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Biomedical subjects

A R Cohen

Publications and source records attributed to A R Cohen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Posterior fossa craniotomy: an alternative to craniectomy.

We describe a simple midline approach to posterior fossa lesions in children that involves removal and replacement of a bone flap. This approach offers several advantages over conventional suboccipital craniectomy. Elevation of the bone flap is facilitated by the relatively small size of the midline bony keel in children. This method is simple, safe and expeditious, and restores normal anatomical planes and improved protection to the contents of the posterior fossa. While this approach has been described previously for individual cases, the authors employ craniotomy as the standard method of access to the posterior fossa in pediatric patients, and suggest a straightforward technique for removing and replacing the bone flap.

Astrocytoma↗
PubMed1999

Current patterns of inflicted head injury in children.

The purpose of this study was to examine the current patterns of head trauma associated with child abuse. We reviewed the records of all patients admitted to our medical center between 1995 and 1997 with a primary diagnosis of head trauma, and analyzed the clinical presentation, mechanism of injury, socioeconomic status and outcome for these patients. Head trauma was deliberately inflicted in 38/405 children (9%). There were 25 boys and 13 girls, with a median age of 5.5 months. Two thirds of the families lived in the inner city. Of the 99 children under the age of 2 years admitted for head trauma, the injury was inflicted in 32 (32%). Acute subdural hematoma was present in 22/32 (69%) of children with inflicted trauma, but in only 5/68 (7%) with accidental trauma. Retinal hemorrhages were present in 17/32 (53%) abused children, but in no cases of accidental trauma (0/68). Deliberately inflicted injury is a frequent cause of serious head trauma in young children. Head injury is a major cause of morbidity and mortality in the abused child. Child abuse cases correlated strongly with low socioeconomic status. Nonaccidental trauma must be considered strongly in children under 2 years of age who present with acute subdural hematoma in the absence of a history of a motor vehicle accident.

Acute Disease↗
PubMed1999

Characterization of a model of hydrocephalus in transgenic mice.

OBJECT: The purpose of this study was to elucidate the pathophysiological characteristics of hydrocephalus in a new transgenic model of mice created to overproduce the cytokine transforming growth factor-beta1 (TGFbeta1) in the central nervous system (CNS). METHODS: Galbreath and colleagues generated transgenic mice that overexpressed TGFbeta1 in the CNS in an effort to examine the role of this cytokine in the response of astrocytes to injury. Unexpectedly, the animals developed severe hydrocephalus and died. The authors have perpetuated this transgenic colony to serve as a model of congenital hydrocephalus, breeding asymptomatic carrier males that are heterozygous for the transgene with wild-type females. One hundred twelve (49.6%) of 226 mice developed clinical manifestations of hydrocephalus, characterized by dorsal doming of the calvaria, spasticity, limb tremors, ataxia, and, ultimately, death. The presence of the TGFbeta1 transgene was determined by performing polymerase chain reaction (PCR) analysis of sample tail slices. Animals with the hydrocephalic phenotype consistently carried the transgene, although some animals with the transgene did not develop hydrocephalus. Animals without the transgene did not develop hydrocephalus. Alterations in brain structure were characterized using magnetic resonance (MR) imaging, gross and light microscopic analysis, and immunocytochemical studies. Magnetic resonance imaging readily distinguished hydrocephalic animals from nonhydrocephalic controls and demonstrated an obstruction at the outlets of the fourth ventricle. Gross and light microscopic examination confirmed the MR findings. The results of immunofluorescent staining of brain tissue slices revealed the presence of the TGFbeta1 cytokine and its receptor preferentially in the meninges and subarachnoid space in both hydrocephalic and control mice. Reverse transcriptase-PCR analysis demonstrated tissue-specific expression of the TGFbeta1, gene in the brains of transgenic mice, and enzyme-linked immunosorbent assay confirmed overexpression of the TGFbeta1 cytokine in brain, cerebrospinal fluid, and plasma. CONCLUSIONS: The transgenic murine model provides a reproducible representation of congenital hydrocephalus. The authors hypothesize that overexpression of TGFbeta1 in the CNS causes hydrocephalus by altering the environment of the extracellular matrix and interfering with the circulation of cerebrospinal fluid. A model of hydrocephalus in which the genetic basis is known should be useful for evaluating hypotheses regarding the pathogenesis of this disorder and should also help in the search for new treatment strategies.

Animals↗
PubMed1998

Human CASK/LIN-2 binds syndecan-2 and protein 4.1 and localizes to the basolateral membrane of epithelial cells.

In Caenorhabditis elegans, mutations in the lin-2 gene inactivate the LET-23 receptor tyrosine kinase/Ras/MAP kinase pathway required for vulval cell differentiation. One function of LIN-2 is to localize LET-23 to the basal membrane domain of vulval precursor cells. LIN-2 belongs to the membrane-associated guanylate kinase family of proteins. We have cloned and characterized the human homolog of LIN-2, termed hCASK, and Northern and Western blot analyses reveal that it is ubiquitously expressed. Indirect immunofluorescence localizes CASK to distinct lateral and/or basal plasma membrane domains in different epithelial cell types. We detect in a yeast two-hybrid screen that the PDZ domain of hCASK binds to the heparan sulfate proteoglycan syndecan-2. This interaction is confirmed using in vitro binding assays and immunofluorescent colocalization. Furthermore, we demonstrate that hCASK binds the actin-binding protein 4.1. Syndecans are known to bind extracellular matrix, and to form coreceptor complexes with receptor tyrosine kinases. We speculate that CASK mediates a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with protein 4.1. Like other membrane-associated guanylate kinases, its multidomain structure enables it to act as a scaffold at the membrane, potentially recruiting multiple proteins and coordinating signal transduction.

Animals↗
PubMed1998

Direct interaction of CASK/LIN-2 and syndecan heparan sulfate proteoglycan and their overlapping distribution in neuronal synapses.

CASK, the rat homolog of a gene (LIN-2) required for vulval differentiation in Caenorhabditis elegans, is expressed in mammalian brain, but its function in neurons is unknown. CASK is distributed in a punctate somatodendritic pattern in neurons. By immunogold EM, CASK protein is concentrated in synapses, but is also present at nonsynaptic membranes and in intracellular compartments. This immunolocalization is consistent with biochemical studies showing the presence of CASK in soluble and synaptosomal membrane fractions and its enrichment in postsynaptic density fractions of rat brain. By yeast two-hybrid screening, a specific interaction was identified between the PDZ domain of CASK and the COOH terminal tail of syndecan-2, a cell surface heparan sulfate proteoglycan (HSPG). The interaction was confirmed by coimmunoprecipitation from heterologous cells. In brain, syndecan-2 localizes specifically at synaptic junctions where it shows overlapping distribution with CASK, consistent with an interaction between these proteins in synapses. Cell surface HSPGs can bind to extracellular matrix proteins, and are required for the action of various heparin-binding polypeptide growth/differentiation factors. The synaptic localization of CASK and syndecan suggests a potential role for these proteins in adhesion and signaling at neuronal synapses.

Amino Acid Sequence↗
PubMed1998

Advances in endoscopic neurosurgery.

This article describes the authors' experience using neuroendoscopes to perform a variety of intracranial procedures with minimal invasiveness to neural tissue. The article also presents the history of neuroendoscopy and provides information about current practice. Surgical technique and intraoperative and postoperative nursing considerations are reviewed.

Endoscopy↗
PubMed1998

Crystal structure of the hCASK PDZ domain reveals the structural basis of class II PDZ domain target recognition.

PDZ domain containing proteins assist formation of cell-cell junctions and localization of membrane protein receptors and ion channels. PDZ domains interact with the C-terminal residues of a particular target membrane protein. Based on their binding specificities and sequence homologies, PDZ domains fall into two classes. The first crystal structure of a class II PDZ domain, that of hCASK, has been solved by multi-wavelength anomalous dispersion phasing. Complex formation with the C-terminus of a neighboring non-crystallographically related PDZ domain reveals interactions between hCASK and its ligand. Class II PDZ domains differ from class I domains by formation of a second hydrophobic binding pocket. The C-terminal carboxylate binding loop of the PDZ domain is structurally conserved in both classes suggesting a generalized carboxylate binding motif (h-Gly-h) where h is a hydrophobic residue.

Amino Acid Sequence↗
PubMed1998

Primary hypothyroidism mimicking a pituitary macroadenoma.

Pituitary macroadenomas occur infrequently in children and can present with visual dysfunction or endocrinopathy. Occasionally, primary end-organ failure can cause reactive enlargement of the pituitary gland that may be clinically and radiographically indistinguishable from pituitary macroadenoma. The authors describe an example of reactive pituitary hyperplasia from primary hypothyroidism that mimicked a pituitary macroadenoma in a child. Recognition of this entity, which responds to medical therapy, is important because it can spare patients unnecessary surgery.

Adenoma↗
PubMed1998

Neurocytoma presenting with intraparenchymal cerebral hemorrhage.

Neurocytomas are uncommon intracranial neoplasms that have only recently been characterized pathologically. Neurocytomas are histologically benign neoplasms that are often quite large when diagnosed, and previous reports have commonly described presentation with mass effect or cerebrospinal fluid outflow obstruction. We describe the first case of neurocytoma presenting with intraparenchymal cerebral hemorrhage.

Adolescent↗
PubMed1998

Syrinx hand.

Explore the source record for details and available documents.

Adolescent↗
PubMed1998

Neonatal applications of neuroendoscopy.

Neuroendoscopy is a minimally invasive technique that has revolutionized the management of multiple intracranial conditions. Neuroendoscopic techniques can be safely applied to the newborn in selected circumstances, but the indications, surgical technique, and the potential pitfalls and complications must be completely understood to ensure a successful outcome in these fragile patients.

Endoscopy↗