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D Leifer

Publications and source records attributed to D Leifer.

At least 19 recordsLinked to original sources
PubMed1995

An astrocytic binding site for neuronal Thy-1 and its effect on neurite outgrowth.

Thy-1, a member of the immunoglobulin superfamily, is one of the most abundant glycoproteins on mammalian neurons. Nevertheless, its role in the peripheral or central nervous system is poorly understood. Certain monoclonal antibodies to Thy-1 promote neurite outgrowth by rodent central nervous system neurons in vitro, suggesting that Thy-1 functions, in part, by modulating neurite outgrowth. We describe a binding site for Thy-1 on astrocytes. This Thy-1-binding protein has been characterized by immunofluroesence with specific anti-idiotype monoclonal antibodies and by three competitive binding assays using (i) anti-idiotype antibodies, (ii) purified Thy-1, and (iii) Thy-1-transfected cells. The Thy-1-binding protein may participate in axonal or dendritic development in the nervous system.

Animals↗
PubMed1994

Myocyte-specific enhancer binding factor 2C expression in human brain development.

Myocyte-specific enhancer binding factor 2C (MEF2C) activates transcription by binding to the myocyte-specific enhancer binding factor 2 (MEF2) regulatory element and has been shown previously to be expressed in muscle and in the brain. We have now studied MEF2C expression in human brain using an antiserum raised against amino acids 140-238 of MEF2C. Western blotting demonstrated that, in fetal brain, MEF2C-immunoreactive bands have the same apparent molecular weight as those in extracts of COS cells transfected with MEF2C complementary DNA. In adult brain, however, MEF2C-immunoreactive bands have a higher molecular weight. In the cerebral cortex, MEF2C immunoreactivity is present in the cortical plate, and is not found in the intermediate zone or ventricular zone. At 14 weeks of gestation, the earliest age examined, MEF2C immunoreactivity is present in cell nuclei throughout the cortical plate. Subsequently, MEF2C immunoreactivity develops a bilaminate and then a trilaminate distribution, and ultimately is expressed preferentially in layers II, IV and VI of mature neocortex. MEF2C immunoreactivity is also found in entorhinal cortex, hippocampus, claustrum, cerebellum and amygdala, and in scattered cells in the thalamus. These findings suggest a role for MEF2C in postmitotic neuronal differentiation, in particular, in the development of certain cortical layers, but also in differentiation of other neurons as well.

Adult↗
PubMed1993

MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex.

We have cloned cDNA encoding a human transcription factor that belongs to the MEF2 (myocyte-specific enhancer-binding factor 2) subfamily of the MADS (MCM1-agamous-deficiens-serum response factor) gene family. This factor, which we have named MEF2C, binds specifically to the MEF2 element and activates transcription via this element. Specific isoforms of this factor are found exclusively in brain and are robustly expressed by neurons in cerebral cortex. In situ hybridization indicates that the factor is expressed preferentially in certain neuronal layers of cortex and that expression declines during postnatal development. The unusual pattern of expression in brain suggests that this transcription factor may be important in the development of cortical architecture.

Amino Acid Sequence↗
PubMed1993

Immunohistochemical patterns of selective cellular vulnerability in human cerebral ischemia.

Although specific patterns of cellular vulnerability have been identified in experimental models of cerebral ischemia, there is little data on the occurrence of similar abnormalities in human ischemia. We therefore used a variety of histochemical methods to define changes affecting specific classes of cells in post-mortem specimens from seven patients with hippocampal and neocortical ischemic lesions. In acute lesions, staining with SMI-32, an antibody directed against nonphosphorylated neurofilaments that labels pyramidal projection neurons, was prominently depleted even when conventional Nissl staining revealed only mild pyknosis. In contrast, staining for other markers such as microtubule-associated protein 2 (MAP-2), another cytoskeletal protein, or parvalbumin, a calcium-binding protein found in gamma-aminobutyric acid (GABA)-ergic interneurons, were relatively preserved. SMI-32 antibody also labeled dystrophic axons and axonal retraction balls in and around acute ischemic lesions. The pattern of differential changes in immunoreactivity was essentially the same in all acute ischemic injuries, including both diffuse lesions in the CA1 field (Sommer's sector) and discrete infarcts in CA1 and neocortex. In addition, immunoreactivity for the immediate early gene product c-fos was enhanced in and around the acute ischemic lesions that we studied. In some very acute lesions, immunoreactivity for glial fibrillary acidic protein (GFAP) was depleted in areas of severe ischemia and necrosis, but, as expected, GFAP immunoreactivity was increased in lesions more than a few days old. In contrast, the loss of SMI-32 immunoreactivity persisted in chronic lesions. These findings are consistent with those of experimental ischemia in animals and confirm the relevance of these studies for human cerebral ischemia. The pattern of selective changes also resembles that of injuries induced directly by excitatory amino acids, which may play a significant role in the pathogenesis of ischemic damage.

Aged↗
PubMed1993

hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors.

The myocyte enhancer-binding factor 2 (MEF2) site is an essential element of many muscle-specific enhancers and promoters that binds nuclear proteins from muscle and brain. Recently, we have cloned a family of MEF2 transcription factors produced by two genes that, at the mRNA level, are broadly expressed and produce tissue-specific isoforms by posttranscriptional processes (Y.-T. Yu, R. E. Breitbart, L. B. Smoot, Y. Lee, V. Mahdavi, and B. Nadal-Ginard, Genes Dev. 6:1783-1798, 1992). Here, we report the isolation and functional characterization of cDNA clones encoding four MEF2 factors derived from a separate gene that we have named hMEF2C. In contrast to those of the previously reported genes, the transcripts of the hMEF2C gene are restricted to skeletal muscle and brain. One of the alternate exons is exclusively present in brain transcripts. The products of this gene have DNA-binding and trans-activating activities indistinguishable from those of the previously reported MEF2 factors. The hMEF2C gene is induced late during myogenic differentiation, and its expression is limited to a subset of cortical neurons. The potential targets for this transcription factor in a subset of neurons are not known at this time. The strict tissue-specific pattern of expression of hMEF2C in comparison with the more ubiquitous expression of other MEF2 genes suggests a different mode of regulation and a potentially important role of hMEF2C factors in myogenesis and neurogenesis.

Alternative Splicing↗
PubMed1992

Leptomeningeal myelomatosis presenting with mental status changes and other neurologic findings.

BACKGROUND: Leptomeningeal myelomatosis is a rare complication of multiple myeloma. METHODS: The authors identified and studied three patients with leptomeningeal myelomatosis and reviewed previous case reports of this condition. RESULTS: The patients described here had intermittent abnormalities in mental status or cranial nerve and brain stem abnormalities. Two of the patients responded dramatically, though transiently, to treatment. In one patient, the clinical findings correlated with lesions visualized by gadolinium-enhanced magnetic resonance imaging. CONCLUSIONS: These patients are typical of those reported previously. Patients with leptomeningeal myelomatosis often have a good response to treatment initially, but long-term survival is rare.

Aged↗
PubMed1992

Selectivity of Thy-1 monoclonal antibodies in enhancing neurite outgrowth.

Thy-1 monoclonal antibodies (MAbs) have previously been shown to promote neurite outgrowth from retinal ganglion cells and a variety of other neurons. We have studied the effect on neurite outgrowth of several Thy-1 MAbs with quantitatively similar binding properties and found that only certain Thy-1 MAbs promote neurite outgrowth. This finding suggests that the antibody effects depend on specific interactions with one or more active sites on the Thy-1 glycoprotein.

Animals↗
PubMed1992

Parietal pseudothalamic pain syndrome. Clinical features and anatomic correlates.

We studied six patients who developed spontaneous hemibody pain following lesions of the parietal lobe. The pain was characterized as burning or icelike, and was associated with impairment of pin and temperature appreciation. Computed tomographic scanning showed that the common area of involvement in all cases was the white matter deep to both the caudal insula and the opercular region of the posterior parietal cortex. We suggest that disruption of the interconnections between these cerebral cortical areas (including the second somatosensory representation, SII) and the thalamus, particularly the intralaminar and ventroposterior nuclei, may be responsible for producing a thalamocortical disconnection syndrome with spontaneous pain as its clinical manifestation.

Adult↗
PubMed1992

Familial bilateral carpal tunnel syndrome: report of two families.

Cases of familial carpal tunnel syndrome without other associated conditions are rare. We report two families in which multiple members had bilateral carpal tunnel syndromes. The pattern was consistent with autosomal dominant inheritance. Electrophysiologic studies were performed on nine of the 15 patients, and they demonstrated bilateral pathology of the median nerves at the wrist in all but one patient, without evidence for subclinical, generalized peripheral neuropathy. Quantitative sensory testing was performed in two cases, and it corroborated the absence of peripheral neuropathy. Five of the six patients who underwent carpal tunnel release improved after surgery.

Adolescent↗
PubMed1992

Thy-1 in hippocampus: normal anatomy and neuritic growth in Alzheimer's disease.

Abnormal neuritic sprouting is a prominent feature of Alzheimer's disease (AD), and the Thy-1 glycoprotein has a role in neurite growth in culture. We therefore investigated the distribution of Thy-1 immunoreactivity in the hippocampus of normal elderly patients and of AD patients. Normally, Thy-1 immunoreactivity, which was more prominent in CA1 than elsewhere in the hippocampus, was located mainly in irregular patches on the perikarya of pyramidal cells, their dendrites and axons. In AD, Thy-1-immunoreactive neurons were reduced in number in CA1, and there was diffuse staining of neurofibrillary tangle-bearing pyramidal cells, but neurofibrillary tangles themselves were not immunoreactive. There was also staining of disorganized arrays of dystrophic neurites, some with spiny processes and bizarre filopodial endings. Some Thy-1-immunoreactive dystrophic neurites entered senile plaques. The data confirm that there is extensive growth of abnormal neurites in AD and suggest that Thy-1 is involved in this process.

Aged↗
PubMed1991

Immunofluorescent characterization of retinal ganglion cell neurites cultured on substrates coated with antibodies against Thy-1.

Neurite outgrowth from rat retinal ganglion cells is enhanced if they are cultured on a substrate coated with antibodies against Thy-1. We show that the ganglion cell neurites that grow on antibodies against Thy-1 display immunoreactivity for microtubule-associated protein 2 and tau, cytoskeletal proteins normally localized to the somatodendritic and axonal compartments, respectively. This result suggests that these neurites are incompletely differentiated and have axonal and dendritic features. We also show that the antibodies against Thy-1 used to coat the substrate bind specifically to ganglion cell membranes within 1 day of culture.

Animals↗
PubMed1991

Neuropathologic asymmetries in the brain of a patient with a unilateral status epilepticus.

Autopsy study of a patient who died after an episode of prolonged unilateral status epilepticus revealed neuronal loss in the hippocampus on the epileptic side, with gliosis confined to the CA1 and CA3 fields. There was loss of the parvalbumin-immunoreactive gamma-aminobutyric acid (GABA)-ergic interneurons in the hippocampus on that side. There was also loss of the normal laminar pattern of substance P staining with increased substance P immunoreactivity in the supragranular plexus on that side. Met-enkephalin immunoreactivity was also increased in the outer molecular layer of the dentate gyrus on the epileptic side. Mossy fibers on the epileptic side stained more strongly with the Hicks' silver stain and with antibodies against glutamate and taurine, but less intensely with antibodies against calbindin. In the contralateral cerebellum, there was Purkinje cell loss, injury to the remaining Purkinje cells, and increased prominence of the Bergmann glia. Our observations show that prolonged unilateral seizure activity can be associated with specific histochemical changes in the human hippocampus.

Cadaver↗
PubMed1990

Clinicopathologic correlations of cranial magnetic resonance imaging of periventricular white matter.

We studied clinical, imaging, and autopsy data on 7 patients who underwent magnetic resonance imaging (MRI) during life. Small periventricular zones of increased T2 signal corresponded to a periventricular cap consisting of subependymal glial accumulations, with some loss of the ependymal lining, and a surrounding pale-staining area of finely textured myelin and axons with an altered glial pattern. The fine-fiber zone is identifiable anatomically as the subcallosal fasciculus. This histologic pattern of subependymal glial accumulations and fine fibers is normal and is often associated with fibrotic small blood vessels. More extensive subcortical MRI changes corresponded, in 1 case, to multiple sclerosis, and in another to subcortical arteriosclerotic encephalopathy (Binswanger's disease) with widespread fiber loss and lacunar changes. Wallerian degeneration secondary to infarction occurred in some areas of MRI abnormality.

Adult↗
PubMed1989

Ocular stroke and carotid artery dissection.

Carotid artery dissection frequently causes transient ipsilateral visual impairment. We present 2 cases of permanent ocular vaso-occlusion sequelae consequent to dissection of the ipsilateral internal carotid, definite in one and probable in the other. In both, the ocular strokes led to the recognition of the underlying carotid vasculopathy.

Adult↗
PubMed1989

Multifocal glioblastoma with liver metastases in the absence of surgery. Case report.

A patient with two intracerebral glioblastomas of differing histology with metastases to the liver in the absence of surgery is reported. The gliomatous nature of the lesions was confirmed by staining for glial fibrillary acidic protein. Histological and immunohistochemical evidence suggests that the metastases arose from the more poorly differentiated of the intracerebral tumors. One of the intracerebral tumors had enhanced expression of the ras p21 oncogene as compared to the other tumors and as compared to nonmalignant brain tissue from this patient.

Aged↗
PubMed1984

Monoclonal antibody to Thy-1 enhances regeneration of processes by rat retinal ganglion cells in culture.

Ganglion cells were dissociated from postnatal rat retinas, identified by specific fluorescent labels, and maintained in culture on a variety of substrates. Regeneration of processes by retinal ganglion cells was enhanced when the cells were plated on glass coated with a monoclonal antibody against the Thy-1 determinant. Plain glass and glass coated with polylysine, collagen, fibronectin, or other monoclonal antibodies supported the growth of neural processes, but were less effective than antibody to Thy-1.

Animals↗