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T B Mapstone

Publications and source records attributed to T B Mapstone.

At least 19 recordsLinked to original sources
PubMed2001

pH alterations "reset" Ca2+ sensitivity of brain Na+ channel 2, a degenerin/epithelial Na+ ion channel, in planar lipid bilayers.

Members of the degenerin/epithelial Na(+) channel superfamily of ion channels subserve many functions, ranging from whole body sodium handling to mechanoelectrical transduction. We studied brain Na(+) channel 2 (BNaC-2) in planar lipid bilayers to examine its single channel properties and regulation by Ca(2+). Upon incorporation of vesicles made from membranes of oocytes expressing either wild-type (WT) BNaC-2 or BNaC-2 with a gain-of-function (GF) point mutation (G433F), functional channels with different properties were obtained. WT BNaC-2 resided in a closed state with short openings, whereas GF BNaC-2 was constitutively activated; a decrease in the pH in the trans compartment of the bilayer activated WT BNaC-2 and decreased its permeability for Na(+) over K(+). Moreover, these maneuvers made the WT channel more resistant to amiloride. In contrast, GF BNaC-2 did not respond to a decrease in pH, and its amiloride sensitivity and selectivity for Na(+) over K(+) were unaffected by this pH change. Buffering the bathing solutions with EGTA to reduce the free [Ca(2+)] to <10 nm increased WT single channel open probability 10-fold, but not that of GF BNaC-2. Ca(2+) blocked both WT and GF BNaC-2 in a dose- and voltage-dependent fashion; single channel conductances were unchanged. A drop in pH reduced the ability of Ca(2+) to inhibit these channels. These results show that BNaC-2 is an amiloride-sensitive sodium channel and suggest that pH activation of these channels could be, in part, a consequence of H(+) "interference" with channel regulation by Ca(2+).

Acid Sensing Ion Channels↗
PubMed2001

Differential gene expression profiling in human brain tumors.

Gene expression profiling of three human temporal lobe brain tissue samples (normal) and four primary glioblastoma multiforme (GBM) tumors using oligonucleotide microarrays was done. Moreover, confirmation of altered expression was performed by whole cell patch clamp, immunohistochemical staining, and RT-PCR. Our results identified several ion and solute transport-related genes, such as N-methyl-d-aspartate (NMDA) receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-2 receptors, GABA(A) receptor subunits alpha3, beta1, beta2, and beta3, the glutamate transporter, the glutamate/aspartate transporter II, the potassium channel K(V)2.1, hK(V)beta3, and the sodium/proton exchanger 1 (NHE-1), that are all downregulated in the tumors compared with the normal tissues. In contrast, aquaporin-1, possibly aquaporins-3 and -5, and GLUT-3 message appeared upregulated in the tumors. Our results also confirmed previous work showing that osteopontin, nicotinamide N-methyltransferase, murine double minute 2 (MDM2), and epithelin (granulin) are upregulated in GBMs. We also demonstrate for the first time that the cytokine and p53 binding protein, macrophage migration inhibitory factor (MIF), appears upregulated in GBMs. These results indicate that the modulation of ion and solute transport genes and heretofore unsuspected cytokines (i.e., MIF) may have profound implications for brain tumor cell biology and thus may identify potential useful therapeutic targets in GBMs.

Aquaporin 1↗
PubMed2001

Nonaccidental pediatric head injury: diffusion-weighted imaging findings.

OBJECTIVE: Diffusion-weighted imaging (DWI) reveals nonhemorrhagic posttraumatic infarction hours to days before conventional computed tomographic scanning or magnetic resonance imaging (MRI). We evaluated the diagnostic utility of DWI in children with nonaccidental head trauma. METHODS: The medical records and imaging examinations obtained between January 1998 and May 2000 for all children less than 2 years of age with presumed or suspected nonaccidental head injury were reviewed retrospectively. Twenty children who had undergone DWI within 5 days of presentation were included in the study. Computed tomographic scans, conventional MRI sequences, and DWI combined with apparent diffusion coefficient (ADC) maps were evaluated. RESULTS: Eleven girls and nine boys (median age, 5 mo) were studied. Eighteen children had presumed nonaccidental head trauma, and two children had suspected nonaccidental head trauma. Of the 18 children with presumed nonaccidental trauma, 16 (89%) demonstrated abnormalities on DWI/ADC, as compared with neither of the two children with suspected nonaccidental trauma. In 13 (81%) of 16 positive cases, DWI revealed more extensive brain injury than was demonstrated on conventional MRI sequences or showed injuries not observed on conventional MRI. DWI combined with ADC maps allowed better delineation of the extent of white matter injury. DWI/ADC abnormalities in the nonaccidental head-injured children were likely to involve posterior aspects of the cerebral hemispheres, with relative sparing of the frontal and temporal poles. Severity on DWI correlated significantly with poor outcome (P < 0.005). CONCLUSION: DWI has broad applications in the early detection of infarction in children with nonaccidental head injury and enhances the sensitivity of conventional MRI. In the patients in this study, early DWI provided an indicator of severity that was more complete than any other imaging modality. The use of DWI may help to identify children at high risk for poor outcome and to guide management decisions.

Accidents, Traffic↗
PubMed2001

Clinical significance of cervicomedullary deformity in Chiari II malformation.

OBJECTIVE: The purpose of this study was to determine if there is a difference in the caudal extent of brain stem herniation and the degree of cervicomedullary deformity between symptomatic and asymptomatic Chiari II patients. METHODS: Magnetic resonance imaging and the clinical presentation of 14 symptomatic and 59 asymptomatic patients were analyzed. The level of the cervicomedullary deformity below the foramen magnum was measured in both groups. The level of the deformity was identified by the cervical vertebral body or disc space level. RESULTS AND CONCLUSION: Review of our results shows no obvious relationship between the level of cervicomedullary deformity and the presenting symptoms or the outcome after surgical decompression. We conclude that the level of herniation and the cervicomedullary deformity is not a reliable marker to determine which patients may become symptomatic and require decompression or to determine prognosis.

Arnold-Chiari Malformation↗
PubMed2000

Neonatal ventriculosubgaleal shunts.

OBJECTIVE: We report on 32 neonates treated with ventriculosubgaleal (VSG) shunts to determine VSG shunt survival and associated complications. METHODS: Between 1993 and 1997, 37 VSG shunts were placed in 32 neonates when the cerebrospinal fluid (CSF) or the abdomen was considered unsuitable for ventriculoperitoneal shunt placement. In each child, a ventricular catheter was attached to 3 cm of a closed-end peritoneal tube via a right-angle connector, which drained into a surgically created subgaleal pocket. RESULTS: The causes of hydrocephalus were as follows: intraventricular hemorrhage (IVH) in 20 neonates, meningitis/ventriculitis in 6, IVH and infection in 2, and other causes in 4. The mean postconception age at the time of VSG shunt insertion was 37.2 weeks (33.1 wk in the IVH group), and the mean weight was 2227 g (1724 g in the IVH group). The average preoperative head circumference was 33.6 cm. The average survival of these 37 VSG shunts (five children had two VSG shunts) was 35.1 days. The complications were as follows: one CSF leakage occurred when sutures were removed; one catheter fell into the ventricle and required removal, and one child died immediately after VSG shunt revision. There were no VSG shunt infections. All surviving children followed for a minimum of 4 months after insertion of a VSG shunt (n = 24) have required a ventriculoperitoneal shunt. Mean follow-up from the time of first VSG shunt insertion was 21.6 months. Four children died as a result of causes unrelated to the VSG shunt. CONCLUSION: VSG shunts offer a simple, effective, and relatively safe means of temporizing hydrocephalus, and they avoid the need for external drainage or frequent CSF aspiration in these medically unstable infants until the CSF characteristics and abdomen are acceptable for ventriculoperitoneal shunting.

Cerebrospinal Fluid Shunts↗
PubMed1999

Ventral brain stem compression in pediatric and young adult patients with Chiari I malformations.

OBJECTIVE: The purposes of this study were as follows: 1) to determine the incidence and degree of ventral brain stem compression (VBSC) in pediatric and young adult patients with Chiari I malformations, and 2) to correlate VBSC with other imaging and clinical factors to help determine what amount of VBSC is successfully treated with a posterior decompressive procedure alone. METHODS: The magnetic resonance images and clinical histories of 40 pediatric and young adult patients with Chiari I malformations were analyzed for subjective grade of VBSC, distance of tonsillar descent, odontoid's relation to Chamberlain's and Wackenheim's line, clival length, foramen magnum diameter, syringomyelia, scoliosis, hydrocephalus, presenting clinical status, treatment, and outcome. To objectively measure the amount of ventral cervicomedullary encroachment by the odontoid and its investing tissues into the rostral spinal canal, a line (B-C2) was drawn between the basion and posteroinferior aspect of the C2 body on a sagittal magnetic resonance image. A line perpendicular to this line, pB-C2, was drawn through the odontoid tip to the ventral dura, and a distance (representing the amount of ventral canal encroachment) was measured. RESULTS: Flattening and distortion of the ventral brain stem were present in 48 and 28% of the patients, respectively. Only two patients had basilar invagination by traditional definitions. pB-C2 measurements correlated with the subjective grade of VBSC (P < 0.05), age, and distance of tonsillar descent (P < 0.05). Eye motion abnormalities and upper cervical osseous anomalies were associated with higher pB-C2 measurements. All patients with a pB-C2 measurement of less than 9 mm were treated successfully with posterior fossa decompression alone despite any subjective VBSC. Some patients with pB-C2 measurements greater than 9 mm had either preoperative neurological deficits or neurological worsening after posterior fossa decompression referable to VBSC. CONCLUSION: Patients with a pB-C2 measurement of less than 9 mm do not require treatment directed at VBSC. In select patients with pB-C2 measurements of 9 mm or greater, reduction of VBSC may be prudent before posterior fossa decompression.

Adolescent↗
PubMed1999

Malignant human gliomas express an amiloride-sensitive Na+ conductance.

Human astrocytoma cells were studied using whole cell patch-clamp recording. An inward, amiloride-sensitive Na+ current was identified in four continuous cell lines originally derived from human glioblastoma cells (CH235, CRT, SKMG-1, and U251-MG) and in three primary cultures of cells obtained from glioblastoma multiforme tumors (up to 4 passages). In addition, cells freshly isolated from a resected medulloblastoma tumor displayed this same characteristic inward current. In contrast, amiloride-sensitive currents were not observed in normal human astrocytes, low-grade astrocytomas, or juvenile pilocytic astrocytomas. The only amiloride-sensitive Na+ channels thus far molecularly identified in brain are the brain Na+ channels (BNaCs). RT-PCR analyses demonstrated the presence of mRNA for either BNaC1 or BNaC2 in these tumors and in normal astrocytes. These results indicate that the functional expression of amiloride-sensitive Na+ currents is a characteristic feature of malignant brain tumor cells and that this pathway may be a potentially useful target for therapeutic intervention.

Amiloride↗
PubMed1998

Death in shunted hydrocephalic children in the 1990s.

Using a combined search of the Children's Hospital (Birmingham, Ala., USA) medical records and the Jefferson County Health Department death records, we reviewed all shunt-related deaths that occurred between January 1990 and July 1996. Of these, we excluded patients who died of nonhydrocephalus-related reasons, such as bronchopulmonary dysplasia, as well as patients who had other serious neurological illnesses such as brain tumor and hydranencephaly. Twenty-eight patients died of shunt-related causes in the 6.5-year period. A survival analysis showed that 96% survived 32 months after first shunting. Of 28 patients, 23 were beyond help prior to medical evaluation. However, at least 10 of these patients had symptoms suggestive of shunt failure at least 24 h and as long as 2 weeks prior to their demise. We conclude that hydrocephalic children still die of shunt failure despite the modern technology of the 1990s. Some of these causes may be avoidable through early detection of symptoms. Guidelines to patients, families, and primary caregivers should be emphasized.

Adolescent↗
PubMed1998

Pitfalls in the diagnosis of ventricular shunt dysfunction: radiology reports and ventricular size.

INTRODUCTION: The diagnosis of shunt malfunction can be difficult even for the experienced clinician and may lead to disastrous circumstances when misinterpreted. Less experienced physicians may rely more on radiographic reports as a primary diagnostic modality. In this study, we evaluated the reliability of using these reports without accurate clinical assessment. METHODS: All shunt revisions seen at Children's Hospital (Birmingham, AL) between January 1996 and August 1996 were reviewed, excluding patients with brain tumors, supratentorial extraaxial fluid collections, and infections. Sixty-eight patients underwent 100 operations for shunt malfunction. All patients had evidence of shunt blockage, disconnection, catheter malposition, or valve pressure incompatibility. The prospective radiographic interpretation of preoperative computed tomography and magnetic resonance imaging scans was reviewed in each case. RESULTS: Twenty-four percent of the reports made no mention of shunt malfunction. In this group, the ventricular system was described as "unchanged," "stable," "normal," "unremarkable," "small," "smaller," "slit," "negative," and "no hydrocephalus," with no other comment to support a diagnosis of shunt malfunction. An additional 9% of reports contained the same terms, while also hinting at some other clinical or radiographic data that suggest the possibility of shunt failure (e.g., a shunt disconnection seen on plain radiographs), despite the scan findings. In all patients in this group, symptoms improved after surgery. CONCLUSION: We conclude that as many as one third of patients presenting with shunt malfunction will not have the diagnosis of shunt malfunction supported by a prospective radiologic interpretation of brain imaging. Although the neurosurgical community can assess the clinical situation to determine the need for surgery, other clinicians can be easily reassured by a radiographic report that does not mention or diagnose shunt malfunction. Today, more than ever, nonneurosurgeons are being called on to evaluate complex clinical situations and may rely on radiographic reports.

Adolescent↗
PubMed1997

A modern analysis of intracranial tumors of infancy.

OBJECTIVE: The management results of pediatric brain tumors should have improved with progress in neurosurgery, intra- and perioperative care, and adjunctive therapy. We assessed the outcomes of 88 consecutive children under 2 years of age with brain tumors managed in the modern era, primarily by two neurosurgeons, and compared the results within the study group over time and to historical controls. METHODS: Medical records were reviewed for diagnosis, location, surgery, surgical morbidity and mortality, adjunctive therapy, and long-term results. Outcomes were available on all 88 patients. RESULTS: Primitive neuroectodermal tumors, astrocytomas, ependymoma, and choroid plexus papillomas in descending order of frequency accounted for two thirds of tumors. Supratentorial location predominated (60%), although in the 1- to 2-year group, there was a slight majority of infratentorial tumors. Surgical mortality and immediate morbidity were 9 and 26%, respectively, with substantial improvements in the last half of the series (2 and 16% with long-term morbidity of 11%). 53 of 88 (60%) of our patients are alive, and all children treated since January 1, 1994, except for 1 operative death, remain alive. CONCLUSION: Children less than 2 years of age remain a multidisciplinary challenge. Improved neuroimaging, surgical and pediatric intensive care management, and neuro-oncological care seems to have improved outcome both with respect to tumor control and neurological function. Aggressive surgery is possible with a good outcome generally expected. Hopefully this will set the stage for either surgical cure in children with benign tumors or combined surgical and adjunctive cure in patients with malignant tumors.

Brain Neoplasms↗
PubMed1993

Urologic consequences of myelodysplasia and other congenital abnormalities of the spinal cord.

Spina bifida and other congenital abnormalities of the spinal cord are relatively common (1 per 1000 births). Early urologic evaluation to determine the extent of neurologic involvement of the lower urinary tract is essential. Urodynamic studies are important in determining voiding pressure and leak pressure and in classifying the type of detrusor and sphincter dysfunction. Therapy is directed toward preservation of the upper tracts. Many nonsurgical (clean intermittent catheterization and anticholinergic drugs) and surgical procedures allow the child to be continent and maintain a normal upper urinary tract. The importance of follow-up is stressed because neurourologic changes frequently occur, and prompt treatment or change of therapy is essential. Today, children with spina bifida are leading healthy, productive lives. A continued multidisciplinary approach to their care is important.

Adolescent↗
PubMed1992

Transcriptional patterns of growth factors and proto-oncogenes in human glioblastomas and normal glial cells.

To document over-expression of proto-oncogenes in tumors, it is necessary to determine the level of expression in the progenitor normal tissue. These studies compare the levels of nuclear transcription of a series of growth-factor related genes and proto-oncogenes in human glioblastoma cell lines with those in three normal glial cell populations. The unusual finding was that levels in the three normal glial cell populations varied considerably for several genes and thus overexpression of a specific gene in a tumor cell when compared to just one normal glial cell population would not necessarily represent overexpression. In this study, we compared the level of 17 genes in 7 tumors to the highest level of each gene found in any of three normal glial cell populations. Over-expression of PDGF-B in 4/7 glioblastoma cell lines, EGFR in 1/7, neu in 1/7 IGF-2 in 1/7 and ros in 2/7 was observed. The variation observed in the normal glial cell populations emphasizes the possibility that the normal glial cell populations represent different glial cell lineages and/or stages of differentiation and that the tumors could have arisen from different normal glial cells. Matching lineages of normal and tumor cells, probably by monoclonal antibody reactions, may be required to accurately define over-expression.

ErbB Receptors↗
PubMed1992

Neurofibromatosis and central nervous system tumors in childhood.

Neurofibromatosis is a multifaceted disease that often results in tumors of the central nervous system. As our understanding of the molecular biology of the disease improves along with better neuroradiology imaging, surgical instrumentation, and adjunctive care, the management schemes for these patients are evolving. This article reviews what is known about neurofibromatosis, common management problems with respect to the central nervous system, and an approach to the handling of these issues.

Brain↗
PubMed1991

Expression of platelet-derived growth factor and transforming growth factor and their correlation with cellular morphology in glial tumors.

This study was undertaken to evaluate the role of two sets of growth factors, platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta), in the induction and maintenance of glial tumors and their phenotypic expression. Explants from eight malignant tumors, five benign tumors, and two nontumor glial cells were analyzed for levels of messenger ribonucleic acid (mRNA) expression of PDGFA, PDGFB, TGF-beta 1, and TGF-beta 2. Results were normalized to the mRNA expression of tubulin, a "housekeeping" gene present in glial cells. Of the 15 explants tested, PDGFB was seen in six, all of which were malignant tumors; PDGFA was seen in all 15 with much higher levels expressed in malignant tumors; and TGF-beta 1 and TGF-beta 2 were seen in all 15 without a clear difference between cell types, although expression tended to be higher in malignant tumors. This project supports the theory that the induction and maintenance of glial tumors is likely to be a multifactorial phenomenon.

Astrocytoma↗