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Biomedical subjects

Susan Smith

Publications and source records attributed to Susan Smith.

45 records · Page 3Linked to original sources
PubMed2002

Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres.

Telomere maintenance is essential for the continuous growth of tumor cells. In most human tumors telomeres are maintained by telomerase, a specialized reverse transcriptase. Tankyrase 1, a human telomeric poly(ADP-ribose) polymerase (PARP), positively regulates telomere length through its interaction with TRF1, a telomeric DNA-binding protein. Tankyrase 1 ADP-ribosylates TRF1, inhibiting its binding to telomeric DNA. Overexpression of tankyrase 1 in the nucleus promotes telomere elongation, suggesting that tankyrase 1 regulates access of telomerase to the telomeric complex. The recent identification of a closely related homolog of tankyrase 1, tankyrase 2, opens the possibility for a second PARP at telomeres. We therefore sought to establish the role of tankyrase 1 at telomeres and to determine if tankyrase 2 might have a telomeric function. We show that endogenous tankyrase 1 is a component of the human telomeric complex. We demonstrate that telomere elongation by tankyrase 1 requires the catalytic activity of the PARP domain and does not occur in telomerase-negative primary human cells. To investigate a potential role for tankyrase 2 at telomeres, recombinant tankyrase 2 was subjected to an in vitro PARP assay. Tankyrase 2 poly(ADP-ribosyl)ated itself and TRF1. Overexpression of tankyrase 2 in the nucleus released endogenous TRF1 from telomeres. These findings establish tankyrase 2 as a bona fide PARP, with itself and TRF1 as acceptors of ADP-ribosylation, and suggest the possibility of a role for tankyrase 2 at telomeres.

Cell Nucleus↗
PubMed2002

Supporting clinical leaders in achieving organisational change.

Clinical leaders in nursing may feel stuck in the middle of conflicting demands from the various members of their organisation and patients' needs. The LEO programme aims to help these clinical leaders identify their problems, agree action plans and ask for the support they need in bringing about positive change in their workplace.

Humans↗
PubMed2002

Lead screening: for the child's sake.

Lead poisoning in children can be devastating to their cognitive and behavioral development. This tragedy can be prevented with information to parents and physicians. This article summarizes the effects of lead poisoning and provides a literature review of previous studies on how often and on whom physicians should conduct blood lead level screenings. It also gives the guidelines for conducting screenings and how to process and treat the results. Health care providers are encouraged to use these guidelines for conducting screenings and follow the recommendations provided by the American Academy of Pediatrics and the Centers for Disease Control and Prevention.

Child, Preschool↗
PubMedDate not supplied

Predictors of intubation success and therapeutic value of paramedic airway management in a large, urban EMS system.

BACKGROUND: Endotracheal intubation (ETI) is commonly used by paramedics for definitive airway management. The predictors of success and therapeutic value with regard to oxygenation are not well studied. OBJECTIVES: 1) To explore the relationship between intubation success and perfusion status, Glasgow Coma Scale (GCS) score, and end-tidal carbon dioxide (EtCO2); 2) to describe the incidence of unrecognized esophageal intubations with use of continuous capnometry; and 3) to document the incremental benefit of invasive versus noninvasive airway management techniques in correcting hypoxemia. METHODS: This was a prospective, observational study conducted in a large urban emergency medical services system. Paramedics completed a telephone debriefing interview with quality assurance personnel following delivery of all patients in whom invasive airway management had been attempted. Continuous capnometry was used for confirmation of tube position in all patients. Descriptive statistics were used to document airway management performance, including first-attempt ETI success, overall ETI success, and Combitube insertion (CTI) success. In addition, the incidence of unrecognized esophageal intubation was recorded. The relationship between intubation success and perfusion status, GCS score, and initial EtCO2 value was explored using logistic regression. Finally, recorded SpO2 values and the incidence of hypoxemia (SpO2 < 90%) at baseline, following noninvasive airway maneuvers, and after invasive airway management were compared for perfusing patients. RESULTS: A total of 703 patients were enrolled over 12 months. First-attempt ETI success was 61%, and overall ETI success was 81%; invasive airway management (ETI or CTI) was unsuccessful in 11% of patients. A single unrecognized esophageal intubation was observed (0.1%). A clear relationship between airway management success and perfusion status, GCS score, and initial EtCO2 value was observed. Only EtCO2 demonstrated an independent association with ETI success after adjusting for the other variables. Significant improvements in mean SpO2 and the incidence of hypoxemia over baseline were observed with both noninvasive and invasive airway management techniques in 168 perfusing patients. CONCLUSIONS: A relationship between intubation success and perfusion status, GCS score, and initial EtCO2 value was observed. Capnometry was effective in eliminating unrecognized esophageal intubations. Both noninvasive and invasive airway management strategies were effective in increasing SpO2 values and decreasing the incidence of hypoxemia, with additional benefit observed with invasive airway maneuvers in some patients.

California↗
PubMedDate not supplied

Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing.

Activated protein C (APC) is a serine protease that plays a central role in physiological anticoagulation, and has more recently been shown to be a potent anti-inflammatory mediator. Using cultured human cells, we show here that APC up-regulates the angiogenic promoters matrix metalloproteinase-2 in skin fibroblasts and umbilical vein endothelial cells, vascular endothelial growth factor in keratinocytes and fibroblasts, and monocyte chemoattractant protein-1 in fibroblasts. In the chick embryo chorioallantoic membrane assay, APC promoted the granulation/remodeling phases of wound healing by markedly stimulating angiogenesis as well as promoting reepithelialization. In a full-thickness rat skin-healing model, a single topical application of APC enhanced wound healing compared to saline control. APC-treated wounds had markedly more blood vessels on day 7 and a significantly lower infiltration of neutrophils at days 4 and 7. The broad spectrum matrix metallo-proteinase, GM6001, prevented the ability of APC to promote wound healing. In summary, our results show that APC promotes cutaneous wound healing via a complex mechanism involving stimulation of angiogenesis and inhibition of inflammation. These unique properties of APC make it an attractive therapeutic agent to promote the healing of chronic wounds.

Animals↗