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Biomedical subjects

L E Becker

Publications and source records attributed to L E Becker.

At least 55 records · Page 3Linked to original sources
PubMed1997

Positive epileptiform discharges in children with neuronal migration disorders.

Most epileptiform abnormalities show a negative polarity on EEG. Focal positive spike waves have rarely been identified in seizure disorders and are generally associated with physiological and neurological impairment. Results of EEG, computed tomography, MRI, and pathologic studies of 15 children with focal neuronal migration disorders who underwent surgery for refractory localization-related epilepsy were compared to examine the association between positive discharges and other findings. Subjects were studied both ictally and interictally by scalp EEG with the International 10-20 system and zygomatic or sphenoidal electrodes, and video EEG telemetry. The 5 children with positive discharges were significantly more likely to develop hemiparesis during the preoperative period (P < or = .025). Correlations were observed between positive discharges and lesions apparent on MRI situated around the rolandic fissure (P < or = .025). Children with positive discharges had a significantly less favorable outcome after surgical treatment (P < or = .025). Positive epilepti-form discharges in children with neuronal migration disorders may signal a more dysfunctional cortex leading to a focal neurological deficit or a more extended lesion than is detected on MRI. This would explain the less favorable outcome of seizures after surgery, since the epileptogenic areas and neuronal migration lesions cannot be completely resected.

Brain↗
PubMed1997

Immunohistochemical expression of cell adhesion molecule L1 in hemimegalencephaly.

We demonstrated immunohistochemically an abnormal expression of the neural cell adhesion molecule L1 in 10 developing brains of children with hemimegalencephaly (HM) aged from 36 weeks gestation to 10 years of age, comparing them with 23 controls aged from 13 weeks of gestation to 14 years. There was dense L1 expression in focal regions of the molecular layer beneath leptomeningeal glioneuronal heterotopia, in areas of cerebral cortex with large neurons, and in the disorganized or neuronal heterotopic sites in the white matter in HM. L1 was also heterogeneously enhanced in the abnormal cortex after 1 year of age, suggesting that axonal growth was delayed. These changes persisted into the older age group in the abnormal areas of cortex in HM. The cell bodies of many enlarged neurons in HM were immunopositive for L1, whereas L1 was usually localized to the processes of normal neurons. The delayed L1 immunoreactivity and enlarged L1-immunopositive neurons may be closely related to the pathogenesis of unilateral megalencephaly with cortical dysplasia and heterotopia.

Adolescent↗
PubMed1997

Evidence of abnormal differentiation in giant cells of tuberous sclerosis.

To characterize the giant cells in tuberous sclerosis, we examined immunoreactivity for nestin, vimentin, microtubule-associated protein 1B (MAP1B), MAP2, neurofilament, and glial fibrillary acidic protein (GFAP) in cortical tubers detected in brain specimens from 6 patients with tuberous sclerosis who had undergone surgical resection for treatment of intractable epilepsy. Giant cells with a neuronal appearance, "neuron-like giant cells," had a round centrally-placed nucleus with a single, prominent nucleolus, and Nissl substance was commonly present in cortex. These neuron-like giant cells demonstrated consistently strong immunoreactivity for neurofilament and MAP1B and occasional immunopositivity for nestin and vimentin and were rarely positive for GFAP. "Indeterminate giant cells," characterized by abundant cytoplasm, an absence of Nissl substance, and one or more eccentric nuclei, demonstrated consistent immunoreactivity for nestin, vimentin, and MAP1B and were rarely positive for neurofilament, but more than half displayed immunoreactivity for GFAP. These observations suggest that the indeterminate giant cells exhibit limited neuronal and inconsistent astroglial characteristics, implying aberrant cellular differentiation in tuberous sclerosis.

Cell Differentiation↗
PubMed1997

Optic chiasmatic-hypothalamic glioma.

Optic chiasmatic-hypothalamic gliomas (OCHGs) have been considered benign tumors and self-limiting in growth potential because of their histological appearance. Unfortunately, most clinical series have reported significant morbidity and mortality especially with the more extensive, posteriorly positioned tumors. The biological behavior of OCHGs is age-dependent, with patients younger than five years and older than 20 years typically having tumors that exhibit aggressive growth. There are no specific pathological features to help differentiate the clinical behavior of such tumors. The emergence of modern imaging techniques, including magnetic resonance imaging (MRI), has facilitated the monitoring of the natural history of the disease and the determination of the effects of therapy. Most patients with OCHGs survive for many years. While the natural history of an OCHG for any individual may be indeterminate, enough data are now available from large series to make recommendations for treatment. Our current treatment policy for patients with OCHGs in the context of NF-I without visual failure is a conservative one involving CSF shunting for hydrocephalus if present and medical therapy for endocrinologic dysfunction. Patients with or without NF-I with visual deterioration or progressive neurological deficits and a rapidly expanding suprasellar mass lesion are treated surgically. After tumor resection, patients whose vision is significantly compromised or who show progression of their disease on serial neuroimaging scans receive chemotherapy. If chemotherapy proves ineffective in disease stabilization, then considerations of radiation therapy are given to children over five years old.

Child, Preschool↗
PubMed1997

Developmental change of the nestin-immunoreactive midline raphe glial structure in human brainstem and spinal cord.

To elucidate the development of the midline raphe glial structure (MRGS) in human brainstem and spinal cord, immunohistochemistry was carried out in 10 developmentally normal brains (age range, 11 weeks postconception to 6 months) using antibodies to nestin and glial fibrillary acidic protein (GFAP). Nestin expression was most extensive in the youngest fetus (11 weeks postconceptional age, PCA), which showed strong immunoreactivity in radial glial fibers in the midline raphe and paramedian areas of brainstem and spinal cord. Nestin-immunoreactive radial glial fibers in the midline raphe gradually decreased in length and intensity, losing contact with the pial surface 20-24 weeks PCA. Radial glial cells in midbrain transformed into subependymal cells at 30 weeks PCA. Some fragments of radial fibers in brainstem and spinal cord could still be detected up to 30 weeks PCA. Weak GFAP immunoreactivity in the midline raphe was found in radial fibers in the dorsal midline of the midbrain and cervical spinal cord at 30 and 38 weeks PCA. This change of nestin positivity was thought to be due to the process remodeling the MRGS, not to the intracellular distribution and any identifiable clinical factors in the stillbirths. This irregularity in the appearance of the MRGS supports its proposed role as a guide for cell migration, a potential source of new astrocytes, and a barrier to aberrant decussation of growing axons.

Brain Stem↗
PubMed1997

Peripheral chemoreceptors in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) is a rare disorder of unknown etiology, characterized by failure of the autonomic control of respiration. The primary defect is believed to involve central respiratory control; however, no specific lesion has been identified. We report two cases of CCHS (one female, 3 mo of age and one male 2 yr of age) in which there was detailed examination of the neural, muscular, and chemoreceptor components of respiratory control. Although no specific abnormalities were identified in the central nervous system (CNS) or muscles of respiration, striking changes were observed in arterial chemoreceptors, carotid bodies (CB), and airway chemoreceptors, neuroepithelial bodies (NEB). In both cases, CB were small (< 50% of control), with a marked decrease in the number of glomus cells identified by immunostaining for tyrosine hydroxylase and serotonin. Ultrastructural analysis of glomus cells in Case 1 showed a marked decrease in the frequency of dense core vesicles (< 20% of control), the storage site of amine and peptide neurotransmitters. Immunostaining for S100 protein, a marker of sustentacular or Type II cells, was increased up to twofold compared with controls. In the lung, the frequency and size of NEB immunostained for bombesin was increased twofold in both cases, suggesting compensatory hyperplasia of airway chemoreceptors. Since intact peripheral chemoreceptors are essential for respiratory control, especially the response to hypoxia, abnormalities in CB and NEB may contribute to the pathophysiology of CCHS and related conditions such as sudden infant death syndrome (SIDS).

Bombesin↗
PubMed1997

Role of glial filaments in cells and tumors of glial origin: a review.

In the adult human brain, normal astrocytes constitute nearly 40% of the total central nervous system (CNS) cell population and may assume a star-shaped configuration resembling epithelial cells insofar as the astrocytes remain intimately associated, through their cytoplasmic extensions, with the basement membrane of the capillary endothelial cells and the basal lamina of the glial limitans externa. Although their exact function remains unknown, in the past, astrocytes were thought to subserve an important supportive role for neurons, providing a favorable ionic environment, modulating extracellular levels of neurotransmitters, and serving as spacers that organize neurons. In immunohistochemical preparations, normal, reactive, and neoplastic astrocytes may be positively identified and distinguished from other CNS cell types by the expression of the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). Glial fibrillary acidic protein is a 50-kD intracytoplasmic filamentous protein that constitutes a portion of, and is specific for, the cytoskeleton of the astrocyte. This protein has proved to be the most specific marker for cells of astrocytic origin under normal and pathological conditions. Interestingly, with increasing astrocytic malignancy, there is progressive loss of GFAP production. As the human gene for GFAP has now been cloned and sequenced, this review begins with a summary of the molecular biology of GFAP including the proven utility of the GFAP promoter in targeting genes of interest to the CNS in transgenic animals. Based on the data provided the authors argue cogently for an expanded role of GFAP in complex cellular events such as cytoskeletal reorganization, maintenance of myelination, cell adhesion, and signaling pathways. As such, GFAP may not represent a mere mechanical integrator of cellular space, as has been previously thought. Rather, GFAP may provide docking sites for important kinases that recognize key cellular substrates that enable GFAP to form a dynamic continuum with microfilaments, integrin receptors, and the extracellular matrix.

Animals↗
PubMed1997

Overexpression of nestin and vimentin in the ependyma of spinal cords from hydrocephalic infants.

The ependyma of the spinal central canal in cases of hydrocephalus shows abnormalities which vary with the aetiology of ventricular dilatation. To determine whether these ependymal changes are developmental or reactive in nature, immunohistochemical findings were compared between nine normal controls and 12 cases of hydrocephalus (three each of congenital aqueductal stenosis. Dandy-Walker malformation, Chiari type II malformation, and post-haemorrhagic hydrocephalus) using antisera to nestin, vimentin and glial fibrillary acidic protein. The main pathological findings were disruption of ependymal layer, apparent pseudostratification of ependyma, expansion, cleft or syrinx formation in relation to the central canal, and ependymal rosette formation. In normal developing fetal spinal cord, nestin and vimentin were expressed mainly in pseudostratified ependymal cells and radial fibres in the median septum. In cases with congenital hydrocephalus (congenital aqueductal stenosis. Dandy-Walker malformation, and Chiari type II malformation), nestin was overexpressed in immature ependymal cells, and strong vimentin immunoreactivity was detected in the long tract of radial fibres in the median septum. Nestin and vimentin were also expressed in small cells and their fibres which covered areas denuded of ependymal cells in cases of Chiari type II malformation and post-haemorrhagic hydrocephalus. Two conclusions are suggested by this report. First, the ependyma of the spinal central canal in congenital hydrocephalus shows a delay in maturation of radial glial cells into mature astrocytes and ependymal cells. Second, areas of ependymal denudation may be repaired by the immature glial cells derived from subependymal cells.

Ependyma↗
PubMed1996

Terminal deletion of the long arm of chromosome 3 [46,XX,del(3)(q27-->qter)].

We report on a terminal deletion of the long arm of chromosome 3 [46,XX,del(3)(q27-->qter)] in a female newborn infant who died 45 hours after delivery and had multiple congenital abnormalities including bilateral anophthalmia, congenital heart disease, and abnormal genitalia. The findings are compared to those of four previously reported cases with terminal del (3q).

Abnormalities, Multiple↗
PubMed1996

Enhanced expression of microtubule-associated protein 2 in large neurons of cortical dysplasia.

To evaluate neuronal cytoarchitectural changes in cortical dysplasia, we examined microtubule-associated protein 2 (MAP2) expression in surgically resected specimens obtained from 20 patients (age range, 3 months to 10 years) treated for intractable epilepsy. Large neurons were investigated in the specimens from all patients and showed significantly strong immunoreactivity with antibodies against MAP2 in the perikaryon and proximal portion of their processes. In situ hybridization with MAP2 antitense riboprobe showed increased hybridization signal intensities in the large neurons, which correlated with the pattern of immunoreactivity for MAP2. We conclude that MAP2 is strongly expressed in the large neurons in cortical dysplasia. The results of preliminary immunoblotting in 1 patient with focal cortical dysplasia showed that the low-molecular-weight form of MAP2 (MAP2c) was strongly expressed in the dysplastic cortex, suggesting that MAP2c may be a major component contributing to the increased expression of MAP2 in the large neurons of cortical dysplasia. Since it has been suggested that MAP2 plays a crucial role in the branching and remodeling of neuronal processes, increased expression of MAP2 may reflect activated plasticity of the large neurons in cortical dysplasia.

Base Sequence↗
PubMed1996

Cellular and molecular pathology of medulloblastoma.

Medulloblastoma is a malignant embryonal tumor predominantly of childhood. It occurs principally in the midline cerebellar region but is prone to invade the meninges and cerebrospinal fluid spaces. It is the principal posterior fossa tumor in children and represents 20% of all brain tumors in this age group. Considerable advances have been made in characterizing the morphologic subtypes, immunophenotypes, and in vitro behavior of cell lines. However, the cell of origin and its relationship to other related primitive neuroectodermal tumors remains uncertain. Although recent advances in the application of proliferation markers and the use of apoptosis in situ labelling have been applied, a prognostically relevant marker applicable to surgical neuropathology remains to be developed. The fundamental molecular pathogenesis of tumor development remains unknown, although recent exciting advances have shown alterations in some members of the PAX family of genes as well as increased expression of neurotrophin receptors. These may prove to be of prognostic significance.

Adult↗
PubMed1996

Expression of stromelysin 1 in human astrocytoma cell lines.

In a wide variety of tumor types, the expression of stromelysin 1 which is one of the matrix metalloproteinases (MMPs) has been shown to correlate with tumor invasion. However, little is known about the distribution of stromelysin in human brain tumors. We have previously shown that a correlation exists between the type IV collagenases, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 transcripts and in vitro invasiveness among 7 human astrocytoma cell lines. In the present study, we analyzed the expression of stromelysin 1 among the same panel of human astrocytoma cell lines and human fibroblasts by northern blot analyses and in situ hybridization. Northern blot analysis demonstrated that SF-126 and U87 MG expressed high level stromelysin 1 transcripts. Following heat shock stimulation, the stromelysin 1 transcript was up-regulated in U87 MG astrocytoma cells. In situ hybridization analysis showed specific intracytoplasmic localization of mRNA for stromelysin in these astrocytoma cell lines. By casein zymography, we have determined that both SF-126 and U87 MG secreted stromelysin 1 protein. We conclude that stromelysin 1 is expressed by certain human astrocytoma cell lines, and this study confirms the importance of continuing to characterize the proteolytic enzyme profile of these tumors to fully understand the molecular mechanisms involved in astrocytoma invasiveness.

Astrocytoma↗
PubMed1996

Overexpression of nestin and vimentin in ependymal cells in hydrocephalus.

In order to elucidate the immunohistochemical features of hydrocephalic ependyma, immunohistochemical examination was undertaken in 11 normal, postmortem brains (age range, 11 weeks' postconception to 6 months after birth) and 12 hydrocephalic brains (three cases each of congenital aqueductal stenosis, Dandy-Walker malformation, Arnold-Chiari type II malformation and posthemorrhagic hydrocephalus) by using antisera to nestin, vimentin and glial fibrillary acidic protein (GFAP). In normal brains, nestin was predominantly expressed in neuroepithelial cells and radial glial fibers during the period of neuronal migration. Vimentin immunoreactivity was principally detected in immature ependymal cells and their basal fibers after the period of neuronal migration, then partly replaced by GFAP reactivity during late gestation. In hydrocephalus, the areas of ependymal disruption were covered with nestin- or vimentin-positive cells. Nestin and vimentin were also expressed in immature ependymal cells or their basal processes in anatomical regions such as the roof or floor plate of the fourth ventricle or the cerebral aqueduct, and the ventral part of the third ventricle. These results suggest that the overexpression of nestin and vimentin in hydrocephalus follows two patterns: a reactive pattern of proliferating immature glial cells associated with ependymal cell loss and an abnormal developmental pattern of immunopositivity associated with anatomical regions in the midline mesencephalon.

Brain↗
PubMed1996

Intraventricular rhabdomyosarcoma after resection of hyperplastic choroid plexus.

Primary intracranial rhabdomyosarcoma is extremely rare. Here, a case that is most consistent with a botryoid rhabdomyosarcoma is described in a 4.5-year-old boy. The case is unique because it was preceded by a congenital Dandy-Walker malformation, choroid plexus hyperplasia and an enormous oversecretion of cerebrospinal fluid during infancy.

Brain Diseases↗
PubMed1996

Accumulation of S100 beta mRNA and protein in cerebellum during infancy in Down syndrome and control subjects.

S100 protein is a 20 kDA calcium-binding protein that accumulates during CNS maturation in mammals. The human gene coding for the beta subunit of S100 protein (S100 beta) is located on chromosome 21, in a subtelomeric position in 21q22.3. In order to investigate the effect of trisomy 21 on S100 beta gene expression, we performed Southern, Northern and Western blot analysis on DNA, RNA and protein, respectively, extracted from the cerebellum of control and Down syndrome (DS) subjects aged 1-18 months. Southern blot analysis revealed a novel EcoRI polymorphism in the S100 beta gene in two of 15 DNA samples examined, and a 1.5 gene dosage for S100 beta in DS. Northern and Western blot analysis showed an approximately 10-fold increase in S100 beta mRNA and protein levels between 1 and 18 months. No differences in the rates of accumulation of S100 beta mRNA and protein were observed between DS and normal subjects. These results demonstrate an increase in S100 beta mRNA and protein levels during infancy indicative of postnatal astrocytic maturation and show that there is no gross deregulation in the expression of the S100 beta gene in DS as a consequence of trisomy 21.

Age Distribution↗
PubMed1996

Synaptic alterations of anterior horn cells in Werdnig-Hoffmann disease.

The most characteristic neuropathologic feature of Werdnig-Hoffmann disease is degenerative change in the anterior horn cells of the spinal cord, the mechanisms of which have not yet been clearly determined. To assess the synaptic changes in the motor neurons, we examined immunoreactivities for synaptophysin in the spinal cord of 11 patients with Werdnig-Hoffmann disease. Decreased synaptophysin immunoreactivity was observed in the anterior horn cell column in all patients with Werdnig-Hoffmann disease and correlated with the degree of degenerative change in the motor neurons. Synaptophysin immunoreactivity was relatively preserved on the surface of the residual anterior horn cells. Both atrophic neurons and chromatolytic neurons had dense accumulations of synaptophysin-immunoreactive products on the surface of the cell body and their proximal processes. These observations suggest that synaptic changes in the anterior horn cell column are secondary to the degenerative processes of the anterior horn cells.

Anterior Horn Cells↗
PubMed1996

Relationship of substance P and gliosis in medulla oblongata in neonatal sudden infant death syndrome.

Substance P and glial fibrillary acidic protein (GFAP) immunohistochemistry was applied to the medulla of neonatal infants who died of sudden infant death syndrome (SIDS). A quantitative analysis of cells demonstrating immunoreactivity to GFAP and substance P in 15 neonatal SIDS cases revealed increased GFAP immunoreactivity in the reticular formation, the dorsal vagal nucleus, and the solitary nucleus and an increase in substance P immunoreactivity in the spinal trigeminal nucleus and the solitary nucleus as compared with that in age-matched controls. GFAP immunopositivity suggests astrogliosis which implies a pathologic insult to neurons in the area of astrogliosis. The failure of neurons in these sites to show enhanced substance P immunopositivity may indirectly indicate altered neurons. Further study of prenatal events may be of importance in clarifying the pathogenesis of neonatal SIDS.

Chi-Square Distribution↗