Spuriously high concentration of serum free thyroxine due to anti-triiodothyronine antibodies.
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Autoantibodies↗
Biomedical subjects
F Gasser
Publications and source records attributed to F Gasser.
New unified nomenclature for genes involved in the oxidation of methanol in gram-negative bacteria.
The system involving the oxidation of methanol to formaldehyde in Gram-negative methylotrophic bacteria is complex. A total of 32 genes have been reported, termed mox, for methanol oxidation, and it is possible that more will be identified. Some mox genes carrying out completely different functions have been given the same designations by different laboratories and others have been given separate designations that were later discovered to be the same. It is now important to change the mox nomenclature to remedy this confusing situation. This communication proposes a new nomenclature for genes involved in methanol oxidation based on currently known linkage groups.
Genes, Bacterial↗
[Effects of amiodarone on thyroid hormonal profile. Updating based on new assay methods].
Amiodarone (A) treatment alters the levels of thyroid hormones. We investigated whether new hormonal assays are also altered by this drug. Thyroid function was determined in 21 patients chronically treated with A and in 30 controls. TSH was determined with a third generation assay. Free T3 and Free T4 levels were determined by 5 different immunoassays. Equilibrium dialysis (E.D.) was considered as the reference assay for FT3 and FT4. With this method FT3 is diminished, reverse T3 ans FT4 are increased whereas TSH remained normal. Only FT3 determined by an assay using a labelled monoclonal antibody (MAB) appears not modified by A. Other methods (chromatography, chemiluminescence and radioisotopic) give results in agreement with E.D. Some of these alterations may be explained by a marked increase in plasma levels of non esterified fatty acids. Hormonal changes induced by A are typically with all but one assays. Whatever the method used the determination of TSH remains necessary to avoid misinterpretation of the thyroid function tests in A-treated patients.
Aged↗
[Assay of free thyroxine by immunoenzyme method in general diseases].
In non thyroid illnesses the degree of serum FT4 levels perturbation may be variable according to the assay used. The performance of a new FT4 immunoenzymatic assay (Enzymmum test, BMF) was evaluated in 78 euthyroid controls and in 99 sick patients with renal insufficiency, severe diabetes, hypoalbuminemia, severe general disease or under heparinate treatment. Results were compared to two RIA assays: by immunoextraction (CA2), known to be little disturbed by hypoalbuminemia and considered as a reference method, and by a labelled antibody (MAB, Amerlex) easier to use. In controls mean values and T4 L confidence intervalls were comparable with the three assays. In patients FT4 levels were diminished in case of renal insufficiency but the mean values obtained by BMF and CA2 did not differ. FT4 levels of heparinate treated patients were elevated with BMF and CA2. Generally patients are better classified as euthyroid with the CA2 assay (5.6% misclassification) than with BMF (11.2%) or MAB (12.4%), particularly in case of serious disease. A good linear correlation was found between the three methods. With the new BMF assay results were grossly comparable to those obtained by other assays. However the determination of FT4 levels alone appeared no sufficient to characterize the patients thyroid status.
Evaluation Studies as Topic↗
[Evaluation of sensitivity of an assay: application to a third-generation thyrotropin (TSH) assay].
The concentration-specific smallest detectable difference (D) between two concentrations (i.e., the sensitivity) was determined from the results of within-run and run-to-run reproducibility studies of a third-generation thyrotropin assay. Only low concentrations were considered (range 0-0.3 m U/l). Assays were performed in singlet or in duplicate. Findings confirmed the value of the assay: the analytic detection limit approximated 0.005 mU/l and the functional detection limit was around 0.01 mU/l. Expressed as a percentage of the concentration, D% was under 20% for levels of less than 0.02 mU/l in within-run studies or of less than 0.03 mU/l in run-to-run studies. With concentrations in excess of 0.05 mU/l, D% was under 10% in within-run studies and slightly above 10% in run-to-run studies. These new detection thresholds for this assay should be taken into account when interpreting clinical results from a single run (TRH test) or from several runs (hormone replacement therapy or suppression test).
Humans↗
[Free triiodothyronine assays using labeled antibody: evaluation and comparison with an analog labeled assay].
We evaluated analytically and clinically two new one-step labelled antibody assays for measuring free triiodothyronine (FT3): the first, radiolabelled with 125I, Amerlex-MAB (MAB) from Kodak Diagnostic, and the second, labelled with peroxidase, Enzymun-test FT3 (BM) from Boehringer Mannheim adapted for the Boehringer ES 600 analyser. The clinical results were compared with those obtained with a radiolabelled analog tracer kit, Amerlex-M (M) from Kodak Diagnostic. The latter kit is known to give low FT3 results in sera with low albumin concentrations. Analytical performances of the automated method (BM) were better than those obtained with the manual method (MAB): intra-assay reproducibility (CV < 3% vs CV about 5%), inter-assay reproducibility (CV < 4% vs CV between 4 and 8%) and mean drift (+1.25% vs -4.3%). The detection limit was low for both kits (< 1 pmol/l). In the euthyroid reference group (n = 98) we observed a significant difference between outpatient and hospitalized patient FT3 concentrations as measured with the M kit only. The reference range was 3.2-6.5 pmol/l for the MAB kit vs 5.4-9.2 pmol/l for the BM kit. This result underlines the problem of standardisation with the FT3 assays. Clinical sensitivity for hyperthyroidism (n = 38) was better for the MAB (92%) than for the BM kit (76%). Specificity in euthyroid L-thyroxine (T4) treated patients (n = 26) was good for both kits (MAB: 92%; BM: 88%).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Thyrotropin assay by chemiluminescence in the diagnosis of dysthyroidism with low thyrotropin and normal thyroid hormones levels].
The performances of a new "3rd generation" chemoluminescence TSH assay (TSH ICMA) with a functional sensitivity of 0.005 mU/l were compared with those of an "ultrasensitive" TSH immunoradiometric assay (TSH IRMA) in a series of patients characterised by a TSH IRMA less than 0.20 mU/l and normal free thyroxin (T4 L) and triiodothyronine (T3 L) concentrations. The 95% cut-off value for hyperthyroidism was 0.03 for TSH ICMA and 0.05 for TSH IRMA. In a first group of 41 subjects undergoing Tc99m thyroid scan, images of multifocal increased uptake or toxic adenoma were associated with a lower TSH ICMA than in patients with a normal isotope scan. TSH ICMA was also lower than TSH IRMA (p < 0.01). At the cut-off value of 0.03 mU/l, the specificity of TSH ICMA was higher than that of TSH IRMA, but the sensitivity were identical. In a second group of 36 patients with severe non-thyroid diseases, TSH ICMA was lower than the cut-off value for hyperthyroidism in 30% of cases, while TSH IRMA was lower than the cut-off value in 40% of cases. A satisfactory concordance was observed between the two methods. In conclusion, the two TSH assays, IRMA and ICMA, provide globally comparable information in subjects with a low TSH and normal T4 L and T3 L. However, the better specificity of TSH ICMA and a smaller overlap with the frank hyperthyroid zone in patients with non-thyroid disease argue in favour of the use of this new assay method.
Aged↗
Gonadotropins induce accumulation of insulin-like growth factor I mRNA in pig granulosa cells in vitro.
Pig granulosa cells have been shown to synthesize insulin-like growth factor (IGF) I peptide in vitro, and this expression is regulated by gonadotropins via the cAMP pathway. By hybridizing an IGF I cDNA probe with total RNA isolated from pig granulosa cells cultured in vitro, we show that these cells contain two IGF I transcripts of about 0.9 kb and 9 kb in size. Treatment of the cells with gonadotropins (follicle-stimulating hormone, luteinizing hormone) or cAMP agonists (dibutyryl-cAMP, forskolin) induces an accumulation of the transcripts which can be abolished by transcriptional inhibitors, but not by translational inhibitors. We thus provide new evidence that pig granulosa cells are a site of IGF I synthesis, and we conclude that (1) gonadotropins increase IGF I mRNA levels; (2) the accumulation of IGF I mRNA results from an increased transcription; (3) the stimulation of IGF I gene transcription does not require ongoing protein synthesis; (4) these effects of follicle-stimulating hormone can be mimicked by cAMP agonists.
Animals↗
Recovery determination in 600 sera analyzed for thyroglobulin with a recently commercialized IRMA kit.
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Antibodies, Monoclonal↗
Complementation of Methylobacterium organophilum mutants affected in pyrroloquinoline quinone biosynthesis genes pqqE and pqqF by cloned Escherichia coli chromosomal DNA.
The hybrid plasmid pBGT3, a derivative of pLA2917 containing a 7.8-kb fragment of Escherichia coli DNA, was found to complement pqqE and pqqF mutants of Methylobacterium organophilum, both impaired in PQQ biosynthesis. The cloned fragment of E. coli DNA did not hybridize with DNA fragments containing pqqE or pqqF previously cloned from M. organophilum. Yet, in M. organophilum mutants, expression of pqqE and pqqF genes from E. coli resulted in a PQQ production estimated at 9-16% of the production observed in M. organophilum wild-type. The growth rate in methanol medium of the complemented M. organophilum mutants was about 60% of that of the wild-type.
Chromosomes, Bacterial↗
Mutants of Escherichia coli producing pyrroloquinoline quinone.
In glucose minimal medium a PTS- strain of Escherichia coli [delta (ptsH ptsI crr)] could grow slowly (doubling time, d = 10 h). When the population reached 5 x 10(6) to 2 x 10(7) cells ml-1, mutants growing rapidly (d = 1.5 h) appeared and rapidly outgrew the initial population. These mutants (EF mutants) do not use a constitutive galactose permease for glucose translocation. They synthesize sufficient pyrroloquinoline quinone (PQQ) to yield a specific activity of glucose dehydrogenase (GDH) equivalent to that found in the parent strain grown in glucose minimal medium supplemented with 1 nM-PQQ. Membrane preparations containing an active GDH oxidized glucose to gluconic acid, which was also present in the culture supernatant of EF strains in glucose minimal medium. Glucose utilization is the only phenotypic trait distinguishing EF mutants from the parent strain. Glucose utilization by EF mutants was strictly aerobic as expected from a PQQ-dependent catabolism. The regulation of PQQ production by E. coli is discussed.
Aerobiosis↗
[Evaluation of thyroid function after myocardial infarction].
The myocardial infarction (M.I.) constitutes an exemplary acute severe affection able to modifie hormonal concentrations. The total and unbound thyroid hormones, reverse T3 (rt3), TSH, and cortisolemia were determined in 24 patients during a period of 21 days in order to compare them to different markers of severity of MI. The initial phase of the disease is characterized by low concentrations of total and free T3 and high concentrations of rT3 combined with more often than not normal total and free T4 and TSH values contrasting with an increase in cortisol levels. The abnormalities were more pronounced the day after admission and then progressively amend. There are several statistic relationship between the marker of severity of MI and thyroid hormones. In the same way total T3 is all the more decreased especially since myoglobin, CPK-MB, ST amplitude and ventricle ejection fraction are more disturbed. Severe forms of MI induces a pseudo central thyroid insufficiency with low T3, low T4 and a tendency to TSH decrease. Total T3 blood levels may usefully contribute to the elaboration of an MI severity index.
Adult↗
Free triiodothyronine concentrations as measured by two one-step radioimmunoassays in nonthyroidal illness.
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Acute Disease↗
Analytical and clinical evaluation of a new one-step non-analogue radioimmunoassay for serum-free thyroxine.
We evaluated analytically and clinically the new one-step non-analogue free thyroxine (FT4) assay (Amerlex-MAB from Amersham), using a labelled monoclonal thyroxine-specific antibody as tracer, in comparison with the Gammacoat two-step FT4 kit (Baxter). Analytical performances of the new kit were excellent: within and between run coefficients of variation were less than 5% in the working range. Clinical sensitivities for hypo- and hyperthyroidism were comparable for both kits (FT4 Amerlex-MAB 95% confidence interval: 12-25 pM). When serum was supplemented with albumin we observed a slight decrease in FT4 values measured by both kits. When oleate was added to serum we noted a moderate increase with the Amerlex-MAB kit up to 10 mM oleate added and a much more marked increase with the two-step kit. Results obtained with patients from particular euthyroid populations, known to have low albumin or high free fatty acids concentrations or to have perturbed FT4 results when measured by an analogue-based method, agreed with those of the in vitro studies. With these patients the specificity of the Amerlex-MAB FT4 results was good but slightly decreased compared with the two-step FT4 method, except for heparin-treated patients who were all classified according to their euthyroidal status (17/17 instead of 13/17 with the two-step kit).
Antibodies, Monoclonal↗
Different sensitivity to anti-triiodothyronine autoantibodies of two direct radioimmunoassays of free triiodothyronine.
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Autoantibodies↗
In vitro and in vivo effects of increased concentrations of free fatty acids on free thyroxin measurements as determined by five assays.
To compare in vitro and in vivo effects of increased concentrations of free fatty acids (FFA) on free thyroxin (FT4) values, we measured FT4 in three pooled sera supplemented with oleate and in serum from 18 euthyroid patients before and after an infusion of fat emulsion (Intralipid). We used five FT4 RIA kits: two two-step methods [Gammacoat, Baxter (GC); Ria-gnost, Behring (RG)], two analog RIAs [Amerlex-M, Amersham (AM); Coat-Ria, BioMérieux (CR)], and one kit with labeled antibodies [Amerlex-MAB*, Amersham (AA)]. In vitro, at the maximum oleate addition of 5 mmol/L, FT4 increased when measured by the GC and RG kits, decreased by the AM kit, and showed no significant change by the CR and AA kits. In vivo, post-Intralipid, FFA concentrations rose significantly and the FT4 changes agreed with the results of the in vitro experiments, except for the RG kit, for which FT4 increased in only nine patients. We conclude that in vitro oleate addition is useful to predict the in vivo effect of increased FFA on FT4 values; moreover, in serum from euthyroid subjects with high concentrations of FFA, FT4 analyzed with the CR or AA kits should better agree with normal results for thyrotropin than FT4 values measured with the other kits.
Chromatography, Gas↗
Mutants of Methylobacterium organophilum unable to synthesize PQQ.
The phenotype of mutants unable to synthesize PQQ is analyzed for different categories of methylotrophic bacteria. The advantages offered by strains dissimilating methylamine through methylated amino-acids are discussed. In M.organophilum, 40% of the mutants unable to grow in methanol medium but with normal methylamine utilization, were affected in PQQ metabolism. The genetic properties of M. organophilum useful to study PQQ mutants are discussed, mainly the use of pSUP106 to create insertion mutations in the bacterial chromosome and to replace wild-type genes by modified genes. An example is given of the possibility to create R' plasmids containing large fragments of M.organophilum DNA. Some physiological properties of a PQQ mutant are described, regarding growth kinetics, PQQ uptake and accumulation.
Coenzymes↗
[Familial hyperthyroxinemia with dysalbuminemia: screening of 21,000 patients at the occasion of thyroid evaluation].
Serum samples from 21,342 patients undergoing evaluation of thyroid status were screened for familial dysalbuminemic hyperthyroxinemia (FDH) using a specific test based on the measure of charcoal uptake of 125I thyroxine (T4) from serum diluted 1:100 with addition of unlabelled 10(-6) M T4. We found 17 cases of FDH: a higher incidence (8:10,000) than previously reported in the general population (1:10,000). The results of thyroid function tests of patients with FDH are presented: total T4 concentration is increased in only 14 subjects; thyrotropin and free T4 measured by an immunoextraction method are the most useful assays to evaluate the clinical status of these patients.
Humans↗