Simultaneous assimilation and contrast effects in judgments of self and others.

Judgments of self and referent others tend to be positively related, as evident in the false consensus effect, but others may also be contrasted from the self, as noted in the false uniqueness literature. In 3 studies that examined the domains of attitudes and traits, evidence of both assimilative and contrastive associations between self- and other-judgements were noted, depending on the form of judgment (objective vs. subjective) and the relevant judgment scale anchor (self vs. others). When self-judgments were made first, objective appraisals of reference groups were contrasted from subjective self-appraisals (after controlling for individual differences in participants' behavioral reports). When judgments of others were made first, objective self-ratings were contrasted from subjective other-judgments. Implications for the false consensus literature and the shifting standards model (M. Biernat, M. Manis, & T. E. Nelson, 1991) are discussed.

Shifting standards and stereotype-based judgments.

Four studies tested a model of stereotype-based shifts in judgment standards developed by M. Biernat, M. Manis, and T. E. Nelson (1991). The model suggests that subjective judgments of target persons from different social groups may fail to reveal the stereotyped expectations of judges, because they invite the use of different evaluative standards; more "objective" or common rule indicators reduce such standard shifts. The stereotypes that men are more competent than women, women are more verbally able than men, Whites are more verbally able than Blacks, and Blacks are more athletic than Whites were successfully used to demonstrate the shifting standards phenomenon. Several individual-difference measures were also effective in predicting differential susceptibility to standard shifts, and direct evidence was provided that differing comparison standards account for substantial differences in target ratings.

The illusion of mental health.

It is argued that researchers' reliance on "objective" mental health scales and disregard for clinical judgment has led to many mistaken conclusions. Specifically, standard mental health scales appear unable to distinguish between genuine mental health and the facade or illusion of mental health created by psychological defenses. Evidence is presented indicating that (a) many people who look healthy on standard mental health scales are not psychologically healthy, and (b) illusory mental health (based on defensive denial of distress) has physiological costs and may be a risk factor for medical illness. Clinical judges could distinguish genuine from illusory mental health, whereas "objective" mental health scales could not. The findings call into question the conclusions of many previous studies that rest on standard mental health scales. They suggest new ways of understanding how psychological factors may influence health. Finally, they suggest that clinical methods (which researchers often malign) may have an important role to play in meaningful mental health research.

Inhibition of acetaminophen and lorazepam glucuronidation in vitro by probenecid.

The effect of probenecid on glucuronidation of acetaminophen and lorazepam in hepatic microsomes from various species was studied to see if in vitro results were consistent with previous in vivo observations. Mouse, rat, and human microsomes were incubated with acetaminophen and probenecid while monkey microsomes were incubated with lorazepam and probenecid. Glucuronidation rates in all species varied with substrate, protein, and detergent concentrations. Mice exhibited faster rates of glucuronidation than rats or humans. All species showed inhibition of glucuronidation of acetaminophen or lorazepam when probenecid was added. Analysis suggested competitive inhibition. Thus, in vitro studies support in vivo results and confirm that the inhibition takes place at the hepatic level.

Medicinal chemistry of imidazoquinolinone dopamine receptor agonists.

(R)-5-(Dipropylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]-quinolin-2( 1H)-on e (1a, U-86170), a potent high intrinsic activity dopamine (D2) agonist, has been prepared in eleven steps from quinoline. In several tests, the compound showed dopamine autoreceptor agonist activity at low doses. It showed postsynaptic agonist activity at somewhat higher doses, reversing the effects of reserpine in mice and increasing striatal acetylcholine levels. The compound showed some serotonergic (5HT1A) activity, but was inactive at other receptors. The related monopropylamine 2 (U-91356), also showed good dopaminergic agonist activity, and had improved metabolic stability and oral bioavailability in the rat and monkey when compared to 1a. Compounds 1a and 2 have been prepared in tritiated form, and [3H]1a (69 Ci/mmol) has found use as a D2 agonist radioligand in binding assays. The dopaminergic (D2) and serotonergic (5HT1A) activities of a series of compounds related to 1a have been evaluated using this ligand, [3H]raclopride, and [3H]8-OH DPAT.

Inhibition of human red blood cell N-acetyltransferase.

Acetanilide and derivatives of benzoic acid, benzamide, salicylic acid, and salicylamide were tested as inhibitors of p-aminobenzoic acid N-acetyltransferase partially purified from peripheral blood of three rapid and two slow dapsone acetylator human volunteers. The 50% inhibition point of these compounds does not provide a kinetic basis for differentiating the rapid and slow dapsone acetylator phenotypes.

Comparison and expectancy processes in human judgment.

This work explored a judgment model proposed by Manis and Paskewitz (1984a). The model suggests that prior experience with the members of a given category affects the assessment of other category members in 2 ways: (a) by providing a basis for comparison and (b) by leading the judge to expect that new exemplars will resemble those previously encountered. In 4 experiments, respondents judged the height of different people on the basis of full-length photographs. The height of the models in an induction series constituted the main independent variable. The effects of contrasting inductions (e.g., short vs. tall women) affected the judges' subsequent assessments in a test series. Both comparison and expectancy processes played a significant role, sometimes opposing one another and sometimes acting in parallel (i.e., supporting one another).

Human N-acetylation genotype determination with urinary caffeine metabolites.

The human acetylation genotype was determined by measuring urinary caffeine metabolites by use of a modification of a previously published HPLC method. The problem of separation of 7-methylxanthine (7X) from 1-methyluric acid (IU) in urine extracts was achieved by adding a phenyl column, in tandem with a C18 reverse-phase column, by means of a methanol:aqueous acetic acid gradient elution system. The urinary molar ratios of (AAMU)/(AAMU + 1U + 1X) and (AAMU)/(1X) were estimated in 20 subjects phenotyped with dapsone, with 100% concordance for the [AAMU]/[1X] ratio. A population study of 42 unrelated individuals exhibited trimodal distribution in acetylation capacity, consistent with the Hardy-Weinberg theory of population genetics. Definitive pedigree analysis of 16 families (75 subjects) resulted in significant similarity between the observed genotypic matings and those expected by classical Mendelian segregation. This noninvasive genotyping method promises to be useful in future investigation of the relationship between the human acetylation polymorphism and clinical disorders.

Metabolism of 4,4'-methylenebis(2-chloroaniline) by canine liver and kidney slices.

4,4'-Methylenebis(2-chloroaniline) (MBOCA) metabolism in canine liver and kidney slices was investigated using HPLC to separate the metabolites. Liver slices metabolized 5-10% of the 14C-MBOCA in 60 min and produced seven metabolites resolved by HPLC. The major metabolite, representing approximately 80% of the metabolism, was 2-amino-5-[(4-amino-3-chlorophenyl)methyl]-3-chlorophenyl hydrogen sulfate, previously identified as the major urinary metabolite in dogs. An MBOCA-glucoside was identified by mild acid hydrolysis, which released MBOCA and glucose. An O-glucuronide was characterized as labile to beta-glucuronidase, stabile to arylsulfatase, and mild acid. It was formed in increased amounts when 2,6-dichloro-4-nitrophenol (DCNP) was added to the incubation. Two other glucuronide metabolites were labile to mild acid and beta-glucuronidase, stabile to arylsulfatase, and were formed in decreased amounts in the presence of D-(+)-galactosamine (D-gal) and p-nitrophenyl sulfate (PNPS). Renal cortical slices metabolized 3-5% of the 14C-MBOCA in 90 min, producing six metabolites. Based on retention time and lability to hydrolysis, three of these, the MBOCA-glucoside, a glucuronide, and 2-amino-5-[(4-amino-3-chlorophenyl)methyl]-3-chlorophenyl hydrogen sulfate were also found as kidney metabolites. One additional sulfur-containing metabolite was labile to mild acid and arylsulfatase. The major kidney metabolite represented 25-40% of the metabolism and was unaffected by mild acid, beta-glucuronidase, arylsulfatase, DCNP, and D-gal. Covalent binding in liver slices was 20-27 pmol/mg of wet weight/60 min and in kidney was 9-13 pmol/mg of wet weight/90 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Structure elucidation and in vitro reactivity of the major metabolite of 4,4'-methylenebis(2-chloroaniline) (MBOCA) in canine urine.

The structure of the major urinary metabolite of 4,4'-methylenebis(2-chloroaniline) (MBOCA) in dogs was identified and the reactivity of the metabolite was characterized in vitro. Arylsulfatase but not beta-glucuronidase hydrolyzed the metabolite in a time- and enzyme concentration-dependent manner. Electron impact mass spectrometry following derivatization and transesterification indicated that the major metabolite was ring hydroxylated and fast atom bombardment mass spectrometry confirmed the molecular weight as a sulfate ester. Proton nuclear magnetic resonance studies indicated that the ring substitution was ortho to an amine. These analytical and enzymatic data supported the proposed structure of the major urinary metabolite of MBOCA in dogs as 5-hydroxy-3,3'-dichloro-4,4'diaminodiphenylmethane-5-sulfate. Protein and DNA binding in vitro and mutagenicity were investigated. During hydrolysis with arylsulfatase, time- and enzyme concentration-dependent protein binding and time-dependent DNA binding were observed. Mutagenicity during enzymatic hydrolysis in the presence of Salmonella typhimurium TA1538 with up to 20 micrograms metabolite/plate was negative and at 50 micrograms/plate the metabolite was cytotoxic. These results indicated that the metabolite was the sulfate conjugate of a reactive molecule. This study demonstrated that the major metabolite of MBOCA in canine urine is an orthohydroxysulfate and thus is similar to the major metabolites of benzidine, 2-naphthylamine, and 4-aminobiphenyl.

Percutaneous absorption, disposition, and excretion of 4,4'-methylenebis(2-chloroaniline) in dogs.

Percutaneous (pc) absorption, disposition, and excretion of 14C-MBOCA (4,4'-methylenebis(2-chloroaniline) ) were investigated in male beagle-type dogs by HPLC and compared to intravenously (iv) administered controls. Following application of 115 muCi MBOCA to a 25 cm2 area of the skin, no measurable radioactivity was detected in blood for the subsequent 24-hr period, but 14C-MBOCA and metabolites were excreted in urine and bile. During the 24-hr collection period, a total of 1.3% of the administered dose was recovered in the urine (0.4% of which was unchanged MBOCA). At 24 hr 0.62% of the dose was recovered in gallbladder bile. Approximately 90% of the administered dose was recovered in skin at the application site. Liver, kidney, and fat were the tissues with highest radioactivity. After a bolus iv injection, MBOCA disappeared rapidly from blood (t 1/2 beta = 0.70 hr). In the 24 hr following iv injection, 46% of the administered dose was excreted in urine (0.54% of which was unchanged MBOCA). At 24 hr 32% of the dose was recovered in gallbladder bile. Tissue radioactivity was 10-20 X higher after iv than pc administration and highest in liver, kidney, fat, and lung. The results demonstrated in a canine model that skin absorption was a viable route of entry for MBOCA and that unmetabolized MBOCA was a small percentage (0.4-0.5%) of the total urinary excretion. MBOCA was rapidly and extensively metabolized and excreted in urine and bile following both iv and pc administration.