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J T Rutka

Publications and source records attributed to J T Rutka.

At least 37 records · Page 2Linked to original sources
PubMed2001

Image-guided, frameless stereotactic sectioning of the corpus callosum in children with intractable epilepsy.

Corpus callosotomy is an effective neurosurgical procedure for children with intractable atonic or drop attack seizures. While this procedure has not changed significantly over the past three decades, some technical issues remain to be resolved. These include the intraoperative determination of the extent of the callosotomy, the need to stage the procedure, as well as side of approach of craniotomy. We report our 8-year experience with corpus callosotomy using a frameless stereotactic image-guided system (ISG Viewing Wand). Seventeen children with atonic seizures underwent sectioning of the corpus callosum. The mean patient age was 10.5 years. Six children underwent complete callosotomy while 11 underwent resection of the anterior two-thirds. MRI 3D reconstruction of the sagittal sinus and draining cerebral veins was undertaken in all cases. The side of the craniotomy was determined on the basis of favorability of the draining veins with respect to the extent of the callosotomy. The extent of the callosotomy was determined by intraoperative feedback using the ISG Viewing Wand((R)). Nine of 11 patients in the partial callosotomy group and 4 of 6 patients in the complete callosotomy group showed significant improvement in atonic seizures. We conclude that the use of frameless stereotaxy can function as an important adjunct in the planning and conduction of successful sectioning of the corpus callosum in children with intractable seizures.

Adolescent↗
PubMed2001

Comparison of electroencephalographic dipoles of interictal spikes from prolonged scalp video-electroencephalography and magnetoencephalographic dipoles from short-term recording in children with extratemporal lobe epilepsy.

We retrospectively compared electroencephalographic (EEG) dipoles of interictal spikes from prolonged video-EEG monitoring with magnetoencephalographic dipoles from short-term recording in four children with extratemporal lobe epilepsy. We analyzed both sets of dipoles using individual interictal spikes and single moving dipole modeling and evaluated the profiles of spike appearance, dipole position, and orientation in EEG and magnetoencephalography. We obtained more than 100 magnetoencephalographic spikes in two patients who manifested frequent interictal EEG spikes throughout both day and night but fewer than 40 magnetoencephalographic spikes in two patients who had interictal EEG spikes mainly during sleep. The dipole positions of EEG and magnetoencephalography were in close proximity and included in the surgical resection area. Most of the dipoles between EEG and magnetoencephalography were oriented perpendicularly. A combination of EEG dipole analysis from prolonged video-EEG monitoring and magnetoencephalographic dipole analysis provides complementary information for presurgical evaluation in children with intractable extratemporal lobe epilepsy.

Adolescent↗
PubMed2001

Tracking the invasiveness of human astrocytoma cells by using green fluorescent protein in an organotypical brain slice model.

OBJECT: Although it is known that malignant astrocytomas infiltrate diffusely into regions of normal brain, it is frequently difficult to identify unequivocally the solitary, invading astrocytoma cell in histopathological preparations or experimental astrocytoma models. The authors describe an experimental system that facilitates the tracking of astrocytoma cells by using nonneoplastic cerebral tissue as the substrate for invasion. METHODS: Cerebral tissue was cut into 1-mm-thick slices and cultured in the upper chamber of a Transwell culture dish on top of a polyester membrane (0.4-mm pore size) that was bathed in medium supplied by the lower chamber. Two astrocytoma cell lines, U-87 MG (U87) and U343 MG-A (U343), were selected because of their differing basal cell motilities in monolayer cultures. The astrocytoma cells were stably transfected with vectors that expressed green fluorescent protein (GFP), either alone or as a fusion protein with the receptor for hyaluronic acid-mediated motility (RHAMM) in either sense or antisense orientations. Stably transfected clones that had high levels of GFP expression were selected using the direct visualization provided by fluorescence microscopy and fluorescence-activated cell-sorter analysis. The GFP-expressing astrocytoma cell clones were implanted into the center of the brain slice and the degree of astrocytoma invasion into brain tissue was measured at different time points by using the optical sectioning provided by the confocal laser microscope. The authors observed that GFP-expressing astrocytoma cells could be readily tracked and followed in this model system. Individual astrocytoma cells that exhibited green fluorescence could be readily identified following their migration through the brain slices. The GFP-labeled U87 astrocytoma cells migrated farther into the brain slice than the U343 astrocytoma cells. The RHAMM-transfected GFP-labeled astrocytoma cells also infiltrated farther than the GFP-labeled astrocytoma cells themselves. The expression of antisense RHAMM virtually abrogated the invasion of the brain slices by both astrocytoma cell lines. CONCLUSIONS: The authors believe that this organotypical culture system may be of considerable utility in studying the process of astrocytoma invasion, not only because it provides a better representation of the extracellular matrix molecules normally encountered by invading astrocytoma cells, but also because the GFP tag enables tracking of highly migratory and invasive astrocytoma cells under direct vision.

Astrocytoma↗
PubMed2001

Computerized brain-surface voltage topographic mapping for localization of intracranial spikes from electrocorticography. Technical note.

The purpose of this paper is to describe the use of computerized brain-surface voltage topographic mapping to localize and identify epileptic discharges recorded on electrocorticographic (ECoG) studies in which a subdural grid was used during intracranial video electroencephalographic (IVEEG) monitoring. The authors studied 12 children who underwent surgery for intractable extrahippocampal epilepsy. Cortical surfaces and subdural grid electrodes were photographed during the initial surgery to create an electrode map that could be superimposed onto a picture of the brain surface. Spikes were selected from ictal discharges recorded at the beginning of clinically confirmed seizures and from interictal discharges seen on ECoG studies during IVEEG recording. A computer program was used to calculate the sequential amplitude of the spikes by using squared interpolation, and they were then superimposed onto the electrode map. Interictal discharges and high-amplitude spike complexes at seizure onset were plotted on the map. This mapping procedure depicted the ictal zone in nine patients and the interictal zone in 12, and proved to be an accurate and useful source of information for planning corrective surgery.

Action Potentials↗
PubMed2001

A method to estimate urinary electrolyte excretion in patients at risk for developing cerebral salt wasting.

OBJECT: Two major criteria are necessary to diagnose cerebral salt wasting (CSW): a cerebral lesion and a large urinary excretion of Na+ and Cl- at a time when the extracellular fluid (ECF) volume is contracted. Nevertheless, it is difficult for the physician to confirm from bedside observation that a patient has a contracted ECF volume. Hyponatremia, although frequently present, should not be a criterion for a diagnosis of salt wasting. A contracted ECF volume is unlikely if there are positive balances of Na+ and Cl-. The goal of this study was to assess the accuracy of calculating balances for Na+ plus K+ and of Cl- over 1 to 10 days in an intensive care unit (ICU) setting. METHODS: A prospective comparison of measured and estimated quantities of Na+ plus K+ and of Cl- excreted over 1 to 10 days in 10 children and 12 adults who had recently received a traumatic brain injury or undergone recent neurosurgery. Plasma concentrations of electrolytes were recorded at the beginning and end of the study period. The total volumes infused and excreted and the concentrations of Na+, K+, and Cl- in the infusate were obtained from each patient's ICU chart. The electrolytes in the patients' urine were measured and calculated. Correlations between measured and calculated values for excretions of Cl- and of Na+ plus K+ were excellent. CONCLUSIONS: Mass balances for Na+ plus K+ and for Cl- can be accurately estimated. These data provide information to support or refute a clinical diagnosis of CSW. The danger of relying on balances for these electrolytes measured within a single day to diagnose CSW is illustrated.

Adolescent↗
PubMed2001

The invasive features of glial and non-central nervous system tumor cells are different on organotypic brain slices from newborn rats.

On radiograms, glial tumors are usually seen to invade in a finger-like fashion, while non-central nervous system (CNS) tumors expand in a mass-like fashion. We prepared organotypic brain slice cultures from newborn rats to investigate the invasive behavior of human brain tumors using glial tumor cell lines (U-87MG, U-373MG, U-251MG, and SF-126) and of non-CNS tumors using cell lines; HT-1080 (human malignant fibrosarcoma), RFRF (human lung carcinoma), MIA-PICA (human pancreatic carcinoma), and Colo38 (human malignant melanoma). We selected an area that was centered at a junction between deep cortical layers and the striatum, punched a hole measuring 0.5-0.7 mm in diameter in this area, implanted different rhodamine-labeled tumor cells at that site, and observed their invasive behavior under an inverted fluorescent microscope. Over the course of several days, all glioma cells invaded in a finger-like fashion; U-373 MG cells invaded farthest. Non-CNS tumors expanded in mass-like fashion into adjacent areas. Using the slice cultures, we also investigated the regulatory effect on tumor invasion of forced expression of glial fibrillary acidic protein (GFAP) after gene transfection. The forced expression of GFAP rendered U-87MG and HT-1080 cells less invasive. Our results show that organotypic brain slice cultures are an excellent medium for studying the invasive features of glial and non-CNS tumors.

Animals↗
PubMed2001

Cytoskeletal-induced alterations in the adhesion of HT-1080 fibrosarcoma cells to extracellular matrix.

We have investigated the adhesion of the human fibrosarcoma cell line, HT-1080, transfected with glial fibrillary acidic protein (GFAP) to a variety of extracellular matrix macromolecules (ECM) including collagen type IV, laminin, and fibronectin. The GFAP-transfectants demonstrated altered adhesiveness to extracellular matrix substrates when compared to controls. GFAP-positive, heavy metal-induced fibrosarcoma cells were more adherent to plastic and collagen type IV than were the parental or uninduced cells. In contrast, GFAP-positive fibrosarcoma cells were less adherent to laminin- or fibronectin-coated dishes than controls. Time course adhesion studies over 9 days showed that the heavy metal-induced fibrosarcoma cells progressively became more adherent to collagen type IV and less adherent to laminin- or fibronectin-coated dishes than did uninduced cells. However, with the removal of heavy metal from the medium, the HT-1080 fibrosarcoma cells were restored to their original adhesive potential. By phase microscopy, uninduced and induced HT-1080 cells demonstrated different morphological features and remained viable in an anchorage-dependent fashion on collagen type IV as a substrate. By way of contrast, GFAP-induced HT-1080 cells were not particularly viable in monolayer culture and readily detached from laminin as a substrate. The expression of beta1 integrin in GFAP-positive fibrosarcoma cells was decreased following heavy metal induction by Western blot analyses. In contrast, the expression of alpha2 integrin was increased whereas alpha5 integrin was unchanged in HT-1080 cells following the induction of GFAP. Gelatin zymography showed that 72 kDa collagenase was less expressed in GFAP-induced clones than in controls. Our data suggest that the forced expression of the intermediate filament, GFAP, in HT-1080 cells may modulate cell adhesion to different ECM substrates through alterations in expression of integrins.

Blotting, Western↗
PubMed2000

Familial posterior fossa brain tumors of infancy secondary to germline mutation of the hSNF5 gene.

We have identified a family afflicted over multiple generations with posterior fossa tumors of infancy, including central nervous system (CNS) malignant rhabdoid tumor (a subset of primitive neuroectodermal tumors, or PNET) and choroid plexus carcinoma. Various hereditary tumor syndromes, including Li-Fraumeni syndrome, Gorlin syndrome, and Turcot syndrome, have been linked to increased risk of developing CNS PNETs and choroid plexus tumors. Malignant rhabdoid tumors of the CNS and kidney show loss of heterozygosity at chromosome 22q11. The hSNF5 gene on chromosome 22q11 has recently been identified as a candidate tumor-suppressor gene in sporadic CNS and renal malignant rhabdoid tumors. We describe a family in which both affected and some unaffected family members were found to have a germline splice-site mutation of the hSNF5 gene, leading to exclusion of exon 7 from the mature cDNA and a subsequent frameshift. Tumor tissue shows loss of the wild-type hSNF5 allele, in keeping with a tumor-suppressor gene. These findings suggest that germline mutations in hSNF5 are associated with a novel autosomal dominant syndrome with incomplete penetrance that predisposes to malignant posterior fossa brain tumors in infancy.

Age of Onset↗
PubMed2000

Alterations of the p53 and pRB pathways in human astrocytoma.

Human astrocytomas are characterized by a number of molecular changes affecting two critical tumor suppressor pathways: the pRB and the p53 pathways. Genetic alterations functionally eliminate pRB and p53 themselves or upstream and/or downstream molecules such as products of the Ink4a/ARF locus, p16Ink4a and p14ARF. As a result, malignant cells are defective in critical cell cycle and apoptosis regulatory elements contributing to unrelenting tumour growth and invasion. Current research aims to discover effective means of reconstituting p53 and pRB pathway components in an effort to attenuate the aggressive phenotype of astrocytoma.

Animals↗
PubMed2000

Perspectives in pediatric neurosurgery.

The new millennium beckons for novel advances in the diagnosis and treatment of pediatric neurosurgical conditions. Almost every aspect of pediatric neurosurgery has changed over the last decade. Undoubtedly with the application of knowledge in molecular biology to human disease many aspects of neurosurgery, especially neuro-oncology and the field of neuro-developmental anomalies, will change appreciably over the next decade. Overall, the trend in surgery in general and neurosurgery in particular is toward less invasive procedures and possibly non-surgical interventions. This review will briefly cover many of the important areas of pediatric neurosurgery. We will describe the state-of-the-art of our subspecialty and discuss possible future directions.

Brain↗
PubMed2000

Expression of p57(KIP2) potently blocks the growth of human astrocytomas and induces cell senescence.

Astrocytic tumors frequently exhibit defects in the expression or activity of proteins that control cell-cycle progression. Inhibition of kinase activity associated with cyclin/cyclin-dependent kinase co-complexes by cyclin-dependent kinase inhibitors is an important mechanism by which the effects of growth signals are down-regulated. We undertook the present study to determine the role of p57(KIP2) (p57) in human astrocytomas. We demonstrate here that whereas p57 is expressed in fetal brain tissue, specimens of astrocytomas of varying grade and permanent astrocytoma cell lines do not express p57, and do not contain mutations of the p57 gene by multiplex-heteroduplex analysis. However, the inducible expression of p57 in three well-characterized human astrocytoma cell lines (U343 MG-A, U87 MG, and U373 MG) using the tetracycline repressor system leads to a potent proliferative block in G(1) as determined by growth curve and flow cytometric analyses. After the induction of p57, retinoblastoma protein, p107, and E2F-1 levels diminish, and retinoblastoma protein is shifted to a hypophosphorylated form. Morphologically, p57-induced astrocytoma cells became large and flat with an expanded cytoplasm. The inducible expression of p57 leads to the accumulation of senescence-associated beta-galactosidase marker within all astrocytoma cell lines such that approximately 75% of cells were positive at 1 week after induction. Induction of p57 in U373 astrocytoma cells generated a small population of cells ( approximately 15%) that were nonviable, contained discrete nuclear fragments on Hoechst 33258 staining, and demonstrated ultrastructural features characteristic of apoptosis. Examination of bax and poly-(ADP ribose) polymerase levels showed no change in bax, but decreased expression of poly-(ADP ribose) polymerase after p57 induction in all astrocytoma cell lines. These data demonstrate that the proliferative block imposed by p57 on human astrocytoma cells results in changes in the expression of a number of cell cycle regulatory factors, cell morphology, and a strong stimulus to cell senescence.

Apoptosis↗
PubMed2000

Systematic approach to dipole localization of interictal EEG spikes in children with extratemporal lobe epilepsies.

OBJECTIVES: To assess the reliability of dipole localization based on residual variances (RV), using equivalent current dipole analysis of interictal EEG spikes in children with extratemporal lobe epilepsy. METHODS: Four pediatric patients with extratemporal lobe epilepsy were studied. Digital EEG was recorded from 19 scalp electrodes. Computer programs for spike detection and clustering analysis were used to select spikes. Dipoles were calculated 5 times for each spike using different initial guesses by the moving dipole model. Standard deviation (SD) of the dipole positions was calculated at each time point in the 5 trials. RESULTS: We analyzed the dipoles at 1097 time points from 4 patients. Among 106 time points with RV < 2%, the SD was < 1 mm in 78 (74%), while in those with SD > 1 mm the dipole positions varied between 2.8 and 52.6 mm. Of dipoles with RV < 1%, 26 of 27 (96%) had an SD < 1 mm; the one dipole with SD > 1 mm varied within 2.5 mm. The dipole localizations with RV < 2% corresponded to the epileptogenic zones identified on intracranial invasive video EEG and intraoperative ECoG. CONCLUSIONS: The systematic approach of equivalent current dipole analysis using spike detection, clustering analysis, and an RV < 2% as a standard is useful for identifying extratemporal epileptic regions.

Adolescent↗
PubMed2000

Molecular biology and neurosurgery in the third millennium.

The application of techniques in molecular biology to human neurosurgical conditions has led to an increased understanding of disease processes that affect the brain and to novel forms of therapy that favorably modify the natural history of many of these conditions. Molecular strategies are currently being either used or sought for brain tumors, stroke, neurodegenerative diseases, vascular malformations, spinal degenerative diseases, and congenital malformations of the central nervous system. Considering that the structure of deoxyribonucleic acid was ascertained by Watson and Crick as recently as 1953, the progress that has been made to implement molecular medicine in clinical practice has been meteoric. More than 2000 patients have been treated in approved gene therapy trials throughout the world. Many of these patients have been treated for neurological diseases for which conventional medical therapies have been of limited utility. As part of this continuing series on advances in neurosurgery in the third millennium, we first reflect on the history of the nascent field of molecular biology. We then describe the powerful techniques that have evolved from knowledge in this field and have been used in many publications in Neurosurgery, particularly within the past decade. These methods include commonly used techniques such as advanced cytogenetics, differential display, microarray technology, molecular cell imaging, yeast two-hybrid assays, gene therapy, and stem cell utilization. We conclude with a description of the rapidly growing field of bioinformatics. Because the Human Genome Project will be completed within 5 years, providing a virtual blueprint of the human race, the next frontier (and perhaps our greatest challenge) will involve the development of the field of "proteomics," in which protein structure and function are determined from the deoxyribonucleic acid blueprint. It is our conviction that neurosurgeons will continue to be at the forefront of the treatment of patients with neurological diseases using molecular strategies, by performing essential research leading to increased understanding of diseases, by conducting carefully controlled studies to test the effects of treatments on disease processes, and by directly administering (by neurosurgical, endovascular, endoscopic, or stereotactic means) the treatments to patients.

Cytogenetics↗
PubMed2000

Molecular insight into medulloblastoma and central nervous system primitive neuroectodermal tumor biology from hereditary syndromes: a review.

Through the study of uncommon familial syndromes, physicians and scientists have been able to illuminate the underlying mechanisms of some of the more common sporadic diseases; this is illustrated best by studies of familial retinoblastoma. A number of rare familial syndromes have been described in which affected individuals are at increased risk of developing medulloblastoma and/or supratentorial primitive neuroectodermal tumors. The descriptions of many of these syndromes are based on patients observed by clinicians in their clinical practice. Determination of the underlying genetic defects in these patients with uncommon syndromes has led to identification of a number of genes subsequently found to be mutated in sporadic medulloblastomas (tumor suppressor genes). Associated genes in the same signaling pathways have also been found to be abnormal in sporadic medulloblastoma. Identification of patients with these rare syndromes is important, as they are often at increased risk for additional neoplasms, as are family members and future children. We review the published literature describing hereditary syndromes that have been associated with an increased incidence of medulloblastoma and/or central nervous system primitive neuroectodermal tumor. Review of the underlying molecular abnormalities in comparison to changes found in sporadic neoplasms suggests pathways important for tumorigenesis.

Central Nervous System Neoplasms↗
PubMed2000

Infantile hemangioendothelioma of the pericranium presenting as an occipital mass lesion. Case report.

The case of a newborn infant with a large midline mass in the occipital region is presented. Skull x-ray films demonstrated multiple radiolucent defects in the occipital bone. A computerized tomography scan revealed an extracranial mass lesion with marked contrast enhancement. A magnetic resonance image demonstrated that the venous drainage of the lesion passed through the occipital bone into the dural venous sinuses. The anatomy of the hindbrain was normal. The neonate was treated by complete surgical removal of the mass. The histopathological diagnosis was infantile hemangioendothelioma, a tumor commonly found in the liver but rarely in this location. The classification, histopathological characteristics, imaging studies, and treatment of this tumor are discussed.

Hemangioendothelioma↗
PubMed2000

Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping.

OBJECT: Medulloblastomas and related primitive neuroectodermal tumors (PNETs) of the central nervous system are malignant, invasive embryonal tumors with predominantly neuronal differentiation that comprise 20% of pediatric brain tumors. Cytogenetic analysis has shown that alterations in chromosome 17, particularly the loss of 17p and the formation of isochromosome 17q, as well as the gain of chromosome 7 are the most common changes among this group of tumors. Comparative genomic hybridization (CGH) studies have largely confirmed these cytogenetic findings and have also identified novel regions of gain, loss, and amplification. The advent of more sophisticated multicolored fluorescence in situ hybridization (FISH) procedures such as spectral karyotyping (SKY) now permits complete recognition of all aberrations including extremely complex rearrangements. The authors report a retrospective analysis of 19 medulloblastoma and five PNET cases studied using combinations of classic banding analysis, FISH, CGH, and SKY to examine comprehensively the chromosomal aberrations present in this tumor group and to attempt to identify common structural rearrangement(s). METHODS: The CGH data demonstrate gains of chromosomes 17q and 7 in 60% of the tumors studied, which confirms data reported in the current literature. However, the authors have also combined the results of all three molecular cytogenetic assays (Giemsa banding, CGH, and SKY) to reveal the frequency of chromosomal rearrangement (gained, lost, or involved in structural rearrangement). CONCLUSIONS: The combined results indicate that chromosomes 7 and 17 are the most frequently rearranged chromosomes (10.1% and 8.9%, respectively, in all rearrangements detected). Furthermore, chromosomes 3 (7.8%), 14 (7%), 10 (6.7%), and 22 (6.5%) were also found to be frequently rearranged, followed by chromosomes 6 (6.5%), 13 (6.2%), and 18 (6.2%). Eight (33%) of 24 tumors exhibited high-level gains or gene amplification. Amplification of MYCN was identified in four tumors, whereas amplification of MYCC was identified in one tumor. One tumor exhibited a high-level gain of chromosome 9p. Additionally, desmoplastic medulloblastomas and large-cell medulloblastomas exhibited higher karyotype heterogeneity, amplification, and aneusomy than classic medulloblastomas.

Brain Neoplasms↗
PubMed1999

Astrocytoma cell interaction with elastin substrates: implications for astrocytoma invasive potential.

Elastin has been identified within the meninges and the microvasculature of the normal human brain. However, the role that elastin plays in either facilitating astrocytoma cell attachment to these structures or modulating astrocytoma invasion has not been previously characterized. We have recently shown that astrocytoma cell lines and specimens produce tropoelastin, and express the 67 kDa elastin binding protein (EBP). In the present report, we have established that astrocytoma cells attach to elastin as a substrate in vitro. The U87 MG astrocytoma cell line demonstrated the greatest degree of adhesion. In addition, all astrocytoma cell lines examined were capable of penetrating and migrating through an intact elastin membrane, and of degrading tritiated-elastin, a process that could be prevented by the pre-incubation of astrocytoma cells with EDTA, but not with alpha1-antitrypsin. Astrocytoma cells were also capable of penetrating 1 mm sections of human brain tissue maintained as organotypic cultures. Interestingly, the invasive potential of cultured astrocytoma cells plated on organotypic cultures of human brain was significantly increased after exposure to elastin degradation products (kappa-elastin), which interact with astrocytoma cell surface EBP. Our data show that astrocytoma cells express a functional 67 kDa EBP, enabling them to potentially recognize and attach to elastin as a substrate. These data also suggest that this elastin receptor may be involved in processes which regulate regional astrocytoma invasion.

Astrocytoma↗