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The early response genes comprising the AP-1 and NF-κB transcription factors are induced by environmental stress and thought to modulate responses to injury processes through the induction of target genes. Exposure to heat and ionizing radiation (IR) has been shown to affect signalling machinery involved in AP-1 and NF-κB activation. Furthermore, regulation of the signalling pathways leading to the activation of these transcription factors has been linked to changes in intracellular oxidation/reduction (redox) reactions. The hypothesis is proposed that exposure to thermal stress and/or IR might alter metabolic processes impacting upon cellular redox state and thereby modify the activity of redox-sensitive transcription factors such as AP-1 and NF-κB. Gel electromobility shift assays (EMSA) demonstrated that heat shock-induced AP-1 DNA-binding activity but inhibited IR-induced activation of NF-κB. A time course showed that activation of the AP-1 complex occurs between 4 and 5 h following thermal stress, and inhibition of IR-induced NF-κB activation also occurs during this time interval. Using a redox-sensitive fluorescent probe [5-(and -6)-carboxy-2′,7′-dichlorodihydrofluorescein diacetate], a shift to 40% less intracellular dye oxidation was observed in HeLa cells 0-4 h post-heat shock (45°C, 15 min) relative to cells held at 37°C. This was followed by a shift to greater dye oxidation between 4 and 12 h after treatment (about 1.8-fold) that returned to control levels by 24 h post-heating. These results show changes in DNA-binding activity closely paralleled apparent heat-induced changes in the intracellular redox state. Taken together, these results provide correlative evidence for disruption of redox-sensitive IR-induced signalling pathways by heat shock and support the hypothesis that this mechanism might play a role in heat-induced alterations in radiation response. [ABSTRACT FROM AUTHOR]

Purpose : Abnormally high levels of the cyclooxygenase (COX)-2 isozyme as well as the prostaglandin metabolites produced by the COX pathway have been observed in a variety of malignancies, including cancers of the skin, pancreas, colon, breast, cervix, prostate, and head and neck. Furthermore, exogenous genotoxic agents, including ionizing radiation (IR), have been shown to induce cellular transformation and to elevate COX-2 activity, whereas exposure to agents that specifically inhibit COX-2 activity have been shown to inhibit transformation. These data suggest a possible role of COX-2 both in IR-mediated cellular transformation processes and cell death. Materials and methods : C3H 10T1/2 and/or HeLa cells were treated with N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) and/or exposed to IR. Following treatment, cells were assayed for neoplastic transformation, clonogenicity, growth rates, cell cycle distribution, micronuclei formation and DNA damage by established methodologies. Statistical tests were performed on data as described. Results : In the present study, experiments in normal murine fibroblast C3H 10T1/2 cells demonstrated that the chemical inhibition of COX-2 activity with moderate doses of NS-398 abrogated IR-induced transformation events by fourfold and protected irradiated C3H 10T1/2 cells from clonogenic cell death. Considering that these doses of NS-398 had no significant effect on cellular proliferation or cell cycle distribution in C3H 10T1/2 cells, the results suggest that inhibition of COX-2 either increases DNA repair or prevents the accumulation of DNA damage. In supplemental experiments, treatment with NS-398 caused a 1.5-fold reduction in IR-induced micronuclei formation and a significant decrease in DNA damage. Conclusions : These results suggest a role for COX-2 inhibitors in the normal tissue response to IR when administered at therapeutically achievable doses and therefore may have clinical implications for radiation oncology patients in the prevention of IR-induced malignancy. [ABSTRACT FROM AUTHOR]

A structural equation model (SEM) examined interrelationships among psychosocial variables known to affect the health and development of well siblings and parents when a child with a chronic illness or disability is a member of the family. Using dyads of 252 well children and parents, socioeconomic status (SES) and family cohesion were associated with the parent-reported behavior of the well sibling. SES also influenced the mood of the mother that in turn influenced family cohesion. The well sibling's knowledge about the illness of the brother or sister, attitude toward the illness, mood, self-esteem, and feelings of social support were interrelated and related to the behavior of the well sibling. The SEM suggests that interventions may be directed at several points in these interactions including boosting knowledge levels of the well sibling, improving family cohesion, and assuring adequate 'income' support to the family through income transfers or in-kind services. [ABSTRACT FROM AUTHOR]

Cartilage extracts with affinity for heat aggregated immunoglobulins were prepared from human articular and bovine nasal cartilage. These extracts, containing predominantly collagen, also bound both to immune complexes (IC) prepared in vitro and to immunoglobulins from sera of many patients with rheumatoid arthritis (RA). Cryoprecipitation of rheumatoid sera removed material reacting with the extract and density gradient fractionation of a positive serum showed correlation between binding to the extract and to Clq. These results indicate that the binding materials in rheumatoid sera were likely to be IC. We suggest that some assays which apparently demonstrate anti-collagen auto antibodies in fact measure IC. These findings also have implications for models of the pathogenesis of RA. [ABSTRACT FROM AUTHOR]

There is much fuzzy thinking and confusion going on at the present time regarding the proper recognition of investment income in the fire and casualty rate making process. Many suggestions have been made for bringing recognition of investment income directly into the various rate making formulae. This approach is fallacious. It considers only a fragment of the over-all matter--the total financial needs of the insurer. Every well managed company periodically reviews its total financial needs and estimates the proportions of this total that can be acquired from the various sources of funds--additions to risk capital (or the equivalent), residue from premiums written, and income from investments. To the extent that income from investments contributes to these total financial needs, a lesser burden is placed on the rates charged. Thus, even though investment income is not directly entered into the rate formulae, it is considered in the rate making process. A bookkeeping entry transferring monies from one account to another does not change, one iota, the total financial needs of a company. It is imperative this concept be understood and appreciated. [ABSTRACT FROM AUTHOR]