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Biomedical subjects

R L Knobler

Publications and source records attributed to R L Knobler.

At least 55 records · Page 3Linked to original sources
PubMed1988

Down-regulation of interferon-gamma-induced class II expression on human glioma cells by recombinant interferon-beta: effects of dosage treatment schedule.

We have examined the influence of human recombinant interferon-beta (IFN-beta) and interferon-gamma (IFN-gamma) on class II antigen expression on cultured glioblastoma multiforme cells by flow cytometry. Class II molecules were not constitutively expressed on these cells, nor induced by IFN-beta. IFN-gamma increased class II expression in a dose-dependent fashion. We demonstrate that IFN-beta is either antagonistic or synergistic with IFN-gamma in class II induction depending upon dose and schedule of administration. Both interferons at 100 IU/ml reduce class II expression by 18%, compared to IFN-gamma alone. Pretreatment with IFN-beta for 72 h, followed by both interferons yielded a 90% reduction. In contrast, lower concentrations (10 IU/ml) of both interferons were synergistic.

Drug Administration Schedule↗
PubMed1988

Trigeminal neuralgia in a patient with multiple sclerosis treated with high cervical spinal cord stimulation. Case report.

A 42-year-old male with advanced multiple sclerosis had severe left-sided trigeminal neuralgia in the maxillary and mandibular divisions that was extremely difficult to control with medications. Glycerol injection in the gasserian cystern provided only temporary results. Two electrodes were implanted epidurally at the C1-2 level, one in the midline and the other to the left of midline. Electrical stimulation produced complete relief from the painful paroxysms.

Adult↗
PubMed1988

Systemic interferon therapy of multiple sclerosis: the pros.

The rationale for the use of interferon (IFN) in the treatment of multiple sclerosis (MS) is based on its recognized antiviral and immunomodulating actions. The pathogenesis of MS is generally believed to be due to an immunologic response in a genetically predisposed individual, localized within the CNS white matter, and triggered by exposure to an environmental agent such as a virus. In a randomized, double-blind, placebo-controlled, crossover trial of systemic natural alpha IFN in 24 patients with exacerbating-remitting MS, patients with a strictly exacerbating-remitting course showed a reduction in the frequency and severity of exacerbations, while those with exacerbations superimposed upon a chronic progressive course did not benefit from this treatment, primarily because of side effects that included fever, malaise, and fatigue. Since the performance of this study, it has been shown that the preparation of natural human alpha interferon used in this trial may lead to side effects in some individuals through the production of immune complexes (ICs). These ICs were due to the generation of antibodies reacting with residual Sendai virus proteins used in the preparation of the IFN, and retained in the final formulation. The encouraging results of this and other preliminary studies of alpha or beta IFN but not gamma IFN therapy in MS, coupled with the current availability of more highly purified interferon preparations, warrants further clinical trials of IFN in MS, focusing on beta interferon preparations in particular.

Adult↗
PubMed1987

Neuroimmunology: modulation of the hamster immune system by photoperiod.

Groups of adult male Syrian hamsters were kept in a long photoperiod (LD 14:10) or a short photoperiod (LD 10:14). After 12 weeks, half of the animals in each light:dark cycle were immunized with an immunogenic amino acid polymer. Exposure to short photoperiod was associated with a significant reduction in testicular, accessory sex organ, splenic and brown fat weights. However, photoperiod length did not influence whole body, thymic, adrenal or kidney weights. Spleens of immunized animals in the long photoperiod were significantly heavier than those of unimmunized animals in the long photoperiod, and both were heavier than spleens from immunized or unimmuized animals in the short photoperiod. This reflected increased splenic lymphocyte and macrophage counts. However, there was no difference in antibody production between animals kept in different photoperiods. These results demonstrate that the daily photoperiod length affects both hamster reproductive competence as well as selected immune parameters (splenic weight and mononuclear cell hyperplasia) but does not alter antibody production.

Adipose Tissue, Brown↗
PubMed1987

Variations in genetic control of susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. I. Differences between susceptible SJL/J and resistant BALB/c strains map near the T cell beta-chain constant gene on chromosome 6.

In some susceptible mouse strains, intracerebral (IC) inoculation of Theiler's murine encephalomyelitis virus (TMEV) results in a persistent infection leading to chronic demyelinating disease. Previous genetic analyses between susceptible SJL/J and resistant C57BL/6 mice indicated a role for multiple unlinked genes in the development of clinical and histopathological disease, including a major influence of the D region of the H-2 complex. In this study, genetic analysis of a different strain combination (susceptible SJL/J and resistant BALB/c) also demonstrates the involvement of multiple genes, but the H-2 genotype (H-2s and H-2d, respectively) does not appear to contribute significantly to susceptibility differences. In both segregation studies and recombinant-inbred (R-I) analysis, clinical and histopathological disease occurs in both H-2s homozygotes and H-2d homozygotes (as well as H-2s/H-2d heterozygotes), with the actual frequency related to the proportion of non-H-2 genome from the susceptible strain. There appear to be at least two non-H-2 genes involved in differential susceptibility of SJL/J and BALB/c to TMEV-induced disease. Analysis of R-I strains generated from BALB/c and SJL/J progenitors indicates linkage of at least one of these non-H-2 genes to those encoding the constant portion of the beta-chain of the T cell receptor on chromosome 6. Many genes may actually be involved, but each strain comparison defines a different subset of these loci--only those at which the two strains in question carry "functionally" different alleles. Thus, different strain comparisons may accent the roles of different genes in resistance to the same infectious organism or disease process. In addition to the genes identified thus far, there may be yet other genes contributing to development of TMEV-induced disease, but their recognition may require analysis of still other strain combinations.

Animals↗
PubMed1987

Reduced S-adenosylmethionine:protein-lysine N-methyltransferase activity (protein methylase III) in shiverer mutant mouse brain.

Mice with the dysmyelinating mutation shiverer were studied by measuring the activity of two protein methylases and myelin marker enzymes in the brain. It was observed that S-adenosylmethionine:protein-lysine N-methyltransferase (protein methylase III, EC. 2.1.1.43) activity is significantly reduced in phenotypically affected homozygous shiverer (shi/shi) mutant mouse brain compared to the unaffected heterozygous littermate brain. This reduction in enzyme activity is manifested mainly by reduced formation of trimethyllysine during the in vitro methylation of histone. In contrast, myelin marker enzymes such as 2',3'-cyclic nucleotide 3'-phosphohydrolase and 5'-nucleotidase as well as S-adenosyl-methionine:protein-carboxyl O-methyltransferase (protein methylase II, EC. 2.1.1.24) activities were not significantly affected in these strains of mice.

5'-Nucleotidase↗
PubMed1987

Heterotopic brain transplants in the study of experimental allergic encephalomyelitis.

A heterotopic transplant paradigm was developed for its potential usefulness in dissecting genetically determined immune and central nervous system (CNS) components in the induction of experimental allergic encephalomyelitis (EAE). EAE is a cell-mediated, organ-specific, autoimmune disease producing inflammatory demyelination in the CNS. Susceptibility to EAE is determined by multiple genes and reflects both immune competence and target tissue responses. Syngeneic fetal CNS was heterotopically transplanted into the anterior chamber of the eye or beneath the capsule of the kidney of adult SJL or (SJL X BALB/c)F1 mice. Transplants usually survived better in the eye than the kidney. Six to eight weeks after transplantation, some mice were immunized for EAE. Immunized mice developed clinical and pathological signs of EAE in 12 to 15 days. The placement of CNS tissue into the eye or kidney prior to immunization did not suppress induction of EAE. Transplants in either location, in immunized mice, manifested perivascular inflammation and demyelination similar to that seen in the host CNS. However, transplants in mice not immunized for EAE, but maintained an equal time period after transplantation, did not demonstrate these features. The ability to produce the specific pathologic lesions of EAE in CNS tissue transplanted outside the CNS allows the design of studies of the tissue localization of genetic restrictions to development of EAE.

Animals↗
PubMed1987

Suppression of acute and relapsing experimental allergic encephalomyelitis with mitoxantrone.

The effect of treatment with the antineoplastic, immunomodulatory agent mitoxantrone on the course of acute and relapsing experimental allergic encephalomyelitis (EAE) in the mouse has been studied. Untreated mice immunized to produce acute EAE had an 81% incidence of clinical disease and 100% incidence of pathologic disease. Mice treated with mitoxantrone at a dose of 0.5 mg/kg daily for the 10 days following immunization did not develop any clinical signs and had minimal pathologic signs of disease. A dose of 0.25 mg/kg gave an intermediate response. Untreated mice immunized for relapsing EAE had a 100% incidence of disease with an average onset of disease on Day 148. Mice treated with mitoxantrone at a dose of 0.05 mg/kg three times weekly for 12 weeks following immunization had a 67% incidence of clinical disease with a significant delay in the average onset date to Day 279. These results indicate that mitoxantrone was highly effective in suppressing development of acute EAE. Mitoxantrone delayed the onset of relapsing EAE in mice, but did not fully inhibit the eventual expression of the disease. These studies suggest that the use of cytotoxic therapies in the treatment of autoimmune diseases may require periodic cycles of therapy to block disease expression.

Acute Disease↗
PubMed1986

Myelin basic protein-specific protein methylase I activity in shiverer mutant mouse brain.

Myelin basic protein (MBP)-specific protein-arginine N-methyltransferase (protein methylase I) activity in homozygous shiverer (shi/shi) mutant mouse brain is significantly higher than in the normal littermate brain at the onset of myelination. While the enzyme activity (expressed as pmol of S-adenosyl-L-[methyl-14C]methionine used/min/mg enzyme protein) increases coincidently during the period of myelination in the normal brain (15-18 days of age), it decreases significantly in the mutant brain during this period of time. These results are in contrast to those found with another dysmyelinating mutant, jimpy (jp/Y) mice, in which the enzyme activity in the mutant brains is similar to that in the normal animals but remains unchanged during the myelination process. There is no difference in the weight and protein concentration of the normal and shiverer mutant brains with corresponding ages, and the histone-specific protein methylase I activity is also unaffected in the shiverer brain.

Animals↗