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Biomedical subjects

H Panitch

Publications and source records attributed to H Panitch.

13 recordsLinked to original sources
PubMed1995

Interferon beta-1b reduces interferon gamma-induced antigen-presenting capacity of human glial and B cells.

Interferon (IFN) beta-1b has been shown to alter the course of multiple sclerosis and to inhibit MHC class II expression, but its effect on antigen presentation has not been examined in a functional assay (Neurology 43 (1993) 655-661). The effect of IFN beta-1b on alloantigen presentation by human antigen-presenting cells (APC) including human fetal astrocytes (HFA) and microglia was examined. The effect of IFN beta-1b on the ability of B cells to present tetanus toxoid (TT) to TT-specific T cell lines was also examined. APC were pre-treated with IFN gamma (100 units/ml), IFN beta-1b (10-2000 units/ml), or a combination of IFN gamma and IFN beta-1b for 3 days and washed thoroughly prior to culture with allogeneic peripheral blood lymphocytes (PBL) for a period of 6 days. Lymphocyte proliferation was then measured by tritiated thymidine uptake. Treatment of the APC with IFN beta-1b resulted in a reduction in the IFN gamma-enhanced alloantigen-induced T cell responses. This reduction ranged between 50 and 70%, was associated with a 30-50% reduction in HLA class II (DR) and 35-40% reduction in ICAM-1 expression on the HFA used as APC. IFN beta-1b pretreatment of B cells reduced their constitutive and IFN gamma enhanced capacity to present TT to TT-specific T cell lines by 50-80%. This was associated with a 30 +/- 11% mean reduction in class II (DR) expression and approximately 50 +/- 1% reduction in ICAM-1 expression in IFN beta-1b + IFN gamma-treated B cells compared to IFN gamma-treated B cells (mean of three experiments).(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1995

Additive effects of copolymer-1 and interferon beta-1b on the immune response to myelin basic protein.

Copolymer-1 (Cop-1) inhibits the T cell response to myelin basic protein (MBP), suppresses experimental autoimmune encephalomyelitis in many animal species, and was recently shown to be effective in the treatment of multiple sclerosis (MS). Interferon beta-1b (IFN-beta), an immune modulator with no antigenic specificity, is already approved for treatment of relapsing-remitting MS. We investigated the combined effect of these two agents on the cellular immune response to MBP. Antigen-specific Th1-like cell lines were generated from two healthy individuals with different MHC phenotypes. Cop-1 inhibited the proliferation of all MBP-specific lines but had no suppressive effect on tuberculin (PPD) or tetanus toxoid (TT)-specific T cell lines from either donor, while IFN-beta non-specifically reduced proliferation of all T cell lines. When combined in vitro, Cop-1 and IFN-beta had additive suppressive effects on proliferation of MBP-specific T cell lines, with 70-100% inhibition depending on the concentration of antigen. Synthesis of the pro-inflammatory cytokines interleukin-2 and IFN-gamma by MBP-specific lines was also inhibited additively (up to 100%). When antigen-presenting cells (APC) were pretreated with Cop-1, IFN-beta or both, T cell proliferation was inhibited in the same additive pattern, even though the inhibitors were not present in culture, indicating that they acted primarily through modulation of APC function. Additive effects were not found with PPD- or TT-specific cell lines. Pretreatment of APC with IFN-beta resulted in dose-dependent reduction in HLA-DR and HLA-DQ expression, which paralleled inhibition of T cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Presenting Cells↗
PubMed1986

Sulfogalactocerebroside and bis-(monoacylglyceryl)-phosphate as activators of spleen glucocerebrosidase.

Sequential extraction of human spleen membranes with sodium cholate and n-butanol removes endogenous lipids and renders glucocerebrosidase activity dependent upon exogenous acidic lipids (e.g., phosphatidylserine, gangliosides) and a heat-stable activator protein (HSF). In the present report, we show that two previously untested lysosomal acidic lipids, namely sulfogalactocerebroside and bis-(monoacylglyceryl)-phosphate (BMP), also activate normal human glucocerebrosidase. In addition, sulfogalactocerebroside also markedly enhanced the activity of glucocerebrosidase isolated from a patient with type 1 (non-neuronopathic) Gaucher's disease, resulting in a specific activity which was 60-80% that of control glucocerebrosidase. Furthermore, when the sulfolipid was used as the activator, glucocerebrosidase from the type 1 patient was 30 times more active than the corresponding glucocerebrosidase from a person with type 2 (neuronopathic) Gaucher's disease. In contrast, the two BMPs, one rich in C26 saturated fatty acid and another rich in C18 unsaturated fatty acids, were relatively poor activators of both mutant glucocerebrosidases while providing excellent reconstitution of control activity.

Animals↗
PubMed1986

Monoclonal gammopathy and neuropathy: myelin-associated glycoprotein reactivity and clinical characteristics.

Immunoblot analysis was performed on the serum from 29 patients with polyneuropathy and monoclonal gammopathy. Nine patients had IgM spikes, and six of the nine had reactivity against myelin-associated glycoprotein (MAG) associated with a slowly progressive, predominantly sensory neuropathy. In contrast, 23 patients who lacked anti-MAG reactivity had more severe sensory motor neuropathy. Thus, IgM monoclonal gammopathy with reactivity against MAG may define a distinct clinical entity.

Adult↗
PubMed1981

Induction of recurrent experimental allergic encephalomyelitis with myelin basic protein.

Recurrent experimental allergic encephalomyelitis (EAE) was induced in Lewis rats by inoculation of human myelin basic protein (MBP) and complete Freund's adjuvant (CFA). The animals developed clinical disease characterized by unsteadiness, ataxic gait, and abnormal posturing of the limbs. Spontaneous remissions and relapses were noted for periods up to 120 days. Histologically there were perivascular infiltrates of mononuclear cells, especially prominent in the cerebellar white matter. There was little evidence of demyelination. This study demonstrates that relapsing EAE may be induced with MBP in the rat. Sensitization with other myelin antigens is not required, although immunity to such antigens may be necessary to induce demyelination. It is postulated that relapsing EAE may be associated with a defect in suppressor cell function.

Animals↗
PubMed1977

The ultrastructure of early visna lesions.

The ultrastructure of visna, a slowly progressive menigo-encephalomyelitis of sheep, was studied in animals sacrificed one month after intracerebral inoculation of visna virus. The major pathological changes, representative of those seen during the first year after infection, consist of inflammation and minor focal destructive lesions of grey and white matter. The inflammatory infiltrates, both subependymal and perivascular as well as of the choroid plexus, were composed mainly of lymphocytes and macrophages with varying numbers of plasma cells. The demyelination seen was of the secondary or Wallerian type. There was no evidence of primary demyelination. Visna virions were not seen in any of the CNS material studied. The ultrastructural findings are compatible with the view that lesions in visna may be induced by a cell-mediated immune response. However, changes characteristic of an autoimmune reaction to myelin antigens were not observed.

Animals↗
PubMed1976

Pathogenesis of visna. I. Sequential virologic, serologic, and pathologic studies.

A total of 56 Icelandic sheep were infected with visna virus by intracerebral injection of strain 1514 and the course of infection was followed for 12 months. Virus was isolated from more than 90 per cent of the animals, primarily from central nervous system and lymphoid tissues. However, titers of free infectious virus were minimal and virus isolation often required the use of tissue explants. All sheep raised serum-neutralizing and complement-fixing antibodies beginning 1 to 3 months after infection. Differences in neutralization titers against the infecting strain (1514) and a reference strain (796) suggested that antigenic drift might occur during prolonged infection. High cerebrospinal fluid neutralization titers in the spinal fluid indicated local antibody production in the central nervous system. Although the incidence of clinical disease during the 1st year of infection was less that 10 per cent, approximately 80 per cent of the sheep examined had central nervous system histologic lesions of variable severity, which were marked 1 month after infection with little progression during the subsequent year. There was a striking correlation between the severity of central nervous system lesions and the frequency of virus isolations from all tissues. These observations provide detailed base line data on visna infection, suggest some of the mechanisms responsible for the persistence of infection and for the slowness and irregularity of disease occurrence, and form the basis for further experiments on the role of immunologic mechanisms in the pathogenesis of this slow infection.

Animals↗
PubMed1976

Pathogenesis of visna. II. Effect of immunosuppression upon early central nervous system lesions.

It was hypothesized that the lesions of visna might represent an immunopathologic process. To test this hypothesis, a 1-month schedule of immunosuppressive treatment was devised, using horse anti-sheep thymocyte serum. In Hampshire sheep, this regime was shown to protect against experimental allergic encephalomyelitis, to inhibit development of tuberculin hypersensitivity, to retard rejection of skin homografts by 3 weeks, and to markedly reduce the number and mitogenic responsiveness of peripheral blood lymphocytes. Two groups of Icelandic sheep received intracerebral inoculations of visna virus, and one group was treated with horse antisheep thymocyte serum supplemented by a short terminal course of cyclophosphamide. Central nervous system lesions were seen in only one of eight suppressed animals at sacrifice 25 days after infection, whereas definite lesions were present in eight of eight infected control animals. The frequency of central nervous system virus isolation was similar in the two groups, indicating that treatment suppressed the cellular proliferative response without preventing the central nervous system phase of infection. Sheep receiving horse antisheep thymocyte serum had a reduced number of virus isolations from peripheral lymphoid tissue, presumably reflecting the lympholytic effect of treatment. These observations are consistent with the immunopathologic hypothesis and suggest several different ways in which suppression could modify the immune response to visna virus.

Animals↗
PubMed1976

Pathogenesis of visna. III. Immune responses to central nervous system antigens in experimental allergic encephalomyelitis and visna.

Experimental allergic encephalomyelitis (EAE) was induced in sheep in pursuit of the hypothesis that an immune response against central nervous system antigens might play a role in the pathogenesis of visna. Nine to 12 days after sensitization with whole sheep brain and complete Freund's adjuvant, approximately 50% of sheep developed a fulminating lethal form of EAE. Following a second sensitization, another 20% of animals developed EAE whereas a residual 30% failed to develop any signs or histologic evidence of disease. A histologic comparison of EAE and visna indicated considerable similarity in the nature of the pathologic process. However, the distribution of lesions was quite different, suggesting cellular responses to two different antigens, Cell-mediated immunity to myelin basic protein, as measured by lymphocyte blast transformation, was minimally elevated in sheep sensitized with whole brain suspension in complete Freund's adjuvant, whereas no response could be detected in visna-infected sheep. Complement-fixing antibody titers to basic protein and to a lipid antigen of brain, probably galactocerebroside, rose briskly after sensitization. In visna-infected sheep, on the other hand, there was no increase in either antibody. A large proportion of both Hampshire and Icelandic sheep had low levels of complement-fixing antibody to central nervous system antigens prior to induction of EAE or infection with visna virus. The origin of this antibody is undetermined, but it appeared to have no effect on the course of either disease. Immunosuppression of sheep with antilymphoid serum prevented induction of EAE. Acute EAE was, thus, successfully induced in sheep and used as a model to measure immune responses to central nervous system antigens and as an index of immunosuppression. However, these comparative studies did not provide any evidence for the role of an autoimmune response, to the two central nervous system antigens tested, in the pathogenesis of visna.

Animals↗