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Biomedical subjects

R P Lisak

Publications and source records attributed to R P Lisak.

At least 19 recordsLinked to original sources
PubMed1997

Induced upregulation of IL-1, IL-1RA and IL-1R type I gene expression by Schwann cells.

We analyzed two distinct phenotypes of Schwann cells (SC), non-differentiated and differentiated, for their ability to produce IL-1alpha and IL-1beta, and to express message for IL-1 receptor antagonist (IL-IRA) and IL-1R type I, in vitro. SC were stimulated with: lipopolysaccharide (LPS), products of activated splenocytes (ASP), products from LPS stimulated SC (SCP), rat recombinant IL-1beta (rrIL-1beta) or dexamethasone. IL-1alpha, IL- 1beta and IL-1RA mRNA levels were highly upregulated after stimulation with LPS, ASP, SCP or rrIL-1beta. SC constitutively expressed low levels of message for IL-1alpha and IL-1beta but not IL-1RA. Specific mRNAs for both IL-1 isotypes were highly upregulated 2 to 4 h after LPS stimulation and then decreased and were undetectable by 24 h. IL-1RA mRNA was detectable after 6 h of LPS stimulation and was maximally upregulated at 24 h. IL-1 gene expression was inducible in both SC phenotypes. IL-1beta could be detected by immunofluorescence in SC, one to three days after LPS stimulation. At the same time IL-1 bioactivity was maximal in SC supernatants. Treatment with either SCP, rrIL-1beta or dexamethasone induced upregulation of IL-1R type I mRNA with maximal expression between 2 to 4 h, in SC. Inducible expression of genes for IL-1alpha, IL-1beta, IL-1RA and IL-1R type I in both differentiated and non-differentiated SC suggest autocrine and paracrine regulation of IL-1 by SC.

Animals↗
PubMed1997

Epstein-Barr virus encephalomyelitis diagnosed by polymerase chain reaction: detection of the genome in the CSF.

A case of encephalomyelitis with polymerase chain reaction detection of Epstein-Barr virus (EBV) in the CSF, and concurrent serologic changes consistent with acute systemic EBV infection is presented and discussed. We document involvement of the brain, spinal cord, and nerve roots, summarize some unusual imaging findings, and note the evolution of CSF oligoclonal bands.

Adult↗
PubMed1996

Arthritis associated with circulating immune complexes following administration of intravenous immunoglobulin therapy in a patient with chronic inflammatory demyelinating polyneuropathy.

Intravenous immunoglobulin is viewed as a relatively safe treatment for several neurologic disorders. I report arthritis associated with elevated circulating immune complexes and abnormalities of serum complement components which is a rare complication with modern preparations of immunoglobulin-gamma.

Antigen-Antibody Complex↗
PubMed1996

In vitro studies of glial cells: what can we learn about demyelinating diseases?

Acquired demyelinating diseases of the central and peripheral nervous systems comprise an important group of neurologic diseases of unknown etiology and incompletely understood pathogenesis. Cultures of glial cells are proving highly useful in investigating the role of both antibodies and cytokines in the pathogenesis of these disorders. While there clearly is need for comparative studies employing more complex systems and using patient derived tissues, glial cell cultures provide important advantages by allowing researchers to characterize the effect of cytokines and growth factors on specific cell types in controlled conditions.

Animals↗
PubMed1995

Circulating, soluble adhesion proteins in cerebrospinal fluid and serum of patients with multiple sclerosis: correlation with clinical activity.

Soluble adhesion protein intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule (E-selectin) were measured in serum and cerebrospinal fluid (CSF) of patients with relapsing-remitting multiple sclerosis (RRMS) in remission and in exacerbation, as well as patients with chronic progressive MS, stable MS, and in patients with other neurological and inflammatory diseases (ONDs). Serum ICAM-1 and E-selectin were significantly elevated in patients with MS over those with ONDs and controls. CSF VCAM-1 and E-selectin were found to be elevated over control and disease control samples. No increase in CSF ICAM-1 was observed. Results were analyzed longitudinally and by MS category. In paired CSF and serum samples from patients in exacerbation, elevated VCAM-1 correlated with increased serum VCAM-1 in 5 of 7 patients. Elevated CSF E-selectin did not correlate with elevations in serum E-selectin.

Analysis of Variance↗
PubMed1995

Myasthenia gravis: immunological mechanisms and immunotherapy.

This review of the immunological aspects of myasthenia gravis and the immunotherapy of the disease emphasizes the current state of knowledge of the immunological events at the neuromuscular junction, and the immunoregulatory abnormalities noted in myasthenic patients. The treatment modalities available to the clinician are discussed in an attempt to provide information that will allow for a rational approach to therapy.

Autoimmune Diseases↗
PubMed1995

Systemic lupus erythematosus: immunopathogenesis of neurologic dysfunction.

Neurologic complications of systemic lupus erythematosus (neuro-SLE) are common. The most frequent manifestations of neuro-SLE are seizures, encephalopathy, and behavioral changes, but a wide variety of other neurologic abnormalities affecting the central and peripheral nervous system and muscle also occur. Although the prevalence of neuro-SLE is high, the diversity of clinical presentations, the multiple potential etiologies, and the absence of sensitive and specific diagnostic tests render diagnosis difficult. Recent advances in understanding mechanisms of neuronal dysfunction combined with advances in imaging techniques, including functional imaging, should help in diagnosis and management. The mechanisms of neurologic injury can be divided into three broad categories. First, neuronal dysfunction may result from direct effects of the immune system on brain cells such as autoantibody binding to cell surface, immune complex deposition with secondary inflammation, and effects of cytokines. Second, immune- mediated injury to supportive structures such as the vasculature may also affect the nervous system by producing ischemia. Finally, the neuraxis may be affected by any one of several immune and non- immune effects of infection, toxins, and metabolic disturbances.

Animals↗
PubMed1995

Acute disseminated encephalomyelitis and isolated central nervous system demyelinative syndromes.

The clinical and pathological characteristics of acute disseminated encephalomyelitis are briefly outlined. The possible relation between acute disseminated encephalomyelitis and other isolated monophasic inflammatory demyelinating episodes in the central nervous system, such as acute optic neuritis, transverse myelitis or brainstem lesions, is noted and the risk of progression to multiple sclerosis is examined. The surprising results of a clinical trial of corticosteroids in optic neuritis are of particular interest in this regard, and we speculate on an explanation in terms of a spread of antimyelin T cell receptor gene usage over time. Finally, the risk factors for the progression of demyelinating ther than optic neuritis to multiple sclerosis are explored. Further work to elucidate better the relationships between these pathological entities is suggested.

Brain↗
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

Interleukin-1 alpha, but not interleukin-1 beta, is a co-mitogen for neonatal rat Schwann cells in vitro and acts via interleukin-1 receptors.

The culture of neonatal rat Schwann cells (SC) with unfractionated cytokines induces an increase in SC proliferation. Previous studies demonstrated that while incubation of SC with interleukin-1(IL-1) does not result in enhanced SC mitogenesis, a mixture of antibodies to IL-1 alpha plus IL-1 beta inhibits cytokine-induced proliferation. We undertook the current studies to: (i) confirm that neither isoform of IL-1 directly causes SC proliferation; (ii) determine if there is a difference in the effect of antibodies to IL-1 alpha versus IL-1 beta; and (iii) determine if IL-1 contribution to cytokine-induced proliferation of SC is mediated via IL-1 receptors. IL-1 alpha or IL-1 beta from several sources, over a wide range of concentrations, failed to induce SC proliferation. Polyclonal antibodies to IL-1 alpha from several suppliers and a monoclonal antibody to IL-1 alpha inhibited SC proliferation, whereas similar antibodies to IL-1 beta had no effect on cytokine-induced SC proliferation. Addition of excess IL-1 alpha to an incubation mixture of unfractionated cytokines plus anti-IL-1 alpha abolished the inhibitory effect of the antibodies. Addition of IL-1 receptor antagonist (IL-1 Ra) to unfractionated cytokines inhibited SC proliferation. Therefore, while neither IL-1 alpha nor IL-1 beta is a solitary mitogen for neonatal rat SC, IL-1 alpha but not IL-1 beta acts as a co-mitogen. Moreover, IL-1 alpha seems to exert its co-mitogenic effect via receptors for IL-1.

Animals↗
PubMed1994

Antibodies to interleukin-6 inhibit Schwann cell proliferation induced by unfractionated cytokines.

We have previously demonstrated that unfractionated cytokines induce proliferation of neonatal rat Schwann cells in vitro. Incubation of Schwann cells with natural or recombinant human interleukin-1 (IL-1) does not induce Schwann cell proliferation, but antibodies to IL-1 inhibit Schwann cell proliferation induced by unfractionated cytokines of human origin. In this study we investigated the effect of interleukin-6 (IL-6), another monokine, on proliferation of rat Schwann cells. Incubation of Schwann cells with recombinant (r) mouse IL-6 and two types of human rIL-6 did not induce proliferation of Schwann cells or of endoneurial fibroblasts. However, antibodies to rhIL-6 inhibited Schwann cell proliferation induced by unfractionated cytokines but had no effect on fibroblast proliferation. Addition of excess rhIL-6 to a mixture of unfractionated cytokines plus anti-rhIL-6 abrogated the inhibitory effect of the anti-rhIL-6. Therefore, IL-6 is a co-mitogen for neonatal Schwann cells in vitro.

Animals↗
PubMed1993

Immunopharmacologic therapy in myasthenia gravis.

Immunotherapy is frequently employed in treatment of patients with myasthenia gravis. Different regimens are not based entirely on controlled or comparative studies. There are few clear guidelines for choosing a particular immunomodulating agent and timing of its introduction. In this article, we have tried to summarize known information about the immunopharmacologic agents used for the treatment of patients with myasthenia gravis.

Adjuvants, Immunologic↗