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Biomedical subjects

R F Kibler

Publications and source records attributed to R F Kibler.

At least 19 recordsLinked to original sources
PubMed1986

Monoclonal antibodies to human myelin basic protein.

SJL/J and (SJL X PL) F1 hybrid mice were immunized with intact human myelin basic protein (MBP) or the three major peptic fragments of MBP, residues 1-38, 39-89, and 90-170. Immune spleen cells were fused with mouse myeloma P3 X 63Ag8 (NS1) cells in the presence of polyethylene glycol. Hybridoma supernatant culture fluids were screened for antibody to MBP by a solid-phase radioimmunoassay (RIA). The specificity of the monoclonal antibody (mAb) was characterized by RIA using the three major MBP peptic fragments and subfragments as well as MBP and MBP fragments of different species with known amino acid sequence differences. Six MBP mAbs were generated, one of them IgM isotype and the remainder IgG isotypes. One mAb each reacted against regions of residues 22-38, 39-69, 70-89, 90-116, and two reacted against residues 118-157. Immunoblots also showed that the five IgG mAbs were reactive against MBP and the peptic fragment of MBP containing the epitope. Immunohistochemical studies showed the IgG mAbs specifically stained myelinated fiber tracts in human brain tissue.

Amino Acid Sequence↗
PubMed1984

Devic's syndrome: antibody to glial fibrillary acidic protein in cerebrospinal fluid.

The cerebrospinal fluid of a patient with Devic's syndrome contained antiglial fibrillary acidic protein antibody. The serum level of antibody was less than that in cerebrospinal fluid, and the antibody was probably synthesized within the central nervous system. Similar antibody was not found in another patient with Devic's syndrome or in patients with multiple sclerosis. The role of the antibody in the patient's illness is uncertain, but is one of the few instances in which antibody against a specific brain antigen has been described in human demyelinating disease.

Antibodies↗
PubMed1984

Multiple sclerosis unrelated to dog exposure.

We conducted a case-control study to evaluate the possible association between exposure to dogs and MS. Seventy cases were compared with 70 age- and sex-matched neighborhood controls and 57 cases with 57 age- and sex-matched clinic controls. No association was found, by age groups or by time periods before onset of MS, between MS and presence of any dog, a small dog, a medium or large dog, or an indoor dog in the household. There was a significant negative association between MS and presence of cats in the household and MS and presence of medium and large dogs in the household, and a significant positive association, for several age groups and time periods, between MS and a history of canine distemper in a household dog. The basis for these significant associations is not clear. This study adds weight to the evidence against an association between exposure to small or indoor dogs and MS.

Adolescent↗
PubMed1983

Failure to detect antibodies to myelin basic protein or peptic fragments of myelin basic protein in CSF of patients with MS.

Using the sodium sulfate precipitation radioimmunoassay and solid-phase radioimmunoassay, we measured antibody to intact human myelin basic protein and myelin basic protein peptic fragments, residues 1-44, 45-89, and 90-170, in CSF. Comparable levels of binding were obtained for MS and normal CSF by both tests. The increased amount of CSF IgG in MS patients cannot be attributed to specific antibody against myelin basic protein or its peptic fragments.

Adult↗
PubMed1983

Search for a multiple sclerosis-specific brain antigen.

Specific reactivity of multiple sclerosis (MS) cerebrospinal fluid (CSF) IgG against central nervous system (CNS) tissue has been sought. Brain proteins were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), reacted with CSF followed by 125I-Staph protein A, and developed for autoradiography. Pooled CSF from MS patients, CSF from individual MS patients, and pooled CSF from patients with other neurologic diseases and from normal patients, were used. Proteins were extracted from the white matter of MS and normal brains and from MS plaque and peri-plaque tissue. No reactivity specific for MS was observed.

Antigens↗
PubMed1982

Basic protein in brain myelin is phosphorylated by endogenous phospholipid-sensitive Ca2+-dependent protein kinase.

Phosphorylation of myelin basic protein (MBP) in rat or rabbit brain myelin was markedly stimulated by Ca2+, and this reaction was not essentially augmented by exogenous phosphatidylserine or calmodulin or both. Solubilization of myelin with 0.4% Triton X-100 plus 4 mM EGTA, with or without further fractionation, showed that Ca2+-dependent phosphorylation of MBP required phosphatidylserine, but not calmodulin. DEAE-cellulose chromatography of solubilized myelin revealed a pronounced peak of protein kinase activity stimulated by a combination of Ca2+ and phosphatidylserine; a protein kinase stimulated by Ca2+ plus calmodulin was not detected. These findings clearly indicate an involvement of phospholipid-sensitive Ca2+-dependent protein kinase in phosphorylation of brain MBP, although a possible role for the calmodulin-sensitive species of Ca2+-dependent protein kinase in this reaction could not be excluded or established. Phosphorylation of MBP in solubilized rat myelin catalyzed by the phospholipid-sensitive enzyme was inhibited by adriamycin, palmitoylcarnitine, trifluoperazine, melittin, polymyxin B, and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7).

Animals↗
PubMed1982

Immunosuppression of experimental allergic encephalomyelitis. III. In vitro evidence for induction of suppressor T lymphocytes in draining lymph node cells of animals immunized with myelin basic protein complexed to lipopolysaccharides.

We recently demonstrated that Lewis rats immunized with bacterial lipopolysaccharides (LPS) precomplexed to guinea pig myelin basic protein (BP) in complete Freund's adjuvant were less effective in inducing experimental allergic encephalomyelitis (EAE) than BP-immunized controls. When tested in vitro both lymph node cells (LNC) and spleen cells (SpC) of animals immunized with BP-LPS were less effective in proliferative responses to various mitogens, which included phytohemagglutinin, concanavalin A, purified protein derivative of tuberculin, LPS, and BP. Of importance immunization of rats with BP complexed to LPS results in the generation of cells in lymph nodes of these animals that suppress the mitogenic response of BP-immunized LNC and also SpC in mixed lymphocyte cultures. The suppressive effect of these cells in mixed lymphocyte culture reaction was found specifically in response to BP and to a lesser extent to LPS in LNC. SpC of BP-LPS immunized animals did not suppress the proliferative response to SpC of BP-immunized animals. Treatment of these LNC with antithymocyte serum and complement abolished this suppressive effect of LNC, suggesting that the immunoregulatory cells in LNC of BP-LPS immunized animals are suppressor T lymphocytes. The parallel between the in vitro induction of suppressor T lymphocytes in the draining LNC and the function of LPS in the development of EAE in Lewis rats suggests a possible immunologic significance of the effect.

Animals↗
PubMed1981

Turnover of myelin proteins of rat brain, determined in fractions separated by sedimentation in a continuous sucrose gradient.

Rats that received intracranial injections of [3H]leucine at 14 days of age were killed on days 17, 24, 38, 55, and 89 post-injection. Brains were homogenized and the myelin membranes separated in a sucrose density gradient. At day 17 sodium dodecylsulfate polyacrylamide gels of water-shocked, delipidated membrane fractions showed a difference in the specific activity of myelin proteins across the gradient. A decrease in specific activity was found in all of the proteins in the denser fractions, compared with the lighter fractions. As time after injection progressed, the difference became more pronounced; a two- to threefold decrease in specific activity was seen across the gradient in the various myelin proteins. The proteins of the lightest membrane fractions retained their high specific activity throughout the experiment in spite of extensive new myelin synthesis. Taking this new myelin into account, the decrease in specific activity in the denser myelin fractions could be explained by isotope dilution. Therefore, proteins present in at least some of the myelin are essentially stable.

Aging↗
PubMed1981

Prevention of experimental allergic encephalomyelitis by bacterial lipopolysaccharides: inhibition of cell-mediated immunity.

The immunization of Lewis rats with bacterial lipopolysaccharides (LPS) precomplexed to guinea pig myelin basic protein (BP) in complete Freund's adjuvant inhibits the development of experimental allergic encephalomyelitis (EAE) in these animals. These protected animals fail to manifest significant in vivo delayed-type hypersensitivity skin tests and in vitro lymphocyte proliferative responses to BP. Our results indicated that LPS induces a nonspecific reduction in immune reactivity of BP in Lewis rats.

Animals↗
PubMed1981

Experimental allergic encephalomyelitis in Lewis rats: inhibition by bacterial lipopolysaccharides and acquired resistance to reinduction by challenge with myelin basic protein.

In 2-mo-old Lewis rats immunized with bacterial lipopolysaccharides (LPS) precomplexed to guinea pig myelin basic protein (BP), the clinical and histologic manifestations of experimental allergic encephalomyelitis (EAE) were diminished compared with BP-treated controls. Similarly, in animals immunized with BP and challenged with BP-LPS at the same time or as long as 5 days after, the immunization with BP also inhibited the disease. That this capacity to reduce the incidence of BP-induced EAE is a unique property of LPS was suggested by the fact that other negatively charged molecules, such as DNA, RNA, and dextran sulphate, were not effective in inhibiting the clinical signs of EAE. After recovery from EAE induced by BP, some animals develop a recurrence of the disease if challenged with BP at appropriate intervals. However, after recovery from mild EAE induced by BP-LPS and after challenges with EAE-initiating BP antigens, secondary EAE was inhibited significantly.

Animals↗
PubMed1980

Prevention of experimental allergic encephalomyelitis in Lewis rats with peptide 68-88 of guinea pig myelin basic protein.

The highly encephalitogenic guinea pig peptide 68-88 has been used to develop an effective and reproducible model of protection in the Lewis rat. Doses as low as 0.1 nmol of peptide protected 70% of rats when injected intraperitoneally six and four weeks prior to challenge with 0.05 nmol of the peptide in complete Freund's adjuvant. Fragments derived from guinea pig peptide 68-88 by selective enzyme cleavage were then tested for their capacity to provide protection in this model system. These fragments had previously been well characterized both biochemically and immunologically. The protection provided by each fragment closely paralleled its capacity to induce disease. This suggests that the region of peptide 68-88 required for protection is similar to that needed for induction of experimental allergic encephalomyelitis and the other T-cell functions of the peptide. B-cells did not appear to participate; peptide 68-85, which has no capacity to produce antibody against peptide 68-88, gave full protection, while peptide 79-88, which contains the major B-cell determinant of the peptide, afforded no protection. Rat peptide 68-88 did not protect against challenge with the guinea pig peptide, demonstrating a critical role for serine 79. These studies support the concept that nonencephalitogenic agents do not protect against experimental allergic encephalomyelitis at doses comparable to those of encephalitogenic agents.

Animals↗
PubMed1979

The immune response of Lewis rats to peptide 68-88 of guinea pig myelin basic protein. I. T cell determinants.

A series of peptides, produced from peptide 68-88 by selective enzyme cleavage, were used to define the amino acid sequences required for the induction of experimental allergic encephalomyelitis (EAE), an in vitro lymphocyte proliferative response (LPR), and serum antibody by peptide 68-88 in the Lewis rat. Here we present data that indicate that the T cell determinants for induction of EAE, an LPR, and helper function in the production of antibody are located in the same region of the molecule and that a minimum of 13 amino acids are involved; i.e., residues 71-85.

Amino Acids↗
PubMed1979

The immune response of Lewis rats to peptide 68-88 of guinea pig myelin basic protein. II. B cell determinants.

A series of peptides, produced from peptide 68-88 by selective enzyme cleavage, were used to define the amino acid sequences reactive with Lewis rat anti-peptide 68-88 antibody. One hundred per cent of 38 rats immunized with peptide 68-88 recognized a B cell determinant residing in the region of residues 80-88. The three carboxy-terminal amino acids, residues 86-88, appeared to confer conformation on this determinant. In roughly two-thirds of the rats, the reactivity with this major B cell determinant was equal to the reactivity with the immunizing peptide. In these rats the anti-peptide 68-88 antibodies were of the IgG2 class. A third of the rats recognized an additional determinant(s) and in these the predominant class of antibody was IgG1.

Animals↗