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J Resch

Publications and source records attributed to J Resch.

13 recordsLinked to original sources

Lithium stimulates proliferation in cultured thyrocytes by activating Wnt/beta-catenin signalling.

BACKGROUND: Lithium, clinically used in the treatment of bipolar disorders, is well known to induce thyroid growth. However, the mechanism involved is only incompletely characterized. Although it is conventionally believed that thyroid proliferation depends on the thyroid-stimulating hormone (TSH)/cAMP/cAMP response element binding protein (CREB) pathway, recent data indicate that Wnt/beta-catenin signalling may be of critical importance. In other cell types lithium activates canonical Wnt signalling by GSK-3beta inhibition, which in turn stabilizes cytosolic free beta-catenin. Here we investigated the potential modulation of Wnt/beta-catenin signalling under lithium treatment in primary and neoplastic human thyrocytes. METHODS: Primary (S18) and neoplastic (NPA, FTC133) thyrocytes treated with and without LiCl were analysed using Western blotting, immunoprecipitation, reporter-gene assay, MTT proliferation assay and transfection studies. RESULTS: LiCl dose-dependently inhibited GSK-3beta, stabilized free beta-catenin and inhibited beta-catenin degradation. Furthermore, LiCl altered the assembly of adherens junction by upregulating the E-cad-herin repressor, Snail, and downregulated E-cadherin expression. At a dose of 5 mM, LiCl significantly increased the proliferative potency of thyrocytes, which appeared to be mediated by beta-catenin, since nuclear beta-catenin stimulated T-cell factor/lymphoid enhancer factor (TCF/LEF)-mediated transcription and upregulated downstream targets like cyclin D1. To characterize the specificity of Wnt/beta-catenin-driven thyrocyte proliferation, we transfected primary thyrocytes and FTC133 cells with dominant negative TCF4 to block Wnt-dependent pathways or with dominant negative CREB to inhibit the TSH/cAMP cascade. In cells transfected with dominant negative CREB lithium-stimulated proliferation was unchanged whereas blocking Wnt/beta-catenin by dominant negative TCF4 reduced proliferation by approx. 50%. CONCLUSION: Our data indicate that Wnt/beta-catenin signalling is of major importance in the control of lithium-dependent thyrocyte proliferation.

Blotting, Western↗

[Geographic distribution of multiple sclerosis and comparison with geophysical values].

This work is based on former investigations describing the similarity between the distribution of MS-frequency and solar particle rays. The analysis of the prevalence values shows clearly that the global MS-frequency is closer related to the geomagnetic than to the geographic latitude. This relation is best described by a Gaussian curve: in temperate latitudes the MS-frequency increases rapidly in pole direction and decreases again in pole-proximity. The MS-distribution shows a spatial relation to the distribution of solar particle rays and geomagnetic activity and to the external radiation belt of the earth. Further considerations are being made including the 11-year-sun-cycle.

Ecology↗

[Caries morbidity in infants and preschool children with reference to social factors of influence].

The caries frequency of 653 children between 2-4 years of age was followed up over 2 years. Only very few of two year old children showed a relative high incidence of caries. Among the 4 year old children the incidence of caries was particularly high. Caries is more prevalent among children who stay at home than among those attending créches. The difference is due to the absence or irregular use of fluoride tablets, to inadequate cleaning of teeth and a high consumption of sweets in the families. Pre-school children without siblings, and those whose parents are working in shifts, should more often undergo stomatological supervision because of their greater risk suspectibility to caries.

Child, Preschool↗

Biparental defensive endowment of eggs with acquired plant alkaloid in the moth Utetheisa ornatrix.

The eggs of Utetheisa ornatrix contain pyrrolizidine alkaloids. These compounds are contributed by both parents, who sequester them as larvae from their food plants. Females receive alkaloid from the males at mating, apparently by seminal infusion, and transmit this alkaloid together with alkaloid of their own to the eggs. Field and laboratory tests showed that the alkaloids protect eggs from predators. The alkaloidal contribution of the male, although smaller than that of the female, itself provides significant egg protection. A previously identified pheromone, derived by the male from the alkaloid and emitted during precopulatory behavior, may announce the male alkaloidal worth to the female.

Animals↗

Serum lipids and lipoproteins as predictors of atherosclerosis. An autopsy study.

A prospective study of autopsy-determined measures of atherosclerosis in aortas and coronary and cerebral arteries was completed for a group of 83 men who were free of clinical cardiovascular disease and cancer when they entered the Cooperative Lipoprotein Phenotyping Study in 1970. Total cholesterol minus high density lipoprotein cholesterol (HDL-C) was significantly associated with measures of atherosclerosis in all three groups of vessels. The patterns of associations for total, low density lipoprotein, and very low density lipoprotein cholesterol were similar but generally weaker and not significant for atherosclerosis in the cerebral arteries. Inverse associations of HDL-C with atherosclerosis in the circle of Willis and aorta were significant, but those for the coronary arteries were not. These associations were independent of other major risk factors for atherosclerosis in multivariate analyses. Similarities between these findings and those for clinical cardiovascular disease in the same cohort indicate that the opposing patterns of increased risk of clinical cardiovascular disease associated with total cholesterol and the decreased risk associated with HDL-C also exists at the level of atherosclerosis in a variety of arteries.

Aorta↗