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Biomedical subjects

G J Knight

Publications and source records attributed to G J Knight.

At least 91 records · Page 5Linked to original sources

Improved 125I radioimmunoassay for cotinine by selective removal of bridge antibodies.

We describe an 125I-based RIA for cotinine, the major metabolite of nicotine. The slope of the dose-response curve was quite shallow (6-8% change in binding per doubling dose), resulting in between-assay CVs of 15 to 20%. This effect occurred because the radioligand formed by linking a cotinine derivative to tyramine manifested greater affinity for the anti-cotinine antibodies than did cotinine itself. We absorbed the serum with a derivative of nicotine coupled to the carrier protein via a chemical bridge similar to that used to form the cotinine/carrier protein immunogen. An RIA in which we used such absorbed serum showed a significantly increased slope of the dose-response curve (11-13% change in binding per doubling dose), and between-assay CVS were only 6 to 8%. We suggest that this improvement results because absorption removes anti-bridge antibodies directed against the chemical-bond common to the cotinine/carrier-protein immunogen and to the cotinine/tyramine radioligand.

Animals↗

Does smoking influence serum alpha-fetoprotein levels in mid-trimester pregnancies?

The effect of cigarette smoking during pregnancy on serum alpha-fetoprotein (AFP) levels was studied in 1925 consecutive women at 16-18 weeks gestation who subsequently had liveborn singleton infants. Cotinine and AFP were measured in sera in all the women and answers to a smoking questionnaire were analysed in 894. Cotinine, a metabolic derivative of nicotine, serves as an objective measure of the average daily absorption of smoking products because of its relatively long half-life. Infants born to women who smoked were, on average, 198 g lighter than those born to non-smokers, even though maternal weights were comparable. Whether analysed by self-reporting or by serum cotinine, cigarette smoking had no measurable effect on serum AFP levels.

Birth Weight↗

Evidence for liver disease preceding amino acid abnormalities in hereditary tyrosinemia.

In hereditary tyrosinemia, an autosomal recessive disorder of infants, it has been postulated that hepatic toxicity arising from defective degradation of tyrosine accounts for the severe liver disease that is a feature of this condition. We measured the concentration of alpha-fetoprotein, a marker for liver disease, and of amino acid in cord blood from three infants with hereditary tyrosinemia and found that the concentration of alpha-fetoprotein was greatly increased at birth, whereas the level of tyrosine was normal or not specifically elevated, and that hypertyrosinemia developed only postnatally. These results indicate that liver disease is prenatal in hereditary tyrosinemia and that therapy aimed at reduction of the elevated tyrosine level is unlikely to be of fundamental value.

Amino Acid Metabolism, Inborn Errors↗

Diagnosis of iron deficiency: mean corpuscular hemoglobin (MCH) as a predictor of iron deficiency in infants.

Hematologic variables were measured in 240 apparently healthy infants ranging from 1-12 months of age attending a well baby clinic. There were 20 infants for each month of age. Hematologic parameters were measured in each infant by Coulter Counter Model S. Serum iron, total iron binding capacity, free erythrocyte protoporphyrin (FEP) and serum ferritin levels were measured in most infants. Their weights together with their serum iron, total iron binding capacity, and serum ferritin were judged to be independent variables of iron status, whereas the hematologic variables were considered to be response variables indicative of iron status. The correlation coefficients among these variables, after excluding redundant variables and transforming to logarithms, were computed. Canonical correlation analysis was applied to the matrix of correlation coefficients to yield the linear function of the independent variables most highly correlated with a linear function of the response variables. The linear function of the response variables was found to be well approximated by the logarithm of the mean corpuscular haemoglobin, which was highly correlated with each of the independent variables.

Anemia, Hypochromic↗

Data from an alpha-fetoprotein pilot screening program in Maine.

In Maine, maternal serum alpha-fetoprotein (AFP) values equaled 2 or more multiples of the median in 4.8% of screened women. Between 2.0 and 2.9 multiples of the median repeat maternal serum AFP testing and sonography were comparable as the next diagnostic step; at 3 multiples of the median or higher sonography was superior. Sonography moved dates back in only ten singleton viable pregnancies with maternal serum AFP elevations; three of these had open fetal defects. Among singletons, all five anencephaly cases, one of two open spina bifida lesions, and all three open ventral wall defects were identified. Three closed singleton neural tube defects and two open spina bifida defects in twins were not detected. Nineteen of 36 multiple gestations had maternal serum AFP 2 or higher multiples of the median. In singletons, maternal serum AFP of 3 or higher multiples of the median indicated a thirtyfold increased risk for fetal death and a sevenfold increased risk for birth weight under 2500 g.

Congenital Abnormalities↗

Relation between maternal weight and serum alpha-fetoprotein concentration during the second trimester.

Maternal serum alpha-fetoprotein concentrations are influenced by maternal weight during the second trimester. Heavier pregnant women have lower median values, apparently as a result of a diluting effect of larger blood volume. This phenomenon is of clinical interest because alpha-fetoprotein concentration in a pregnant woman's serum is one of the factors considered in assessing risk of poor outcome. A revision of the reference interval for alpha-fetoprotein to take body weight into account might improve its use as a diagnostic aid, especially in heavier women.

Body Weight↗

Use of soluble and Staphylococcus aureus-immobilized second antibody compared in a radioimmunoassay for human alpha-fetoprotein.

Staphylococcus aureus cells coated with rabbit anti-goat immunoglobulin G were compared with soluble second antibody in a radioimmunoassay for human serum alphafetoprotein. Recovery of primary immune complexes with use of the bacterial immunoadsorbant (a) allowed second-antibody incubation time to be shortened from 3 h to 20 min at 37 degrees C, (b) decreased by 80% the amount of second antibody required per assay, thereby significantly reducing assay costs, and (c) provided a convenient and reproducible method for separation of free and bound antigen. The ease of preparation and the uniformity and stability of the S. aureus second-antibody reagent are additional advantages that may be useful in other radioimmunoassay procedures.

Antibodies, Bacterial↗

An evaluation of the Ramco kit for serum ferritin assay.

The determination of serum ferritin levels may be of diagnostic importance in medicine. To establish whether values obtained using a commercially available kit (Ramco) were adequate for this purpose, a comparison was undertaken using a two-site immunoradiometric assay that had been developed and standardized in our laboratories. Over the range 6 micrograms/l to greater than 2 000 micrograms/l there was a correlation coefficient between the two methods of 0,8284 (P less than 0.001). It is concluded that the Ramco kit is suitable for use in clinical practice.

Blood Chemical Analysis↗

The age, nutritional status and major diagnoses of outpatients at the Red Cross War Memorial Children's Hospital.

In 1961 a study of the age, sex, race, nutritional status and common diagnoses of children attending the Red Cross War Memorial Children's Hospital in Cape Town during one 12-month period was reported. A similar study was undertaken during two 2-week periods in 1972--1973. Comparison of the studies shows: (i) that a greater number of older children attended the hospital in 1972/1973; (ii) that the proportion of malnourished children whose percentage of expected weight for age was less than 66% had decreased from 8--10% to 5,5--6%; and (iii) that the overall pattern of disease had not changed appreciably, most of the children presenting with minor or preventable conditions.

Age Factors↗

Solid-phase enzyme immunoassay for hepatitis B surface antigen.

A solid-phase enzyme immunoassay is described for measuring hepatitis B surface antigen in human serum or plasma. Immunologically purified antibody labeled with horseradish peroxidase was used as the indicator. In the assay system, antibody-coated controlled-pore glass is used as a solid support and there are three sequential incubations, totaling 2 h, at room temperature. Results for serially diluted positive and reference sera compare favorably to radioimmunoassay in sensitivity and specificity.

False Positive Reactions↗