Sensory over-responsivity and atypical neural responses to socially relevant stimuli in autism.

Although aversive responses to sensory stimuli are common in autism spectrum disorder (ASD), it remains unknown whether the social relevance of aversive sensory inputs affects their processing. We used functional magnetic resonance imaging (fMRI) to investigate neural responses to mildly aversive nonsocial and social sensory stimuli as well as how sensory over-responsivity (SOR) severity relates to these responses. Participants included 21 ASD and 25 typically-developing (TD) youth, aged 8.6-18.0 years. Results showed that TD youth exhibited significant neural discrimination of socially relevant versus irrelevant aversive sensory stimuli, particularly in the amygdala and orbitofrontal cortex (OFC), regions that are crucial for sensory and social processing. In contrast, ASD youth showed reduced neural discrimination of social versus nonsocial stimuli in the amygdala and OFC, as well as overall greater neural responses to nonsocial compared with social stimuli. Moreover, higher SOR in ASD was associated with heightened responses in sensory-motor regions to socially-relevant stimuli. These findings further our understanding of the relationship between sensory and social processing in ASD, suggesting limited attention to the social relevance compared with aversiveness level of sensory input in ASD versus TD youth, particularly in ASD youth with higher SOR.

Involvement of HLA class I alleles in natural killer (NK) cell-specific functions: expression of HLA-Cw3 confers selective protection from lysis by alloreactive NK clones displaying a defined specificity (specificity 2).

This study was designed to identify the target molecules of the natural killer (NK) cell-mediated recognition of normal allogeneic target cells. As previously shown, the gene(s) governing the first NK-defined allospecificity (specificity 1) were found to be localized in the major histocompatibility complex region between BF gene and HLA-A. In addition, the analysis of a previously described family revealed that a donor (donor 81) was heterozygous for three distinct NK-defined allospecificities (specificities 1, 2, and 5). HLA variants were derived from the B-Epstein-Barr virus cell line of donor 81 by gamma irradiation followed by negative selection using monoclonal antibodies specific for the appropriate HLA allele. Several variants were derived that lacked one or more class I antigen expressions. These variants were analyzed for the susceptibility to lysis by NK clones recognizing different allospecificities. The loss of HLA-A did not modify the phenotype (i.e., "resistance to lysis"). On the other hand, a variant lacking expression of all class I antigens became susceptible to lysis by all alloreactive clones. Variants characterized by the selective loss of class I antigens coded for by the maternal chromosome became susceptible to lysis by anti-2-specific clones. Conversely, variants selectively lacking class I antigens coded for by paternal chromosome became susceptible to lysis by anti-1 and anti-5 clones (but not by anti-2 clones). Since the Cw3 allele was lost in the variant that acquired susceptibility to lysis by anti-2 clones and, in informative families, it was found to cosegregate with the character "resistance to lysis" by anti-2 clones, we analyzed whether Cw3 could represent the element conferring selective resistance to lysis by anti-2 clones. To this end, murine P815 cells transfected with HLA Cw3 (or with other HLA class I genes) were used as target cells in a cytolytic assay in which effector cells were represented by alloreactive NK clones directed against different specificities. Anti-2-specific clones efficiently lysed untransfected or A2-, A3-, and A24-transfected P815 cells, while they failed to lyse Cw3-transfected cells. NK clones recognizing specificities other than specificity 2 lysed untransfected or Cw3-transfected cells. Thus, the loss of Cw3 resulted in the de novo appearance of susceptibility to lysis, and transfection of the HLA-negative P815 cells with Cw3 resulted in resistance to lysis by anti-2 clones. Therefore, we can infer that Cw3 expression on (both human and murine) target cells confers selective protection from lysis mediated by anti-2 NK clones.

Relationship between restorations and the level of the periodontal attachment.

Two hundred and forty stained extracted teeth with a restoration on one proximal surface and with no restoration on the opposite surface were investigated for the position and quality of the restoration and the position of the periodontal attachment. Only 27% of restorations were of good quality, 60% had overhangs and 13% deficiencies. The mean difference in loss of periodontal attachment (LOA) between the two surfaces for all teeth was 0.36 mm when the distance from the cemento-enamel junction to the periodontal membrane on the unrestored surfaces was subtracted from that on the restored surfaces. If allowance is made for those restorations located apical to the cemento-enamel junction, the LOA difference was 0.18 mm.