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Biomedical subjects

D C Kilpatrick

Publications and source records attributed to D C Kilpatrick.

At least 91 records · Page 5Linked to original sources

Severe pre-eclampsia in multiparous women: indication of an environmental triggering agent?

Two case histories are described with conflicting implications for the etiopathogenesis of pre-eclampsia. In both, typical proteinuric pre-eclampsia developed despite a history of previous normotensive pregnancy. In the first case, the disease was associated with a change of husband, consistent with the view that pre-eclampsia arises from an inadequate maternal immune response to paternal antigens inherited by the fetus. The second case, however, concerned a woman who developed pre-eclampsia for the first time in her third pregnancy by the same reproductive partner. We conclude that either more than one underlying cause can result in the clinical syndrome of pre-eclampsia, or that pre-eclampsia is caused by an environmental factor. The possibility that pre-eclampsia may be initiated by an infectious agent is briefly explored in the light of the clinical histories described and well-established epidemiological, clinical and laboratory data.

Adult↗

Feto-maternal HLA compatibility does not have a major influence on human pregnancy except for lymphocytotoxin production.

Several studies have supported the hypothesis that the maternal immune response to incompatible paternal HLA antigens present on the conceptus may influence pregnancy outcome. In order to relate feto-maternal histocompatibility directly to pregnancy course and characteristics, complete HLA-A, B and DR types were obtained from 132 healthy family groups consisting of mothers, fathers and neonates. The distribution of feto-maternal HLA compatibility was heavily skewed towards incompatibility, with 90% of fetuses being mismatched at 2 or 3 loci. There was no segregation distortion of paternal haplotypes, however, and the number of feto-maternal mismatches was close to that expected theoretically. More than 2% of the neonates were perfectly HLA-A, B and DR compatible with their mothers. The degree of feto-maternal HLA disparity showed no significant correlation with sex of neonate, birthweight, placental weight, maternal plasma alpha-fetoprotein or parity of the mother. Feto-maternal HLA disparity did, however, correlate significantly with maternal lymphocytotoxin production, even after allowance was made for parity (P less than 0.01). We conclude that feto-maternal HLA compatibility per se does not have a major influence on pregnancy outcome, and in particular is unlikely to predispose to spontaneous abortion; so an absence of antigen sharing between spouses experiencing recurrent spontaneous abortions should not be regarded in itself as a contraindication to offering immunotherapy to such couples.

Antilymphocyte Serum↗

Inhibition of human lymphocyte transformation by tomato lectin.

The lectin from tomato (Lycopersicon esculentum) fruits was found to be non-mitogenic for human lymphocytes in culture and actually suppressed spontaneous DNA synthesis. It also inhibited the transformation of human peripheral blood lymphocytes induced by recall antigens or allogeneic cells in vitro. This inhibition was most effective when the lectin was present from the beginning of the culture period, and could be abolished by the simultaneous addition of oligomers of N-acetylglucosamine. The tomato lectin was able to bind to several major lymphocyte cell surface glycoproteins, but not to the major histocompatibility (HLA) antigens. The binding of tomato lectin to lymphocytes could be inhibited by wheat germ agglutinin (WGA), but not by concanavalin A. Tomato lectin could agglutinate monocytes and B lymphocytes as well as T lymphocytes. Human serum used to supplement the culture medium supporting lymphocyte transformation was equally effective after passage through a tomato lectin-Sepharose column. The inhibition of lymphocyte transformation brought about by tomato lectin was not stopped by exogenously added interleukin 1 and/or interleukin 2, even at very high concentrations.

Binding, Competitive↗

Tomato lectin resists digestion in the mammalian alimentary canal and binds to intestinal villi without deleterious effects.

Experiments were designed to investigate whether orally consumed tomato lectin could resist the digestive process and function as a lectin within the alimentary canal. Rats fed on a tomato lectin-rich diet passed faeces containing serologically detectable tomato lectin, and the lectin could be shown by immunoperoxidase staining bound to intestinal villi. Moreover, radioactivity was mainly recovered from the alimentary canal 3h after 125I-labelled tomato lectin administration with only traces in the circulation or internal organs. Radioactivity absorbed into the human circulation after consumption of 125I-labelled tomato lectin was also less than that expected for a digestable protein.

Administration, Oral↗

A diffusable factor in Scottish coagulation factor concentrates can inhibit lymphocyte transformation in vitro.

Coagulation factor VIII and IX concentrates produced in Scotland inhibited human lymphocyte transformation induced by lectins or the recall antigen, purified protein derivative of tuberculin (PPD). Although concanavalin A could bind factor VIII directly and PHA could bind factor IX directly, most of the inhibition was not due to direct clotting factor - lectin interaction nor to simple toxicity. Most of the inhibitory activity from both clotting factors could be removed by dialysis. A similar degree of inhibition was observed when the buffers used to prepare the concentrates were substituted for the concentrates themselves, and a comparable concentration of sodium citrate was also found to be inhibitory. Coagulation factor VIII partially purified by gel filtration was not found to have an appreciable effect on lymphocyte transformation in vitro.

Cells, Cultured↗

A comparison of tomato (Lycopersicon esculentum) lectin with its deglycosylated derivative.

A deglycosylated derivative of tomato (Lycopersicon esculentum) lectin was prepared with the use of trifluoromethanesulphonic acid. Its properties were generally similar to those of the native lectin, but differences were evident in terms of relative agglutinating activity towards sheep, (untreated) human and trypsin-treated human erythrocytes. The two forms of tomato lectin were used in conjunction with a battery of specific antisera to investigate structural relatedness among solanaceous lectins. Immunological cross-reactivity between tomato, potato and Datura lectins depends on the integrity of the glycosylated region of those lectins; that between Datura lectin and other seed lectins, however, has a separate structural basis.

Cross Reactions↗

Histocompatibility antigen frequencies in patients with chronic lymphocytic leukaemia: possible identification of a subgroup with relatively benign disease.

A series of 57 patients with chronic lymphocytic leukaemia was typed for HLA-A, B and DR antigens and compared with a control population of equal size. There was an increased frequency of HLA-A1 and B8 in the patient group, although it was not statistically significant after allowance for the number of specificities tested. A subgroup of patients lacking both A1 and B8 differed from the others in sex ratio, degree of lymphocytosis and incidence of hypogammaglobulinaemia at presentation. This subgroup also had less need for treatment within 6 months of presentation. While these findings must be considered preliminary, it is possible that tissue typing may help to identify patients with a relatively benign form of the disease.

Aged↗

A re-examination of the incidence of circulating immune complexes in normal pregnancy.

Circulating immune complexes were detected in 20% of serum samples from pregnant patients by the liquid-phase C1q-binding assay. Two other immune complex assays yielded negative results with the same samples. A careful case study was also carried out in which serum samples from before, during and after a normal pregnancy were analysed. The results are discussed in relation to the contradictory data previously published in this field.

Antigen-Antibody Complex↗

Purification and separation of tomato isolectins by chromatofocusing.

Tomato lectin can be rapidly separated from a crude extract of tomato fruit proteins by chromatofocusing. The lectin is recovered from a PBE94 column in two peaks, each with a specific activity comparable to that of lectin purified by affinity chromatography on ovomucoid-Sepharose. Both isolectins consist of a single polypeptide chain (Mr 68,000) and have similar properties.

Chromatography, Affinity↗