Circadian rhythms, cyclic fluctuations in many physiological and psychological functions, are thought to influence adjustment to shiftwork. A widely acknowledged individual difference in circadian rhythms, commonly called morningness, indicates preferences associated with morning or evening activities. Various self-report instruments have been developed to measure morningness, although little measurement data have been published for these scales. Because morningness scales are being used to select workers for night shiftwork, psychometric evaluations of these scales are needed. Psychometric assessments of undergraduate responses (N = 501) on three widely used scales indicate internal (interitem) measurement deficiencies in all three. Therefore, a 13-item scale was developed that distills the best items from two of these scales. Relationships between the new composite scale and external criteria are comparable with or stronger than similar relationships between the published scales and external criteria.
Thyrotoxic patients treated with Iodine-131 (131I) often present with low thyroxine (T4), normal triiodothyronine (T3) and raised thyrotropin (TSH) concentrations in serum. We have developed a rat model of this low T4, raised TSH state. Rats were injected with 50, 150 or 450 mu Ci 131I. A dose of 50 mu Ci 131I caused no significant effect on thyroid function, as assessed by serum parameters whereas both 150 mu Ci and 450 mu Ci 131I caused a significant fall in serum T4 concentration accompanied by a significant rise in TSH concentration. In all groups serum T3 concentration was not significantly altered when compared to controls. The clearance of 131I from the rats showed a single exponential curve (t 1/2 3.38 +/- 0.61 days) over the range of 131I doses used. Differing body weights had no effect on the serum T4 changes induced by 131I.
The expected decreases of serum total T4, total T3, T4 binding prealbumin, and T4 binding globulin (TBG) concentrations were found in a selected series of patients with nonthyroidal illnesses (NTI). An increase in percent dialysable fraction of T4 was also found. Although serum TBG concentrations were decreased, the proportion of a slow moving form of TBG, designated slow TBG (STBG) was increased, the absolute concentration being not significantly different from that measured in controls. Thus the observed decrease in TBG in NTI occurs in the normal TBG fraction which binds T4 much more avidly than does STBG. It is suggested that the increase in the proportion of STBG, due to a decrease in normal TBG, has an important role in the pathogenesis of the increase in percent dialysable fraction of T4 in serum from patients with NTI.
Severe nonthyroidal illnesses have been associated with increases in nonesterified fatty acids (NEFA) and the dialyzable fraction of thyroxin (T4) in plasma. We have further investigated their possible relationship in severe nonthyroidal illnesses as well as in induced in vivo and in vitro situations involving increased NEFA. We demonstrate that there is no relationship between NEFA and the dialyzable fraction of T4, either in severe nonthyroidal illnesses or in the other situations, unless plasma NEFA concentrations exceed 5 mmol/L in normal persons or 1.7 mmol/L in nonthyroidal illnesses, and that this concentration was not reached in the patients we studied, with one exception. We conclude that NEFA are unlikely to contribute to an inhibition of the binding of T4 to the binding proteins that might be present in plasma of patients with severe nonthyroidal illnesses unless their NEFA concentrations are very high.
The Amerlex Free Thyroxin (T4) Radioimmunoassay Kit (Amersham International Ltd.) is a new direct equilibrium radioimmunoassay for free T4 based on an antiserum with very high affinity for T4, and a unique 125I-labeled T4 analog as tracer. It is a very simple single-tube radioimmunoassay, making use of Amerlex particles to separate antibody-bound from free species. Interassay precision (CV) is 3.7% at 13 pmol/L and 2.3% at 30 pmol/L; within-assay precision is 4.2% at 21 pmol/L. The reference interval is 11-22 pmol/L. The assay did not misclassify any patients tested who had untreated myxedema or untreated thyrotoxicosis. The free T4 assay excelled both the free T4 index and the T4/T4-binding globulin ratio in correcting for increased thyroxin-binding globulin from pregnancy, and it was better than the index but not better than the ratio in correcting for increased thyroxin-binding globulin in users of oral contraceptives.
SUMMARY. The measurement of serum free T4 (FT4) by analogue methods has been severely criticised because the T4 analogue binds to albumin. Amersham have recently introduced a method utilising horseradish peroxidase-labelled-T4 (HRP-T4) designed to overcome this problem and have incorporated it into the Amerlite enhanced luminescence immunoassay system. We have critically evaluated this method for its analytical and clinical validity.Experiments in which anti-albumin was added to normal serum suggested that the HRP-T4 label did not bind to endogenous albumin while the addition of albumin caused no significant change in FT4 concentration. Adding oleic acid up to 5 mmoljL to simulate increased non-esterified fatty acid concentration did not increase the apparent FT4.Serum sampled from subjects independently allocated to clinical groups were compared with an euthyroid group. The untreated hyperthyroid group values were distinctly elevated while the untreated hypothyroid group were appropriately low. Oestrogen therapy, low TBG, familial dysalbuminaemic hyperthyroxinaemia and non-thyroidal illness groups all reflected their euthyroid status, as did pregnancy samples which also showed a tendency to lower values in late pregnancy, consistent with previous observations.In conclusion, the Amerlite FT4 method appears to overcome some of the problems associated with analogue methods. A small survey showed it to be diagnostically valid in a wide variety of clinical states.The measurement of serum free T4 (FT4) concentration, which has long been advocated as a useful test of thyroid function, became more practical as a routine procedure with the development of the antibody-coated tube method! followed by the labelled T4 analogue technique.' It was claimed that the T4 analogue did not compete with any of the bound T4 moieties for T4 antiserum. However, serious objections to this claim were raised both on practical! and theoretical" grounds. The binding of the analogue to serum albumin in particular, caused major inherent problems in the analogue kits.Recently Amersham International pic (Aylesbury, UK) have released a new method for FT4 in association with the Amerlite immunoassay system. With the problems associated with the analogue methods in view, we have assessed the Amerlite FT4 for its methodological soundness and diagnostic performance. Materials and methods ANALYTICAL PROCEDUREThe FT4 method is performed on the Amerlite assay system which uses enhanced luminescence incorporating micro titre well technology with automatic washing, dose response assessment and data reduction. The Amerlite FT4 kit methodology is similar in concept to the analogue-type methods. In the analogue methods, a radioactively labelled analogue of T4 is used which is designed to bind to anti-T4 antibodies with an affinity equal to T4 but not to bind to the serum binding proteins. By contrast, the Amerlite FT4 system uses horseradish peroxidase (HRP)-eonjugated T4 in place of an analogue. The HRP is said to prevent the conjugated T4 from attaching 517
Hepatic iron content is increased in patients with PCT and phlebotomy-induced iron depletion corrects the clinical and biochemical phenotype. Approximately 20 percent of patients with PCT are homozygous for mutations of the hemochromatosis gene (HFE) but the cause of iron overload in most patients is unknown. Hepatic URO-D activity is markedly reduced when PCT is manifest and URO-D activity improves following iron depletion. Most patients with PCT have no mutations of the URO-D gene (sporadic PCT) but approximately 1/3 of cases are heterozygous for URO-D mutations (familial PCT) (BLOOD. 2000; 95:1565–71). To determine the mechanism by which iron overload causes PCT we created 3 murine models: Mice with one null allele of Uro-d (Uro-d+/−) and 2 null Hfe alleles (Hfe−/ −) (PNAS.2001; 98:259–64); Uro-d+/− mice treated with iron-dextran, aminolevulinic acid (ALA) and polychlorinated biphenyls (PCB) and; wild type mice treated with iron, ALA and PCB (J. Biochem. Mol. Toxicol.2001; 15:287–93). All models accumulate uroporphyrin in the liver and all have hepatic URO-D activity of 25% or less but Western blots revealed no change in URO-D protein. An iron deficient diet prevented the PCT phenotype in Uro-d+/−, Hfe−/ − animals and greatly attenuated the phenotype in animals treated with ALA and PCB (Env. Toxicol. Pharmacol.2005; 417–23). Liver homogenates from all porphyric models were heat denatured and clarified by centrifugation. The supernatants inhibited the activity of purified recombinant human URO-D (rhURO-D) by approximately 60%. The inhibitory activity was further purified by solid phase extraction and HPLC. The fraction containing the inhibitory activity did not fluoresce. Mass spectrometry of this fraction demonstrated a dominant peak with a mass of 835 Da and an absorption maximum of approximately 500 nM, the optical signature of a porphomethene. An inhibitor with identical properties was generated by partially oxidizing the uroporphyrinogen (837 Da) substrate of URO-D under UV light. Full oxidation of either the inhibitor purified from porphyric mouse liver or from partially oxidized, enzymatically generated uroporphyrinogen (either isomer I or III) yielded a compound with a mass of 831 Da and an absorption maximum of approximately 400 nM, indicating that the fully oxidized inhibitor was uroporphyrin. Tandem mass spectrometry of the 835 Da inhibitor indicated that the inhibitor was a tetrapyrrole. Collectively these data indicate that the inhibitor is a porphomethene derived form uroporphyrinogen through oxidation of a single bridge carbon between adjacent pyrrole rings. An inhibitor of rhURO-D was also identified in heat-denatured cytosol from liver biopsy samples obtained from four humans with PCT. We conclude that clinical expression of PCT requires an iron dependant oxidation reaction that generates a porphomethene inhibitor of URO-D.
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