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Biomedical subjects

L E Becker

Publications and source records attributed to L E Becker.

At least 289 records · Page 16Linked to original sources
PubMedDate not supplied

Aberrant neuronal development in hemimegalencephaly: immunohistochemical and Golgi studies.

Immunohistochemical and Golgi studies were performed on 6 patients with hemimegalencephaly. Immunohistochemical staining demonstrated glial, neuronal, and myelin heterotopia in the leptomeninges, cortex, and white matter with glial fibrillary acidic protein, myelin basic protein, and synaptophysin antisera. Golgi studies revealed small and deformed neurons in the superficial layers around abnormal sulci, and hypertrophic neurons with an increased number of dendrites and spines in the deeper cortex. The coexistence of a cell migration disorder, proliferation, and hypertrophy in each patient may imply a growth factor disturbance that controls cell proliferation. These unilateral cerebral malformations suggest that early surgical excision may be beneficial.

Astrocytes↗
PubMedDate not supplied

Postnatal maturation of phrenic nerve in children.

The phrenic nerve at the pericardial level was examined postmortem in 17 children, ages 3 days to 8 years. Detailed macroscopic and histologic examination of the central nervous system in all patients disclosed no abnormalities. Quantitative developmental studies demonstrated that myelinated axons doubled in number from birth to age 1 year when a plateau was reached. The main period of growth in diameter of myelinated axons also corresponded to the first year when median diameters increased from 1.75 microns at 3 days of age to 3.0 microns by 8 months of age. Unmyelinated axons also grew significantly in the first 11 months when median diameters reached 1.4 microns. There was no significant increase in axonal diameter at later ages. The slope of the regression line for the number of myelin lamellae on axonal diameters increased with age until 6 months of age, whereas the dispersion around the regression lines decreased in the same period. This finding suggests a direct relationship between myelination and axonal growth. Significant maturation of the phrenic nerve occurs during the first year of life.

Axons↗
PubMedDate not supplied

Comparison of SPECT, EEG, CT, MRI, and pathology in partial epilepsy.

Twenty children with partial epilepsy who had surgery between the ages of 4 1/2 months and 18 years were studied preoperatively with electroencephalography (EEG), computed tomography (CT), and technetium-99m hexamethylpropyleneamineoxime 99mTc-HmPAO single photon emission computed tomography (SPECT; 20 interictal, 4 postictal). Fourteen had magnetic resonance imaging (MRI). All had an epileptiform focus (12 unilateral, 8 predominantly unilateral) on EEG. The combination of interictal and postictal regional cerebral blood flow (rCBF) abnormalities alone correlated with EEG foci in 16 of 20 patients. Interictal rCBF abnormalities correlated with EEG foci in 14 of 20. CT findings correlated with EEG foci in 14 of 20. MRI findings correlated with EEG foci in 13 of 14. Pathology demonstrated tumor in 6, cortical dysplasia in 4, mesial temporal sclerosis in 3, Sturge-Weber in 2, cavernous hemangioma in 1, Rasmussen encephalitis in 1, porencephalic cyst and gliosis in 1, and cysts found at surgery (but normal histology) in 2. Interictal and postictal SPECT, EEG foci, and CT findings each correlated with the pathology site in 17, 19, and 15 patients, respectively. MRI correlated with pathology site in 13 of 14 patients. Postictal and interictal abnormalities of rCBF correlated with EEG and pathology as frequently as CT. In 5 patients with normal CT scans and in 1 with a normal MRI, postictal and interictal rCBF correlated with EEG and pathology results; however, these 6 patients all had abnormalities on CT or MRI. SPECT, therefore, may be considered a valuable additional diagnostic procedure in the evaluation of epilepsy surgery candidates in that it adds to the evidence of abnormality at the involved site.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Abnormal dendritic development in maple syrup urine disease.

The neuropathology of a 6-year-old boy with maple syrup urine disease revealed spongy appearance of the white matter and marked edema of the brainstem. Golgi studies demonstrated aberrant orientation of neurons together with abnormalities of dendrites and dendritic spines. Similar changes were observed in a patient with dihydropteridine reductase deficiency. Disorders of amino acid metabolism may be associated with alterations in the terminal stages of neuronal migration and maturation.

Brain↗
PubMedDate not supplied

Focal cortical dysplasia in children with localization-related epilepsy: EEG, MRI, and SPECT findings.

A retrospective analysis was conducted of 9 children with focal cortical dysplasia and localization-related epilepsy who underwent epilepsy surgery. Focal cortical dysplasia includes malformed lesions with extensive abnormalities of neuronal morphology, architecture, and lamination. The patients were examined by EEG and video EEG telemetry, CT, MRI, and SPECT using 99mTc-HmPAO. EEG disclosed interictal localized epileptiform activity in 8 patients and nonepileptiform activity with slow waves in 1. Ictal EEG telemetry demonstrated a predominantly localized seizure onset in 8 patients and MRI demonstrated an abnormal loss of gray and white matter distinction in 6. Decreased regional cerebral blood flow (rCBF) was detected in 4 patients by interictal SPECT, and increased rCBF in the same epileptogenic focus in 2 by postictal SPECT. Pathologic analysis found focal cortical dysplasia in 8 patients. One had extensive focal polymicrogyria, pachygyria, and extensive white matter heterotopias. It is concluded that MRI can detect focal cortical dysplasia, which corresponds to the epileptogenic focus on EEG, and SPECT may help to detect a functional abnormality in the same region.

Adolescent↗
PubMedDate not supplied

No induction versus anti-IL2R induction therapy in simultaneous kidney pancreas transplantation: a comparative analysis.

UNLABELLED: The optimal immunosuppressive regimen for simultaneous kidney pancreas transplantation (SKPT) is still not established. We conducted a study to compare the safety and efficacy of no induction versus anti-IL-2 receptor induction protocols in SKPT recipients receiving the same maintenance regimen. METHODS: Sixty-three SKPT recipients were divided into two groups: no induction group (n = 42) and anti-IL-2 receptor induction group (n = 21). All patients were maintained on tacrolimus, mycophenolate mofetil, and prednisone. Primary endpoints were 1-year acute rejection incidence and patient and graft survivals. RESULTS: Demographic characteristics were similar between the groups. Acute rejection incidence at 1 year was equal in both groups (28.6%). Kidney and pancreas allograft survival in the no induction group were 78.6% and 76.2%, and in the anti-IL-2R induction group, 81% and 71.4%, respectively (P = NS). Patient survival was also similar: 83.3% in the no induction versus 85.7% in the anti-IL-2R induction group. Deaths due to sepsis were higher in the anti-IL-2R induction group, albeit not significantly. CONCLUSION: The use of a no-induction protocol in SKPT is safe and effective immunosuppression that also reduces transplantation costs.

Adult↗
PubMedDate not supplied

Co-expression of nestin and vimentin intermediate filaments in invasive human astrocytoma cells.

Intermediate filaments (IFs) are highly diverse intracytoplasmic proteins within the cytoskeleton which exhibit cell type specificity of expression. A growing body of evidence suggests that IFs may be involved as collaborators in complex cellular processes controlling astrocytoma cell morphology, adhesion and proliferation. As the co-expression of different IF subtypes has been linked to enhanced motility and invasion in a number of different cancer subtypes, we undertook the present study to examine the expression of vimentin and nestin in a panel of human astrocytoma cell lines whose tumorigenicity, invasiveness and cytoskeletal protein profiles are well known. Astrocytoma cells were examined for IF protein expression by immunofluorescence confocal and immunoelectron microscopy. The motility of all cell lines was determined by computerized time-lapse videomicroscopy. Invasive potential of astrocytoma cells was determined using Matrigel as a barrier to astrocytoma cell invasion in vitro. Vimentin was expressed by all astrocytoma cell lines. On the other hand, nestin was variably expressed among the different cell lines. The most motile and invasive astrocytoma cell line in our study was antisense GFAP-transfected U251 (asU251) astrocytoma cells which showed marked up-regulation of nestin expression compared to the U251 parental cell line and controls. The U87 astrocytoma cell line also demonstrated high nestin expression levels and was associated with an increased basal motility rate and a high degree of invasiveness through Matrigel. U343 astrocytoma cells did not express nestin, but had high levels of GFAP. It had the lowest motility rate and invasiveness of all the astrocytoma cell lines examined. Taken together, these data suggest that for the astrocytoma cell lines examined in this study, nestin and vimentin co-expression may serve as a marker for an astrocytoma cell type with enhanced motility and invasive potential. Further studies are required to determine the mechanism by which dual-IF protein expression alters other cytoskeletal or cell surface receptor protein components important in the process of astrocytoma invasion.

Astrocytoma↗
PubMedDate not supplied

Tuberin expression in ganglioglioma.

The expression of tuberin in neurosurgically resected gangliogliomas was investigated. Neither neoplastic astrocytes nor abnormal, multipolar large neurons showed immunoreactivity for tuberin. The reduced immuno-histochemical staining for tuberin was consistent with the reduction observed in Western blot analysis. Eosinophilic granular bodies and Rosenthal fibers were strongly immunoreactive for tuberin. The accumulation of tuberin in astrocytes with intracellular degenerative changes suggests increased expression in reactive cells, and perhaps a broader role for tuberin in central nervous system disease.

Adolescent↗
PubMedDate not supplied

Vascular pathology in galactosialidosis.

This article immunohistochemically and ultrastructurally examines a brain with galactosialidosis, focusing on the structure of blood vessel endothelium. Lysosomes were observed in the expanded cytoplasm of the endothelial cells, which were vacuolated by light microscopy. Immunoreactivity for CD31, one of the vascular cell adhesion molecules, was minimal to faint in endothelial cells with vacuolations. The loss of CD31 immunoreactivity and breakdown of vascular cell adhesion molecules in vacuolated endothelial cells seem to promote the development of brain infarctions. Moreover, diffuse and various degrees of axonal damage, most likely caused by vascular disorder in cerebral or cerebellar white matter, was reported using the amyloid precursor protein (APP) immunohistochemical method.

Amyloid beta-Protein Precursor↗
PubMedDate not supplied

Tumor cell apoptosis present at diagnosis may predict treatment outcome for patients with medulloblastoma.

PURPOSE: To determine if the degree of tumor cell apoptosis at diagnosis predicts outcome, tissue sections of medulloblastoma were examined and the amount of apoptosis and progression-free survival were correlated. PATIENTS AND METHODS: The study cohort consisted of 43 children in whom medulloblastoma was diagnosed between 1984 and 1995: 29 patients at high risk (HR) treated with radiation and chemotherapy, and 14 children at low risk (LR) treated with radiation alone. A terminal deoxynucleotidyl transferase (TdT) end-labeling assay was used to detect apoptosis in paraffin-embedded tissue sections prepared at diagnosis. RESULTS: Progression-free survival was examined in cohorts of children whose tumors were divided into quartiles based on the apoptotic index (AI) of their pretreatment tumor specimens. A comparison of these four groups of children revealed an association between AI and outcome (p = 0.03); patients with tumors in the highest AI quartile had substantially improved outcome compared to all other patients combined (p = 0.02). In this cohort of patients treated with different therapies, assignment at the time of diagnosis to LR and HR groups based on widely-accepted clinical criteria was not closely associated with outcome (p = 0.47). CONCLUSION: AI is a strong indicator of treatment outcome for children with medulloblastoma after treatment with cytotoxic therapy, independent of risk group. Because HR and LR patients included in this study received different modalities of cytotoxic therapy, it is possible that AI predicts outcome independent of the precise antineoplastic therapy a patient receives.

Adolescent↗
PubMedDate not supplied

Chronic focal encephalitis (Rasmussen syndrome): six cases.

Six of 81 (7.4%) patients with medically intractable epilepsy treated by selective cortical excision at The Hospital for Sick Children, Toronto, Canada, since 1974 were found to have inflammatory changes in the excised specimens of cerebral cortex. The clinical and histopathological findings in these cases resemble the chronic encephalitic syndrome described by Rasmussen. We confirm the unsatisfactory seizure control and the guarded neurological and intellectual prognosis that has been associated with Rasmussen syndrome.

Adolescent↗
PubMedDate not supplied

CD44 expression in tuberous sclerosis.

CD44, a cell adhesion molecule, mediates cell-cell and cell-matrix interactions. In the central nervous system, CD44 is expressed in astrocytic processes, predominantly in white matter and subpial regions, suggesting its involvement in the maintenance of a stable central nervous system cytoarchitecture. In this study, we investigated immunohistochemically the expression of CD44 and glial fibrillary acidic protein in neurosurgically resected specimens of patients with or without tuberous sclerosis. In controls, CD44 immunoreactivity was noted in the processes of astrocytes close to blood vessels and subpial cortex. Glial fibrillary acidic protein immunoreactivity was noted in both cell bodies and cytoplasmic processes of astrocytes in white matter. In tubers, CD44 antigen was also noted in the processes of astrocytes close to blood vessels and pial surface, and in abundance in the network of astrocyte processes. Moreover, CD44 antigen showed immunoreactive halos around balloon cells in tubers and around tumor cells in subependymal lesions. Glial fibrillary acidic protein antigen was noted in both cell bodies and cytoplasmic processes of some balloon cells in tubers, but not in tumor cells. In Western blot analyses, the CD44 immunoreactive band was more intense in tubers or subependymal giant-cell tumors than in control tissue. This increase in CD44 antigen seemed to correlate with the degree of astrogliosis. Immunoreactivity surrounding the cell surfaces of balloon or tumor cells suggests that the clustering of these cells may be due to the expression of CD44. Glial fibrillary acidic protein immunoreactive band was detected in tubers, but not in subependymal giant cell tumors.

Adolescent↗
PubMedDate not supplied

Intracranial meningiomas in children.

Thirteen cases of intracranial meningioma presenting in childhood were encountered at the Hospital for Sick Children in Toronto over a 51-year period. The clinical features, radiology, operative findings and outcome are reviewed.

Adolescent↗
PubMedDate not supplied

Intracranial germ cell tumors in children: an immunohistochemical and electron microscopic study.

From a review of a series of 1,474 intracranial tumors occurring in children, we identified 49 patients (3.3%) with primary intracranial germ cell tumors: 65% germinomatous, 26% nongerminomatous (8 teratomas, 3 endodermal sinus, and 2 choriocarcinomas), and 8 degrees 10 mixed. Placental alkaline phosphatase was present in all germinomas tested. Human chorionic gonadotropin was identified in 7 patients, cytokeratin in 6, and alpha-fetoprotein in 4. The results of immunostaining with antisera against glial fibrillary acidic protein, desmin, and vimentin were essentially negative. Electron microscopy played an important role in confirming the diagnosis in patients with endodermal sinus and mixed tumors. The correct identification of mixed and non-germ-cell tumors requires adequate tumor sampling and proper preparation of tissue for immunohistochemical and electron microscopic examination.

Biomarkers, Tumor↗