The gene encoding a novel protein designated nm23-H1, which was recently identified as identical to the A subunit of nucleotide diphosphate kinase from human erythrocytes, has been proposed to play a role in tumor metastasis suppression. We report that untreated neuroblastoma tumors contain a cellular polypeptide (M, = 19,000) designated p19, identified in two-dimensional electrophoretic gels, which occurs at significantly higher levels (P = 0.0001) in primary tumors containing amplified N-myc gene. The partial amino acid sequence obtained for pl9 is identical to the sequence ofthe human nm23-H1 protein.An antibody to the A subunit of erythrocyte nucleotide diphosphate kinase reacted exclusively with p19. In this study, significantly higher levels of p19/nm23 occurred in primary neuroblastoma tumors from patients with advanced stages (III and IV) relative to tumors from patients with limited stages (I and II) of the disease. Even among patients with a single copy of the N-myc gene, tumors from patients with stages mI and IV had statistically significantly higher levels of p19/nm23 than tumors from patients with stages I and H. Our findings indicate that, in contrast to a proposed role for nm23-H1 as a tumor metastasis suppressor, increased p19/nm23 protein in neuroblastoma is correlated with features of the disease that are associated with aggressive tumors. Therefore, nm23-H1 may have distinct if not opposite roles in different tumors. (J. Clin. Invest. 1991. 88:341-345.)

Objectives: Evaluation of in vitro efficacy of three different implant surface decontamination methods in a peri-implant bone defect model. Material and methods:A total of 180 implants were stained with indelible red color and distributed to standardized peri-implant bone defect resin models with a circumferential defect angulation of 30°, 60°, or 90° (supraosseous defect). Sixty implants were assigned to each type of defect. All implants were cleaned by the same examiner. For each type of defect, 20 implants were cleaned for 2 min with one of 3 devices: curette (CUR), sonicscaler (SOSC), or air abrasion with glycine powder (APA).Thereafter, photographs were taken from both sides of each implant and the cumulative uncleaned implant surface area was measured by color recognition technique.Scanning electron micrographs (SEM) were examined to assess morphologic surface damages.

High level expression of the nm23-Hl gene, which encodes for a nucleoside diphosphate kinase, has been found to correlate with diminished metastasis in some tumors but not in others. We have previously identified the protein product of the nm23-H1 gene in two-dimensional electrophoretic gels and have designated it p19/nm23. In neuroblastoma, higher levels of p19/ nm23, which are associated with amplification of the N-myc oncogene, large tumor mass, and metastasis, were observed in advanced stage tumors compared with limited stage disease. Because of the variable expression of nm23-H1 in different tumors, we have investigated the relationship between amounts of the protein and cell proliferation. The levels of p19/nm23 were compared between resting and mitotically stimulated normal human PBLs and in leukemia cells. The amount of p19/ nm23 increased in normal lymphocytes in response to mitotic stimulation and paralleled the increase in DNA synthesis. In leukemia cells obtained from patients with different subtypes of acute leukemia, p19/nm23 levels were also increased relative to resting normal lymphocytes. Treatment of mitotically stimulated lymphocytes with cyclosporin, which inhibits proliferation, blocked the increase in pl9/nm23; treatment of the leukemia cell line HL-60 with dimethylsulfoxide, which induces terminal differentiation, resulted in diminished levels of p19/nm23. Our data therefore provide evidence that nm23-Hl expression is related to cell proliferative activity. (J. Clin. Invest. 1992. 89:919-924.)

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