Exploring the structure of strength-related attitude features: the relation between attitude importance and attitude accessibility.

One of the most significant current controversies in the attitude literature involves the latent structure of attitude attributes related to their strength. Four studies were conducted to explore whether 2 strength-related attributes (importance and accessibility) are affected identically by various manipulations (which would suggest that they reflect a single latent construct) and whether the attributes cause one another (which would suggest they are distinct constructs). Three laboratory experiments and I survey study show that (a) repeated expression and personal relevance manipulations have different effects on importance and accessibility and (b) increased importance can cause heightened accessibility. Thus, these 2 attitude attributes appear to constitute related but independent constructs. These studies therefore help to illuminate the nature of attitude strength and the interplay of its sources.

Survey research.

For the first time in decades, conventional wisdom about survey methodology is being challenged on many fronts. The insights gained can not only help psychologists do their research better but also provide useful insights into the basics of social interaction and cognition. This chapter reviews some of the many recent advances in the literature, including the following: New findings challenge a long-standing prejudice against studies with low response rates; innovative techniques for pretesting questionnaires offer opportunities for improving measurement validity; surprising effects of the verbal labels put on rating scale points have been identified, suggesting optimal approaches to scale labeling; respondents interpret questions on the basis of the norms of everyday conversation, so violations of those conventions introduce error; some measurement error thought to have been attributable to social desirability response bias now appears to be due to other factors instead, thus encouraging different approaches to fixing such problems; and a new theory of satisficing in questionnaire responding offers parsimonious explanations for a range of response patterns long recognized by psychologists and survey researchers but previously not well understood.

Development of attitude strength over the life cycle: surge and decline.

This article explores the relation of age to manifestations and antecedents of attitude strength. Three studies demonstrate that susceptibility to attitude change is greater during early and late adulthood than during middle adulthood. Three additional studies demonstrate that attitude importance, certainty, and perceived quantity of attitude-relevant knowledge are greater in middle adulthood than during early or late adulthood. These antecedents may therefore explain life cycle shifts in susceptibility to change. Susceptibility to change, importance, certainty, and perceived knowledge differ from one another in terms of their correlations with education, gender, and race, challenging the notion that attitude strength is a unitary construct. Evidence that people incorrectly believe that susceptibility to change declines steadily over the life course reinforces the distinction between operative and meta-attitudinal measures of attitude strength.

Origins of attitude importance: self-interest, social identification, and value relevance.

Five studies examined the relations between attitude importance and 3 of its hypothesized determinants: self-interest, social identification with reference groups or reference individuals, and cherished values. Verbal protocols, multivariate analysis of survey data, and laboratory experimentation revealed that (1) people's theories of the causes of attitude importance pointed to all 3 hypothesized predictors, (2) the 3 predictors each had significant, unique statistical associations with importance, and (3) a manipulation of self-interest yielded a corresponding change in importance. These results help clarify the nature and origins of attitude importance, challenge the widely believed claim that self-interest has little or no impact on political cognition, and identify new likely consequences of social identification processes and values.

Aging and susceptibility to attitude change.

Two hypotheses about the relation between age and susceptibility to attitude change were tested. The impressionable years hypothesis proposes that individuals are highly susceptible to attitude change during late adolescence and early adulthood and that susceptibility drops precipitously immediately thereafter and remains low throughout the rest of the life cycle. The increasing persistence hypothesis proposes that people become gradually more resistant to change throughout their lives. Structural equation models were applied to data from the 1956-1960, 1972-1976, and 1980 National Election Panel Studies in order to estimate the stability of political attitudes and unreliability in measures of them. The results support the impressionable years hypothesis and disconfirm the increasing persistence hypothesis. A decrease in the over-time consistency of attitude reports among 66- to 83-year-olds was found to be due to increased random measurement error in their reports, not to increased attitude change.

Augmentation of antitumor efficacy by the combination of recombinant tumor necrosis factor and chemotherapeutic agents in vivo.

We evaluated the in vivo antitumor effects of the combination of recombinant human tumor necrosis factor (rhTNF) and three chemotherapeutic agents in an established murine tumor model. C57BL/6 mice bearing a subdermal weakly immunogenic 3-methylcholanthrene-induced sarcoma (MCA-106) received one i.v. dose of cyclophosphamide (Cy) (100 mg/kg), doxorubicin (5 mg/kg), or 5-fluorouracil (75 mg/kg) on either Day 8, 10, or 12. All animals received one i.v. dose of rhTNF (4 or 6 micrograms/mouse) on Day 10. The most effective time for administration of the chemotherapeutic agent was determined to be 48 h following rhTNF administration of all agents tested. The combined results of four separate experiments evaluating tumor size on Day 28 following tumor inoculation revealed that the groups treated with 4 or 6 micrograms of rhTNF and Cy (on Day 12) had tumor size reductions of 70 and 94%, respectively, compared to untreated controls (P2 less than 0.005). Mice treated with Cy alone, or with 4 or 6 micrograms of rhTNF alone had tumor size reductions of 30, 35, and 41%, respectively, compared to untreated controls (P2 less than 0.02). Analysis of cure rates demonstrates that the combination of Cy with 4 or 6 micrograms tumor necrosis factor cured 35 and 48% of the animals, respectively (P2 less than 0.01), compared to 10, 0, and 14% of mice treated with single agent Cy, 4 micrograms rhTNF, or 6 micrograms rhTNF, respectively. The timing of Cy and TNF administration was critical since administration of Cy prior to or concurrent with rhTNF was not effective in reducing tumor area or increasing cure rates over those achieved with either agent alone. Mice treated with doxorubicin alone had an increase in tumor size of 139 +/- 29% over untreated controls (P2 less than 0.05) on Day 28 following tumor inoculation and none were cured. In contrast, mice treated with doxorubicin plus 4 or 6 micrograms rhTNF exhibited early reductions in tumor size such that on Day 28 the average tumor areas were decreased by 66 +/- 34% (P2 less than 0.05) and 73 +/- 1% (P2 less than 0.02) of untreated controls with cure rates of 29% and 43% (P2 less than 0.02), respectively. However, the combination of 6 micrograms rhTNF plus doxorubicin led to substantial lethal toxicity with only 29% of mice surviving treatment. 5-Fluorouracil alone resulted in an increase in tumor area of 164% (P2 less than 0.05) over that of untreated controls on Day 28 following tumor inoculation.(ABSTRACT TRUNCATED AT 400 WORDS)

Combination cytokine immunotherapy with tumor necrosis factor alpha, interleukin 2, and alpha-interferon and its synergistic antitumor effects in mice.

The antitumor activity of combination therapy with recombinant human tumor necrosis factor alpha (rhTNF-alpha), recombinant human interleukin 2 (rhIL-2), and recombinant hybrid alpha-interferon A/D (rhIFN-alpha A/D) was assessed against established weakly immunogenic (MCA-106) and nonimmunogenic (MCA-102) sarcomas at both s.c. and visceral (hepatic) sites. C57BL/6 mice were treated with a single i.v. dose of rhTNF-alpha followed by rhIL-2 (75,000 units) and rhIFN-alpha A/D (75,000 units) i.p. twice daily for 5 consecutive days. Substantial improvements were observed when the combination of rhTNF-alpha, rhIL-2, and rhIFN-alpha A/D was administered, as measured by regression of tumor, prolongation of survival, and improved cure rates, compared with any combination of two cytokines or any cytokine alone against the MCA-106 sarcoma. These findings were consistent in both the s.c. and single hepatic tumor models. For example, treatment of the MCA-106 s.c. tumor bearers with the triple cytokine combination resulted in cures of 16 of 18, 17 of 18, and 12 of 18 mice receiving rhTNF-alpha dosages of 2, 4, and 6 micrograms, respectively, compared with 2 of 18, 7 of 18, and 9 of 18 at 2, 4, and 6 micrograms of rhTNF-alpha plus rhIL-2 without rhIFN-alpha A/D. Established 10-day single liver tumor weights when treated with the triple combination therapy were 54 and 25 mg in treatment groups receiving 2 and 4 micrograms of rhTNF-alpha, compared with 376 and 302 mg with the same amounts of rhTNF-alpha alone (P less than 0.004). Mice bearing hepatic sarcomas treated with triple cytokine combination therapy had cure rates of 50% and 67% at rhTNF-alpha doses of 2 and 4 micrograms, compared with no survivors with rhTNF-alpha alone. No improved antitumor effects resulted from therapy with any cytokine alone or in combination against the nonimmunogenic MCA-102 sarcoma. Possible in vivo mechanisms by which these three cytokines synergize are discussed.

Studies of the mechanisms of toxicity of the administration of recombinant tumor necrosis factor alpha in normal and tumor-bearing mice.

Tumor-bearing mice have a greater sensitivity to the acute lethal effects of the administration of high-dose recombinant human tumor necrosis factor alpha (rhTNF-alpha) compared to normal, non-tumor-bearing mice. We studied whether or not the presence of tumor per se was responsible for the enhanced rhTNF-alpha toxicity. Tumor-bearing mice underwent tumor excision or sham operation before the systemic administration of rhTNF alpha at staged times (0.5-24 h) following surgery. There was little survival difference between sham-operated tumor-bearing mice and tumor-bearing mice undergoing tumor excision (at 24 h, treatment with 12 micrograms rhTNF-alpha, survival:sham-operated tumor bearers = 0/12, excised tumor-bearers = 0/12; p2 less than 0.01 compared to non-tumor-bearers). Mice without tumors receiving sham operation, had minimal toxicity (10 of 12 mice surviving). The injection of 3 ml Ringer's lactate i.p. before i.v. rhTNF-alpha therapy increased survival in tumor-bearing animals; following pretreatment with Ringer's lactate 30/42 mice survived 12 micrograms rhTNF-alpha compared to 6/42 surviving a similar rhTNF-alpha dose without hydration (P2 less than 0.001). Since the production of oxygen free-radical metabolites has been postulated to play a role in the acute toxicity of rhTNF-alpha, bismuth subnitrate was used to induce the enzyme metallothionein to act as a natural scavenger for these metabolites. Daily oral bismuth subnitrate treatments improved survival of mice with MCA-106 or MCA-102 sarcoma and of mice without tumors, with higher rhTNF-alpha doses (12-20 micrograms), without reducing the therapeutic effect of rhTNF-alpha against the weakly immunogenic MCA-106 sarcoma. These studies suggest methods for reducing the toxicity of rhTNF-alpha administration in clinical trials.

IL-4 regulation of murine lymphokine-activated killer activity in vitro. Effects on the IL-2-induced expansion, cytotoxicity, and phenotype of lymphokine-activated killer effectors.

The in vitro incubation of B6 splenocytes with purified, mouse rIL-4 for 4 to 5 days was sufficient to generate lymphokine-activated killer (LAK) activity. In addition, rIL-4 augmented LAK cytotoxic activity when combined with rIL-2, as measured in a 4 h 51Cr-release assay against fresh, syngeneic MCA-sarcoma (MCA-102 and MCA-105) cells. Interestingly, this augmentation was not observed against the cultured YAC-1 target. LAK generation and augmentation of cytotoxicity by rIL-4 was species-specific, because human rIL-4 (up to 20,000 U/ml) failed to elicit these effects in the mouse splenocyte cultures. When 5-day B6 LAK cells (splenocytes incubated in rIL-2 at 1000 U/ml for 5 days) were split and recultured in the combination of rIL-2 plus rIL-4 for 4 additional days at least a twofold greater expansion in cell number resulted compared to similar cells cultured in either rIL-2 or rIL-4 alone. Moreover, LAK cells expanded in rIL-2 plus rIL-4 exhibited substantial increases in in vitro cytolytic activity (on a per cell basis) against MCA-102 and MCA-105 sarcoma cells, but not against YAC-1 targets. FACS analysis or negative selection using Lyt-2 or NK-1.1 mAb plus C revealed no differences in effector phenotype(s) of LAK cells expanded in rIL-2 alone compared to rIL-2 plus rIL-4 to account for the differences observed in both expansion and cytolytic activity by rIL-4. The majority of cells was Thy-1+, Lyt-2+, T3+, and ASGM-1+. However, a marked increase in the granule-associated serine esterase, BLT-E, was found only in LAK cells expanded in the combination of both lymphokines. Collectively, these studies show that rIL-4 has potent regulatory activities on splenic LAK generation, expansion, and cytotoxic function in the mouse.

The role of attitude importance in social evaluation: a study of policy preferences, presidential candidate evaluations, and voting behavior.

According to a number of social psychological theories, attitudes toward government policies that people consider important should have substantial impact on presidential candidate preferences, and unimportant attitudes should have relatively little impact. Surprisingly, the accumulated evidence evaluating this hypothesis offers little support for it. This article reexamines the hypothesis, applying more appropriate analysis methods to data collected during the 1968, 1980, and 1984 American presidential election campaigns. The impact of policy attitudes on candidate preferences was indeed found to depend on the importance of those attitudes, just as theory suggests. The analysis also documented two mechanisms of this increased impact: People for whom a policy attitude is important perceive larger differences between competing candidates' attitudes, and important attitudes appear to be more accessible in memory than unimportant ones.