Enhanced salt intake in oxytocin deficient mice.

The maternal roles of oxytocin (OT) are well known, but recent work suggests that OT is also a vital component in fluid balance regulation. To explore the role of OT in salt/volume regulation, we studied NaCl intake in a genetically modified mouse strain lacking OT. Using male control and OT knockout mice (OTKO), we determined the circadian pattern of salt and water intake under need-free conditions. For the study of intake, a two-bottle choice system was used to provide access to water and 2% NaCl with computerized monitoring of licking activity. Salt licking activity (licks/24 h) for controls was 59 +/- 22 vs. 380 +/- 105 in OTKO (P < 0.05). The volume of salt consumed (ml/24 h) was 0.4 +/- 0.1 in controls vs. 1.8 +/- 0.4 in OTKO (P < 0.01). There was no statistical difference in the consumption of water between the groups. However, the initiation of water intake was shifted, with an advancement of almost 3 h in OTKO (P < 0.01). Differences in the timing of salt intake could not be determined due to the low volume of salt consumed by controls. Taken together, these data show that removal of OT amplifies the salt-seeking behavior associated with normal daily fluid fluctuations. The fact that OTKO voluntarily consume a normally aversive salt solution further implies that OT is a powerful regulator of circadian salt appetite.

Object relations as a predictor of adjustment in conjugal bereavement.

The impact of object relations on adjustment in conjugal bereavement was examined. At approximately 6 months postbereavement, 46 midlife bereaved participants engaged in a narrative interview in which they were asked to discuss their past relationship with their deceased spouse. The Westen et al. object relations scoring system was applied to these narratives. Participants also completed depression and grief-specific symptom measures at 6 months and again at 14 and 25 months postbereavement. Object relations correlated differently with grief-specific symptoms and depression: it was more strongly negatively associated with 6 month postloss grief-specific symptoms while more strongly negatively correlated with depression at 25 month postloss. In a growth curve analysis, more mature object relations was also predictive of a faster rate of decrease in depression over time. The results were discussed in terms of current theoretical perspectives on what is required in successful adaptation to conjugal bereavement.

A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro.

In earlier studies, we provided statistical evidence that individual differences in the angiotensinogen gene, the precursor of the vasoactive hormone angiotensin II, constitute inherited predispositions to essential hypertension in humans. We have now identified a common variant in the proximal promoter, the presence of an adenine, instead of a guanine, 6 bp upstream from the initiation site of transcription, in significant association with the disorder. Tests of promoter activity and DNA binding studies with nuclear proteins suggest that this nucleotide substitution affects the basal transcription rate of the gene. These observations provide some biological insight about the possible mechanism of a genetic predisposition to essential hypertension; they may also have important evolutionary implications.

The physiological state as a modifier of radiation-induced cytotoxicity in heterogeneous murine tumor cells growing in vitro.

The oxic radiation response (cytotoxicity) of two heterogeneous murine tumor-cell lines cultured in vitro was studied as a function of the cell's physiological state at the time of X-irradiation. The proliferating (P) 66 and 67 cells displayed equal radiosensitivities; however, the quiescent (Q) cells were considerably more radiosensitive than the P cells, and the 66Q cells were even more radiosensitive than the 67Q cells. Also, the 66Q cells continued to proliferate slowly with about 85 per cent in the G1 phase and 10 per cent in the S phase, while the 67 Q cells displayed a more complete G1 arrest (92-95 per cent). A detailed analysis of the metabolic status vs cell-cycle age (i.e. G1 vs S phase) indicated that the cell-cycle age was the predominant factor influencing radiation-induced cytotoxicity in 67 cells. The data also showed that in the plateau phase Q-cell cultures, pH and cell contact were not influencing factors and that the increased radiosensitivity of the Q cells could not be explained on the basis of energy deprivation. Moreover, the 66Q, but not the 67Q cells displayed an increased sensitivity in addition to that caused by the predominant cell-cycle age shift. This extra increase in radiosensitivity is of unknown metabolic origin, but could be related to cellular membrane fragility in the stressed 66Q cells since this extra component of Q-cell radiosensitivity was reduced both by refeeding (metabolic activation) 4 h before X-irradiation and by delayed plating while incubating the cells in Q medium at 37 degrees C after X-irradiation.