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Biomedical subjects

F C Westall

Publications and source records attributed to F C Westall.

15 recordsLinked to original sources

Brain-derived fibroblast growth factor: identity with a fragment of the basic protein of myelin.

Fibroblast growth factors (FGF) isolated from bovine brain have been identified chemically and immunologically as components of the myelin basic protein. The intact bovine basic protein molecule (170 residues), prepared by the standard acid extraction procedure, lacked mitogenic activity (tested at concentrations up to 10 microgram/ml). However, the polypeptide FGF-2, identified as residues 44-153 of the basic protein, was maximally mitogenic for fibroblasts at 10 ng/ml and polypeptide 44-166 (FGF-1) was maximally active at 100 ng/ml. Pituitary-derived FGF is a potent a growth factor as FGF-2, but appears to be biochemically and immunologically distinct from brain-derived FGF. FGF released in the central or peripheral nervous system as a consequence of myelin damage and basic protein proteolysis could provide a physiological stimulus for wound healing and myelin repair.

Amino Acid Sequence

High dose inhibition of the tryptophan peptide induced encephalitogenicity.

In a previous publication (Immunol. Comm. 3:219, 1974) a hypothesis was proposed that the high dose inhibition of encephalitogenicity in giunea pigs seen with the tryptophan peptide, phe ser trp gly ala glu gly gln arg, and not observed with the whole myelin basic protein which contains this sequence, was the result of competitive inhibition by non-encephalitogenic fragments of the tryptophan peptide produced in vivo possibly by exopeptidases. I present data which disagrees with this hypothesis.

Animals

Hyperacute allergic encephalomyelitis: a single determinant.

HEAE cannot be induced in either guinea pigs using 10(10) or 20x10(10) organisms of B. pertussis or in rabbits using 4x10(10) organisms of B. pertussis and basic protein from the following species: guinea pig, Lewis rat, human, bovine, porcine, monkey and rabbit. The only encephalitogenic region for Lewis rats which also produces HEAE in Lewis rats is not encephalitogenic in either rabbits or guinea pigs. Therefore it seems highly probably that there is only one HEAE determinant for all species which are able to express HEAE.

Acute Disease

Encephalitogenic regions for the Lewis rat within the myelin basic protein.

The sequence, phe lys asn ile val thr pro arg thr pro pro pro ser gln gly lys gly arg gly leu ser ser arg phe ser trp gly ala glu gly gln isolated from the peptic digestion of guinea pig myelin basicprotein is able to produce EAE in Lewis rats. The synthetic peptide phe lys phe gly gly arg asp ser arg, an analog of residues 154-162, is encephalitogenic in Lewis rats when B. pertussis is used as the adjuvant.

Amino Acid Sequence

Further definition of the encephalitogenic region for guinea pigs.

The effect on encephalitogenicity of using a serinyl substitution for the glutaminyl group in the peptide ser arg phe ser trp gly ala glu gly gln arg is reported. We conclude from these results that the function of the glutaminyl residue is assisting this peptide to produce allergic encephalomyelitis in guinea pigs is as a hydrogen donor-receptor.

Amino Acid Sequence

Induction of allergic encephalomyelitis using hydrosoluble mycobacterial fractions.

Experimental allergic encephalomyelitis has been induced in guinea pigs employing bovine myelin basic protein as the antigen and a hydrosoluble tetrasaccharide-heptapeptide from delipidated cells of the human mycobacterial strain H37Ra as adjuvant. The maximum response was observed using 33 mug of antigen and 12.5 mug of adjuvant per animal.

Adjuvants, Immunologic

Antigen, host and adjuvant requirements for induction of hyperacute experimental autoimmune encephalomyelitis.

A hyperacute form of experimental autoimmune encephalomyelitis (HEAE) was induced in Lewis rats using small doses (3.2 mug) of guinea pig myelin basic protein as immunogen and B. pertussis vaccine as adjuvant. Myelin basic proteins from species other than guinea pig (rat, man, monkey, pig, ox, rabbit and sheep) induced only ordinary EAE with this adjuvant. HEAE was more readily distinguished from ordinary EAE by clinical criteria (early onset, with a rapid and severe course, and high incidence of cerebral signs and mortality) than by histologic signs which, although characteristic of HEAE. were not pathognomonic for HEAE, HEAE was transferred to x-irradiated syngeneic recipient rats with lymph node cells from appropriately immunized donors. The Brown Norway (BN) strain of rat was found susceptible to induction of ordinary EAE, but not HEAE, using large doses of either rat or guinea pig myelin basic proteins. The unique immunogenicity of the guinea pig basic protein must be due to a different antigenic determinant from the determinant(s) which is shared by rat and guinea pig myelin basic proteins and which without B. pertussis induces ordinary EAE. The adjuvant action of B. pertussis in inducing HEAE in the Lewis rat is most likely mediated through an immunocompetent T lymphocyte.

Adjuvants, Immunologic

Induction of allergic encephalomyelitis using hydrosoluble adjuvant and the tryptophan region of myelin basic protein.

Experimental allergic encephalomyelitis has been induced in guinea pigs using the encephalitogenic tryptophan peptide as antigen and a hydrosoluble adjuvant extracted from Mycobacterium tuberculosis, var. hominis, strain H37Ra. The maximum response was observed using 100mug of adjuvant per animal. This is a quantity of adjuvant substantially higher than was necessary to induce disease utilizing the whole myelin basic protein as antigen.

Adjuvants, Immunologic