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The present study extended laboratory-based findings of demand-withdraw communication into marital conflict in the home and further explored its linkages with spousal depression. U.S. couples (N = 116) provided diary reports of marital conflict and rated depressive symptoms. Hierarchical linear modeling results indicated that husband demand-wife withdraw and wife demand-husband withdraw occurred in the home at equal frequency, and both were more likely to occur when discussing topics that concerned the marital relationship. For both patterns, conflict initiator was positively linked to the demander role. Accounting for marital satisfaction, both demand-withdraw patterns predicted negative emotions and tactics during marital interactions and lower levels of conflict resolution. Spousal depression was linked to increased likelihood of husband demand-wife withdraw.

Guided by a family stress perspective, we examined the hypothesis that discussing money would be associated with the handling of marital conflict in the home. Analyses were based on dyadic hierarchical linear modeling of 100 husbands' and 100 wives' diary reports of 748 conflict instances. Contrary to findings from previous laboratory-based surveys, spouses did not rate money as the most frequent source of marital conflict in the home. However, compared to non-money issues, marital conflicts about money were more pervasive, problematic, and recurrent, and remained unresolved, despite including more attempts at problem solving. Implications for professionals who assist couples in managing their relationships and family finances are discussed.

Extending research based on newlywed couples, this study investigated longitudinal associations between marital satisfaction and depressive symptoms in a community sample of 296 couples in established relationships (M = 13.25 years, SD = 5.98) with children (M age = 11.05 years, SD = 2.31). Support was found for reciprocal relations between marital satisfaction and depressive symptoms in couples with established relationships. Further extending previous work, the study showed that relationship length and hostile marital conflict were significant moderators of these linkages. Husbands in longer term relationships were more vulnerable to depressive symptoms in the context of marital problems compared with husbands in shorter term relationships. At higher levels of marital conflict, the negative relationship between marital satisfaction and depressive symptoms was strengthened. Reflecting an unexpected finding, increased conflict buffered spouses from marital dissatisfaction in the context of depressive symptoms., (Copyright 2008 APA, all rights reserved.)

This study addresses multiple gaps in understanding the implications of marital conflict resolution for children. Mothers' diary home reports (N = 102 mothers, N = 578 reports) of marital conflict resolution (i.e., compromise, apology, submission, agreement to disagree, withdrawal) and of children's responses, along with the reactions of children (N = 163) to analogue presentations of the same conflict endings in the laboratory, were examined. The significance of specific marital conflict endings, including the emotionality of endings, was supported and demonstrated for the first time in the home. Parents' and children's appraisals of resolution were generally similar, although for some endings these appraisals differed, supporting the notion that children are sensitive to the broader implications of conflict endings for interparental relations and family functioning. Children's responses to conflict resolution were related to their broader adjustment, further indicating the significance of conflict endings to understanding the impact of marital conflict.

To elucidate the processes that underlie the established association between psychopathology and marital functioning, researchers have given attention to how symptomatic individuals manage their interpersonal contexts, particularly during the handling of disagreements. In the current study, the authors evaluate the role of marital conflict strategies in relation to wives' and husbands' psychological distress levels. A sample of 100 community-based couples completed assessments of psychological distress and diaries describing marital conflict that occurred at home during a 15-day reporting period. Findings from multilevel modeling of dyadic data revealed associations between both spouses' psychological distress and multiple behavioral and emotional conflict expressions in the home. Psychological symptoms uniquely predicted the occurrence of certain conflict expressions, even when accounting for global negative marital sentiments. The findings encourage subsequent consideration of marital conflict expressions and resolution strategies when studying processes involved in the marriage-psychological adjustment link., (PsycINFO Database Record (c) 2007 APA, all rights reserved)

Children's immediate aggressive responding to exposure to marital conflict was examined. Participants were 108 families with 8- to 16-year-old children (53 boys, 55 girls), with diary records of children's reactions to marital conflict in the home completed by 103 mothers (n = 578 records) and 95 fathers (n = 377 records) during a 15-day period. Child responses to analog presentations of marital conflict tactics were also obtained. Exposure to destructive conflict tactics and negative parental emotionality increased the likelihood of aggressive behavior in children when they witnessed marital conflict, whereas constructive conflict tactics and positive parental emotionality decreased the probability of aggression. Conflict topics presumed to be threatening to the child (child- or marital-related) also heightened the likelihood of aggression. Aggressive responding to conflict in both home and laboratory predicted externalizing behavior problems. Fathers' and mothers' separate diary reports, and child responses to analog presentation of conflict, provided generally consistent findings. An exposure hypothesis for marital conflict as an influence on child aggression is discussed.

This study investigated relations between spouses' dysphoria and constructive and destructive emotions and tactics displayed by husbands and wives throughout marital conflicts. Behavioral observations were made of 267 couples' interactions during marital conflict resolution tasks. Husbands' and wives' dysphoria levels were related to particular negative marital conflict expressions and the absence of positive strategies, even after taking into account couples' marital satisfaction and their partners' levels of dysphoria. Moreover, in comparison with wives' dysphoria, husbands' dysphoria was associated with more pervasive impairments in couples" conflict strategies evident in multiple contexts of conflict resolution, including discussion of relatively minor sources of disagreement. Implications for the treatment of depressed or maritally discordant couples are discussed.

Mothers' and fathers' reports of marital conflicts in the home were obtained (n = 1,638 and 1,281 conflicts, respectively), including conflicts in front of the children (n = 580 and 377, respectively). Participants were 116 families with children 8 to 16 years old (M = 10.82 years, SD = 2.17; 58 boys, 58 girls). Children's emotional responses indicated distinctions between distressing conflict tactics (i.e., threat, personal insult, verbal hostility, defensiveness, nonverbal hostility, marital withdrawal, physical distress) and those that increased their emotional security (i.e., calm discussion, support, affection). Analyses based on cross-reporter informants of parental conflict and child responses strengthened confidence in the findings. Conflict tactics were related to marital functioning, and children's emotional reactions during marital conflicts were associated with their adjustment.

Addressing a gap in methodological approaches to the study of links between marital conflict and children, 51 couples were trained to complete home diary reports on everyday marital conflicts and children's responses. Parental negative emotionality and destructive conflict tactics related to children's insecure emotional and behavioral responses. Parental positive emotionality and constructive conflict tactics were linked with children's secure emotional responding. When parents' emotions and tactics were considered in the same model, negative emotionality was more consistently related to children's negative reactions than were destructive conflict tactics, whereas constructive conflict tactics were more consistently related to children's positive reactions than parents' positive emotionality. Differences in children's responding as a function of specific parental negative emotions (anger, sadness, fear) and parent gender were identified.

Characteristics of marital conflict when children (8-16 years) were present versus absent were compared on the basis of 47 mothers' and fathers' reports during a 15-day period. Mothers described 669 incidents of marital conflict, and fathers described 551 incidents. About two thirds of the conflicts occurred in children's absence. Contrary to predictions, conflicts in which children were present were more negative (e.g., more negative emotions, more destructive conflict tactics) and more often about children than were child-absent conflicts. Although parents may attempt to protect children from conflict exposure, children tend to be exposed to a relatively hostile and emotionally negative subset of the marital conflicts that occur in the home.

(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), is a bis-naphthalimide anticancer tumoricidal agent currently in phase I clinical trials. DMP 840 exhibits curative activity in human tumor xenografts, where it shows selectivity for human solid tumors over murine leukemias. In contrast to the selectivity found for DMP 840 in vivo, DMP 840 exhibits potent antiproliferative activity in vitro against a variety of human and murine leukemia and solid tumor cell lines in culture, with inhibitory doses that reduce the number of treated cells to one half (IC50) values ranging from 2.3 to 53 nM. DMP 840 was growth inhibitory to three doxorubicin-resistant cell lines with IC50 values also in the nanomolar range. Clonogenic survival experiments showed that DMP 840 was equally cytotoxic to both exponentially growing and quiescent human clone A colon carcinoma cells. A 1-h incubation of DMP 840 (1.22-12 microM) caused 5-log cell kill in KB-3-1 human epidermoid carcinoma, clone A human colon carcinoma, and L1210 murine leukemia cell lines. The rapid cell killing by DMP 840 in clonogenic survival experiments and initial mechanism of action studies was consistent with a DNA-interactive mechanism for DMP 840 cytotoxicity. Mechanism of action studies in L1210 leukemia cells demonstrated that DMP 840 inhibited the incorporation of thymidine and uridine into DNA and RNA with IC50 values of 0.55 and 0.08 microM, respectively. DMP 840 produced DNA single-strand breaks in a dose-dependent manner. Double-strand breaks were not observed with DMP 840 treatment, even at higher concentrations of compound. Chinese hamster ovary (CHO) and P388 cells resistant to camptothecin and containing a mutant form of topoisomerase I were also used to evaluate whether DMP 840 was cross-resistant with agents active against topoisomerase I. While the CHOR line was 163-fold resistant to camptothecin, the CHOR line was only 1.7-fold resistant to DMP 840. In summary, DMP 840 is a DNA-interactive agent that demonstrates excellent antiproliferative activity in vitro against cultured tumor cells from both human and murine sources. Its mechanism of tumoricidal activity may be novel.

The novel anticancer drug candidate brequinar sodium (DuP 785, NSC 368390, 6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinoline- carboxylic acid sodium salt) was shown previously to be an inhibitor of dihydroorotate dehydrogenase, the fourth enzyme of the de novo pyrimidine biosynthetic pathway. Brequinar sodium inhibits the activity of this enzyme isolated from mammalian sources only but not those forms isolated from yeast or bacteria, which also use ubiquinone as the cofactor. Brequinar sodium also does not inhibit the activity of a soluble Zymobacterium oroticum dihydroorotate dehydrogenase which uses NAD+ as a cofactor. Brequinar sodium inhibits L1210 dihydroorotate dehydrogenase with mixed inhibition kinetics with respect to either the substrate (dihydroorotate) or the cofactor (ubiquinone Q6) with Ki' values in the 5-8 nM range. Our results suggest that brequinar sodium inhibits dihydroorotate dehydrogenase by binding to the enzyme at a unique site that is distinct from the dihydroorotate or the ubiquinone-binding site. This binding site appears to be unique to the mammalian enzyme, because brequinar sodium does not inhibit the yeast, Escherichia coli, or Z. oroticum forms of the enzyme.

The novel anticancer drug candidate brequinar sodium [DuP 785, NSC 368390, 6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinoline carboxylic acid sodium salt] inhibits dihydroorotate dehydrogenase, the fourth enzyme in the de novo pyrimidine biosynthetic pathway leading to the formation of UMP. Sixty-nine quinoline 4-carboxylic acid analogs were analyzed as inhibitors of L1210 dihydroorotate dehydrogenase. This structure-activity relationship study identified three critical regions of brequinar sodium and its analogs, where specific substitutions are required for the inhibition of the activity of dihydroorotate dehydrogenase. The three principal regions are: (i) the C(2) position where bulky hydrophobic substituents are necessary, (ii) the C(4) position which has a strict requirement for the carboxylic acid and its corresponding salts, and (iii) the benzo portion of the quinoline ring with appropriate substitutions. These results will be useful in the elucidation of the precise nature of the interaction between brequinar sodium and dihydroorotate dehydrogenase.