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Biomedical subjects

B Jubelt

Publications and source records attributed to B Jubelt.

34 records · Page 2Linked to original sources
PubMed1989

Anti-thymocyte serum delays clearance of poliovirus from the mouse central nervous system.

Antibody is of primary importance for protection from poliovirus-induced paralysis (poliomyelitis) and from other enterovirus infections. However, the components of the immune response involved in the clearance of an established enterovirus infection of the central nervous system (CNS) are not known. To assess the effect of thymus-dependent immune functions on a CNS poliovirus infection, adult BALB/c mice inoculated intracerebrally with the W-2 strain of human poliovirus type 2 (PV2) were treated with anti-thymocyte serum (ATS) and analyzed for clinical disease, virus persistence, antibody responses, and T-cell proliferation (Tprlf). Half (22 of 44) of the ATS-treated mice showed paralysis and death as compared to 27% (17 of 62) of control mice treated with normal rabbit serum. Virus persisted in the brain for 45 days after infection in 43% (13 of 30) of ATS-treated mice as compared to 3% (1 of 30) of controls. Tprlf to PV as well as Tprlf and antibody responses to control antigens were markedly reduced in ATS-treated mice. However, antibody responses to PV in ATS-treated mice were not suppressed, suggesting that PV may be a T-cell-independent antigen. These findings indicate that ATS-suppressible functions contribute to the clearance of PV from the mouse CNS, apparently via a sensitized T-cell mechanism.

Animals↗
PubMed1989

Clearance of a persistent human enterovirus infection of the mouse central nervous system by the antiviral agent disoxaril.

Enteroviruses can cause persistent central nervous system (CNS) infections in agammaglobulinemic individuals. Because these infections are rarely cured by passive administration of antibody, a chemotherapeutic approach would be advantageous. In this study, the efficacy of the antienterovirus (and antipicornavirus) drug disoxaril was demonstrated in a murine model of persistent enterovirus infection. Disoxaril is a hydrophobic antiviral compound that blocks picornavirus uncoating. The W-2 strain of human poliovirus type 2 (PV2) persists in the CNS of immunosuppressed mice and causes late paralysis. Mice were inoculated intracerebrally with PV2, immunosuppressed with cyclophosphamide, and treated intragastrically with disoxaril at 50, 100, or 200 mg/kg per day in two divided doses beginning on postinfection day 20. At 200 mg/kg per day, disoxaril significantly decreased the incidence of clinical disease, i.e., paralysis and death. Assays for virus revealed more rapid clearance of virus from the CNS in the drug-treated group. No drug-associated toxicity was observed. Residual isolates of virus were not drug-resistant, suggesting that the appearance of drug resistance during prolonged treatment may not be a clinical problem.

Animals↗
PubMed1987

Lansing poliovirus infection in mice: antibody demonstrable by enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation but not by neutralization.

Adult mice infected intracerebrally (i.c) with the Lansing strain of type 2 human poliovirus (HPV2) failed to develop a systemic neutralizing antibody response until 2 months post-infection (p.i). In contrast, an enzyme-linked immunosorbent assay (ELISA) demonstrated an antibody response of IgM and IgG classes beginning at day 1 p.i. with peak levels reached by 5 weeks p.i. This response was slightly greater in paralyzed than in nonparalyzed animals. Immunoprecipitation of poliovirus proteins from cytoplasmic extracts and disrupted purified virion preparations revealed antibodies to three capsid proteins, two capsid precursor proteins, and one nonstructural protein. Finally, neither neutralizing antibody nor definite virus replication was detected after oral, intraperitoneal, or intravenous routes of inoculation. We conclude that the lack of a systemic neutralizing antibody response in mice is probably due to an insufficient amount of infectious virus and consequently viral neutralizing epitopes reaching extraneural lymphoid tissues.

Animals↗
PubMed1987

Neurological manifestations of the post-polio syndrome.

Patients with late effects of poliomyelitis, i.e., PPS, are being seen at an ever increasing frequency by general physicians, neurologists, and orthopedists. An appropriate time interval for the onset of late manifestations has elapsed since the major epidemics of poliomyelitis in the 1940s and 1950s. Post-polio neurological manifestations primarily include new weakness, atrophy, muscle pain, and fasciculations. Fortunately, the weakness is of a very slow, progressive nature. Abnormal laboratory studies include routine EMG, demonstrating chronic denervation; SFEMG, demonstrating increased fiber density, increased jitter, and blocking; and muscle biopsy most often revealing fiber-type grouping of chronic denervation and small isolated angular (or angulated) fibers and group atrophy in some series, both suggestive of active denervation. Unfortunately, both EMG and muscle biopsy studies suffer from a lack of specificity as they do not appear to distinguish asymptomatic from symptomatic (new weakness, PPMA) patients with prior poliomyelitis. Although the cause of PPMA is unknown, electrophysiological (SFEMG) and muscle biopsy studies suggest that the process involves a loss or dropout of axon terminals of reinnervated motor units. The axons terminal dropout could be due to dysfunction in the cell soma, the axon, or the terminals themselves. Whether motor neuron exhaustion, a persistent viral infection, or immune-mediated mechanisms play a role in the pathogenesis of the late weakness is unclear at present and will require further investigation. Treatment at this time is of a supportive nature. A major controversy involves the role of strengthening exercises in these patients since experimental animal studies suggest that excessive exercise of denervated muscles leads to increased weakness. Clearly, a better understanding of PPS and PPMA will allow more effective management of these patients' problems and might also provide insight into other motor neuron and neuromuscular junction diseases.

Aging↗
PubMed1986

Structural brain correlates of emotional disorder in multiple sclerosis.

Eighty-seven patients with definite multiple sclerosis (MS) were examined neurologically and administered the Mini-mental State examination (MMS) to assess cognitive disability at the beginning and end of a one-year study. A CT scan was performed in 37. A group of 16 patients with stable spinal cord injuries (SCI) were studied in a similar manner. Of the MS patients, 47% had a mean General Health Questionnaire (GHQ) score in the abnormal range. This was a higher rate than in SCI patients (P = 0.004). Mean depression scores were similar in MS and SCI patients, but MS patients with brain involvement were more depressed than those with cord lesions only (P = 0.05). Depression score was unrelated to functional disability but was correlated with the degree of neurological impairment (P = 0.03). Euphoric patients were more likely to have brain involvement (P = 0.006), to have progressive MS (P less than 0.0001), and to have enlarged ventricles (P = 0.04) and were more impaired cognitively (P = 0.04) than noneuphoric patients. These results suggest that depression in MS patients is partly determined by the presence of brain involvement, but that it is also an emotional reaction to the disorder. Euphoria and cognitive disorder are reflections of brain involvement.

Adult↗
PubMed1986

Ultrastructural immunohistochemical localization of poliovirus during virulent infection of mice.

Ultrastructural immunohistochemistry was used to localize type 2 human poliovirus (HPV 2) during virulent infection of mice caused by the Lansing strain. In the spinal cord, immune-reaction product was exclusively localized within neurons and their processes. The absence of viral antigen in glial, endothelial and inflammatory cells further supports the strict neuronotropicity of HPV. In addition, viral antigen and virus-like particles were localized in synaptic complexes and axons, including preterminal axons. This clear demonstration of HPV in neuronal cell bodies, their axons, and synaptic elements strongly supports the hypothesis of HPV dissemination in the central nervous system via axonal transport.

Animals↗
PubMed1984

Characterization of genetic changes occurring in attenuated poliovirus 2 during persistent infection in mouse central nervous systems.

Genomic changes occurring in the attenuated W-2 strain of poliovirus 2 during persistent infection of the central nervous system of immunosuppressed mice were analyzed. The RNase T1 oligonucleotide fingerprints of 34 different viruses, isolated from the brains and spinal cords of paralyzed and nonparalyzed mice during a 105-day period, were used to quantitate and compare the mutations occurring in each isolate. Although mice were inoculated with plaque-purified virus, genetically distinct viruses were recovered from the central nervous system. The number of oligonucleotide changes occurring in isolates from paralyzed mice generally was greater than that observed in isolates from nonparalyzed mice. However, differences in the extent of mutation in isolates from the two groups of mice did not appear to be related to the level of virus replication. In paralyzed mice, the number of oligonucleotide changes on average was greater in viruses isolated during the first 60 days of the infection than in the last 45 days. The number of oligonucleotide changes was essentially constant throughout the infection, however, in viruses isolated from the brains of nonparalyzed mice. In addition, several specific oligonucleotide changes were found only in viruses isolated from paralyzed animals.

Animals↗
PubMed1984

Poliovirus infection of cyclophosphamide-treated mice results in persistence and late paralysis: I. Clinical, pathologic, and immunologic studies.

An attenuated human poliovirus infection of cyclophosphamide (CY)-treated mice was developed as a model of persistent CNS enterovirus infections and as an investigation of the interaction of virus with motor neurons during persistence. Ten percent of mice inoculated intracerebrally with undiluted virus developed clinical disease by day 90, but of those treated with CY, 80% developed disease. At higher virus dilutions plus CY there was a marked increase in the incubation period. The latest onset of clinical disease occurred on day 146. Only paralyzed animals had pathologic changes in the spinal cord and virus antigen in anterior horn cells. Neutralizing antibodies were suppressed by CY, as were humoral and cellular immune responses to other antigens.

Animals↗
PubMed1984

Poliovirus infection of cyclophosphamide-treated mice results in persistence and late paralysis: II. Virologic studies.

An attenuated human poliovirus infection of cyclophosphamide (CY)-treated mice resulted in a persistent CNS infection. Persistence in asymptomatic animals occurred in 46% of CY-treated mice but in only 3% of untreated animals, and was confined primarily to the brain. Virus replication in the brain peaked by day 3 for all inoculum dilutions, but was lower with diluted virus. High virus titers in the spinal cord were found only in paralyzed animals and occurred late in the infection following inoculation of diluted virus. Thus, the level of virus replication in the brain was directly related to the amount of virus inoculated, and was correlated with the rapidity of virus transit to the spinal cord and the incubation time to paralysis.

Animals↗
PubMed1984

Enterovirus and mumps virus infections of the nervous system.

Enteroviruses and mumps viruses are the most common causes of viral aseptic meningitis and mild acute encephalitis. Given is an overview of their pathogeneses, epidemiologies, clinical manifestations, diagnoses, and treatments.

Central Nervous System Diseases↗
PubMed1982

Hematogenous origin of the inflammatory response in acute poliomyelitis.

To determine the origin of the inflammatory response, and in particular the microglial rod cell response, in acute viral encephalitis, 4-week-old Swiss mice were injected with tritiated thymidine to label actively dividing cells prior to infection with the Lansing type 2 strain of poliovirus. As expected, the majority of polymorphonuclear and mononuclear leukocytes within the central nervous system perivascular infiltrates were shown to be hematogenous in origin. As early as 24 hours after infection, isotope-labeled cells having light histological and ultrastructural features consistent with microglia and microglial rod cells were identified within brain parenchyma and were shown to participate in neuronophagia and formation of glial nodules. Supraependymal and suprachoroidal cells were also shown to contain the label. However, neither endothelial cells nor pericytes contained label as determined by electron microscopy. These studies support a hematogenous origin for all cellular elements of the classic inflammatory response in viral infections of brain.

Animals↗
PubMed1980

Comparative studies of five strains of mumps virus in vitro and in neonatal hamsters: evaluation of growth, cytopathogenicity, and neurovirulence.

The growth and cytopathogenicity of five strains of mumps virus were examined in six types of cell cultures and in neonatal hamsters. These strains included the MJ and RW strains, both recent cerebrospinal fluid isolates: the neuroadapted Kilham strain; the Enders strain adapted to chick embryo; and the Jeryl Lynn vaccine strain adapted to chick cell culture. The MJ, RW, and Kilham strains all produced infectious virus without restriction in vitro, but the RW strain did not cause obvious cytopathic effect; the MJ and Kilham strains were cytopathic. The Enders and Jeryl Lynn strains adapted to chick embryo cells were cytopathic and productive in chick cell culture but were restricted in ability to grow productively in vitro on mammalian cell types, even failing to produce noninfectious particles in some cases. In vitro cytopathogenicity was a host-independent property of a specific virus strain, but the type of cytopathic effect manifest in culture (eg, fusion, cytoplasmic vacuoles) depended on both the strain and the host cell. The ability of a virus strain to invade the brain parenchyma and infect neurons in vivo appeared to correlate with the strain's cytopathogenicity and not with passage history or adaptive status.

Animals↗
PubMed1980

Pathogenesis of human poliovirus infection in mice. I. Clinical and pathological studies.

Human poliovirus infection in mice was studied to determine the similarities to human poliomyelitis, the selective vulnerability of neurons to infection, the role of the immune response in age-dependent susceptibility, and possible viral persistence. Mice inoculated intracerebrally (ic) with the Lansing type 2 poliovirus developed a disease with clinical, pathological, and age-dependent features resembling human poliomyelitis. Adult mice had a shorter incubation period (50% paralysis, Day 8 vs. Day 13) and a higher incidence of paralysis (97% vs. 79%) than newborns. Only paralyzed animals had pathologic changes in the spinal cord, and these corresponded to the degree of paralysis. Fluorescent antibody staining showed that selective infection of neurons was most intense in the anterior horn motor neurons of the spinal cord. There was no extraneural virus replication and no systemic neutralizing antibody response. Cyclophosphamide immunosuppression enhanced rather than diminished disease, indicating that maturation of immune responses did not explain the relative resistance of newborns to paralysis.

Animals↗
PubMed1980

Pathogenesis of human poliovirus infection in mice. II. Age-dependency of paralysis.

The mechanism of resistance of newborn mice to poliovirus-induced paralysis was studied by comparing regional virus replication in the adult and in the newborn central nervous systems (CNS) after intracerebral (ic) and intraspinal inoculation. Initial virus replication in the brains was similar in both age groups. Paralysis correlated with replication of virus in the spinal cord to a constant threshold, and this replication in newborns was delayed. Intraspinal inoculation of newborns eliminated the delay, indicating that neonatal anterior horn motor neurons were fully susceptible to infection. Cordectomy prevented the spread of virus, despite patent cerebrospinal fluid (CSF) pathways. Thus, poliovirus appeared to spread within the CNS via an axonal transport system. Known maturational changes in the fast transport system may explain the relative resistance of immature mice to poliovirus-induced paralysis.

Age Factors↗