PubMed Health⌕ Search

Biomedical subjects

J Lazarus

Publications and source records attributed to J Lazarus.

At least 37 records · Page 2Linked to original sources
PubMed1998

A role for helix 3 of the TRbeta ligand-binding domain in coactivator recruitment identified by characterization of a third cluster of mutations in resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) has hitherto been associated with thyroid hormone beta receptor (TRbeta) mutations which cluster in two regions (alphaalpha 310-353 and alphaalpha 429-461) of the hormone-binding domain and closely approximate the ligand-binding cavity. Here, we describe a third cluster of RTH mutations extending from alphaalpha 234-282 which constitute a third boundary of the ligand pocket. One mutant, T277A, exhibits impaired transactivation which is disproportionate to its mildly reduced ligand affinity (Ka). T3-dependent recruitment of coactivators (SRC-1, ACTR) by mutant receptor-RXR heterodimers was reduced in comparison with wild-type. Cotransfection of SRC-1 restored transactivation by T277A. In the TRbeta crystal structure this helix 3 residue is surface-exposed and is in close proximity to residues L454 and E457 in helix 12 which are known to be critical for coactivator interaction, suggesting that they all constitute part of a receptor-coactivator interface. The transcriptional function of other mutants (A234T, R243W/Q, A268D, Delta276I, A279V, R282S) in this cluster correlated with their reduced Ka and they inhibited wild-type TRbeta action in a dominant negative manner. DNA binding, heterodimerization and corepressor recruitment were preserved in all mutants, signifying the importance of these attributes for dominant negative activity and correlating with the absence of natural mutations in regions bordering the third cluster which mediate these functions.

Amino Acid Sequence↗
PubMed1998

Interleukin-6 levels are not increased in women with postpartum thyroid dysfunction.

Postpartum thyroid dysfunction (PPTD) is an autoimmune-mediated thyroid destructive process. Human interleukin-6 (IL-6) is a cytokine found to be increased in subacute thyroiditis, amiodarone-induced thyrotoxicosis, Graves' disease, and other thyroid destructive processes. We report serum IL-6 levels in PPTD in two independent studies. New York Study: In a previous prospective study we demonstrated that PPTD occurred in 25% (7/28) of women with type 1 diabetes mellitus. IL-6 determinations were made on the frozen serum samples of these 28 women during each trimester of their pregnancy and at 1.5, 3, 6, 9, and 12 months postpartum. IL-6 levels were found to be similar in women with PPTD compared with women without PPTD (mean 3.06+/-2.25 vs. 2.51+/-2.21 pg/mL; p = 0.15). No difference in IL-6 levels was found between the pre- and the postpartum periods (mean 2.67+/-1.82 vs. 3.04+/-2.44 pg/mL; p = 0.30) in all 28 women. Cardiff Study: Serum IL-6 levels were measured on frozen serum samples of 30 women with PPTD. IL-6 levels were below the detection limit (25 fmol/L or 0.65 pg/mL) in 94 (67%) of these samples. No significant difference in the mean serum IL-6 levels were found between any time points in the study. There was no correlation between serum IL-6 levels, thyroid peroxidase (TPO)- antibodies and serum thyrotropin (TSH) levels at any time point. IL-6 levels during pregnancy or postpartum were not found to be significantly different in women with PPTD compared with women without PPTD.

Adult↗
PubMed1998

A comparison of the performance of rating scales used in the diagnosis of postnatal depression.

The results of a study looking into the association between thyroid status and depression in the postpartum period were reanalysed to explore the psychometric properties of the rating scales employed. The performance of the Edinburgh Postnatal Depression Scale was found to be superior to that of the Hospital Anxiety and Depression Scale in identifying RDC-defined depression, and on a par with the observer-rated Hamilton Rating Scale for Depression, which it also matched for sensitivity to change in mood state over time. The anxiety subscale of the Hospital Anxiety and Depression Scale performed well, reflecting the fact that anxiety represents a prominent symptom in postnatal depression.

Adult↗
PubMed1997

Free food or earned food? A review and fuzzy model of contrafreeloading

Animals will work (e.g. lever press) for 'earned' food even though identical 'free' food can easily be obtained from a nearby dish. This phenomenon, called contrafreeloading, appears to contradict a basic tenet of most learning, motivation and optimal foraging theories; namely that animals strive to maximize the ratio of reward, or benefit, to effort, or cost. This paper reviews the factors that have been found to affect the level of contrafreeloading, to try to explain the behaviour. In experiments involving intensive training, contrafreeloading may be explained on the basis of secondary reinforcement and/or differential exposure to the alternative food sources. However, contrafreeloading also occurs without prior training. Contrafreeloading declines with increasing hunger and with increases in the effort required to obtain the earned food: it also has an inverted-U relationship with the degree of stimulus change associated with the earned food. A fuzzy logic model is developed to predict the outcome of interactions between these factors. The model successfully simulates previous empirical findings and provides novel, testable predictions. It is argued that contrafreeloading does not contradict reinforcement theory, provided that the sensory reinforcement obtained from stimuli associated with the earned food is also taken into account. A functional explanation of why such stimuli are reinforcing, and of contrafreeloading itself, is based upon the advantage of gathering information for animals living in changing environments (i.e. an information primacy model). Animals work for earned food in order to update their estimate of a currently sub-optimal food source because, in the longer term, it may unpredictably become the optimal place to feed. Contrafreeloading is therefore a behaviour that, under natural conditions, is adaptive.

Journal Article↗
PubMed1995

Cognitive function, thyroid status and postpartum depression.

Impairment of cognitive function can occur with thyroid disorder and also with depression. Since depression occurs in conjunction with postpartum autoimmune thyroiditis, the question arises as to whether any impairment of cognitive function in postpartum women is related to change in thyroid status or to depressed mood. A total of 242 women (110 thyroid antibody-positive and 132 antibody-negative) were assessed at 8, 12, 20 and 28 weeks postpartum in the outpatients of a district general hospital. Thyroid antibody levels (antimicrosomal and antithyroglobulin) were monitored at monthly intervals, together with plasma T3, T4 and thyroid-stimulating hormone. The main outcome measures were Research Diagnostic Criteria for depression, the 17-item Hamilton Depression Rating Scale and the Edinburgh Postnatal Depression Scale, together with reaction time and digit span. Subjects with postnatal depression showed detectable cognitive impairment independent of thyroid antibody status and actual thyroid dysfunction.

Antibodies↗