The family of matrix metalloproteinases is a family of closely related enzymes that play an inportant role in physiological and pathological processes of matrix degradation. The most distinctive characteristic of interstitial collagenases (fibroblast and neutrophil collagenases) is their ability to cleave interstitial coilagens at a single peptide bond; however, the precise region of the enzyme responsible for this substrate specificity remains to be defined. To address this question, we generated truncated mutants of neutrophil collagenase with various deletions in the COOH-terminal domain and chimeric molecules between neutrophil collagenase and stromelysin and assayed the expressed enzymes against type I collagen and the general substrate, casein. Our data suggest that substrate specificity for interstitial collagen is determined by a 16-aa sequence in the COOH-terminal domain of neutrophil collagenase and is influenced by the integrity of a disulfide-defined loop at the COOH terminus for maximal activity. It was found that a relatively large region of 62-aa residues influenced the relative efficiency of collagenolytic activity. In addition to the region that conferred this specificity, a site at the COOH side of the presumptive zinc-binding locus was found to be necessary for general catalytic activity. Mutation of a critical aspartic residue at position 253 within this area resulted in complete loss of proteolytic activity, suggesting that Asp-253 might function as one of the ligands for divalent cations, which are essential for enzymatic activity.The family of matrix metalloproteinases (MMPs) is a family of closely related enzymes that play an important role in a variety of physiological and pathological processes, including embryonic development (1), tumor invasion (2), and arthritis (3, 4). The human MMP gene family contains at least two distinct interstitial collagenases (5, 6), three types of stromelysins (7-9), putative metalloproteinase 1 (10), and two gelatinases, 72-kDa type IV collagenase (11, 12) and 92-kDa type V collagenase (13,14). When the primary structures of MMPs are compared, it is apparent that they are structurally homologous molecules consisting of defined functional domains (13,15 MATERIALS AND METHODSPlasmid Construction of Truncated Mutants of NC (TrNCs). The NC 7.2 cDNA containing a full-length coding region for NC was used to create TrNCs with various deletions in the COOH-terminal sequence (6). The size of the TrNC is identified by amino acid residue numbers starting from the initiating Met (Fig. 1). A premature stop codon was introduced by PCR. The primer (5'-GCTCGAATTCGGGC-TCGCCAGGGAAGGGCCCTACCC-3') complementary to the 5' end of NC 7.2 incorporated a unique EcoRI restriction site and was used for construction of all the mutants. Primers at the 3' end contained sequences for a stop codon at various intervals and a unique Not I restriction site. The isolated fragments were digested with EcoRI and Not I and then ligated into these sites in the expression vector pcDNA I (...

Purpose – Offenders with a learning disability present with greater clinical need than those without a learning disability. However, for this client group, access to and engagement with psychological and criminogenic interventions are often limited. The purpose of this paper is to discuss a potentially useful approach to this issue. Design/methodology/approach – A single case study design was used to evaluate an introductory group programme, delivered over 12 weekly sessions, in a forensic learning disability service. Semi-structured interviews were used alongside psychometric measures, which were completed prior to, and following completion of, the group, in order to assess the individual's experience of the group, their emotional understanding and difficulties, and readiness to change. Findings – Readiness to change and emotional understanding improved following completion of the programme. Self-reported emotional difficulties showed improvement, although not all staff reports corroborated this. Notably, the service user reported a positive experience, with increased confidence and motivation to attend further groups. Research limitations/implications – Generalisation from the results of single case studies is limited. Although results suggest that motivation to engage further has increased, more research is required to assess whether this impacts on actual ability to engage. Practical implications – Offering an introductory programme prior to further, more criminogenically focused intervention may be more effective than offering these interventions as the first stage of treatment. Originality/value – An introductory group programme may be potentially helpful in providing the foundation knowledge, confidence and motivation necessary to attend further intervention focusing on criminogenic need for offenders with a learning disability.

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