Evoked Potentials in Hyperkinetic and Normal Children Under Certainty and Uncertainty: A Placebo and Methylphenidate Study

Differences between hyperkinetic children and normal children and the effects of methylphenidate on hyperkinetic children were investigated under conditions of differential attentional demands. Auditory average evoked potentials were recorded from vertex using a single/double click guessing paradigm under conditions of certainty and uncertainty. Under conditions of certainty (low attention), in which the subject was told the identity of each stimulus in advance, few significant group differences were found. Under conditions of uncertainty (high attention), in which the subject was asked to guess which stimulus would be presented, large group differences were found. In response to the second click the P200 component was found to be smaller and the N250 component was larger in hyperkinetic children than in normal children. Treatment with methylphenidate “normalized” the evoked potentials of the hyperkinetic children making them more like those of normal children. The findings are believed: 1) to reflect the deficit in attention observed behaviorally in hyperkinetic children, 2) to support a model of hypoarousal in hyperkinetic children, and 3) to reflect the behavioral “normalization” observed in hyperkinetic children treated with melhylphenidate.     

Isochromosome 17q in primitive neuroectodermal tumors of the central nervous system

We have prepared karyotypes from 22 primitive neuroectodermal tumors (PNETs) from pediatric patients ranging in age from 10 months to 16 years. Twenty-one cases were newly diagnosed, primary, posterior fossa tumors. One case was a recurrent tumor in a patient previously treated with radiation. Cytogenetic results were obtained from direct preparations and/or short-term (1-10 day) culture. Three tumors had apparently normal karyotypes. Nineteen tumors demonstrated numerical and/or structural abnormalities. The most frequent structural chromosomal changes were deletions and nonreciprocal translocations. Four tumors contained double minutes. Several chromosomes appear to be nonrandomly involved in PNETs. These include chromosomes 5, 6, 11, 16, 17, and a sex chromosome. The most consistent change, however, was an i(17q), present in one-third (8/22) of the cases. Strikingly, in three of these eight tumors, the i(17q) was the only structural abnormality observed. An i(17q) is not specific for pediatric PNETs, as it is also seen in leukemias and other solid tumors. However, in PNETs it may be a primary change related to tumor development and/or progression. Clinically, there was no correlation of the cytogenetic findings with histologic features of the tumors, size of the tumor, extent of metastasis, or surgical resection.     

An antigen processing polymorphism revealed by HLA-B8-restricted cytotoxic T lymphocytes which does not correlate with TAP gene polymorphism

In previous studies of antigen presentation through HLA-B27, we identified a healthy person whose lymphoblastoid cells do not present three B27-restricted viral epitopes to specific cytotoxic T lymphocytes (CTL), despite adequate cell surface expression of HLA-B2702 of normal sequence. Similar findings were observed in all members of his family sharing the HLA-A3-B2702 haplotype. The original donor, NW, carries HLA-B8 on his other class I haplotype, which his daughter, HW, has inherited. We now report a failure to present an HLA-B8-restricted epitope from influenza nucleoprotein following viral infection of NW cells, although exogenous added peptide is still presented normally. However, cells from HW, which do not carry the A3-B2702 haplotype, present the expected epitope after viral infection. Another B8-restricted epitope, from human immunodeficiency virus-gag, is presented equally well by both cell lines when infected with gag-vaccinia. This antigen processing phenotype does not correlate with any of the known human TAP-1 and TAP-2 polymorphisms.     

Effects of selective NMDA and non-NMDA blockade in the nucleus accumbens on the plus-maze test

Effect of blocking N-methyl-D-aspartic acid (NMDA) and non-NMDA-glutamatergic receptors on performance in the plus-maze was studied in male rats bilaterally cannulated into the nucleus accumbens (Acc). Rats were divided into seven groups that received either 1 microl injections of saline, (+/-)2-amino-7-phosphonoheptanoic acid (AP-7, 0.2, 0.5, or 1 microg) or 2,3 dioxo-6-nitro-1,2,3,4,tetrahydrobenzo-(f)quinoxaline-7-sulphonamide disodium (NBQX, 0.2, 0.5, or 1 microg) 15 min before testing. Time spent in open arm, time per entry, end arrivals, open, closed, and total arm entries, relationship between open-, closed-, and total arm entries, rearing, face-, head-, and body grooming, and number of fecal boli were recorded. Time spent in the open arm increased under AP-7 (0.5 and 1 microg; P<.01) and NBQX (1 microg; P<.05) treatment, whereas time per entry was increased only with AP-7 (1 microg; P<.05). Open arm entries were increased by the intermediate doses of AP-7 (0.5 microg; P<.01) and NBQX (0.5 microg; P<.05); end arrivals were increased by the intermediate dose of AP-7 (0.5 microg/1 microl, P<.05). The frequency of rearing, grooming, and closed arm entries was not affected by the treatment. We conclude that NMDA and non-NMDA-glutamatergic blockade in the Acc lead to a behavioral disinhibition of cortical influences with the median doses, but that at higher doses the blockers have an anxiolytic-like effect.     

Trying to stop smoking: Effects of perceived addiction,attributions for failure,and expectancy of success

This paper reports the results of a postal questionnaire completed by 2343 smokers who had contacted a television company for help with stopping smoking. Of these, 1848 (78.9%) completed a follow-up questionnaire 1 year later. This indicated that 797 had tried to stop, 709 had tried to cut down, and 164 had become abstinent. Analyses show that the intention to try to stop smoking was dependent not only on the perceived health benefit, but also on the subjects' confidence that they would succeed if they tried to stop. As predicted by Weiner's [(1979). J. Educ. Psychol.71: 3–25] model of achievement motivation, those who attributed other smokers' failures at quitting to stable factors had lower expectancies of success, as had those who saw themselves as more addicted. When the follow-up data are considered, reported attempts at quitting were strongly related to previously declared intentions, and reported abstinence was related to previous confidence (expectancy of success) and perceived addiction. There is no support for hypotheses concerning self-other differences in attribution, or defensive attribution, in subjects' attributions for their own failures at cessation. Implications for antismoking interventions are discussed.This research was facilitated to various extents by grants from the British Council, the Department of Health and Social Security, the Medical Research Council, and the Social Science Research Council, London. When the data were collected, all authors were at the Addiction Research Unit, Institute of Psychiatry, University of London.     

QUANTITATIVE EVOKED POTENTIAL CORRELATES OF THE PROBABILITY OF EVENTS

A late positive-going component (P₃) of the average evoked potential recorded from human scalp was shown to be quantitatively related to a priori stimulus probability both when the S was told the identity of the stimulus before it was presented and when the S was not told, and was instructed to guess. In the guessing situation, the amplitude of P₃ was much larger and was influenced not only by the a priori probability of events determined by the experimenter but also by the interaction of these probabilities with the S's guessing behavior. The amplitude of the late positive component was inversely related to the proportion of trials in which a particular event was associated with a particular guess, i.e., the proportion of hits and misses. It was larger the more unexpected the outcome of the guess. This relationship held for different methods of manipulating the probability of two events.     

Mapping of a restriction fragment length polymorphism associated with defective DR beta 4 chain expression to the HLA-DRB1 gene

The HLA-DR beta 4 chain, encoded by the DRB4 gene, carries two DRw53 determinants normally expressed by DR4, DR7, and DR9 individuals. However, some DR7 individuals (DR7, Dw11) fail to express the DR beta 4 chain. At the genomic level, a HindIII restriction fragment length polymorphism can be detected in these individuals with a DR beta cDNA probe. The association of this altered HindIII fragment with defective beta 4 chain expression suggested the possibility that the polymorphic fragment was derived from the DRB4 gene and might, therefore, be related to the defect in expression. However, detailed Southern blot analysis has now mapped the polymorphic fragment to the 3' end of the DRB1 gene, approximately 100 kb away from the defective DRB4 gene. Although the alteration in the DRB1 gene might involve sequences important in regulating the expression of the DRB4 gene, it is more likely that the association results from strong positive linkage disequilibrium between these DR beta chain genes.     

Regulation of in vitro cytotoxic T lymphocyte generation. II. Demonstration of noncytotoxic alloantigen-specific suppressor T lymphocytes

Both allospecific suppressor T lymphocytes (TsS) and nonspecific suppressor T lymphocytes (TsN) are activated in alloantigen-stimulated mixed leukocyte cultures (MLC). TsS and TsN can suppress cytotoxic T lymphocyte (CTL) induction upon transfer to fresh (second) MLC stimulated by the same alloantigens as in the first MLC (TsS or TsN) or by third-party alloantigens (TsN only). Evidence that TsS and TsN functions are performed by different T cell sets has been restricted to radioresistance of the former but not the latter. Separation of TsS from CTL has proven even more difficult. Methods are reported here which have allowed in vitro induction and functional separation of TsS from CTL and TsN in a totally allogeneic system. TsS are resistant to combined exposure to pyrilamine, a histamine1 antagonist and local anesthetic, during suppressor cell induction, and to X or gamma irradiation thereafter, while CTL precursors (CTL-P) and TsN are more sensitive to such treatments. This allowed us to use these treatments to generate TsS that are not contaminated with functional CTL, CTL-P or TsN. These data show that TsS regulate CTL induction by interacting with responding cell populations, rather than by cytotoxic depletion of stimulator cells.