An investigation of pretend play, mental state terms and false belief understanding: In search of a metarepresentational link

The aim of this study was to investigate the association between false belief comprehension, the exhibition of pretend play and the use of mental state terms in pre-school children. Ferry children, aged between 36 and 54 months were videotaped engaging in free play with each parent. The exhibit-ion of six distinct acts of pretend play and the expression of 16 mental sr:ate terms were coded during play. Each child was also administered a pantomime task and three standard false belief casks. Reliable associations were also found between false belief performance and the pretence categories of object substitution and role assignment, and the exhibition of imaginary object pantomimes. Moreover, the use of mental state terms was positively correlated with false belief and the pretence categories of object substitution, imaginary play and role assignment, and negatively correlated with the exhibition of body part object pantomimes. These findings indicate that the development of a mental state lexicon and some, bur not all, components of pretend play are dependent on the capacity for metarepresentational cognition.

T cell-mediated and non-specific inflammatory mechanisms contribute to the skin pathology of HPV 16 E6E7 transgenic mice

One of three lines of mice transgenic for the E6 and E7 genes of human papillomavirus type 16 (HPV16) expressed from an alpha A-crystallin promoter also expresses the transgene ectopically in the skin. This line, designated alpha ACE6E7#19, develops skin disease from 3 months of age, characterised by epidermal hyperplasia and eventual skin loss. Administration of complete Freund's adjuvant (CFA) to alpha ACE6E7#19 mice, but not to nontransgenic littermate controls, induced local epidermal hyperplasia which was histologically similar to the spontaneously arising skin pathology. Local application of 2,4-dinitrochlorobenzene (DNCB) to DNCB-sensitised aACE6E7#19 mice, but not DNCB-sensitised controls, also induced hyperplasia. Treatment with cyclosporin A (CsA) or systemic depletion of CD4+ cells significantly reduced the incidence of skin disease. These data suggest that local inflammation, and cytokines produced by T helper cells, contribute to the induction of hyperplastic skin disease in alpha ACE6E7#19 mice. Spontaneous skin disease with similar histological appearance, frequency, age of onset and severity in alpha ACE6E7#19 mice was observed in scid-/- aACE6E7#19 mice, despite immune paresis. Antigen-specific immune responses and T-cell cytokines a re therefore not necessary for the induction of skin disease. We propose that epidermal hyperplasia associated with HPV16 E6 and E7 expression in skin is accelerated by local secretion of pro-inflammatory cytokines, whose production can be enhanced by activated CD4+ T cells.

A novel stable inhibitor of endopeptidases EC 3.4.24.15 and 3.4.24.16 potentiates bradykinin-induced hypotension

We have developed a novel inhibitor of the metalloendopeptidases EC 3.4.24.15 (EP24.15) and EC 3.4.24.16 (EP24.16), N-[1-(R, S)-carboxy-3-phenylpropyl]-Ala-Aib-Tyr-p-aminobenzoate (JA2), in which alpha-aminoisobutyric acid (Aib) is substituted for an alanine in a well-described but unstable inhibitor, cFP-AAY-pAB. This substitution increases the resistance of the inhibitor to degradation without altering potency. In the present study, we investigated the effects of JA2 (5 mg/kg) on the responses of mean arterial pressure to bradykinin, angiotensin I, and angiotensin II in conscious rabbits. The depressor responses to both low (10 ng/kg) and high (100 ng/kg) doses of bradykinin were increased 7.0 +/- 2.7-fold and 1.5 +/- 0.3-fold, respectively, during the 30 minutes after JA2 administration (mean+/-SEM, n=8). Bradykinin potentiation was undiminished 4 hours after JA2 injection. In contrast, the hypertensive effects of angiotensins I and II were unaltered, indicating that the bradykinin-potentiating effects were not due to angiotensin-converting enzyme inhibition. These data suggest that JA2 is not only a potent and specific inhibitor of EP24.15 and EP24.16 but is also stable in vivo. Furthermore, the potentiation of bradykinin-induced hypotension by JA2 suggests for the first time a role for one or both of these peptidases in the metabolism of bradykinin in the circulation.

Metal-directed synthesis routes to a 16-membered tetraazamacrocycle with two pendant primary amine groups

The reaction of the bis(propane-1,3-diamine)copper(II) ion with paraformaldehyde and nitroethane in dry methanol under basic conditions produces a macrocyclic product, (cis-3,11-dimethyl-3,11-dinitro-1,5,9,13-tetraazacyclohexadecane)copper(II) perchlorate, in low yield, compared with the good yield obtained in the parallel chemistry possible even under aqueous conditions using palladium(II) as a template. The palladium complex was reduced with zinc amalgam in dilute aqueous acid to yield the metal-free 16-membered macrocyclic hexaamine, in this case re-complexed and characterised by an X-ray crystal structure as the (cis-3,11-dimethyl-1,5,9,13-tetraazacyclohexadecane-3,11-diamine)copper(II) perchlorate. The copper ion is found in a tetragonally elongated and trigonally-distorted octahedral environment, with all six of the ligand nitrogens coordinated, the two primary amine pendant groups occupying cis sites. (C) 2000 Elsevier Science S.A. All rights reserved.

Multiple conformational epitopes are recognized by natural and induced immunity to the E7 protein of human papilloma virus type 16 in man

The reactivity of sera from patients with cervical cancer with the E7 protein of human papilloma virus type 16 (HPV16) was estimated using a novel non-radioactive immunoprecipitation assay and four established protein-and peptide-based immunoassays. Six of 14 sera from patients with cervical cancer and 1 of 10 sera from healthy laboratory staff showed repeated reactivity with E7 in at least one assay. Four of the 7 reactive sera were consistently reactive in more than one assay, but only one was reactive in all four assays. Following immunization with E7, 2 of 5 patients with cervical cancer had increased E7-specific reactivity, measurable in one or more assays. No single assay was particularly sensitive for E7 reactivity, or predictive of cervical cancer. Mapping of E7 reactivity to specific E7 peptides was unsuccessful, suggesting that natural or induced E7 reactivity in human serum is commonly directed to conformational epitopes of E7, These results suggest that each assay employed with is study measures a different aspect of E7 reactivity, and that various reactivities to E7 may manifest following HPV infection or immunization. This finding is of significance for monitoring of E7 immunotherapy and for serological screening for cervical cancer. Copyright (C) 2000 S.Karger, AG. Basel.

Attention Deficit Hyperactivity Disorder and substance use disorders: is there a causal link?

Attention-deficit hyperactivity disorder (ADHD), characterized by restless, inattentive and hyperactive behaviours, is a relatively common childhood disorder that affects approximately 5% of the general population. There has been controversy about whether ADHD increases risks of developing substance use disorders. The available evidence suggests that, in the absence of conduct disorder, ADHD is not associated with an increased risk of substance use problems in males. There is only limited evidence on the role of ADHD in the aetiology of substance use disorders among females. While ADHD has traditionally been considered as a childhood disorder, it may also occur in adults; research needs to examine the extent to which ADHD in adulthood increases the risk of substance use disorders.

The link between prejudiced attitudes and discriminatory behaviour: The role of ingroup norms

In the present research, a reconceptualisation of the role of norms in the link between prejudiced attitudes and discriminatory behaviour — along the lines suggested by the social identity perspective — was tested. In the first study, group salience and group norm were manipulated. As expected, participants ascribed negative traits to significantly fewer Asian university students when they had received consensus information along these lines from a salient ingroup rather than from a salient outgroup. These results were replicated on a measure of strength of motivation to appear nonprejudiced. In a second study, group salience and norm were once again manipulated and strength of attitude and perceived group threat were measured. As predicted, people's negative attitudes towards globalisation were more likely to predict congruent behavioural responses to the extent that the group norm supported the attitude and group salience was high, particularly when high levels of group threat were perceived.

The chemistry of 5-oxodihydroisoxazoles .16. A new synthesis of pyrroles, furans, thiophens and their benzo analogues

Ethyl 5-oxo-2-phenyl-2,5-dihydroisoxazole-4-carboxylate (2) was photolysed at 300 mn in the presence of phenols, enols, anilines, enamines, aryl thiols and thioenols affording enamines. Treatment of these enamines with Lewis or protic acids gives the respective benzo and five-membered ring systems.

E7 oncoprotein of human papillomavirus type 16 expressed constitutively in the epidermis has no effect on E7-specific B- or Th-repertoires or on the immune response induced or sustained after immunization with E7 protein

A line of FVB (H-2(q)) mice transgenic for the E6/E7 open reading frames of Human Papillomavirus type 16 driven from the alpha-A crystallin promoter expresses E7 mRNA in lens and skin epithelium. E7 protein is detectable in adult skin, coinciding with the development or inflammatory skin disease, which progresses to papillomata and squamous carcinomata in some mice. By examining the outcome of parenteral immunization with E7 protein, we sought to determine whether endogenous expression of E7 in skin had induced a preexisting immune outcome, i.e., specific immunity or tolerance, or whether the mice remain naive (''ignorant'') to E7. Our data show that the antibody response to defined E7 B-epitopes, the proliferative response to Th epitopes, and the delayed-type hypersensitivity (DTH) response to whole E7 did not differ between groups or young and old E6/E7 transgenic mice (likely having different degrees of lifetime exposure to E7 protein) or between E6/E7-transgenic and nontransgenic parental strain control mice. Although an E7-specific CTL response could not be induced in the H-2(q) background of these mice, incorporation of a D-b allele into the genome allowed comparison of D-b-restricted CTL responses in E6/E7 transgenic and nontransgenic mice. Experiments indicated that the E7-immunization-induced CTL response did not differ significantly between E6/E7 transgenic and nontransgenic mice. We interpret these results to indicate that in spite of expression of E7 protein in adult skin, E6/E7 transgenic mice remain immunologically naive (ignorant) of E7 epitopes presented by immunization. (C) 1997 Academic Press.