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Biomedical subjects

J W Rose

Publications and source records attributed to J W Rose.

At least 19 recordsLinked to original sources
PubMed1997

Multiple sclerosis presenting as transverse myelopathy: clinical and MRI features.

We described specific MRI features of MS presenting with acute partial transverse myelopathy. We reviewed the clinical histories and MRI studies of brain and spinal cord of 24 patients, using axial and sagittal images of the spinal cord to define patterns of signal abnormality in the context of clinical presentation, course, and vertebral column structural pathology. The heterogeneity of spinal cord tract involvement was greater than previously reported, with signal abnormality identified within the central cord, crossing the gray-white junction, and involving all four major funiculi. Correlation between spinal cord MRI findings and neurologic deficits was strong (100% by axial images; 96% by sagittal images). Serial spinal cord MRI demonstrated the dynamic nature of the signal abnormalities over time and in response to high-dose steroid treatment. No cranial MRI abnormality initially was seen in 36% of cases with evidence of demyelinating disease on concurrent spinal MRI.

Adult↗
PubMed1996

Binding of a novel 50-kilodalton alboaggregin from Trimeresurus albolabris and related viper venom proteins to the platelet membrane glycoprotein Ib-IX-V complex. Effect on platelet aggregation and glycoprotein Ib-mediated platelet activation.

Binding of the multimeric adhesive glycoprotein, von Willebrand Factor (vWF), to the platelet membrane glycoprotein (GP) Ib-IX-V complex mediates platelet adhesion and initiates signal transduction leading to platelet activation. Recently described viper venom proteins that bind to the GP Ib alpha-chain and inhibit vWF binding provide novel probes for studying receptor function. We have purified a 50-kDa form of alboaggregin from the white-lipped tree viper (Trimeresurus albolabris) and two 25-kDa proteins, CHH-A and CHH-B, from the timber rattlesnake (Crotalus horridus horridus) in addition to a previously described 25-kDa alboaggregin and echicetin. Complete or partial amino acid sequencing of CHH-A, CHH-B, and 50-kDa alboaggregin and cross-reactivity of these proteins with an anti-botrocetin antiserum confirmed that they were disulfide-linked heterodimers or higher multimers of the C-type lectin protein family. These proteins, together with 25-kDa alboaggregin and echicetin, specifically bound to GP Ib alpha within the N-terminal peptide domain, His-1-Glu-282, and inhibited vWF binding with comparable IC50 values (approximately 0.2 microgram/mL). However, cross-blocking studies between these structurally related proteins and anti-GP Ib alpha monoclonal antibodies demonstrated that the venom protein binding sites were not congruent. Further, the 50-kDa alboaggregin, but not the other venom proteins, potently induced platelet activation as assessed by dense granule serotonin release or elevation of cytosolic ionized calcium. Treatment of platelets with the 50-kDa alboaggregin was associated with activation of protein kinase C and tyrosine kinase(s), resulting in a platelet protein phosphorylation profile similar to that seen on shear-stress-induced vWF binding to platelets. These results suggest that the 50-kDa alboaggregin induces cytoplasmic signaling coincident with its binding to the GP Ib-IX-V complex and provides a potentially useful probe for studying the mechanism of vWF-dependent platelet activation.

Amino Acid Sequence↗
PubMed1996

Multiple sclerosis.

Multiple sclerosis is a chronic disease that begins in late adolescence or adulthood. It is highly variable in its expression and severity. It is believed to be autoimmune in nature. The cause is unknown; both genetic and environmental factors have been implicated in the pathogenesis. MS generally presents with the acute or subacute onset of neurologic abnormalities that may wax and wane over many years. Diagnosis is generally made by means of observation of the clinical course in conjunction with a neurologic examination and laboratory tests. These tests may include magnetic resonance imaging of the head and spine, lumbar puncture, and evoked potentials. Treatment is based on general supportive care, the use of corticosteroids for relapses, and symptomatic management of ongoing problems. The frequency of relapses can be reduced with interferon-beta (Betaseron). Copolymer 1 and interferon-beta la are being evaluated by the U.S. Food and Drug Administration for approval for use for reduction in the frequency of relapses in relapsing-remitting MS. Treatment of chronic progression is often attempted with immunosuppressive agents such as corticosteroids, azathioprine, and cyclophosphamide. Use of other agents is being investigated.

Adolescent↗
PubMed1995

Uptake of systemically administered human anticerebellar antibody by rat Purkinje cells following blood-brain barrier disruption.

Paraneoplastic cerebellar degeneration accompanying gynecological or breast malignancies is frequently associated with an autoantibody response, termed "type I" or "anti-Yo" directed against cytoplasmic antigens of cerebellar Purkinje cells. The role of this antibody response in the pathogenesis of paraneoplastic cerebellar degeneration is unknown; however, it is also not known whether anti-Purkinje cell antibodies from the systemic circulation bind to target Purkinje cell antigens under the conditions of brain inflammation and blood-brain barrier disruption, which are frequently present at the onset of cerebellar symptoms. Inbred Lewis rats received intraperitoneal injections of type I or normal IgG in the setting of blood-brain barrier disruption induced by adoptive transfer of experimental allergic encephalomyelitis (EAE) and were killed after 24, 48, and 96 h. Brains of these animals were studied histologically for evidence of EAE and immunohistochemically for binding of human or endogenous rat IgG to target neurons. Rat IgG was detected around vessels and in Purkinje cells of all animals studied. Human IgG was detected around vessels of all animals. In animals examined 96h after receiving type I human IgG, human IgG was identified within processes of Purkinje cells and within occasional Purkinje cell bodies. Uptake of type I IgG by other cell types was not observed, and neuronal uptake of IgG was not seen in brains of animals receiving normal human IgG. Our data demonstrate that circulating type I IgG is internalized by cerebellar Purkinje cells in the setting of blood-brain barrier disruption and suggest a mechanism by which an antibody response directed against cytoplasmic antigens of Purkinje cells may reach target antigens at the onset of paraneoplastic cerebellar degeneration.

Animals↗
PubMed1995

Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group.

We studied copolymer 1 (Copaxone) in a multicenter (11-university) phase III trial of patients with relapsing-remitting multiple sclerosis (MS). Two hundred fifty-one patients were randomized to receive copolymer 1 (n = 125) or placebo (n = 126) at a dosage of 20 mg by daily subcutaneous injection for 2 years. The primary end point was a difference in the MS relapse rate. The final 2-year relapse rate was 1.19 +/- 0.13 for patients receiving copolymer 1 and 1.68 +/- 0.13 for those receiving placebo, a 29% reduction in favor of copolymer 1 (p = 0.007) (annualized rates = 0.59 for copolymer 1 and 0.84 for placebo). Trends in the proportion of relapse-free patients and median time to first relapse favored copolymer 1. Disability was measured by the Expanded Disability Status Scale (EDSS), using a two-neurologist (examining and treating) protocol. When the proportion of patients who improved, were unchanged, or worsened by > or = 1 EDSS step from baseline to conclusion (2 years) was evaluated, significantly more patients receiving copolymer 1 were found to have improved and more receiving placebo worsened (p = 0.037). Patient withdrawals were 19 (15.2%) from the copolymer 1 group and 17 (13.5%) from the placebo group at approximately the same intervals. The treatment was well tolerated. The most common adverse experience was an injection-site reaction. Rarely, a transient self-limited systemic reaction followed the injection in 15.2% of those receiving copolymer 1 and 3.2% of those receiving placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Usher's syndrome and multiple sclerosis. Review of an individual with Usher's syndrome with a multiple sclerosis-like illness.

We describe an individual with Type I Usher's syndrome and a multiple sclerosis-like illness. MRI scan showed vermian atrophy on T1-weighted images and multiple white matter lesions in the periventricular areas on T2-weighted images. Although MRIs demonstrating increased signal intensity on weighted images are reported in some individuals with Usher's syndrome, the cerebrospinal fluid findings are not described in these cases. In the present case, oligoclonal bands were present in the spinal fluid. The possibility of a linkage between the two diseases is raised.

Adult↗
PubMed1993

Characterization of the integrin specificities of disintegrins isolated from American pit viper venoms.

A new series of homologous disintegrins was isolated from the venoms of new world pit viper genus Bothrops, Crotalus, and Lachesis. The relative activities of each disintegrin in blocking adhesive protein binding activities of GPIIb-IIIa, alpha v beta 3, and alpha 5 beta 1 were determined and correlated with their primary amino acid sequences. Four disintegrins contained the RGDW sequence and were found to be approximately twice as effective in blocking the binding of fibrinogen to GPIIb-IIIa than inhibiting the binding of vitronectin to alpha v beta 3 in solid-phase ligand binding assays (IC50 = 7.3 and 17.2 nM, respectively). A second group of seven disintegrins contained the RGDNP sequence and were found to be more potent inhibitors of vitronectin binding to alpha v beta 3 than fibrinogen binding to GPIIb-IIIa (IC50 = 4.3 and 19 nM, respectively). The RGDNP containing disintegrins were also greater than 10-fold more potent than RGDW containing disintegrins in blocking the adhesion of cells mediated by alpha 5 beta 1. These data illustrate that amino acid sequences immediately adjacent to the RGD site of disintegrins can create an extended RGD locus which coupled with conformational display of the RGD sequence may be involved in determining integrin selectivity and affinity. This information has been used in separate studies to design conformationally constrained integrin antagonists with high affinity for platelet GPIIb-IIIa.

Amino Acid Sequence↗
PubMed1993

Design of potent and specific integrin antagonists. Peptide antagonists with high specificity for glycoprotein IIb-IIIa.

Members of the snake venon-derived, "disintegrin" peptide family containing the Arg-Gly-Asp (RGD) amino acid sequence are among the most potent inhibitors of the binding of adhesive proteins to platelet glycoprotein (GP) IIb-IIIa. However, GPIIb-IIIa antagonists containing the RGD sequence are not integrin specific and inhibit the adhesive functions of many other RGD-dependent integrins. The single disintegrin peptide, barbourin, containing a conservative amino acid substitution of Lys (K) for Arg (R) in the RGD sequence, is however, highly specific for GPIIb-IIIa. Using this information we have tested the hypothesis that both structural and conformational elements of barbourin are important for its high affinity and selectivity for platelet GPIIb-IIIa by synthesizing a series of conformationally constrained, disulfide-bridged peptides containing the KGD amino acid sequence. Incorporation of the KGD sequence into a cyclic peptide template, followed by systematic optimization of the cyclic ring size, optimization of secondary hydrophobic binding site interactions, and the derivatization of the lysyl side chain functionality of the KGD sequence has resulted in peptide analogs which display inhibitory potency and GPIIb-IIIa selectivity comparable to that of barbourin. This study demonstrates that the specificity and potency of the disintegrin family of antagonists, in particular barbourin, can be mimicked by small, conformationally restrained peptides.

Amino Acid Sequence↗
PubMed1993

Augmentation of adoptively transferred experimental allergic encephalomyelitis by administration of a monoclonal antibody specific for LFA-1 alpha.

We investigated the effect of an anti-leukocyte function antigen 1 (LFA-1 alpha) monoclonal antibody, M17/4.2, on murine relapsing experimental allergic encephalomyelitis (EAE). In vitro investigations demonstrated that M17/4.2 inhibited proliferation with concanavalin A or myelin basic protein. Control mice treated with phosphate buffered saline (PBS) developed a mild to moderate disease at 7-10 days followed by a long-term relapsing clinical course. With administration of M17/4.2, the time of disease onset was unchanged; however, the severity of the disease was greatly augmented, resulting in early mortality. The pathology correlated well with the clinical course. M17/4.2 mice showed more inflammation and demyelination than PBS or anti-CD4 treated mice. Therefore, this anti-LFA-1 specific monoclonal antibody augmented EAE.

Animals↗
PubMed1993

Neuropathology of herpes simplex virus encephalitis in a rat seizure model.

Herpes simplex virus type 1 (HSV-1) is the cause of a serious and often fatal encephalitis. Patients who survive herpes simplex encephalitis (HSE) experience behavioral abnormalities including profound cognitive dysfunctions. We have developed a rat model of acute HSE to investigate the cognitive impairments caused by HSV-1 central nervous system (CNS) infection. Following intranasal inoculation of Lewis rats with a neurovirulent strain of HSV-1, animals shed virus in both ocular and nasal secretions and developed clinical signs of infection, including partial complex motor seizures that eventually generalized. Homogenization assays demonstrated infectious virus in the trigeminal ganglia, olfactory bulbs, and the piriform and entorhinal cortices. Histopathological assessment revealed inflammatory and hemorrhagic lesions in the trigeminal ganglia, olfactory bulbs, amygdala, hippocampus, the piriform and entorhinal cortices, and the spinal trigeminal nuclei. Viral antigens and nucleic acids were also detected within these structures by immunofluorescence microscopy and in situ hybridization, respectively. Viral-induced astrocytic hypertrophy in the CNS was demonstrated by glial fibrillary acidic protein immunoreactivity. Together, these results indicate that HSV-1 has the ability to invade, replicate, and induce site-specific CNS damage in the Lewis rat.

Animals↗
PubMed1992

Establishment and characterization of a human primitive neuroectodermal tumor cell line from the cerebral hemisphere.

The primitive neuroectodermal tumors (PNET) comprise a class of malignant nervous system neoplasms that afflict children. These tumors consist of cells that are morphologically identical to the primitive neuroepithelial cells normally seen in early stages of neural embryogenesis, supporting the notion that PNET result from a disturbance in the process of normal neuronal or glial differentiation. In the central nervous system, PNET occur most commonly in the cerebellum (medulloblastomas), but only occasionally in the cerebral hemispheres. We report here the establishment and characterization of a new human cell line (PFSK) derived from a PNET from the cerebral hemisphere of a child. The growth characteristics of PFSK cells were typical of an immortalized, transformed cell line. Cytogenetic and molecular genetic studies showed that three different sublines were present. In one of these sublines, sequences from chromosome 17 had been lost during establishment in culture. Immunocytochemical studies showed that PFSK cells expressed nestin, an intermediate filament protein normally expressed by neuroepithelial stem cells during neurulation. The PFSK cells did not express antigens typically found in terminally differentiated neurons or glia, indicating that this tumor cell line might represent neuroepithelial stem cells prior to commitment to a neuronal or glial lineage.

Brain Neoplasms↗
PubMed1992

Discordance of the T-cell receptor alpha-chain gene in familial multiple sclerosis.

We studied restriction fragment length polymorphisms of the T-cell receptor alpha-chain (TCR alpha) gene in DNA obtained from 99 individuals of 14 multiplex families with multiple sclerosis (MS). Thirty-four family members had definite MS and two had probable MS. Six normal family members had abnormal cranial MRIs. Linkage analysis utilized constructed haplotypes of EcoRV, Sst I, and Taq I polymorphisms. With penetrance values from 0.1 to 0.7, and scoring the normal individuals with abnormal MRIs as either unknown or affected, LOD scores were between -3.16 and -7.95 for the autosomal dominant model. For the autosomal recessive model with a penetrance range from 0.1 to 1, the LOD scores ranged from -6.77 to -23.08. These findings do not support a direct role of TCR alpha in the inheritance of MS.

Adult↗
PubMed1992

Atypical herpes simplex encephalitis: clinical, virologic, and neuropathologic evaluation.

An atypical form of herpes simplex encephalitis produced by HSV-1 documented in the present article demonstrates that (1) prominent EEG abnormality may correlate with subtle increase in signal intensity on MRI; (2) the disease may start with prominent involvement of the cingulate gyri; and (3) viral infection of the brainstem may cause early onset of severe neurologic dysfunction and coma.

Brain Stem↗
PubMed1992

Acute VIth cranial nerve dysfunction in multiple sclerosis. Evaluation by magnetic resonance imaging.

VIth nerve palsy is not frequently considered a presenting sign of multiple sclerosis (MS); however, MS has been documented as a fairly common cause of VIth nerve dysfunction. In the present study we have evaluated the clinical features and magnetic resonance imaging (MRI) findings in four MS patients with acute VIth nerve palsy. Diplopia as a result of acute VIth nerve palsy was the prominent symptom leading to the diagnosis of MS in all of the individuals. Other signs specifically localizing to the ipsilateral brainstem were absent in these patients. Cranial MRI revealed multiple white matter lesions with a periventricular predominance in all four patients and pontine white matter lesions in three of the patients. These lesions were either adjacent to the VIth nerve nucleus or involved the fasciculus of the VIth nerve or both.

Abducens Nerve↗
PubMed1991

Barbourin. A GPIIb-IIIa-specific integrin antagonist from the venom of Sistrurus m. barbouri.

Sixty-two snake venoms were screened to identify those which specifically inhibit the adhesive protein binding function of the glycoprotein (GP) IIb-IIIa complex, the receptor-mediating platelet aggregation. Although 52 of these venoms inhibited GPIIb-IIIa, only one of these, from the southeastern pigmy rattlesnake, Sistrurus m. barbouri, was specific for GPIIb-IIIa versus other integrins. The peptide responsible for this activity, termed barbourin, was sequenced and found to be highly homologous to other peptides of the viper venom GPIIb-IIIa antagonist family but was the first member which did not contain the Arg-Gly-Asp (RGD) amino acid sequence, believed to be required for inhibition of receptor function. Instead, barbourin contains the sequence, Lys-Gly-Asp (KGD). The conservative Lys for Arg substitution appears to be the sole structural feature which imparts integrin specificity to barbourin, since venom peptide analogs with Lys substitutions were also specific for GPIIb-IIIa. Thus, barbourin represents a new structural model useful for designing potent and GPIIb-IIIa-specific compounds that may have therapeutic value as platelet aggregation inhibitors.

Amino Acid Sequence↗
PubMed1991

Discordance of T-cell receptor beta-chain genes in familial multiple sclerosis.

Restriction fragment length polymorphisms of the T-cell receptor beta-chain gene were studied in DNA obtained from 96 individuals from 14 multiplex families with multiple sclerosis (MS). Thirty-four family members had definite MS and two had probable MS. Five normal family members had abnormal findings on cranial magnetic resonance imaging (MRI) scans. Linkage analysis was performed using the BglII and the KpnI polymorphisms. With penetrance values from 0.1 to 0.7, and altering the scoring of the normal individuals with abnormal findings on MRI scans from "unknown" to "affected," log of the odds scores between -4.59 to -12.76 were found for the autosomal dominant model. For the autosomal recessive model with a penetrance range from 0.1 to 1.0, the LOD scores ranged from -8.20 to -32.98. These findings do not support a direct role of T-cell receptor beta-chain gene in the inheritance of MS.

Alleles↗