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Biomedical subjects

T Oglesby

Publications and source records attributed to T Oglesby.

7 recordsLinked to original sources
PubMed1995

The control of hyperacute rejection by genetic engineering of the donor species.

Activation of endogenous complement is inhibited both in the soluble phase and at the membrane surface by a group of structurally similar proteins. A possible solution to hyperacute rejection is to produce donor animals transgenic for human complement regulators. Mouse cells expressing the human complement regulatory proteins decay accelerating factor (DAF) or membrane cofactor protein (MCP) were produced both by hybridoma technology and by transfection with the appropriate cDNAs. The expression of either or both of these products protected the mouse cell from lysis by human (though not rabbit) complement in the presence of naturally occurring human anti-mouse antibody. This effect could be abrogated by the addition of monoclonal antibody against DAF or MCP. Hyperacute rejection of discordant organ xenografts is mediated by human complement. A 6.5 kilobase minigene for DAF has been microinjected into porcine fertilised ova. Forty-five pigs transgenic for human DAF have been produced. Of these, 65% transcribe message. The amount of message produced varied substantially from animal to animal and was independent of copy number integrated. Expression of human DAF on the porcine lymphocyte surface could be detected and this was able to downregulate human complement activation. Amounts of protein expressed on different tissues varied both from pig to pig and within animals from tissue to tissue. The pigs grow and develop normally with no evidence of ill effects due to possession of the transgene.

Animals↗
PubMed1995

Ontogeny of membrane cofactor protein: phenotypic divergence in the fetal heart.

Human adult cells are protected from complement-induced damage in part by membrane cofactor protein (MCP, CD46). To examine fetal characteristics which might influence autoantibody-mediated diseases acquired in utero, such as heart block in neonatal lupus, the tissue expression of MCP was studied. Using a high ratio of acrylamide:bisacrylamide, immunoblots of tissues from six fetuses (aged 19-24 weeks) probed with rabbit anti-MCP antibodies revealed a band at 60 KD in addition to the known 65 KD and 55 KD isoforms which comprise the codominant allelic system of MCP. Five fetuses expressed the most common MCP polymorphism (predominance of the 65 KD isoform, upper band alpha-phenotype) in the kidney, spleen, liver and lung. In contrast, all hearts from these five fetuses demonstrated a different pattern in which there was a marked decrease in the intensity of the 65 KD band and accentuation of the lower molecular weight bands. In a sixth fetus, which expressed the second most common polymorphism (equal expression of the 65 KD and 55 KD MCP isoforms, alpha beta-phenotype), the heart was similar to the other tissues. These studies confirm the expression of MCP in early gestational life. Preferential expression of the MCP beta-isoform in the majority of fetal hearts irrespective of the phenotype of other organs, suggests tissue-specific RNA splicing or post-translational modification which may relate to autoantibody-mediated injury in diseases such as neonatal lupus.

Antigens, CD↗
PubMed1992

Expression of human decay accelerating factor or membrane cofactor protein genes on mouse cells inhibits lysis by human complement.

Mouse cells expressing the human complement regulatory proteins decay accelerating factor (DAF) or membrane cofactor protein (MCP) were produced both by hybridoma technology and by transfection with the appropriate cDNAs. The expression of either or both of these products protected the mouse cell from lysis by human (though not rabbit) complement in the presence of naturally occurring human anti-mouse antibody. This effect could be abrogated by the addition of monoclonal antibody against DAF or MCP. These data suggested that the production of animals transgenic for human complement regulatory proteins should in principle be similarly protected from hyperacute xenograft rejection.

Animals↗
PubMed1988

A controlled trial comparing sulfasalazine, gold sodium thiomalate, and placebo in rheumatoid arthritis.

One hundred eight-six patients with active rheumatoid arthritis were evaluated in a double-blind, randomized study that compared treatment with sulfasalazine (SSZ) (2 mg/day), gold sodium thiomalate (GST) (50 mg/week), and placebo (PBO). The 37-week course of therapy was completed by 109 patients. While marked improvement was seen in all 3 treatment groups, the only statistically significant differences between SSZ or GST and PBO were in a decreased erythrocyte sedimentation rate and increased grip strength in the right hand. GST is known to be superior to PBO, and the response of the GST-treated group was similar to that seen in other trials. The response of the PBO group, however, was much greater than in other placebo groups we have studied. SSZ was similar in efficacy to injectable gold, but was better tolerated. Because of adverse drug reactions (most commonly, rash, stomatitis, and proteinuria), 41% of patients were withdrawn from the GST treatment. Untoward drug effects (most frequently, rash and gastrointestinal distress) caused 16% of patients to be withdrawn from SSZ therapy.

Adolescent↗