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Biomedical subjects

L Barron

Publications and source records attributed to L Barron.

At least 37 records · Page 2Linked to original sources
PubMed1991

Linkage disequilibrium and recombination make a telomeric site for the Huntington's disease gene unlikely.

In a Scottish family in which Huntington's disease (HD) was segregating, recombination was observed between the D4S115/S111 and D4S43/S95 loci, with the HD gene associated with the more proximal D4S43/S95 locus. Analysis of linkage disequilibrium in Scottish families showed significant non-random association between the HD gene and alleles at the D4S95 and D4S98 loci. This adds to previous evidence that the HD locus is not sited at the telomere of chromosome 4.

Alleles↗
PubMed1990

First-trimester maternal serum biochemical indicators in Down syndrome.

A set of 21 early maternal serum samples (19 first-trimester and two at 14 weeks) from pregnancies resulting in a child with Down syndrome was matched for gestation and length of storage with 63 samples from unaffected pregnancies. The concentrations of alpha-fetoprotein (AFP), unconjugated oestriol (uE3), human chorionic gonadotrophin (hCG), pregnancy-specific beta 1-glycoprotein (SP1), and placental alkaline phosphatase (PALP) were measured. The ratios of the medians for Down syndrome pregnancies compared with the medians for controls were AFP 0.71, uE3 0.67, hCG 1.43, SP1 0.79, and PALP 0.92. Although the differences between the medians for affected and unaffected pregnancies were not significant, the trends for AFP, uE3, and hCG confirm earlier findings on first-trimester samples.

Alkaline Phosphatase↗
PubMed1989

Predictive testing for Huntington's disease with linked DNA markers.

Availability of new DNA markers, more tightly linked to the Huntington's disease (HD) locus than the original G8 (D4S10) probes, has improved predictive accuracy for both presymptomatic and prenatal exclusion testing. 50 predictive tests were carried out on high-risk individuals. 6 of these were on first-trimester chorionic villus biopsy specimens; in 2 cases the HD gene was not transmitted to the fetus while in 4 cases no exclusion could be made. The remaining 44 tests were on adults with either 25 or 50% risk of manifesting the disease; 19 had a greatly increased risk and 25 a substantially decreased risk of HD. Family structures in Scotland are suitable for testing about 75% of potentially affected individuals, and the new generation of DNA markers makes virtually all families fully informative.

Adult↗
PubMed1988

Prenatal diagnosis of cystic fibrosis by microvillar enzyme assay on a sequence of 258 pregnancies.

Prenatal diagnosis of cystic fibrosis by microvillar enzyme assay on amniotic fluid supernatant has been carried out on 258 sequential pregnancies with a 1 in 4 recurrence risk, all with known outcome. In general the three enzymes evaluated, gamma-glutamyltranspeptidase, aminopeptidase M and the intestinal isoenzyme of alkaline phosphatase, showed a high degree of concordance. However, there were two unusual patterns of microvillar enzyme activity; in seven cases a low gamma-glutamyltranspeptidase activity was associated with elevated values of intestinal alkaline phosphatase, and in ten cases there were isolated low values of intestinal alkaline phosphatase. The former pattern was found to be associated with cystic fibrosis in five cases, while the latter was associated with a normal outcome in all ten cases. A retrospective analysis of enzyme values suggested that the optimal system for minimizing false positives and false negatives was to define foetal cystic fibrosis as a sample where two of the three microvillar enzymes were below a cut-off of half the median value for the gestational week. If such scoring were applied to the cases where conventional microvillar enzyme patterns were observed, the false positive rate was 2.3% and the false negative rate 4.4% between 17 and 20 weeks of gestation.

Amniotic Fluid↗
PubMed1988

Measurement of placental alkaline phosphatase in maternal plasma as an indicator of subsequent low birthweight outcome.

Placental alkaline phosphatase (P-ALP) was measured by a specific monoclonal antibody-based immunoassay in plasma samples of 117 women who subsequently were delivered of an infant of birthweight less than 2.5 kg. P-ALP values greater than twice the normal median were found in 32% of maternal plasma samples from low birthweight cases in one series and in 35% in another series, while in normal outcome controls the corresponding value was 8%. The differences were highly significant. The proportion of low birthweight cases with elevated maternal P-ALP values appears to be very similar between 15 and 34 weeks gestation. At 16-18 weeks gestation there is a significant positive correlation (r = 0.40) between P-ALP and maternal plasma alpha-fetoprotein (AFP) values in low birthweight cases. The use of P-ALP assay in combination with AFP assay appears to improve the detection of pregnancies with subsequent low birthweight outcome.

Alkaline Phosphatase↗
PubMed1988

Prospective prenatal screening for fetal abnormalities using a quantitative immunoassay for acetylcholinesterase.

An immunoassay based on a monoclonal antibody specific for acetylcholinesterase (AChE) was used prospectively over a two year period to screen second trimester amniotic fluids for fetal abnormalities. All 26 cases of spina bifida, three of which had normal alphafetoprotein (AFP) concentrations and ultrasound scans, were detected by the immunoassay. Four clear fluids, with abnormal AFP concentrations, had normal AChE titres and yielded normal outcomes. Some difficulties were encountered with both the AChE immunoassay and polyacrylamide gel testing when amniotic fluids were contaminated with old blood. However, the quantitative nature of the AChE immunoassay and its independence of operator experience make it an ideal adjunct to AFP assay for routine screening of amniotic fluids.

Acetylcholinesterase↗
PubMed1986

A monoclonal antibody assay technique for plasma and red cell acetylcholinesterase activity in Alzheimer's disease.

Acetylcholinesterases (AChE) in human plasma and red cells have been considered as possible markers for Alzheimer's disease. Findings however vary widely and no significant pattern has emerged. The present study has used a new technique for AChE assay based on a monoclonal antibody raised against red cell AChE. This allows AChE isoenzymes to be measured directly in the presence of non-specific cholinesterases without the need for inhibitors. AChE activity in plasma and red cells was assayed in Alzheimer's disease, multi-infarct dementia, Huntington's and alcoholic Korsakoff syndrome, and the results compared both between groups and with normal controls. No significant differences in either red cell or plasma enzyme activity were found by any of these comparisons. Our findings do not suggest that in the dementias peripheral AChE activity reflects altered central cholinergic function, nor that it is likely to prove a useful marker for Alzheimer's disease.

Acetylcholinesterase↗
PubMed1985

First trimester diagnosis of hypophosphatasia with a monoclonal antibody to the liver/bone/kidney isoenzyme of alkaline phosphatase.

Prenatal diagnosis of hypophosphatasia was made by alkaline phosphatase (ALP) assay on a chorionic villus sample taken in the first trimester. Monoclonal antibodies against the liver/bone/kidney (LBK) and placental isoenzymes of ALP were used, and the bound isoenzymes were quantified by an amplification system. Very low activities of the LBK isoenzyme indicated an affected fetus. Diagnosis was confirmed by ultrasound scan at 15 weeks' gestation, and by ALP measurement in amniotic fluid supernatant and fetal serum.

Adult↗
PubMed1985

Prospective prenatal diagnosis of cystic fibrosis.

An immunoassay based on monoclonal antibodies with specificity for the three major isoenzymes of alkaline phosphatase (ALP) has been used in second-trimester prenatal diagnosis of cystic fibrosis (CF). 140 pregnancies with a 1-in-4 risk of CF were assessed prospectively, and outcomes are reported for 100 of these. In 9 cases the diagnosis could not be confirmed or excluded, in 65 cases the infant was normal, and in 15 the infant had CF. In the remaining 11 cases, in which the pregnancy was terminated, the diagnosis of CF was confirmed in the abortus by measurement of albumin and protease levels in meconium scraped from the fetal ileum. Of the 26 cases of CF in the prospective series, 23 (88%) had values of intestinal ALP below half the median value for the corresponding week of gestation. Among those with normal outcomes 3 of 65 (4.6%) were below half-median. When prospective and retrospective data are summed the sensitivity of the test was 91% (39 of 43) and the false-positive rate 6% (5 of 81). This is probably an acceptable form of prenatal diagnosis of CF for the high-risk mother.

Amniotic Fluid↗
PubMed1985

Prenatal diagnosis of neural-tube defects with a monoclonal antibody specific for acetylcholinesterase.

An immunoassay for acetylcholinesterase (AChE), based on a monoclonal antibody (AE-2), gave the following results when applied to a panel of amniotic fluids: (a) among 651 samples with normal outcome and normal alphafetoprotein (AFP) values there were 2 (0.31%) false positives; (b) of 9 samples with normal outcome and raised AFP values 1 had a raised AChE titre; (c) all 48 samples from anencephaly cases had raised AChE values; (d) among 49 samples from open spina bifida cases (2 of which had normal AFP values), 48 had raised AChE titres. It is suggested that a monoclonal-antibody-based immunoassay may displace polyacrylamide gel electrophoretic analysis of AChE as a complementary test to AFP in prenatal diagnosis of neural-tube defects, since it is a quantitative test largely independent of operator skill and experience.

Acetylcholinesterase↗
PubMed1984

A screening assay for monoclonal antibodies based on the availability of a polyclonal antiserum.

A double-sandwich enzyme-linked immunospecific assay (ELISA) has been developed for screening hybridoma clones for monoclonal antibodies against human alpha-fetoprotein (AFP). The assay uses commercial polyclonal antiserum to bind alpha-fetoprotein from biological fluids, and the complex then binds the specific monoclonal antibodies in hybridoma culture supernatants. The sandwich is completed with commercial peroxidase-linked anti-mouse immunoglobulin. In exploring the variables of this system, it was found that the quality of the polyclonal anti-alpha-fetoprotein antiserum was the most critical factor. The assay functioned with as little as 10 ng alpha-fetoprotein from cord serum or amniotic fluid. A variety of commercial peroxidase-linked second antibodies was satisfactory, and both IgG and IgA class monoclonals were detected. Comparison of the ELISA with a standard radioimmunoassay showed the former to perform very adequately as a general hybridoma screening assay.

Antibodies, Monoclonal↗
PubMed1984

Comparison of activated charcoal and gastric lavage in the prevention of aspirin absorption.

Effectiveness of initial treatment of aspirin (ASA) overdosage was evaluated by comparing treatment with activated charcoal (AC) to treatment with gastric lavage in combination with AC. Dogs were used as subjects in four experimental groups. All subjects were administered an overdose of 500 mg/kg of ASA. Treatment was performed 30 minutes later on all groups except controls. Treatment with AC alone resulted in a 17% reduction (P greater than .05) of peak plasma salicylate levels compared with controls. When lavage preceded administration of AC, a 37% reduction (P less than .05) occurred. There was a 48% reduction (P less than .025) in plasma salicylate levels when lavage was preceded and followed by administration of AC. This study demonstrates that gastric lavage in combination with AC is more effective in reducing ASA absorption than AC given alone.

Animals↗
PubMed1984

Approaches to the production of monoclonal antibodies specific for concanavalin A binding and non-binding forms of alphafetoprotein.

Attempts have been made to make monoclonal antibodies which would react preferentially with either the concanavalin A (con A) binding or non-binding from of human alphafetoprotein (AFP). Mice were immunised with con A non-binding AFP in a variety of schedules, and their spleens used in four separate fusions. Despite identification of 467 hybridomas secreting anti-AFP antibodies, no monoclonals could be found with consistent or reproducible specificity for either con A binding or non-binding AFP. Ten of the hybridomas were grown as ascitic tumours. The resulting ascitic fluids defined 4 discrete epitopes on the AFP molecule. There was no apparent difference in the binding of a particular monoclonal antibody to its target epitope in the con A binding and non-binding forms of AFP. This finding is discussed in the light of current knowledge of the molecular structure of the carbohydrate chains of con A binding and non-binding forms of AFP.

Antibodies, Monoclonal↗
PubMed1982

Enzyme-linked immunospecific assays for human alphafetoprotein using monoclonal antibodies.

Two sandwich-type enzyme-linked immunospecific assays for human alphafetoprotein (AFP) have been developed. In both assays monoclonal antibodies were immobilised by absorption to the wells of microtitre plates and used to trap AFP in the samples offered. Bound AFP was then quantitated by completing the sandwich with peroxidase-conjugated anti AFP, which was either of polyclonal or monoclonal type. The monoclonal to monoclonal sandwich enable AFP measurements to be made in the range 100 to 1000 kU/l. The polyclonal to monoclonal sandwich covered an AFP range of 10 to 1000 kU/l. Both assays were rapid and robust and extremely sparing in the use of antibody.

Antibodies, Monoclonal↗
PubMed1982

Monoclonal antibodies to human alpha-foetoprotein: analysis of the behaviour of three different antibodies.

Three mouse monoclonal antibodies directed to different epitopes on human alpha-foetoprotein have been produced. Two are of IgG1 subclass and the third is IgA. The polyethylene glycol-dependent immunoprecipitation system, designed for conventional antisera, had to be adapted before reproducible results could be obtained with the reagents. In this adapted system, as well as in a radioimmunoassay using solid-phase second antibody, a mixture of the 3 monoclonal antibodies exhibits cooperativity. However, the sensitivity of the radioimmunoassay with pooled monoclonals is not good as that of conventional antiserum. Low affinity monoclonal antibodies have been used for immunopurification of the antigen, whilst the high affinity one is useful for antigen quantitation in a labelled antibody-dependent system which requires absolute antibody specificity.

Animals↗
PubMed1982

Maternal plasma alpha-fetoprotein and low birthweight: a prospective study throughout pregnancy.

Maternal plasma alpha-fetoprotein (AFP) was measured serially between 15 weeks gestation and term in 520 patients. Thirty-seven of these women were delivered of normal singleton infants with birthweights less than 2.5 kg. The median plasma AFP values in this group of women were highest between 15 and 20 weeks gestation and then declined steadily towards term. It is concluded that the use of maternal plasma or serum AFP in the early detection of low birthweight babies is optimal in the period most suitable for screening for fetal neural tube defects.

Female↗