Robert Lisak - Academia.edu (original) (raw)
Papers by Robert Lisak
Journal of Neurochemistry, 1986
Skundric DS, Lisak RP. Role of neuropoietic cytokines in development and progression of diabetic ... more Skundric DS, Lisak RP. Role of neuropoietic cytokines in development and progression of diabetic polyneuropathy: from glucose metabolism to neurodegeneration. Exp Diabesity Res. 2003,Oct-Dec;4(4):303-312. http://dx. Diabetic neuropathy develops as a result of hyper-glycemia-induced local metabolic and microvascular changes in both type I and type II diabetes mellitus. Diabetic neuropathy shows slower impulse conduction, axonal de-generation, and impaired regeneration. Diabetic neuropa-thy affects peripheral, central, and visceral sensorimotor and motor nerves, causing improper locomotor and vis-ceral organ dysfunctions. The pathogenesis of diabetic neu-ropathy is complex and involves multiple pathways. Lack of success in preventing neuropathy, even with successful treatment of hyperglycemia, suggests the presence of early mediators between hyperglycemia-induced metabolic and enzymatic changes and functional and structural properties of Schwann cells (SCs) and axons. It is feasible t...
Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expressi... more Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins
Neuroimmunology and Neuroinflammation, 2020
Proceedings of the National Academy of Sciences, 2019
Muscle & Nerve, 1981
Opinion statementThe treatment of patients with myasthenia gravis should be individualized accord... more Opinion statementThe treatment of patients with myasthenia gravis should be individualized according to the extent (ocular versus generalized) and severity (mild to severe) of disease, the presence or absence of concomitant disease (including but not limited to other autoimmune diseases and thymoma), and, to a lesser degree, the age of the patient. Thymectomy should be performed in patients with generalized disease, especially those who have detectable levels of circulating antibodies to acetylcholine receptor (anti-AChR), as it should be in all patients thought to have an operable thymoma (observed on imaging studies of the chest). Symptomatic therapy consists of anticholinesterase drugs (usually pyridostigmine); occasionally, other drugs are required to reduce the muscarinic side effects. At times, patients need immunosuppressive or immunomodulatory therapy with glucocorticoids, azathioprine, cyclosporine or cyclophosphamide, plasma exchange, and intravenous immunoglobulin. Remission, whether spontaneous or pharmacologically induced, or significant improvement can be achieved in most patients, but some treatments entail significant side effects and considerable cost.
Science, 1979
Thirteen of 31 rabbits immunized repeatedly with bovine brain galactocerebroside developed experi... more Thirteen of 31 rabbits immunized repeatedly with bovine brain galactocerebroside developed experimental allergic neuritis, manifested by flaccid paresis and hypesthesia of four limbs, 2 to 11 months after the initial inoculation. Electrophysiological studies revealed multifocal conduction block of peripheral nerves. Perivenular demyelinative lesions associated with phagocytic mononuclear cells occurred in spinal ganglia, roots, and less frequently in distal nerves.
Neuroscience Letters, 1980
Multiple Sclerosis, 2007
Objective To examine patient and significant other characteristics as predictors of significant o... more Objective To examine patient and significant other characteristics as predictors of significant other well-being. Methods A total of 74 persons with multiple sclerosis (MS) and their significant others participated. Executive functioning was measured using neuropsychological tests. Awareness of cognitive deficit was measured as the discrepancy between the patient's reports of their abilities and objective test results. Awareness of functional deficit was measured as the discrepancy between the patient's and significant other's reports of the patient's functional abilities. Patient neurobehavioral disturbance was measured using a significant-other rated questionnaire. Significant other perceived social support and well-being (ie, psychological distress, life satisfaction, and general health status) were assessed using questionnaires filled out by the significant other. Results Executive dysfunction, neurobehavioral disturbance, and lack of awareness of functional defi...
Expert Opinion on Drug Metabolism & Toxicology, 2006
The past decade has witnessed a revolution in the treatment of multiple sclerosis (MS), the most ... more The past decade has witnessed a revolution in the treatment of multiple sclerosis (MS), the most common demyelinating disorder of the human CNS. After being considered as an untreatable disease for more than a century, six disease-modifying treatments have been approved between 1993 and 2006. Glatiramer acetate (GA) is a worldwide drug approved for the treatment of relapsing-remitting MS in 1996. The drug is a synthetic copolymer of four amino acids based on the composition of myelin basic protein, one of several putative autoantigens implicated in the pathogenesis of MS. Three separate double-blind, placebo-controlled trials have established its efficacy in relapsing-remitting MS. Observations from an ongoing study, the longest prospective study in MS therapeutics so far, suggest that the effect of GA in reducing the relapse rate and neurological disability is maintained over a 10-year period. Independent investigators have identified several putative immunological mechanisms of action of GA, with the unique observation of the generation of GA-reactive T-helper 2 (anti-inflammatory) polarised lymphocytes within days to weeks of initiating therapy and sustaining an anti-inflammatory milieu for years in the peripheral immune system and, presumably, in the CNS. Emerging data from immunological and imaging studies quantifying axonal injury in the brain point towards neuroprotective abilities of GA. Combined with its remarkable safety and tolerability, long-term efficacy and neuroprotective effect, GA presents it self as a first-line choice in relapsing-remitting MS, and holds immense promise in developing its potential as a combination therapy in MS, as well as extending its indications to other neurodegenerative diseases.
Annals of Neurology, 1980
Acta Neurologica Scandinavica, 2005
Brain Sciences
The melanocortins and their receptors have been extensively investigated for their roles in the h... more The melanocortins and their receptors have been extensively investigated for their roles in the hypothalamo-pituitary-adrenal axis, but to a lesser extent in immune cells and in the nervous system outside the hypothalamic axis. This review discusses corticosteroid dependent and independent effects of melanocortins on the peripheral immune system, central nervous system (CNS) effects mediated through neuronal regulation of immune system function, and direct effects on endogenous cells in the CNS. We have focused on the expression and function of melanocortin receptors in oligodendroglia (OL), the myelin producing cells of the CNS, with the goal of identifying new therapeutic approaches to decrease CNS damage in multiple sclerosis as well as to promote repair. It is clear that melanocortin signaling through their receptors in the CNS has potential for neuroprotection and repair in diseases like MS. Effects of melanocortins on the immune system by direct effects on the circulating cell...
Neurology - Neuroimmunology Neuroinflammation
Importance: Multiple sclerosis patients have been considered a higher-risk population for COVID-1... more Importance: Multiple sclerosis patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, no study has identified clinical characteristics of multiple sclerosis associated with worse COVID-19 outcomes. Objective: To evaluate the clinical characteristics of multiple sclerosis, including staging, degree of disability, and disease-modifying therapy use that are associated with worse outcomes from COVID-19. Design: Prospective cohort study looking at the outcomes of multiple sclerosis patients with COVID-19 between March 1st and May 18th, 2020. Setting: This is a multicenter study of three distinct hospital systems within the U.S. Participants: The study included 40 consecutive patients with nasopharyngeal/oropharyngeal PCR-confirmed COVID-19 infection. Exposures: Multiple sclerosis staging, severe disability (based on baseline-extended disability status scale equal to or greater than 6.0) and ...
Multiple Sclerosis Journal
Journal of Neurochemistry, 1986
Skundric DS, Lisak RP. Role of neuropoietic cytokines in development and progression of diabetic ... more Skundric DS, Lisak RP. Role of neuropoietic cytokines in development and progression of diabetic polyneuropathy: from glucose metabolism to neurodegeneration. Exp Diabesity Res. 2003,Oct-Dec;4(4):303-312. http://dx. Diabetic neuropathy develops as a result of hyper-glycemia-induced local metabolic and microvascular changes in both type I and type II diabetes mellitus. Diabetic neuropathy shows slower impulse conduction, axonal de-generation, and impaired regeneration. Diabetic neuropa-thy affects peripheral, central, and visceral sensorimotor and motor nerves, causing improper locomotor and vis-ceral organ dysfunctions. The pathogenesis of diabetic neu-ropathy is complex and involves multiple pathways. Lack of success in preventing neuropathy, even with successful treatment of hyperglycemia, suggests the presence of early mediators between hyperglycemia-induced metabolic and enzymatic changes and functional and structural properties of Schwann cells (SCs) and axons. It is feasible t...
Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expressi... more Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins
Neuroimmunology and Neuroinflammation, 2020
Proceedings of the National Academy of Sciences, 2019
Muscle & Nerve, 1981
Opinion statementThe treatment of patients with myasthenia gravis should be individualized accord... more Opinion statementThe treatment of patients with myasthenia gravis should be individualized according to the extent (ocular versus generalized) and severity (mild to severe) of disease, the presence or absence of concomitant disease (including but not limited to other autoimmune diseases and thymoma), and, to a lesser degree, the age of the patient. Thymectomy should be performed in patients with generalized disease, especially those who have detectable levels of circulating antibodies to acetylcholine receptor (anti-AChR), as it should be in all patients thought to have an operable thymoma (observed on imaging studies of the chest). Symptomatic therapy consists of anticholinesterase drugs (usually pyridostigmine); occasionally, other drugs are required to reduce the muscarinic side effects. At times, patients need immunosuppressive or immunomodulatory therapy with glucocorticoids, azathioprine, cyclosporine or cyclophosphamide, plasma exchange, and intravenous immunoglobulin. Remission, whether spontaneous or pharmacologically induced, or significant improvement can be achieved in most patients, but some treatments entail significant side effects and considerable cost.
Science, 1979
Thirteen of 31 rabbits immunized repeatedly with bovine brain galactocerebroside developed experi... more Thirteen of 31 rabbits immunized repeatedly with bovine brain galactocerebroside developed experimental allergic neuritis, manifested by flaccid paresis and hypesthesia of four limbs, 2 to 11 months after the initial inoculation. Electrophysiological studies revealed multifocal conduction block of peripheral nerves. Perivenular demyelinative lesions associated with phagocytic mononuclear cells occurred in spinal ganglia, roots, and less frequently in distal nerves.
Neuroscience Letters, 1980
Multiple Sclerosis, 2007
Objective To examine patient and significant other characteristics as predictors of significant o... more Objective To examine patient and significant other characteristics as predictors of significant other well-being. Methods A total of 74 persons with multiple sclerosis (MS) and their significant others participated. Executive functioning was measured using neuropsychological tests. Awareness of cognitive deficit was measured as the discrepancy between the patient's reports of their abilities and objective test results. Awareness of functional deficit was measured as the discrepancy between the patient's and significant other's reports of the patient's functional abilities. Patient neurobehavioral disturbance was measured using a significant-other rated questionnaire. Significant other perceived social support and well-being (ie, psychological distress, life satisfaction, and general health status) were assessed using questionnaires filled out by the significant other. Results Executive dysfunction, neurobehavioral disturbance, and lack of awareness of functional defi...
Expert Opinion on Drug Metabolism & Toxicology, 2006
The past decade has witnessed a revolution in the treatment of multiple sclerosis (MS), the most ... more The past decade has witnessed a revolution in the treatment of multiple sclerosis (MS), the most common demyelinating disorder of the human CNS. After being considered as an untreatable disease for more than a century, six disease-modifying treatments have been approved between 1993 and 2006. Glatiramer acetate (GA) is a worldwide drug approved for the treatment of relapsing-remitting MS in 1996. The drug is a synthetic copolymer of four amino acids based on the composition of myelin basic protein, one of several putative autoantigens implicated in the pathogenesis of MS. Three separate double-blind, placebo-controlled trials have established its efficacy in relapsing-remitting MS. Observations from an ongoing study, the longest prospective study in MS therapeutics so far, suggest that the effect of GA in reducing the relapse rate and neurological disability is maintained over a 10-year period. Independent investigators have identified several putative immunological mechanisms of action of GA, with the unique observation of the generation of GA-reactive T-helper 2 (anti-inflammatory) polarised lymphocytes within days to weeks of initiating therapy and sustaining an anti-inflammatory milieu for years in the peripheral immune system and, presumably, in the CNS. Emerging data from immunological and imaging studies quantifying axonal injury in the brain point towards neuroprotective abilities of GA. Combined with its remarkable safety and tolerability, long-term efficacy and neuroprotective effect, GA presents it self as a first-line choice in relapsing-remitting MS, and holds immense promise in developing its potential as a combination therapy in MS, as well as extending its indications to other neurodegenerative diseases.
Annals of Neurology, 1980
Acta Neurologica Scandinavica, 2005
Brain Sciences
The melanocortins and their receptors have been extensively investigated for their roles in the h... more The melanocortins and their receptors have been extensively investigated for their roles in the hypothalamo-pituitary-adrenal axis, but to a lesser extent in immune cells and in the nervous system outside the hypothalamic axis. This review discusses corticosteroid dependent and independent effects of melanocortins on the peripheral immune system, central nervous system (CNS) effects mediated through neuronal regulation of immune system function, and direct effects on endogenous cells in the CNS. We have focused on the expression and function of melanocortin receptors in oligodendroglia (OL), the myelin producing cells of the CNS, with the goal of identifying new therapeutic approaches to decrease CNS damage in multiple sclerosis as well as to promote repair. It is clear that melanocortin signaling through their receptors in the CNS has potential for neuroprotection and repair in diseases like MS. Effects of melanocortins on the immune system by direct effects on the circulating cell...
Neurology - Neuroimmunology Neuroinflammation
Importance: Multiple sclerosis patients have been considered a higher-risk population for COVID-1... more Importance: Multiple sclerosis patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, no study has identified clinical characteristics of multiple sclerosis associated with worse COVID-19 outcomes. Objective: To evaluate the clinical characteristics of multiple sclerosis, including staging, degree of disability, and disease-modifying therapy use that are associated with worse outcomes from COVID-19. Design: Prospective cohort study looking at the outcomes of multiple sclerosis patients with COVID-19 between March 1st and May 18th, 2020. Setting: This is a multicenter study of three distinct hospital systems within the U.S. Participants: The study included 40 consecutive patients with nasopharyngeal/oropharyngeal PCR-confirmed COVID-19 infection. Exposures: Multiple sclerosis staging, severe disability (based on baseline-extended disability status scale equal to or greater than 6.0) and ...
Multiple Sclerosis Journal