In eukaryotic cells, histone gene expression is one of the major events that mark entry into S phase. While this process is tightly linked to cell cycle position, how it is regulated by the cell cycle machinery is not known. Here we show that NPAT, a substrate of the cyclin E-Cdk2 complex, is associated with human replication-dependent histone gene clusters on both chromosomes 1 and 6 in S phase. We demonstrate that NPAT activates histone gene transcription and that this activation is dependent on the promoter elements (SSCSs) previously proposed to mediate cell cycle-dependent transcription. Cyclin E is also associated with the histone gene loci, and cyclin E-Cdk2 stimulates the NPAT-mediated activation of histone gene transcription. Thus, our results both show that NPAT is involved in a key S phase event and provide a link between the cell cycle machinery and activation of histone gene transcription.
Inflammatory myofibroblastic tumors (IMTs) are neoplastic mesenchymal proliferations featuring an inflammatory infiltrate composed primarily of lymphocytes and plasma cells. The myofibroblastic cells in some IMTs contain chromosomal rearrangements involving the ALK receptor tyrosine-kinase locus region (chromosome band 2p23). ALK-which is normally restricted in its expression to neural tissues-is expressed strikingly in the IMT cells with 2p23 rearrangements. We now report a recurrent oncogenic mechanism, in IMTs, in which tropomyosin (TPM) N-terminal coiled-coil domains are fused to the ALK C-terminal kinase domain. We have cloned two ALK fusion genes, TPM4-ALK and TPM3-ALK, which encode ϳ95-kd fusion oncoproteins characterized by constitutive kinase activity and tyrosylphosphorylation. Immunohistochemical and molecular correlations, in other IMTs, implicate non-TPM ALK oncoproteins that are predominantly cytoplasmic or predominantly nuclear, presumably depending on the subcellular localization of the ALK fusion partner. Notably, a TPM3-ALK oncogene was reported recently in anaplastic lymphoma, and TPM3-ALK is thereby the first known fusion oncogene that transforms, in vivo, both mesenchymal and lymphoid human cell lineages. (Am J Pathol 2000, 157:377-384)
BACKGROUND: Spine surgery is complicated by an incidence of 1% to 9% of surgical site infection (SSI). The most common organisms are gram-positive bacteria and are endogenous, that is are brought to the hospital by the patient. Efforts to improve safety have been focused on reducing SSI using a bundle approach. The bundle approach applies many quality improvement efforts and has been shown to reduce SSI in other surgical procedures. OBJECTIVE: To provide a narrative review of practical solutions to reduce SSI in spine surgery. METHODS: Literature review and synthesis to identify methods that can be used to prevent SSI. RESULTS: SSI prevention starts with proper patient selection and optimization of medical conditions, particularly reducing smoking and glycemic control. Screening for staphylococcus organisms and subsequent decolonization is a promising method to reduce endogenous bacterial burden. Preoperative warming of patients and timely administration of antibiotics are critical to prevent SSI. Skin preparation using chlorhexidine and alcohol solutions are recommended. Meticulous surgical technique and maintenance of sterile techniques should always be performed. Postoperatively, traditional methods of tissue oxygenation and glycemic control remain essential. Newer wound care methods such as silver impregnation dressing and wound-assisted vacuum dressing are encouraging but need further investigation. CONCLUSION: Significant reduction of SSIs is possible, but requires a systems approach involving all stakeholders. There are many simple and low-cost components that can be adjusted to reduce SSIs. Systematic efforts including understanding of pathophysiology, prevention strategies, and system-wide quality improvement programs demonstrate significant reduction of SSI.
1. The risk of developing CASP after lumbar fusion occurs at a mean annual incidence of 0.6% to 3.9%. Strength of Statement: Strong. 2. Patients older than 60 years or who have pre-existing facet/disc degeneration may have an increased risk of developing CASP. Strength of Statement: Strong. 3. The risk of developing CASP may be greater after multilevel fusions and fusions adjacent to but not including the L5–S1 level, and may increase when performing a laminectomy adjacent to a fusion. Strength of Statement: Strong.
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