c-myc, N-myc and L-myc are the three members of the myc oncoprotein family whose role in the pathogenesis of many human neoplastic diseases has received wide empirical support. In this review, we ®rst summarize data, derived mainly from non-clinical studies, indicating that these oncoproteins actually serve quite di erent roles in vivo. This concept necessarily lies at the heart of the basis for the observation that the deregulated expression of each MYC gene is reproducibly associated with only certain naturally occurring malignancies in humans and that these genes are not interchangeable with respect to their aberrant functional consequences. We also review evidence implicating each of the above MYC genes in speci®c neoplastic diseases and have attempted to identify unresolved questions which deserve further basic or clinical investigation. We have made every attempt to review those diseases for which signi®cant and con®rmatory evidence, based on studies with primary tumor material, exists to implicate MYC members in their causation and/or progression.

All biological functions mediated by the c-myc oncoprotein require an intact transactivation domain (TAD). We compared TAD mutants for their ability to promote apoptosis of 32D myeloid cells in response to interleukin-3 (IL-3) deprivation and exposure to chemotherapeutic drugs, and to activate ornithine decarboxylase, an endogenous c-myc target. Di erent sub-regions of the TAD were required to mediate each function. cDNA microarrays were then used to identify multiple c-mycregulated transcripts, some of which were also modulated by IL-3 or cytotoxic drugs, as well as by speci®c subregions of the TAD. Several of the c-myc-regulated transcripts had also been previously identi®ed as targets for IFN-g. The functional consequences of their deregulation were manifested by a marked sensitivity of c-myc-overexpressing cells to IFN-g-mediated apoptosis. Our results establish that several well-characterized functions of c-myc are separable and correlate with the expression of a novel group of target genes, some of which also mediate the apoptotic action of IFN-g.

Mycobacteriophage L5 is a temperate phage of the mycobacteria that forms stable lysogens in Mycobacterium smegmatis. Lysogeny is maintained by the putative repressor, the gene 71 product, which also mediates immunity to superinfection. We show here that there are three promoters located upstream of gene 71 which are active in an L5 lysogen but which do not require any phage-encoded proteins. In early lytic growth, gene 71 is also transcribed from a promoter, Pleft, located at the right end of the genome and which appears to be a target of gp71 regulation. A model is given for the regulation of L5 life cycles.

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BackgroundNo published study has analyzed emergency department (ED) utilization by human immunodeficiency virus (HIV)-positive adults in the highly active antiretroviral therapy (HAART) era.AimsThe purpose of this study is to describe the demographic and HIV-specific variables associated with ED utilization by HIV-positive adults and their diagnoses when discharged from the ED or subsequently from the hospital.MethodsWe conducted a retrospective cohort study of all HIV-positive adults cared for at a tertiary center HIV clinic and ED (1 January–31 December 2006). Demographic, HIV clinical, and HIV lab variables were abstracted from the clinic database. ED/hospital diagnoses coded by the ICD-9 Diseases/Injuries Tabular Index were abstracted from identified discharge records. We used multivariate logistic regression to compute odds ratios (OR) of ED utilization based on the abstracted variables. We described the cohort and diagnoses using descriptive statistics.ResultsA total of 356 patients met inclusion criteria. Their mean age was 42.7 years, and 77.2% of included patients were male; 52.5% were Caucasian and 47.5% non-Caucasian; 72 patients (20.2%) presented to the ED during the study period [153 visits; 37 (10.4%) required hospitalization (61/153 visits)]. Income level and mean 2006 viral load had a significant association (p < 0.05) with ED utilization. Of 155 ICD-9 ED discharge diagnoses, ill-defined symptoms/signs (25.2%), injury (18.7%), and musculoskeletal disorders (11.6%) were most prevalent. Of 450 ICD-9 hospital discharge diagnoses, endocrine/metabolic (13.3%), psychiatric (12.2%), infectious/parasitic (12%), and circulatory disorders (11.8%) were most prevalent.ConclusionIn this study of HIV-positive adults, income level and mean 2006 viral load had a significant association with ED utilization. Noninfectious diagnoses were alone most prevalent in ED discharged, but not hospitalized, patients.