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S Hruby

Publications and source records attributed to S Hruby.

At least 37 records · Page 2Linked to original sources
PubMed1985

Sites in myelin basic protein that react with monoclonal antibodies.

The epitopes (antigenic sites) for seven monoclonal antibodies (MAbs) evoked in rats or mice by guinea pig or monkey myelin basic protein (BP) have been located in four different sequences of the BPs extracted from various species. Six of the MAbs were evoked by guinea pig BP. (1) One epitope, possibly a pair, is included within residues 1-14 of all BPs tested and reacts with two rat IgG MAbs. (2) A definite pair of overlapping epitopes includes the central Phe91-Phe92 sequence. One epitope is contained entirely within sequence 90-99 and reacts with a rat IgG MAb. The substitution of Ser in chicken BP for Thr97 destroys this epitope. The other epitope appears to include residues on the amino side of Phe44 and even of His32 and suggests some tertiary structure in BP. This epitope reacts with a mouse IgM MAb that does not recognize the chicken substitution. (3) The third epitope lies within residues 114-121, specifically including Trp118, and reacts with a rat IgG MAb. A cross-reacting epitope probably includes residues 44-45 in certain species (guinea pig and bovine but not rabbit). (4) Another pair of epitopes is located within residues 131-140 but is severely species-restricted. This region in guinea pig BP evoked a species-specific mouse IgM MAb. The same region in monkey BP evoked the seventh MAb, a mouse IgG, which reacts with human, chimpanzee, monkey, bovine, and rat-18.5 kDa BPs and to a lesser extent rabbit BP but not with guinea pig, pig, or chicken BPs. Some tertiary structure in guinea pig BP is also suggested by the reactivities with the IgM MAb. All of the MAbs react with myelin in histologic preparations, but the optimum method of preparation of the tissue varies with each.

Amino Acid Sequence↗
PubMed1984

Epitopes in myelin basic protein reactive with monoclonal antibodies.

The epitopes (antigenic determinants) evoked by guinea pig or monkey myelin basic protein (BP) for 7 monoclonal antibodies (MAb) have been localized to 4 different sequences of the BPs extracted from various species. The first pair of epitopes is included within residues 1-14 and reacts with 2 rat IgG MAbs having slightly different specificities. The second pair of epitopes overlap within the sequence 86-100, requiring the Phe(91)-Phe(92) residues. One includes only residues 90-100 and reacts with a rat IgG MAb, the other is longer and reacts with a mouse IgM MAb. The third epitope lies within residues 114-124 (specifically including the single Trp) and reacts with a rat IgG MAb. A cross-reacting epitope in the amino half of the molecule is present in certain species (human, bovine and guinea pig). The fourth pair of epitopes includes residues 131-140 and is severely species-restricted. A mouse IgM MAb reacts practically only with guinea pig BP. Another IgG MAb reacts with human, chimpanzee, monkey, bovine and rat-18.5 kDa BPs, to a much lesser extent with rabbit and rat-14 kDa BPs and not with guinea pig, pig or chicken BPs. A cross-reacting epitope in the amino half of the molecule may be present in the more reactive species.

Animals↗
PubMed1984

Myelin basic protein and its antibodies in the cerebrospinal fluid in experimental allergic encephalomyelitis, multiple sclerosis and other diseases.

Our studies have revealed no essential differences between EAE in monkeys and MS and other CNS diseases in humans. High concentrations of BP occur early, especially if no anti-BP antibodies are also present. Lower concentrations of BP follow and may be associated with the presence of anti-BP antibodies. In EAE these antibodies come from the relatively strong peripheral sensitization to BP and enter the CSF through a damaged blood-brain barrier; in MS they come from the relatively weak immunologic stimulation probably evoked by previous attacks of the disease. Proteolytic enzymes also enter the CSF and produce peptide fragments of BP whose differing antigenic compositions permit antibodies to some fragments to coexist with other fragments unrelated antigenically but detected as "BP" in vitro. Since oligoclonal immunoglobulins (IgG) occur more often in MS than in other diseases, one can expect to find BP, anti-BP antibodies and oligoclonal IgG more often in MS, but even the combination is not specific for MS. Consideration of the temporal and immunochemical relationships as well as of the differential diagnosis provides a basis for the understanding of the significance of BP, its antibodies and other immunoglobulins in the CSF.

Animals↗
PubMed1981

Species restriction of a monoclonal antibody reacting with residues 130 to 137 in encephalitogenic myelin basic protein.

A monoclonal antibody (immunoglobulin G1) has been produced that reacts against myelin basic protein present in or extracted from the brains of many mammals-with certain important exceptions. Because of known species differences in amino acid sequences of basic protein and of certain peptide fragments, the binding site for this particular antibody appeared likely to include residues 130 to 137. Confirmation of this hypothesis was obtained by amino acid composition of the major immunoreactive peptides produced by thermolysin digestion of human basic protein and isolated by high-performance liquid chromatography.

Amino Acid Sequence↗
PubMed1979

Has myelin basic protein received a fair trial in the treatment of multiple sclerosis?

Autosensitization to some central nervous system antigen still remains one of the best hypotheses for the continuing pathogenesis of multiple sclerosis (MS). Enough is now known about the cause, pathogenesis, and treatment of experimental allergic encephalomyelitis (EAE) to test this hypothesis. Reports of therapeutic failure of the encephalitogen myelin basic protein (BP) in the treatment of MS have their counterparts in similar therapeutic failures in EAE. Only highly inbred strain 13 guinea pigs respond consistently to BP therapy, and this only when BP is administered in relatively high doses. Noninbred guinea pigs respond much less well to simple BP therapy, and monkeys hardly at all. In both strains of monkeys so far studied, a nonspecific adjunctive factor--an antibiotic in Macaca mulatta and a steroid in Macaca fascicularis--is also required. Accordingly, human trials of the therapeutic efficacy of BP in MS should include its administration in large concentrations together with an adjunctive agent.

Adjuvants, Immunologic↗
PubMed1979

Myelin basic protein treatment of experimental allergic encephalomyelitis in monkeys.

Treatment of experimental allergic encephalomyelitis (EAE) in two strains of monkeys with large amounts of myelin basic basic protein (BP) fails unless an adjunct is also used. In both strains the adjunct by itself is more effective than BP by itself, but in the one strain which could be investigated sufficiently, the combination can be made almost totally effective in reversing EAE. The adjunct varies with the strain of monkey, an antibiotic in Macaca mulatta and a steroid in Macaca fascicularis. Similar adjunctive treatments should be considered in the management of multiple sclerosis, for EAE remains one of the best studied models.

Amino Acids↗
PubMed1979

Degradation of myelin basic protein by cerebrospinal fluid: preservation of antigenic determinants under physiological conditions.

Cerebrospinal fluid contains several proteolytic enzymes that can degrade myelin basic protein (BP) under physiological conditions into peptide fragments of various sizes which still contain antigenic determinants capable of binding antibodies to BP. These enzymes are optimally active in either acid (pH 4) or nuetral (pH 7 to 8) conditions and can be characterized by the nature of the BP peptide fragments produced. Proteinases resembling cathepsin D, thrombin, plasmin (fibrinolysin), or kallikrein are present in variable amounts in CSF. No relationship to any particular disease has yet been established.

Cathepsins↗
PubMed1977

Synthetic galactocerebrosides evoke myelination-inhibiting antibodies.

Synthetic galactodihydrocerebrosides with widely different fatty acid components can evoke myelination-inhibiting antibodies in rabbits. Whether these are the only such haptens involved in experimental immunizations of other species or in spontaneous human diseases is not yet known.

Animals↗
PubMed1976

Fat embolism in kwashiorkor.

Fat embolism from the grossly fatty liver of an infant with kwashiorkor is described. Globules of fat were seen at necropsy in the hepatic veins, in the right atrium and ventricle of the heart and in the pulmonary artery. Sections of the lung showed fat emboli in numerous branches of the pulmonary artery. Examination of lung sections taken at necropsy from 40 patients who had severe kwashiorkor failed to show similar fat embolism.

Embolism, Fat↗