The effects of three compounds on the cell cycle of HL-60 promyeloid leukemia cells has been examined. Ciclopirox olamine, an antifungal agent, and the compound Hoechst 768159 reversibly block the cell cycle at a point occurring roughly 1 h before the arrest mediated by aphidicolin, an inhibitor of DNA polymerase OL activity, which acts in early S phase. Similar results are also obtained with the compound mimosine, a plant amino acid. Based on these data, it is concluded that all three agents inhibit cell cycle traverse at or very near the GUS phase boundary and identify a previously undefined reversible cell cycle arrest point. Key terms: Flow cytometry, G1 phase block, mimosine, ciclopirox olamineThe elucidation of the biochemical events that regulate the induction of DNA synthesis in mammalian cells is of fundamental importance to an understanding of cellular growth control. In particular, the transcriptional and posttranscriptional events that control the G1 to S phase transition have been the subject of intensive research in recent years. It has been demonstrated that the expression of a number of genes required for DNA synthesis increases in the late G1 or early S phase. These include thymidine kinase (6,28), dihydrofolate reductase (121, and DNA polymerase a (33). In addition, the posttranslational modification of several proteins occurs prior to or at the GUS border. The phosphorylation of the 34 kDa protein (p34) encoded by the mammalian cdc2 gene occurs in late Gli early S phase in serum-stimulated mouse 3T3 fibroblasts (20,23). A change in the phosphorylation state of the product of the retinoblastoma susceptibility locus, which may also be important in cell cycle progression, also occurs near the GUS boundary (2,4,9,22).Compounds that perturb the cell cycle a t or near the GUS phase boundary will be essential in determining the role of these different biochemical events in the induction cells of DNA synthesis. The resolution of physical techniques such as cell sorting and centrifugal elutriation is not sufficient to subdivide adequately the late Gliearly S phase on the basis of DNA content or cell volume and density. Although a number of agents have been described that reversibly block cell cycle progression, most of these act in S phase. These include aphidicolin (APH), which blocks DNA polymerase c1 activity (13); 5-fluorodeoxyuridine, which inhibits thymidylate synthase (15); and hydroxyurea, which acts on ribonucleotide reductase (27). Of these S phasespecific inhibitors, APH has been shown to act earliest in S phase (29). APH inhibits DNA replication by interfering with the binding of deoxynucleotide triphosphates to DNA polymerase (13). Both molecular and kinetic (1,7,10,11,21,26,29,31,34) studies indicate that APH blocks cell cycle progression in S phase cells that are undergoing active DNA replication and prevents the entry of cells into S phase just beyond the GliS border. The cloning and characterization of the eukaryotic chromosomal replication origins, which are DNA sequences associated w...
Tobacco use and secondhand tobacco-smoke (SHS) exposure are major national and international health concerns. Pediatricians and other clinicians who care for children are uniquely positioned to assist patients and families with tobacco-use prevention and treatment. Understanding the nature and extent of tobacco use and SHS exposure is an essential first step toward the goal of eliminating tobacco use and its consequences in the pediatric population. The next steps include counseling patients and family members to avoid SHS exposures or cease tobacco use; advocacy for policies that protect children from SHS exposure; and elimination of tobacco use in the media, public places, and homes. Three overarching principles of this policy can be identified: (1) there is no safe way to use tobacco; (2) there is no safe level or duration of exposure to SHS; and (3) the financial and political power of individuals, organizations, and government should be used to support tobacco control. Pediatricians are advised not to smoke or use tobacco; to make their homes, cars, and workplaces tobacco free; to consider tobacco control when making personal and professional decisions; to support and advocate for comprehensive tobacco control; and to advise parents and patients not to start using tobacco or to quit if they are already using tobacco. Prohibiting both tobacco advertising and the use of tobacco products in the media is recommended. Recommendations for eliminating SHS exposure and reducing tobacco use include attaining universal (1) smoke-free home, car, school, work, and play environments, both inside and outside, (2) treatment of tobacco use and dependence through employer, insurance, state, and federal supports, (3) implementation and enforcement of evidence-based tobacco-control measures in local, state, national, and international jurisdictions, and (4) financial and systems support for training in and research of effective ways to prevent and treat tobacco use and SHS exposure. Pediatricians, their staff and colleagues, and the American Academy of Pediatrics have key responsibilities in tobacco control to promote the health of children, adolescents, and young adults.
Drowning is a leading cause of injury-related death in children. In 2017, drowning claimed the lives of almost 1000 US children younger than 20 years. A number of strategies are available to prevent these tragedies. As educators and advocates, pediatricians can play an important role in the prevention of drowning. BACKGROUND Drowning is the leading cause of injury death in US children 1 to 4 years of age and the third leading cause of unintentional injury death among US children and adolescents 5 to 19 years of age. 1 In 2017, drowning claimed the lives of almost 1000 US children. Fortunately, childhood unintentional drowning fatality rates have decreased steadily from 2.68 per 100 000 in 1985 to 1.11 per 100 000 in 2017. Rates of drowning death vary with age, sex, and race and/or ethnicity, with toddlers and male adolescents at highest risk. After 1 year of age, male children of all ages are at greater risk of drowning than female children. Overall, African American children have the highest drowning fatality rates, followed in order by American Indian and/or Alaskan native, white, Asian American and/or Pacific Islander, and Hispanic children. For the period 2013-2017, the highest drowning death rates were seen in white male children 0 to 4 years of age (3.44 per 100 000), American Indian and/or Alaskan native children 0 through 4 years (3.58), and African American male adolescents 15 to 19 years of age (4.06 per 100 000). 1 Drowning is also a significant source of morbidity for children. In 2017, an estimated 8700 children younger than 20 years of age visited a hospital emergency department for a drowning event, and 25% of those children were hospitalized or transferred for further care. 1 Most victims of nonfatal drowning recover fully with no neurologic deficits, but severe long-term neurologic deficits are seen with extended submersion times (.6 minutes), prolonged resuscitation efforts, and lack of early bystander-initiated cardiopulmonary resuscitation (CPR). 2-4 The American Academy of Pediatrics issues this revised policy statement because of new information and research regarding (1) populations at
Drowning is a leading cause of injury-related death in children. In 2018, almost 900 US children younger than 20 years died of drowning. A number of strategies are available to prevent these tragedies. As educators and advocates, pediatricians can play an important role in prevention of drowning.
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