The transcription factor GHF-1, but not the splice variant GHF-2, cooperates with thyroid hormone and retinoic acid receptors to stimulate rat growth hormone gene expression

When Staphylococcus aureus strain 8325 was grown at 30 degrees C and heat shocked at 40 degrees C the rate of cell autolysis in buffer with or without Triton X-100 was reduced. Treatment of growing cells with other agents (CdCl2, ethanol, NaCl) known to induce heat shock proteins also resulted in cells that showed a decreased rate of autolysis. Heat shocked cells showed lower rates of freeze-thaw autolysin activity on purified cell walls, and isolated crude cell walls from heat shocked cells had lower rates of autolytic activity compared to controls. No differences in the peptidoglycan hydrolase activity profiles of control and heat shocked cells were detected by renaturing sodium dodecyl sulfate polyacrylamide gel electrophoresis. It is proposed that autolysins are damaged by heat shock and their targeting to the cell wall is impaired, possibly by complexing with heat shock proteins, which may also inhibit autolysin activity. Heat shock also inhibited the autolytic activity of methicillin-resistant and related-susceptible strains, and the possible relationship of this to the expression of methicillin resistance is discussed.     

Tumor necrosis factor receptors in neuroblastoma SKNBE cells and their regulation by retinoic acid

The human neuroblastoma cell line SKNBE can be differentiated either by serum removal or by adding to the culture medium different morphogens, for instance, retinoic acid (RA), cyclic AMP derivatives, and phorbol esters. Both the differentiated and undifferentiated cells express the two types of membrane tumor necrosis factor (TNF) receptors (TNFRs) of 55 and 75 kDa (p55 and p75 TNFR, respectively) and also their soluble forms. After RA addition the number of the surface TNFRs per cell is increased approximately twofold, but the kinetics of expression are different, depending on the receptor type. The level of the mRNAs of 2.4 and 4.2 kb, which, respectively, encode the p55 and p75 TNFRs, is also increased during the time course of differentiation, and the kinetics of their expression are biphasic. In contrast, the number of TNFRs and the level of their encoding mRNAs remain unchanged after exposure of the cells to both a phorbol and a cyclic AMP derivative.     

Different functions for the thyroid hormone receptors TRalpha and TRbeta in the control of thyroid hormone production and post-natal development

Par-4 is a widely expressed protein that sensitizes both prostatic and non-prostatic cells to apoptosis. Constitutive- or regulated- overexpression of Par-4 caused a reduction in the levels of the anti-apoptotic protein Bcl-2. Replenishment of Bcl-2 levels abrogated susceptibility to Par-4-dependent apoptosis, suggesting that Par-4-mediated apoptosis requires downmodulation of Bcl-2 levels. The inverse correlation between Par-4 and Bcl-2 expression was recapitulated in human prostate tumors. Par-4 but not Bcl-2 was detected in the secretory epithelium of benign prostatic tumors and in primary and metastatic prostate cancers that are apt to undergo apoptosis. Moreover, xenografts of human, androgen-dependent CWR22 tumors showed Par-4 but not Bcl-2 expression. By contrast, androgen-independent CWR22R tumors derived from the CWR22 xenografts showed mutually exclusive expression patterns of Par-4 and Bcl-2. These findings suggest a mechanism by which Par-4 may sensitize prostate tumor cells to apoptosis.     

Cross-talk between retinoic acid and interferons: molecular mechanisms of interaction in acute promyelocytic leukemia cells

All-trans retinoic acid (ATRA) and interferons (IFNs) are active anticancer agents. ATRA is capable of inducing complete remission in acute promyelocytic leukemia (APL) patients, whereas IFNalpha is successfully used in the treatment of the stable phase of chronic myeloid leukemia. ATRA and IFNs have shown synergistic interactions in various experimental conditions and represent a potentially useful therapeutic combination in the treatment of various types of leukemias and solid tumors. The molecular basis of these interactions are poorly understood and need to be elucidated. In this review, we summarize a series of recent observations concerning the molecular mechanisms underlying the cross-talk between the intracellular pathways activated by ATRA and IFNs in APL cells. In APL blasts, IFNs regulate the expression of retinoic acid receptors, and ATRA, in turn, modulates the levels and the state of activation of members of the Jak-STAT second messenger pathway. This demonstrates a two-way interaction between ATRA and IFNs, which leads to cross-modulation of genes normally under the control of the retinoid and the cytokine. These data may be relevant in the context of a rational use of the combination between ATRA and IFNs in the clinical management of myeloid leukemias.     

Alpha1-adrenergic and dopaminergic receptors are involved in the anoretic effect of corticotropin-releasing factor in goldfish

This study investigates the noradrenergic and/or dopaminergic receptors subtypes involved in the anoretic action of CRF in goldfish. Agonists and antagonists of alpha1- and alpha2-adrenoceptors, and D1- and D2-dopaminergic receptors were intracerebroventricularly (i.c.v.) administered alone or in combination with CRF in the case of antagonists. Food intake and hypothalamic content of catecholamines and their metabolites were measured at 2 h postinjection. On one hand, alpha1-adrenergic receptor antagonist, but not alpha2, blocked the anoretic effect of CRF. Moreover, we found a blockade of CRF-induced anoretic action by pretreatment with specific D1- and D2-dopaminergic antagonists. On the other hand, the i.c.v. administration of CRF reduced hypothalamic norepinephrine (NE) and dopamine (DA) content, without modifications in their metabolism. Thus, our results suggest that the anoretic effect of CRF appears to be mediated by alpha1-adrenergic and dopaminergic receptors in fish. Second, the reduction in hypothalamic NE and DA synthesis could be due to a direct effect of CRF treatment and/or a secondary effect of food intake reduction.     

Correlation between urinary epidermal growth factor excretion and serum thyroid hormone in premature and term neonates

We investigated a possible causal relation between exposure to organic solvents in Danish workers (housepainters, typographers/printers, carpenters/cabinetmakers) and onset of multiple sclerosis. Data on men included in the Danish Multiple Sclerosis Register (3,241 men) were linked with data from the 1970 census from the National Bureau of Statistics in Denmark, which has data on occupational status for 1,768,846 men between 15 and 74 years of age. From this census, we ascertained a group of 124,766 "solvent-exposed" men and an "unexposed" group of 87,501 male electricians, bricklayers, and butchers. Over a follow-up period of 20 years, we observed no increase in the incidence of multiple sclerosis among men presumed to be exposed to organic solvents. It was not possible to obtain data on potential confounders, and the study design has some potential for selection bias. Nevertheless, the study does not support existing hypotheses regarding an association between occupational exposure to organic solvents and multiple sclerosis.