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D C Kilpatrick

Publications and source records attributed to D C Kilpatrick.

At least 37 records · Page 2Linked to original sources
PubMed1999

Immunological aspects of the potential role of dietary carbohydrates and lectins in human health.

BACKGROUND: Little is known regarding the immunobiology of dietary carbohydrate intake and its relevance to human health, although foodstuffs contain many simple and complex carbohydrates. SYNOPSIS: Lectins, immunoglobulins, viruses, bacteria and host cells interact with each other forming a delicate equilibrium within the alimentary canal which may be perturbed by saccharide intake. The ways in which these components may interact at different sites within the alimentary canal are discussed, as are the possible influences on mucosal immunity and the induction of oral tolerance. The possible systemic influences of absorbed saccharides at loci remote from the gut are considered in terms of inhibition of dietary and endogenous lectins, inhibition of bacterial attachment, and alteration of leukocyte homing behaviour. Finally, possible means by which dietary carbohydrates might modify various specific diseases are considered. CONCLUSIONS: It is probable that dietary carbohydrates can alter the equilibria between lectins, secretory IgA and micro-organisms in the alimentary canal, and this consideration could be exploited to promote health. The possible effects of dietary saccharides on allergy/oral tolerance or on recognition events at gut-remote sites warrant further investigation.

Animals↗
PubMed1999

Mannan-binding lectin deficiency is associated with unexplained recurrent miscarriage.

Mannan-binding lectin (MBL) is a plasma protein which, upon binding to microbial carbohydrate structures, elicits activation of the complement system. The level of MBL is genetically determined. It has been reported that the frequency of low plasma levels of MBL is increased in patients with unexplained recurrent miscarriages (RM). In the present study plasma MBL levels were determined in 146 Danish women with RM and 41 of their husbands together with 49 Scottish RM women and 41 of their husbands. In both countries MBL levels were also investigated in a total of 444 controls. Based on the control data, a cut-off MBL level < 50 ng/ml was selected to define MBL deficiency. The typical odds ratio for MBL deficiency among female patients in the two populations was 1.68 (95% confidence limits 1.01-2.80, P<0.05) whereas it was 1.57 (95% confidence limits 0.72-3.42, not significant) for the male partners of the patients. There was a significant correlation between the frequency of MBL deficiency in RM women and the number of previous miscarriages (P < 0.01), whereas no such correlation was found in the husbands. The results indicate that maternal MBL deficiency is associated with RM. Maternal MBL deficiency might impair the immune defence against microorganisms at the feto-maternal interface.

Abortion, Habitual↗
PubMed1999

Mannan binding lectin concentration and risk of miscarriage.

Recurrent miscarriage is associated with low concentrations of mannan-binding lectin (MBL), but it is not known below which value relative MBL deficiency becomes a significant risk factor. The sera of 397 patients (male and female) suffering from recurrent miscarriage and 376 controls were assayed for MBL and the data analysed. It was found that the lower the cut-off value, the greater the statistical strength of the association. It was concluded that only MBL concentrations </=0.1 microg/ml were clinically significant in this context. A corollary of this conclusion is that genotyping for point mutations in the structural gene for MBL would be a much less sensitive means of identifying couples at risk of experiencing recurrent miscarriage.

Abortion, Habitual↗
PubMed1998

Mannan binding lectin and the sudden infant death syndrome.

Mannan binding lectin (MBL) may be important for innate immunity and some cases of sudden infant death syndrome (SIDS) may be preceded by bacterial infection. Therefore, relative MBL deficiency might be associated with susceptibility to SIDS. We measured MBL concentrations in 46 SIDS infants and 26 controls. The proportion of subjects with low MBL values was similar in the two groups. However, the mean for the SIDS group (3 micrograms/ml) was higher than that of the controls (2.2 micrograms/ml; P < 0.05). We interpret this difference as due to acute phase responses and suggest these findings are consistent with the view that some cot deaths are preceded by bacterial infections.

Bacterial Infections↗
PubMed1998

Phospholipid-binding activity of human mannan-binding lectin.

Some C-type lectins possess phospholipid-binding ability, which may be of physiological importance. Human mannan-binding lectin (MBL) was found to bind specifically to solid-phase phosphatidylserine (PS), phosphatidylinositol (PI) and phosphatidylcholine (PC), but not cardiolipin (CL), in a concentration-dependent manner. This property was inhibited by EDTA and by monosaccharides, and exhibited a similar pH dependence to the carbohydrate (mannan)-binding activity of MBL. These findings may be of immunological relevance.

Animals↗
PubMed1998

Factors affecting cardiolipin antibody assays: modification with polyethylene glycol compound.

Anti-cardiolipin antibody (aCL) measurement is only semi-reproducible, and current assays detect irrelevant as well as clinically significant antibodies. Factors found to influence results included the source of the enzyme-linked immunoabsorbent assay (ELISA) plate, and its pretreatment with solvents; the nature of the blocking solution; and the composition of the diluent used for reagents. Fetal calf serum (FCS) in the diluent appeared to reduce nonspecific (clinically irrelevant) binding and was not simply a source of beta2-glycoprotein-1 (beta2GP1). A polyethylene glycol compound was found to be an effective blocking agent, and its use enhanced the discrimination between positive and negative samples. A high level of variation may be inherent in aCL-ELISA methodology, but the use of polyethylene glycol compound appeared to be a helpful modification.

Antibodies, Anticardiolipin↗
PubMed1998

Developmental variation in stem-cell markers from human fetal liver and umbilical cord blood leukocytes.

Fetal tissues containing haematopoietic stem cells (HSC) are of potential value for allogeneic transplantation and gene therapy. Flow cytometry was used to investigate CD34+ cells from human fetal livers and umbilical cord (placental) blood (UCB). CD34+ cells, expressed as a proportion of CD45-positive leukocytes, were much more abundant in fetal livers (mean 38%) than in UCB (mean 0.3%), but fetal liver cells had lower proportions of CD34+HLA-DR+ and CD34+ CD38+ subsets. In fetal liver, there was a strong and highly significant inverse correlation between CD34+ cells (as a proportion of total leukocytes) and gestational age; no such relationship was found for subsets of CD34+ cells coexpressing CD38 or CDw90 (Thy-1), but CD34+HLA-DR+ cells were less abundant in first-compared to second-trimester livers. In UCB, a trend towards decreasing CD34+ cells (as a proportion of total leukocytes) with increasing gestational age in late pregnancy was also observed. The composition of fetal leukocytes changes during development, and therefore the timing of fetal HSC harvesting could be of relevance to transplantation outcome.

Antigens, CD↗
PubMed1997

Isolation of human mannan binding lectin, serum amyloid P component and related factors from Cohn fraction III.

Cohn Fraction III, a waste product of plasma fractionation, is a source of several proteins involved in host defence as part of the innate immune system. Here a procedure is described for purifying mannan binding lectin and serum amyloid P component to virtual homogeneity from Cohn Fraction I + III, and their separation from other mannan-binding factors and from C-reactive protein. It is suggested that products derived from Cohn Fraction III could have therapeutic potential, either for specific substitution therapy or as a combined package of innate immune factors.

C-Reactive Protein↗
PubMed1997

Anti-cardiolipin antibodies in sexual partners of recurrent aborters.

The presence of anti-cardiolipin antibodies (aCL) in women is an established risk factor for fetal loss, but these autoantibodies had not previously been investigated in the male partners of recurrent aborters. The prevalence of aCL in 144 male partners of couples with a history of recurrent miscarriage was 4.2%, which compares with 2.8% for 177 female partners of such couples, 5.9% of 254 blood donors (128 male, 126 female) and 0% of 74 women of good obstetric history sampled in the puerperium. In recurrent miscarriage couples, the presence of aCL in the women was associated with a poorer history and outlook, but these associations were not evident in couples where the male partner had aCL. The aCL of male partners also differed from those of their spouses in being less likely to show higher activity towards phosphatidylserine than towards phosphatidylcholine. A particular sub-population of aCL may be strongly represented in the male partners, the clinical significance of which remains to be established.

Abortion, Habitual↗
PubMed1997

Mannan binding protein in sera positive for rheumatoid factor.

Low levels of mannan binding protein (MBP) may protect against rheumatoid arthritis and other inflammatory conditions associated with agalactosyl IgG. MBP concentrations were measured in 99 sera found to be positive for rheumatoid factor, at least 41 of which were from patients with rheumatoid arthritis, and the values compared to the data from 352 controls. MBP was undetectable in similar proportions of patients' and control sera (4.0 and 4.3%, respectively), and low values generally were similarly distributed in the two groups. Overall, however, the patient values were distorted upwards relative to controls, consistent with an acute-phase response. These findings do not refute the proposed role for MBP-agalactosyl IgG-mediated complement activation in the pathogenesis of rheumatoid arthritis, but certainly provide no support for that hypothesis.

Arthritis, Rheumatoid↗
PubMed1996

Human mannan binding protein in pre-eclampsia.

Mannan binding protein (MBP) was measured in the sera of 95 patients with proteinuric pre-eclampsia and in 76 sera from the husbands of those patients. No significant difference was found in comparison with 352 blood donors. However, couples experiencing recurrent pre-eclampsia had significantly lower levels of MBP than those associated with primiparous couples with pre-eclampsia. The latter finding was derived from data inspection and not from a prior hypothesis, and therefore requires independent confirmation preferably from a larger series.

Blood Donors↗
PubMed1996

HLA-B27 determination by polymerase chain reaction.

A method for determining the presence or absence of HLA-B27 by selective amplification of a region in the third exon of the HLA-B27 gene common to B*2701 to B*2705 inclusive, was evaluated. This polymerase chain reaction/sequence specific primer (PCR-SSP) method gave perfect correlation with serological typing on 40 individuals of previously determined HLA type and on 50 further clinical samples evaluated blind. It was concluded that HLA-B27 determination by PCR-SSP is simple, reliable, cost-effective and convenient for laboratory staff.

Base Sequence↗
PubMed1996

HLA-dependent TNF secretory response may provide an immunogenetic link between pre-eclampsia and type 1 diabetes mellitus.

Tumour necrosis factor (TNF) may be relevant to the pathogenesis of both pre-eclampsia and type 1 diabetes, and there is evidence than human TNF alpha responses to stimuli are HLA-DR dependent. To test the hypothesis that pre-eclampsia and diabetes may share a common immunogenetic susceptibility, 92 pre-eclampsia patients were compared with 264 general population controls. The relative frequencies of individual HLA-DR antigens in pre-eclamptics were found to correlate with reported relative TNF alpha responses for those antigens. Moreover, putative high responder HLA-DR1, DR3 and DR4 alleles were significantly (p < 0.001) more frequent in pre-eclampsia patients (79%) than in controls (59%). This hypothesis could explain the weak association between pre-eclampsia and diabetes and may help resolve the apparently conflicting literature on HLA in pre-eclampsia.

Diabetes Mellitus, Type 1↗
PubMed1995

Association between mannan binding protein deficiency and recurrent miscarriage.

The distribution of mannan binding protein (MBP) in blood donor sera was determined by enzyme-linked immunosorbent assay to establish normal concentrations. Abnormally low MBP concentrations were found in 16% (21 out of 135) of female partners and 14% (15 out of 108) of male partners of couples experiencing recurrent miscarriage, compared with < 5% of obstetrically normal controls (P < 0.005). This relationship was even stronger (9.5 versus 1.0%) and more significant (P < 0.002) when only subjects presumed to be homozygous for the mutant allele responsible for MBP deficiency were considered. By immunohistochemistry, MBP could be demonstrated in first trimester placenta. We suggest that low concentrations of MBP within the feto-placental unit increase susceptibility to fetal loss, possibly via an infection-induced placental cytokine imbalance.

Abortion, Habitual↗