Search PubMed⌕ Search

Biomedical subjects

C J Pearce

Publications and source records attributed to C J Pearce.

At least 37 records · Page 2Linked to original sources
PubMed1986

Serum iodothyronine concentrations during introduction of thyroxine replacement therapy in hypothyroidism.

Serum concentrations of total and free T4 (TT4 and FT4), total and free T3 (TT3 and FT3), rT3, T4 binding globulin (TBG), T3 uptake (T3U) and TSH were measured in 12 patients with severe hypothyroidism before and during the introduction of replacement therapy with oral T4. The dose of T4 was increased by increments of 50 micrograms at intervals of 4 weeks to a total of 200 micrograms daily. There was a linear correlation between the concentrations of FT3 and FT4 (FT3 = 1.35 + 0.23FT4, r = 0.916, P less than 0.001). The correlation between TT3 and TT4 was more complex: the data were best fitted by the expression TT3 = 0.195 square root TT4, (r = 0.936, P less than 0.001). The relatively greater rise in TT3 initially may reflect a greater binding of T3 by TBG when the concentration of T4 is low. TBG concentration fell after 50 and 100 micrograms of T4 but did not change at the higher doses. There was a simple linear relation between TT4 and rT3 (rT3 = -0.022 + 0.0027TT4, r = 0.921, P less than 0.001). The expected inverse relation between TSH concentration and the thyroid hormones was seen, the three closest correlations being between the logarithm of the TSH concentration and FT3, the ratio T4/TBG and FT4 (r = 0.927, -0.917 and -0.900 respectively). These correlations were significantly better (P less than 0.05) than the correlations with untransformed TSH values. Suppression of TSH occurred while FT3 tended to remain within normal limits, but FT4 was often raised.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The effect of amiodarone on thyroxine kinetics.

Amiodarone was given by daily intraperitoneal injection (10 mg/kg body weight) to a group of 11 New Zealand white rabbits. Over 6 weeks there were significant increases (P less than 0.01) in plasma total T4 concentration (43 +/- 8 to 60 +/- 13 nmol/l; mean +/- 1 SD) and rT3 concentration (0.12 +/- 0.06 to 0.31 +/- 0.16 nmol/l) and a significant fall in total plasma T3 (2.3 +/- 0.3 to 1.7 +/- 0.2 nmol/l). The plasma clearance of T4 in rabbits treated with amiodarone for 6 weeks was significantly reduced relative to controls (64 +/- 25 vs 109 +/- 19 ml/kg per day, P less than 0.01) but the production rate was unchanged (3.8 +/- 1.8 vs 3.7 +/- 1.4 nmol/kg per day). In the amiodarone treated animals the increased plasma T4 concentration was entirely accounted for by the reduced clearance. It is inferred that the normal output of T4 by the thyroid is pituitary dependent and that TSH secretion is sustained in the presence of hyperthyroxinaemia because of amiodarone induced partial inhibition of T4 utilization by the thyrotroph.

Amiodarone↗
PubMed1985

Iodothyronine kinetics in the rabbit: an experimental model.

Turnover studies of thyroxine (T4), 3,5,3'-tri-iodothyronine (T3) and 3,3',5'-tri-iodothyronine (rT3) have been performed in the rabbit. A novel modification of a conventional radioimmunoassay has been used to measure specific 125I-labelled iodothyronines in small volumes of plasma in the presence of other 125I-labelled metabolites. Kinetic analysis of plasma disappearance of tracer was performed by a new theoretical approach. For T4 the mean (+/- S.D.) plasma concentration, clearance and production rates were 34 +/- 12 nmol/l, 109 +/- 19 ml/kg per day and 3.7 +/- 1.4 nmol/kg per day respectively (n = 9). For T3 the corresponding values were 2.04 +/- 0.42 nmol/l, 1.52 +/- 0.29 litres/kg per day and 3.07 +/- 0.76 nmol/kg per day (n = 8), and for rT3 0.12 +/- 0.04 nmol/l, 5.7 +/- 1.7 litres/kg per day and 0.69 +/- 0.23 nmol/kg per day (n = 8). The combination of these two new methodologies affords a simple and convenient means of studying iodothyronine metabolism under normal and abnormal conditions. The techniques employed may be generally applied to turnover studies of other compounds of physiological interest which can be measured by radioimmunoassay.

Animals↗
PubMed1984

Total and free thyroid hormone concentrations in patients receiving maintenance replacement treatment with thyroxine.

Total and free serum concentrations of thyroxine and triiodothyronine were measured in 122 subjects with hypothyroidism who were clinically well while receiving conventional replacement treatment with thyroxine. In a third of patients concentrations of total and free thyroxine were raised, often considerably; nevertheless concentrations of total and free triiodothyronine were usually normal. Though significant correlations were obtained between total triiodothyronine concentrations and total thyroxine concentrations (p less than 0.001) and between the triiodothyronine concentrations and free thyroxine concentrations (p less than 0.001) the slope of the line of the regression equation describing these correlations was small, hence large increases in both total and free thyroxine concentrations were accompanied by only modest increases in total and free triiodothyronine concentrations. The presence of total or free thyroxine concentrations above normal in patients taking thyroxine therefore are not necessarily of clinical consequence. In the assessment of adequacy of replacement treatment with thyroxine the most logical combination of in vitro thyroid function test results may be a normal thyrotrophin concentration and normal free triiodothyronine concentration.

Adult↗
PubMed1984

Total serum thyroxine and triiodothyronine; a comparison between Graves' disease and hyperthyroxinaemia due to thyroxine replacement.

Serum concentrations of total thyroxine (T4) and total triiodothyronine (T3) were measured in a group of patients (n = 113) presenting with untreated hyperthyroidism due to Graves' disease and in subjects receiving oral T4 replacement (n = 93) in whom the total T4 concentration was supraphysiological (greater than 150 nmol/l). The mean total T4 concentration in the hyperthyroid group was 226 nmol/l, SD 59, range 151-420, and the mean total T3 concentration was 6.8 nmol/l, SD 2.73, range 3.1-17.5. For the group receiving T4 the mean total T4 concentration was 175 nmol/l, SD 25, range 150-258, and the mean total T3 concentration was 2.66 nmol/l, SD 0.45, range 1.7-4.2. In the hyperthyroid group a highly significant linear correlation was found between total T4 and total T3, T3 = 0.0354 T4 - 1.21, r = 0.761, P much less than 0.001, while in the patients taking T4 this correlation was less close, T3 = 0.0073 T4 + 1.39, r = 0.398, P much less than 0.001. The two groups are readily distinguished by expressing total T4 as a molar ratio of total T3. In the hyperthyroid group the mean T4:T3 ratio was 35.6, SD 7.8, range 19.9-56.1, compared to the patients on T4 where the mean T4:T3 ratio was 67.0, SD 11.7, range 44.3-114 (t = 22.5, P much less than 0.0001). An arbitrarily chosen value of 50 for the T4:T3 ratio affords a simple and convenient means of distinguishing the two categories: in only 3 patients with Graves' disease (2.6%) was the ratio above this, and it was below in only 5 patients (5.4%) taking T4.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1983

Free thyroid hormone concentrations in subjects with various abnormalities of binding proteins: experience with amerlex free-T4 and free-T3 assays.

Free thyroid hormone concentrations measured by Amerlex assays were studied in subjects with inherited disorders of thyroxine-binding globulin (TBG) synthesis, variant albumins with a high avidity for T4, and iodothyronine-binding autoantibodies. Free T4 (fT4) and free T3 (fT3) levels were normal in euthyroid subjects with TBG deficiency and excess. Free T3 concentration was in the low normal range in subjects having a variant albumin but fT4 (Amerlex) was erroneously elevated because of the enhanced affinity of the 125I-T4 analogue employed in the assay for the abnormal albumin. The 125I-T3 analogue used in the fT3 assay does not bind more strongly to this variant albumin than to normal albumin. Amerlex assays for fT4 and fT3 in patients with iodothyronine-binding autoantibodies to thyroglobulin give variable results according to the specificity of the autoantibodies: non-specific antibodies cause extraordinarily high values even in hypothyroid patients; fT3 measurements may be appropriate in patients with T4-specific antibodies and even in some with T3-specific antibodies. The presence of such antibodies should be suspected if the results of Amerlex assays for fT4 and fT3 are discordant or are inconsistent with the clinical picture or TSH levels.

Autoantibodies↗
PubMed1981

Autoantibodies to thyroglobulin cross reacting with iodothyronines.

Serum thyroxine was consistently unmeasurable by radioimmunoassay in an elderly patient with myxoedema after successful treatment with oral thyroxine. Abnormal binding of thyroxine was suspected and shown to be due to the presence in serum of antibodies of the IgG variety. The characteristics of these antibodies with respect to their binding of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and human thyroglobulin (Tg) were systematically studied. Three preparations of Tg, and t4, T3 and rT3 were examined for their ability to compete with 125I-Tg, 125I-T4, 125I-T3 and 125I-rT3 for binding to the antibodies. For each tracer used the order of competitive efficiency was Tg greater than T4 greater than T3 greater than rT3. This provides for the first time direct evidence that iodothyronine reacting antibodies occurring in man are generated against Tg. All three iodothyronines were able to inhibit tracer binding of labelled iodothyronines completely, the order of effectiveness being T4 greater than T3 greater than rT3, suggesting antibodies with one type of binding site and that these were probably raised against a Tg sequence incorporating T4, although there was some evidence for the existence of a minor subpopulation of antibodies with higher specificity for T3. Complete displacement of labelled Tg by cold iodothyronines, however, was not possible. The experimental evidence suggests two classes of Tg antibodies, 70% of which were directed towards the T4 containing region, and 30% directed against other part(s) of the Tg molecule. Despite the presence of such Tg antibodies conventional haemagglutination tests of the patient's serum for Tg antibodies were negative.

Aged↗
PubMed1980

A comparison of three methods for quantitation of variant hemoglobin fractions.

Three methods, cellulose acetate electrophoresis-densitometry (CAE-D), cellulose acetate electrophoresis-elution (CAE-E), and microchromatography (MGC), were evaluated to determine the best method for quantitating variant hemoglobins. Evaluations were performed in two phases. In Phase I samples of known hemoglobins were obtained and Hb S and/or Hb C were quantitated by the three methods to evaluate agreement of results. In Phase II reference samples were prepared. The Hb S concentrations from each method were compared to the reference value to determine the effect of varying concentrations of Hb S on the methods. Cellulose acetate electrophoresis-densitometry proved to be the best method for quantitating variant hemoglobins in which the concentration was greater than 35 percent. Microchromatography was shown to be the best method when Hb S was approximately 30 percent. Either the microchromatography or the cellulose acetate electrophoresis-elution method proved to be a good method for quantitating approximately 25 percent Hb S.

Anemia, Sickle Cell↗
PubMed1978

Sub-unit assembly in the biosynthesis of neomycin. The synthesis of 5-O-beta-D-ribofuranosyl and 4-O-beta-D-ribofuranosyl-2,6-dideoxystreptamines.

The preparation of the deoxy- analogues of two pseudodisaccharide fragments of neomycin, 5-O-beta-D-ribofuranosyl-2,6-dideoxy-streptamine and 6-deoxyneamine is described. When added to the growth medium of a deoxystreptamine-idiotroph of Streptomyces rimosus forma paromomycinus only the latter was incorporated into antibiotic, suggesting an obligatory order for the assembly of sub-units. 4-O-beta-D-Ribofuranosyl-2,6-dideoxystreptamine was also prepared. When added to the growth medium of a deoxystreptamine-idiotroph of Streptomyces fradiae it was converted into the 6-deoxyneomycins, apparently after hydrolysis to 2,6-dideoxystreptamine. The structure of the protected derivatives of the ribofuranosyl 2,6-dideoxystreptamines, potentially useful intermediates for the synthesis of novel antibiotics, was shown by using 15C NMR spectroscopy.

Hexosamines↗
PubMed1976

The role of the pseudo-disaccharide neamine as an intermediate in the biosynthesis of neomycin.

By using wild-type and deoxystreptamine-negative mutants of Streptomyces fradiae grown in media containing [6(-3)H]glucose or [U-14C]glucose, and by subsequent hydrolysis of the labelled neomycin produced, neamines labelled with 3H in both rings I and II, but with 14C in ring I only, were prepared. A mixture of these two forms of neamine was converted by deoxystreptamine-negative Streptomyces rimosus forma paromomycinus into neomycin (not paromomycin) with a 30% yield. The3H: 14C ratio in this neomycin was the same as the measured in neamine produced by hydrolysis of the neomycin, and in unused neamine reisolated from the incubation medium. The 3H:14C ratio in the neomycin was not affected by the presence of unlabelled deoxystreptamine during the incubation. The radioactivity in the neomycin was associated with rings I and II only. It is concluded that the added neamine is incorporated into antibiotic intact, without initial hydrolysis, and that the probable first step in the subunit assembly of neomycin is the formation of neamine.

Disaccharides↗