differentiation state of these cultures was then tested both microscopically and biochemically. Cultures were checked for myotube formation, the activity of creatine phosphokinase and the presence of sarcomeric actin. In C2C12 cells, the extent of differentiation was greater in the serum-free than in the serum-containing system. In both media types, the C2C12 cells produced sarcomeric actin, showing the presence of sarcomere structure in the myotubes. In L6 cells, however, myotubes were readily formed in medium containing 2% horse serum, but not in the serum-free system. In addition, the ability of C2C12 cells to differentiate on substrates coated with extracellular matrix proteins was shown to be media-dependent. The presence of extracellular matrix proteins did not enable L6 cells to form myotubes when cultured in serum-free media. Primary cultures of chick myoblasts were able to differentiate in both media tested, with Dulbecco's modified Eagle medium containing horse serum being a more efficient medium for cell fusion. This study shows a divergence in muscle cell line responses in three cell lines, two of which are typically used as 'model systems' for understanding muscle growth and development.

Actins↗

PubMed2000

Activation of translation in pituitary gonadotrope cells by gonadotropin-releasing hormone.

The neuropeptide GnRH is a central regulator of mammalian reproductive function produced by a dispersed population of hypothalamic neurosecretory neurons. The principal action of GnRH is to regulate release of the gonadotropins, LH and FSH, by the gonadotrope cells of the anterior pituitary. Using a cultured cell model of mouse pituitary gonadotrope cells, alphaT3-1 cells, we present evidence that GnRH stimulation of alphaT3-1 cells results in an increase in cap-dependent mRNA translation. GnRH receptor activation results in increased protein synthesis through a regulator of mRNA translation initiation, eukaryotic translation initiation factor 4E-binding protein, known as 4EBP or PHAS (protein, heat, and acid stable). Although the GnRH receptor is a member of the rhodopsin-like family of G protein-linked receptors, we show that activation of translation proceeds through a signaling pathway previously described for receptor tyrosine kinases. Stimulation of translation by GnRH is protein kinase C and Ras dependent and sensitive to rapamycin. Furthermore, GnRH may also regulate the cell cycle in alphaT3-1 cells. The activation of a signaling pathway that regulates both protein synthesis and cell cycle suggests that GnRH may have a significant role in the maintenance of the pituitary gonadotrope population in addition to directing the release of gonadotropins.

5' Untranslated Regions↗

PubMed2000

Neuron-specific expression of the rat gonadotropin-releasing hormone gene is conferred by interactions of a defined promoter element with the enhancer in GT1-7 cells.

Neuroendocrine control of the reproductive cascade is mediated by GnRH, which in mammals is produced by a subset of neurons scattered throughout the hypothalamus and forebrain. Utilizing a cultured cell model of GnRH neurons (GT1-7 cells), two regulatory regions in the rat GnRH 5' flanking DNA were identified as essential for cell-type specificity: a 300-bp enhancer and a 173-bp conserved proximal promoter. Using transient transfections to compare expression in GT1-7 cells to a non-GnRH-expressing cell type (NIH 3T3), we show that the GnRH enhancer and the proximal promoter each play roles in conferring this specificity. Deletion of footprint 2 (FP2; -26 to -76) from the promoter when coupled to the GnRH enhancer diminishes reporter activity in GT1-7 cells more strongly than in NIH 3T3 cells. Furthermore, deletion of FP2 from the promoter when coupled to the heterologous Rous sarcoma virus 5'-long terminal repeat promoter abolishes the difference in reporter activity between GT1-7 and NIH 3T3 cells, suggesting that FP2 of the GnRH promoter is necessary for cell-specific expression. In addition, FP2 alone is sufficient to confer cell-specific expression and can interact with the GnRH enhancer to augment reporter gene expression specifically in GT1-7 cells. Finally, a 31-bp sequence from within FP2 (-63 to -33) synergistically activates transcription when coupled with the GnRH enhancer in GT1-7 cells but not in NIH 3T3 cells. Thus, this 31-bp region contains elements necessary for interaction between the GnRH enhancer and promoter. We show that two of five protein complexes that bind to the -63 to -33 region are GT1-7 cell specific, and both of them appear to be homeodomain proteins. The identification of a cell-specific element in the GnRH proximal promoter significantly advances our understanding of the transcriptional basis for neuron-specific GnRH gene expression.

3T3 Cells↗

PubMed1999

Pelvic inflammatory disease in adolescents.

Pelvic inflammatory disease is the most significant consequence of sexually transmitted infections. Statistics suggest that adolescents have a significantly higher rate of PID than does any other age group. Even asymptomatic and minimally symptomatic PID can lead to adhesions, infertility, and ectopic pregnancy, so clinicians should maintain a high index of suspicion when evaluating female adolescents with lower abdominal pain. Empiric treatment, including appropriate partner notification and treatment, should be initiated early.

Adolescent↗

PubMed1999

Activin A regulation of gonadotropin-releasing hormone synthesis and release in vitro.

Activin is essential for the regulation of normal mammalian reproductive function at both the pituitary and gonadal levels. However, its central actions in the control of the hypothalamic-pituitary-gonadal axis remain largely unexplored. The present study aims to determine whether activin could regulate the reproductive axis at the level of the hypothalamus, through control of the GnRH neuroendocrine system. Using the GnRH-secreting GT1-7 neuronal cell line as a model system, we demonstrate expression of mRNAs encoding activin receptor types I, IB, and II. We examined the effects of activin A on GnRH protein secretion and mRNA levels in GT1-7 cells. Treatment with rh-activin A regulated both GnRH protein secretion and GnRH mRNA expression in the GT1-7 cells in a time-dependent fashion. Using transient transfection assays, we explored a potential transcriptional basis for these changes. Activin A increased reporter gene activity driven by minimal GnRH enhancer and promoter elements, suggesting that activin may regulate GnRH gene expression at the level of transcription. Lastly, activin A treatment of male rat hypothalami, in vitro, increased GnRH protein secretion. Collectively, molecular and physiological evidence support the presence of an activin system which might act at a hypothalamic site to regulate mammalian reproduction via activation of GnRH synthesis and release.

Activin Receptors↗

PubMed1999

Positron emission tomography using [18F] fluorodeoxyglucose and [11C] l-methionine to metabolically characterize dysembryoplastic neuroepithelial tumors.

Dysembryoplastic neuroepithelial tumors are unique and benign congenital tumors occurring frequently in children and adolescents. Differentiation from other low-grade tumors is important for management. Five patients with confirmed dysembryoplastic neuroepithelial tumors were studied with positron emission tomography using glucose and protein metabolic uptake in an attempt to categorize these tumors metabolically. Functional brain mapping also was obtained to aid in operative management. Results of the study conclude that dysembryoplastic neuroepithelial tumors, although having similar neuroimgaing characteristics to other low-grade tumors, are distinguished by a unique metabolic profile. They are inactive tumors with no significant glucose or protein metabolic activity. The combination of preoperative positron emission tomographic metabolic studies with functional brain mapping allowed for prediction of tumor type, defined eloquent areas of cortical function, and improved approach and resection of the tumors with minimal risk of neurologic impairment.

Adolescent↗

PubMed1999

Functional brain mapping using positron emission tomography scanning in preoperative neurosurgical planning for pediatric brain tumors.

OBJECT: The purpose of this report is to demonstrate the value of functional brain mapping using the positron emission tomography (PET) method for preoperative neurosurgical planning in children with brain tumors. Brain maps were used to characterize the relationship between potentially resectable tumors and functionally eloquent brain areas. METHODS: Five children, ranging in age from 3 to 13 years, with hemispheric brain tumors adjacent to eloquent cortex were studied. Magnetic resonance (MR) imaging was used to identify the brain tumors; PET imaging after injection of [18F] fluorodeoxyglucose (FDG), [11C]L-methionine (CMET), or a combination of the two was performed to grade the tumors; and a [15O] H2O uptake study was used to characterize the anatomical relationships of the tumors to functional cortex. The cortical activation maps were obtained during control periods and during behavioral tasks and were used to document motor, visual, and speech and language organizational areas. Wada tests were performed in two patients. Language and speech activation was concordant with the results of Wada testing. CONCLUSIONS: Functional brain mapping using PET scans and coregistered MR images provided the neurosurgeon with precise definitions of structural and functional cortical areas; this altered surgical management in some cases and/or was used to predict outcome. The combination of PET imaging with FDG and/or CMET and measurements of [15O] water uptake was useful in characterizing and grading tumors and instrumental in achieving effective neurosurgical planning. Postoperative results in the five cases suggest that preoperative functional brain mapping has the potential to improve outcome by defining a surgical plan to maximize resection and minimize the risk of neurological sequelae.

Adolescent↗

PubMed1999

Murine viruses in an island population of introduced house mice and endemic short-tailed mice in Western Australia.

House mice (Mus domesticus) were recently introduced to Thevenard Island, off the northwest coast of Western Australia. This island is also habitat for an endangered native rodent, the short-tailed mouse (Leggadina lakedownensis). Concerns have been raised that house mice may pose a threat to L. lakedownensis both through competition and as a source of infection. To assess the threat to L. lakedownensis posed by viral pathogens from M. domesticus, a serological survey was conducted from 1994 to 1996 of both species for evidence of infection with 14 common murine viruses (mouse hepatitis virus, murine cytomegalovirus, lymphocytic choriomeningitis virus, ectromelia virus, mouse adenovirus strains FL and K87, minute virus of mice, mouse parvovirus, reovirus type 3, Sendai virus, Theiler's mouse encephalomyelitis virus, polyoma virus, pneumonia virus of mice, and encephalomyocarditis virus) and Mycoplasma pulmonis. Despite previous evidence that populations of free-living M. domesticus from various locations on the Australian mainland were infected with up to eight viruses, M. domesticus on Thevenard Island were seropositive only to murine cytomegalovirus (MCMV). Antibodies to MCMV were detected in this species at all times of sampling, although seroprevalence varied. Infectious MCMV could be isolated in culture of salivary gland homogenates from seropositive mice. In contrast, L. lakedownensis on Thevenard Island showed no serological evidence of infection with MCMV, any of the other murine viruses, or M. Pulmonis, and no virus could be isolated in culture from salivary gland homogenates. Although MCMV replicated to high titers in experimentally infected inbred BALB/c laboratory mice as expected, it did not replicate in the target organs of experimentally inoculated L. lakedownensis, indicating that the strict host specificity of MCMV may prevent its infection of L. lakedownensis. These results suggest that native mice on Thevenard Island are not at risk of MCMV infection from introduced house mice, and raise interesting questions about the possible selective survival of MCMV in small isolated populations of M. domesticus.

Animals↗

PubMed1998

Expression of GATA-4 in migrating gonadotropin-releasing neurons of the developing mouse.

The hypothalamic gonadotropin-releasing hormone (GnRH) neurons are important regulators of reproductive function. During development, these cells arise in the olfactory placode and migrate to the central nervous system, where they form a diffuse population of neurosecretory cells that mediate central nervous system control of reproduction. Little is known of the mechanisms regulating the differentiation of these cells. Studies of the transcriptional regulation of the GnRH gene have demonstrated the importance of the GATA family of zinc-finger transcription factors in gene expression. Although GATA factors are not highly expressed in mature GnRH-secreting neurons, we report that GATA-4 is highly expressed in migrating GnRH neurons in the developing mouse. We also report that a second DNA binding activity regulating GnRH gene expression at the site of GATA-factor action persists in mature hypothalamus and may also play a role in gene expression in the differentiated GnRH neuron.

Animals↗

PubMed1998

Analyzing glycoproteins separated by two-dimensional gel electrophoresis.

Two-dimensional (2-D) electrophoresis is the preferred method for separating the glycoforms of proteins. The isoforms usually present as 'trains' of spots in the first dimension and may also differ in molecular weight. The primary goal for analyzing the carbohydrate content of glycoprotein spots is to understand the 'rules' which govern the migration of glycoproteins in 2-D electrophoresis. These rules can then be used to produce predictive vectors to interpret changes in glycosylation patterns. Techniques for the analysis of oligosaccharides released from glycoproteins which have been electroblotted to PVDF membrane after one-dimensional (1-D) and 2-D preparative gel electrophoresis are described. The oligosaccharides are removed enzymatically (PNGase F of N-linked oligosaccharides) or chemically (beta-elimination of O-linked oligosaccharides) and separated by high performance anion exchange chromatography (HPAEC-PAD) and identified by electrospray ionization mass spectrometry (ESI-MS) or analyzed directly by ESI-MS. After enzymic removal of the N-linked oligosaccharides the protein spots can be further analyzed by Edman sequence tagging for identification and quantitation of the protein and by acid hydrolysis for monosaccharide analysis of the O-linked oligosaccharides. These approaches have been proved on 1-D PAGE electroblotted bovine fetuin and human glycophorin A and then used to analyze two abundant proteins which separate as glycoforms on 2-D PAGE preparative narrow range (pH 4.5-5.5) blots of human plasma: alpha2-HS glycoprotein (human fetuin) and alpha1-antitrypsin (alpha1-protease inhibitor). It is apparent that both the macroheterogeneity (site occupation) and microheterogeneity (diversity of structures) of the glycosylation contribute to the separation of protein isoforms in 2-D PAGE.

Amidohydrolases↗

PubMed1998

A general approach to desalting oligosaccharides released from glycoproteins.

Desalting of sugar samples is essential for the success of many techniques of carbohydrate analysis such as mass spectrometry, capillary electrophoresis, anion exchange chromatography, enzyme degradation and chemical derivatization. All desalting methods which are currently used have limitations: for example, mixed-bed ion-exchange columns risk the loss of charged sugars, precipitation of salt by a non-aqueous solvent can result in co-precipitation of oligosaccharides, and gel chromatography uses highly crosslinked packings in which separation of small oligosaccharides is difficult to achieve. We demonstrate that graphitized carbon as a solid phase extraction cartridge can be used for the purification of oligosaccharides (or their derivatives) from solutions containing one or more of the following contaminants: salts (including salts of hydroxide, acetate, phosphate), monosaccharides, detergents (sodium dodecyl sulfate and Triton X-100), protein (including enzymes) and reagents for the release of oligosaccharides from glycoconjugates (such as hydrazine and sodium borohydride). There is complete recovery of the oligosaccharides from the adsorbent which can also be used to fractionate acidic and neutral glycans. Specific applications such as clean-up of N-linked oligosaccharides after removal by PNGase F and hydrazine, desalting of O-linked glycans after removal by alkali, on-line desalting of HPAEC-separated oligosaccharides and beta-eliminated alditols prior to electrospray mass spectrometry, and purification of oligosaccharides from urine are described.

Amidohydrolases↗

PubMed1998

Multiple factors interacting at the GATA sites of the gonadotropin-releasing hormone neuron-specific enhancer regulate gene expression.

Neuron-specific expression of the GnRH gene is dependent on an upstream multicomponent enhancer. This enhancer is functional in a small population of GnRH-producing hypothalamic neurons which, through the secretion of GnRH, mediates central nervous system control of reproductive function. GnRH enhancer function requires activation by the GATA family of transcription factors that act through tandem consensus GATA-binding motifs, GATA-A and GATA-B. Here we show that two newly identified DNA-binding factors, termed GBF-A1/A2 and GBF-B1, bind the GnRH enhancer at sites overlapping the GATA factor-binding motifs. In vitro bindings of GATA, GBF-A1/A2, and GBF-B1 to the GnRH enhancer sequences are independent. Specific mutation of either the consensus GATA motif or the GBF-B1 site of GATA-B does not alter binding of the overlapping factor in vitro. Utilizing a GnRH-expressing neuronal cell line as a model system, we show by transient transfection that GBF-B1 is necessary for enhancer activity and independently activates the GnRH promoter. Transactivation of the GnRH enhancer in GT1 cells and in NIH 3T3 cells by GATA-4 is modulated by GBF-B1 binding, suggesting GBF-B1 interferes with GATA factor binding through a steric mechanism.

Animals↗

PubMed1997

Correlation of thallium uptake with left ventricular wall thickness by cine magnetic resonance imaging in patients with acute and healed myocardial infarcts.

Myocardial infarction (MI) is characterized by cellular necrosis which undergoes fibrotic transformation over time. Cine magnetic resonance imaging (MRI) offers high-resolution 3-dimensional images of the left ventricular myocardium, allowing sampling of the myocardial wall thickness over the entire left ventricle. Tomographic (single-photon emission computed tomography [SPECT]) thallium images also provide 3-dimensional information on the location and level of thallium uptake, which has been shown to correlate with myocardial viability. The purposes of this study were: (1) to examine the relation between both end-diastolic and end-systolic wall thickness and normalized thallium-201 uptake over the left ventricle in a group of patients with MI, (2) to examine the relation between regional wall thickening and normalized thallium uptake, and (3) to examine the relation between thallium uptake and wall thickness both early and late after infarction. Twenty-four patients with MI underwent stress, redistribution, and reinjection thallium SPECT imaging and cine MRI within several days. Seventeen patients underwent imaging late after infarction and 7 underwent imaging early after infarction. Normalized thallium activity was correlated with MRI wall thicknesses at both end-diastole and end-systole for 18 segments for each ventricle. In addition, end-diastolic and end-systolic wall thicknesses were grouped by their corresponding thallium activity levels into percentiles. End-systolic wall thickness correlated significantly with normalized thallium uptake in 14 of 18 segments, end-diastolic wall thickness in only 4 of 18 segments, and wall thickening in only 3 of 18 segments. Mean values for end-diastolic and end-systolic wall thicknesses corresponding to severely reduced (<50%) normalized thallium activity were 9.9 +/- 1.1 and 8.5 +/- 0.6, respectively. Using receiver-operating curve analysis, end-systolic wall performed as a better diagnostic parameter than end-diastolic wall for identifying severely reduced thallium activity levels. For all levels of thallium activity, end-diastolic wall thicknesses were all thinner late versus early after MI, whereas end-systolic wall thickness was thinner only in the segments corresponding to severely reduced thallium activity. Based on these results, end-systolic wall thickness is the best noninvasive anatomic parameter of myocardial scar.

Adult↗

PubMed1997

Myositis induced by naked DNA immunization with the gene for histidyl-tRNA synthetase.

Polymyositis is regarded as an autoimmune inflammatory muscle disease. A major subgroup of patients have autoantibodies to cellular histidyl-transfer RNA synthetase (HRS). We have analyzed the role of the autoantigen HRS in the induction of murine myositis in a comparative study of inoculation of BALB/c mice with recombinant HRS protein versus naked DNA coding for HRS. Adult BALB/c mice produced antibodies to human HRS following inoculation with HRS protein and adjuvant, but myositis was not observed. Alternatively, expression plasmid DNA constructs encoding full-length and truncated human HRS were inoculated intramuscularly in gene transfer studies. DNA-inoculated mice produced relatively low anti-HRS antibody titers. However, in contrast to recombinant HRS protein-inoculated mice, HRS gene transfer induced pathology with evidence of cellular infiltration of perivascular and endomysial regions of the inoculated muscle. Multiple inoculations of a plasmid construct encoding a hybrid molecule consisting of HRS and the transferrin receptor cytoplasmic tail induced the highest levels of antibodies and persisting cellular infiltration. Unlike HRS, expression of influenza virus hemagglutinin (HA) following inoculation of an HA plasmid did not induce myositis. Transfer of naked DNA constructs expressing HRS is likely to provide valuable information on the autoimmune response to this protein and its role in the development of myositis.

Animals↗

PubMed1997

Dynamic imaging of neutrophil migration in three dimensions: mechanical interactions between cells and matrix.

Fluorescence confocal microscopy was used to obtain three-dimensional (3-D) images of human neutrophils migrating through a 3-D matrix of amniotic membrane with a temporal resolution of 30-60 s and a spatial resolution of approximately 2 microm in the z-dimension. Neutrophils migrating in response to a chemoattractant gradient within a 3-D matrix were apparently able to generate traction by use of lateral pseudopods inserted into footholds in the matrix as evidenced by matrix distortion. Similar anchored pseudopods were seen in cells migrating across polycarbonate membranes with 0.8-microm pores; the presence of these pores increased cell polarization and migration compared with cells on membranes without pores. Expansion of pseudopods distal to narrow constrictions in the matrix and porous filters was observed and appeared to be used to pull cells through the openings. Neutrophils deformed parts of the elastic amnion matrix during migration without permanently altering the substrate. Contact guidance of neutrophils crawling along matrix fibrils was also observed. These observations show that neutrophils migrating in 3-D are able to utilize mechanical structures in the matrix, not present on 2-D surfaces, to generate traction for locomotion.

Actin Cytoskeleton↗

PubMed1997

Use of positron emission tomography for presurgical localization of eloquent brain areas in children with seizures.

Successful surgical management of a neoplastic or nonneoplastic seizure focus in close proximity to or within eloquent brain areas relies on precise delineation of the relationship between the lesion and functional brain areas. The aim of this series was to validate the usefulness and test the efficacy of noninvasive presurgical PET mapping of eloquent brain areas to predict surgical morbidity and outcome in children with seizures. To identify eloquent brain areas in 15 children (6 female and 9 male; mean age 11 years) with epileptogenic lesions PET images of regional cerebral blood flow were performed following the administration of [(15)O]water during motor, visual, articulation, and receptive language tasks. These images with coregistered magnetic resonance (MR) images were then used to delineate the anatomic relationship of a seizure focus to eloquent brain areas. Additional PET images using [18F]fluoro-2-deoxy-D-glucose (FDG) and [11C]methionine (CMET) were acquired to help localize the seizure focus, as well as characterize the lesion. Patient surgical management decisions were based on PET mapping in combination with coregistered MR images, PET-FDG findings, and the anatomic characteristics of the lesion. At follow-up 1-26 months after surgery, all patients that underwent temporal lobectomy (9 patients) and extratemporal resection (4 patients) for a neoplastic or nonneoplastic seizure focus are seizure-free with minimal postoperative morbidity. Of prime importance, no child sustained a postoperative speech or language deficit. PET imaging was also well tolerated without procedural complications. Based on PET mapping, a nonoperative approach was used for 2 children and a biopsy only was used in one child. When cortical injury involved prenatally determined eloquent cortex, PET demonstrated reorganization of language areas to new adjacent areas or even to the contralateral hemisphere. Integration of anatomical and functional data enhanced the surgical safety, defined optimal surgical approach, delineated the seizure focus from eloquent brain areas, facilitated maximum resection and optimized the timing of surgery, thereby minimizing surgical morbidity while maximizing surgical goals. PET measurements of FDG and CMET uptake were also helpful in localizing the seizure focus and grading the tumors. PET used for brain mapping in children provides the surgeon with strategic preoperative information not readily attainable with traditional invasive Wada testing or intraoperative cortical stimulation. PET mapping may also improve the outcome of extratemporal resections by allowing aggressive seizure focus resection. In addition, serial brain maps may optimize timing for surgical intervention by demonstrating reorganization of eloquent cortex often seen in younger children after cortical injury. Our results suggest that noninvasive presurgical brain mapping has the potential to reduce risk and improve neurologic outcome.

Adolescent↗