SMARCAD1, a novel human helicase family-defining member associated with genetic instability: cloning, expression, and mapping to 4q22-q23, a band rich in breakpoints and deletion mutants involved in several human diseases.

Members of the DEAD/H box-containing helicase superfamily include proteins essential to genome replication, repair, and expression. We report here the cloning and initial characterization of a novel human member of this protein family, designated hHel1 (human helicase 1), now designated SMARCAD1 by HUGO. This DEAD/H box-containing molecule has seven highly conserved sequence regions that allow us to place it in the SNF2 family of the helicase superfamily. Uniquely, though, hHel1 contains two DEAD/H box motifs, a property not reported to be shared by any other SNF2 family members. This defines a new subfamily consisting of hHel1 and its homologues. In addition to these DEAD/H box/ATP-binding motifs, hHel1 has a putative nuclear localization signal and several regions that may mediate protein-protein interactions. Expression analysis indicates that hHel1 transcripts are ubiquitous, with particularly high levels in endocrine tissue. We have mapped the gene for hHel1 to human chromosome 4q22-q23; this region is rich in breakpoints and deletion mutants of genes involved in several human diseases, notably soft tissue leiomyosarcoma, hepatocellular carcinoma, and hematologic malignancies. Our observation that human Hel1 gene overexpression is present in an E1A-expressing cell line with increased capacity for gene reactivation events by genomic rearrangement suggests that human Hel1 may play a role in genetic instability development.

Evidence-based esthetic dentistry.

Evidence-based clinical practice integrates the best available evidence with clinical expertise. This article presents a clinical case scenario and, using a four-step, evidence-based approach, demonstrates how to (1) ask an evidence-based question; (2) search MEDLINE for the best evidence; (3) critically appraise the evidence; and (4) apply the evidence to the patient. The procedure is demonstrated with the sample question, Does bleaching of bonded porcelain veneers increase marginal leakage? A MEDLINE search strategy was developed for synonyms of the key words that best identify the problem, the intervention, and the outcome. The synonyms were combined using the Boolean operator "or" to identify a "sensitive" (i.e., inclusive) universe of 140,000 journal articles. These categories were then combined using the Boolean operator "and" to identify the most "specific" (i.e., exclusive) four articles from among the 140,000. Finally, to find the best evidence, the articles were limited to "humans" and "randomized controlled trials." This identified one article. Critical appraisal of the limited data in this one article indicates that the methods are valid and statistically significant, but because of the methods employed, may not be clinically important. Evidence-based methods take one to the edge of the available information universe in about 15 minutes. The results can be both exhilarating and sobering. They can indicate the depth or limits of available information and suggest gaps in the knowledge-base that require further study. Most importantly, however, the results allow practitioners to communicate incisively and truthfully with patients and to make more informed clinical choices.