In this paper the effectiveness of preventive or therapeutic interventions aiming at enhancing parental sensitivity and children's attachment security is addressed. Sixteen pertinent studies have been reviewed, and 12 studies have been included in a quantitative meta-analysis (N = 869). Results show that interventions are more effective in changing parental insensitivity (d = .58) than in changing children's attachment insecurity (d = .17). Longer, more intensive, and therapeutic interventions appear to be less effective than short-term preventive interventions. Interventions which are effective at the behavioral level may not necessarily lead to changes in insecure mental representations of the parents involved. The implications of changes at the behavioral level (sensitivity; attachment) without accompanying changes at the representational level will be discussed.

Cosmid clones containing the gene for human adenosine deaminase (ADA) were isolated. The gene is 32 kb long and split into 12 exons. The exact sizes and boundaries of the exon blocks including the transcription start sites were determined. The sequence upstream from this cap site lacks the TATA and CAAT boxes characteristic for eukaryotic promoters. Nevertheless, we have shown in a functional assay that a stretch of 135 bp immediately preceding the cap site has promoter activity. This 135‐bp DNA fragment is extremely rich in G/C residues (82%). It contains three inverted repeats that allow the formation of cruciform structures, a 10‐bp and a 16‐bp direct repeat and five G/C‐rich motifs (GGGCGGG) disposed in a strikingly symmetrical fashion. Some of these structural features were also found in the promoter region of other genes and we discuss their possible function. Knowledge of the exact positions of the intron‐exon boundaries allowed us to propose models for abnormal RNA processing that occurs in previously investigated ADA‐deficient cell lines.

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In order to determine the molecular basis of adenosine deaminase (ADA) deficiency in cells derived from patients with severe combined immunodeficiency (SCID) disease, we used a human ADA cDNA clone (1) to analyse the organization and transcription of the ADA gene in both normal and ADA-SCID cells. In five lymphoblastoid ADA-SCID cell lines we could detect no deletions or rearrangements in the ADA gene and its flanking sequences. Furthermore, synthesis and processing of ADA mRNA appeared to be normal in the ADA-SCID cells, and ADA-specific mRNA from two ADA-SCID cells could be translated in vitro into a protein with the molecular weight of normal ADA; this protein, however, could hardly be precipitated with an ADA antiserum. The results indicate that in these two ADA-SCID cell lines, the lack of ADA activity is not due to transcriptional or translational defects, but to subtle changes in the configuration of the protein affecting both its enzymatic and immunological characteristics.

We have cloned and sequenced an adenosine deaminase (ADA) gene from a patient with severe combined immunodeficiency (SCID) caused by inherited ADA deficiency. Two point mutations were found, resulting in amino acid substitutions at positions 80 (Lys to Arg) and 304 (Leu to Arg) of the protein. Hybridization experiments with synthetic oligonucleotide probes showed that the determined mutations are present in both DNA and RNA from the ADA‐SCID patient. In addition, wild‐type sequences could be detected at the same positions, indicating a compound heterozygosity. Studies with ADA expression clones mutagenized in vitro showed that the mutation at position 304 is responsible for ADA inactivation.