Search PubMed⌕ Search

Biomedical subjects

A R Cohen

Publications and source records attributed to A R Cohen.

At least 19 recordsLinked to original sources
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↗
PubMed1997

Superior in vivo response of recombinant factor VIII concentrate in children with hemophilia A.

OBJECTIVE: Our previous experience with highly purified plasma-derived factor VIII (pdFVIII) concentrates showed that adult dosage recommendations were not applicable to children. In this study, we compared the in vivo response and recovery of recombinant factor VIII (rFVIII) with those of highly purified pdFVIII concentrate in children with hemophilia A. STUDY DESIGN: Ten boys with severe factor VIII deficiency and no concurrent bleeding episodes participated in a masked, prospective, crossover study comparing factor VIII coagulant activity after infusion of 50 units of pdFVIII and rFVIII products per kilogram of body weight. RESULTS: Mean peak factor VIII response with rFVIII was 1.91% +/- 0.14%, significantly better than the response observed with highly purified pdFVIII of 1.5% +/- 0.15% (p = 0.007). Mean peak factor VIII recovery was 100.5% with rFVIII versus 78.7% with pdFVIII (p = 0.007). Positive correlations between response to rFVIII and body surface area (r = 0.734, p = 0.015), body weight (r = 0.762, p = 0.01), and plasma volume (r = 0.659, p = 0.03) were observed. CONCLUSIONS: Infusion of rFVIII produced a significantly better response and recovery in vivo than infusion of highly purified pdFVIII in children. The response in children after infusion of rFVIII was similar to the response previously observed in adults.

Adult↗
PubMed1997

Screening for hereditary spherocytosis by use of automated erythrocyte indexes.

OBJECTIVE: To determine whether the mean corpuscular hemoglobin concentration (MCHC) or other erythrocyte indexes, as determined by automated cell counters, remains a useful screening test for identifying patients with hereditary spherocytosis (HS). METHODS: Erythrocyte indexes from 112 children with HS who had not undergone splenectomy were compared with those measured in an equal number of healthy, age-matched children. All indexes were derived from measurements obtained by aperture impedance. RESULTS: Mean corpuscular hemoglobin concentration in the HS group was 35.9 gm/dl, significantly higher than in normal control subjects (34.3 gm/dl; p < 0.001). Mean erythrocyte distribution width also was significantly higher in patients with HS (19.3 vs 12.6; p < 0.001). The MCHC distinguishes individuals with HS, with an area under the receiver operating characteristic curve of 0.86. Although not disease specific, an erythrocyte distribution width > 14 has 85% sensitivity and 97% specificity and an area under the receiver operating characteristic curve of 0.92. An MCHC > 35 gm/dl has a sensitivity of 70% and a specificity of 86%. Combining the MCHC and erythrocyte distribution width increases the area under the receiver operating characteristic curve to 0.97. Specificity is 100% and likelihood ratio is infinite when both the MCHC and erythrocyte distribution width are elevated. CONCLUSIONS: The automated MCHC is an effective screening test to identify children with HS. An elevated erythrocyte distribution width adds additional specificity and is itself a powerful screening tool. The combination of the two tests is an excellent predictor for the diagnosis of HS.

Adolescent↗
PubMed1997

Neurologic complications of treatment of childhood acute immune thrombocytopenic purpura with intravenously administered immunoglobulin G.

We studied the incidence, associated morbidity, and impact on health care charges of neurologic complications in 38 children with acute immune thrombocytopenic purpura (ITP) treated with intravenously administered IgG. Thirteen patients (34%) had transient neurologic complications, manifested by severe headache, nausea, and, rarely, aseptic meningitis. Computed tomography was performed in nine patients. Twelve patients were hospitalized longer than was required for their ITP alone. Neurologic complications caused by the IgG preparations used in the treatment of childhood ITP occur more frequently than has previously been suggested and may substantially increase the cost of treatment.

Acute Disease↗
PubMed1997

The role of neuroendoscopy in the treatment of pineal region tumors.

The authors describe a technique for the initial management of patients with pineal region neoplams and symptomatic hydrocephalus. Endoscopic third ventriculostomy and, if possible, tumor biopsy are performed through a single precoronal burr hole. When indicated, formal tumor resection can be performed nonemergently, without the need for ventricular drainage or shunting.

Adult↗