Biomedical subjects

Sandra Fischer

Publications and source records attributed to Sandra Fischer.

5 recordsLinked to original sources

PubMed2006

Tumor-derived Ikaros 6 acetylates the Bcl-XL promoter to up-regulate a survival signal in pituitary cells.

We reported the expression of the lymphoid zinc finger transcription factor Ikaros (Ik) in the endocrine pituitary gland, where the usual isoforms, Ik1 and Ik2, are thought to play multiple physiological roles. The gene is alternatively spliced to yield a dominant negative isoform, Ik6, in nearly half of human pituitary tumors. We show here that the tumor-specific truncated Ik6 isoform promotes pituitary tumor AtT20 corticotroph and GH4 mammosomatotroph cell growth, evidenced by increased S-phase entry, colony formation in soft agar, and growth of xenografts in vivo. Ik6-mediated cell growth was associated with enhanced protection against apoptosis and up-regulation of the antiapoptotic factor Bcl-XL but not the related Bcl-2 family member. The effect of Ik6 on Bcl-XL induction was not reproduced by small interfering RNA-mediated Ik-down-regulation, indicating that this effect is not mediated entirely by disruption of Ik1 action. In cotransfection studies, Ik1 attenuated and Ik6 enhanced Bcl-XL promoter activity. The effect of Ik6 was mimicked by histone deacetylation inhibition but not by methylation inhibition. Furthermore, chromatin immunoprecipitation confirmed the ability of Ik6 to selectively acetylate histone 3 sites but not influence methylation of the Bcl-XL promoter. Thus, the contribution of Ik6 to tumor pathogenesis involves up-regulation of an antiapoptotic signal generated through selective acetylation of the Bcl-XL promoter.

Acetylation↗

PubMed2006

An essential role for the hematopoietic transcription factor Ikaros in hypothalamic-pituitary-mediated somatic growth.

Ikaros transcription factors play critical functions in the control of lymphohematopoiesis and immune regulation. Family members contain multiple zinc fingers that mediate DNA binding and homooligomerization or heterooligomerization. Ikaros is abundantly expressed in pituitary mammosomatotrophs, where it deacetylates histone 3 sites on the proximal growth hormone (GH) promoter to silence gene expression. Ikaros-null mice display stunted growth with reduced circulating levels of the GH target factor insulin-like growth factor I (IGF-I). Ikaros-deficient mice have small anterior pituitary glands with a disproportionately reduced somatotroph population. Systemic administration of GH results in increased IGF-I levels and enhanced somatic growth. In contrast, reconstitution with WT lymphocytes was not sufficient to rescue the stunted growth phenotype of Ikaros-deficient mice. Ikaros was identified in mouse hypothalamic arcuate nuclei, where it colocalized with GH-releasing hormone (GHRH); in contrast, Ikaros-null mice lack GHRH immunoreactivity in the hypothalamus. Overexpression of Ikaros enhanced GHRH promoter activity and induced endogenous GHRH gene expression. These findings unmask a wider role for Ikaros in the neuroendocrine system, highlighting a critical contribution to the development of the hypothalamic-pituitary somatotrophic axis.

Animals↗

PubMed2006

Canadian survey of the use of sedatives, analgesics, and neuromuscular blocking agents in critically ill patients.

OBJECTIVES: To characterize the perceived utilization of sedative, analgesic, and neuromuscular blocking agents, the use of sedation scales, algorithms, and daily sedative interruption in mechanically ventilated adults, and to define clinical factors that influence these practices. DESIGN: Cross-sectional mail survey. PARTICIPANTS: Canadian critical care practitioners. MEASUREMENTS AND MAIN RESULTS: A total of 273 of 448 eligible physicians (60%) responded. Respondents were well distributed with regard to age, years of practice, specialist certification, size of intensive care unit and hospital, and location of practice. Twenty-nine percent responded that a protocol/care pathway/guideline for the use of sedatives or analgesics is currently in use in their intensive care unit. Daily interruption of continuous infusions of sedatives or analgesics is practiced by 40% of intensivists. A sedation scoring system is used by 49% of respondents. Of these, 67% use the Ramsay scale, 10% use the Sedation-Agitation Scale, 9% use the Glasgow Coma Scale, and 8% use the Motor Activity Assessment Scale. Only 3.7% of intensivists use a delirium scoring system in their intensive care units. Only 22% of respondents currently have a protocol for the use of neuromuscular blocking agents in their intensive care unit, and 84% of respondents use peripheral nerve stimulation for monitoring. In patients receiving neuromuscular blocking agents for >24 hrs, 63.7% of respondents discontinue the neuromuscular blocking agent daily. Intensivists working in university-affiliated hospitals are more likely to employ a sedation protocol and scale (p < .0001), as are intensivists working in larger intensive care units (>or=15 beds, p < .01). Intensivists with anesthesiology training (and no formal critical care training) are more likely to use a protocol and sedation scale, and critical care-trained intensivists are more likely to use daily interruption. Younger physicians (<40 yrs) are more likely to practice daily interruption (p = .0092). CONCLUSIONS: There is significant variation in critical care sedation, analgesia, and neuromuscular blockade practice. Given the potential effect of practices regarding these medications on patient outcome, future research and educational efforts related to evidence-based protocols for the use of these agents in mechanically ventilated patients might be worthwhile.

Adult↗

PubMed2002

Surgical procedure logging with use of a hand-held computer.

OBJECTIVE: To evaluate the feasibility of incorporating hand-held computing technology in a surgical residency program, by means of hand-held devices for surgical procedure logging linked through the Internet to a central database. SETTING: Division of General Surgery, University of Toronto. DESIGN: A survey of general surgery residents. METHODS: The 69 residents in the general surgery training program received hand-held computers with preinstalled medical programs and a program designed for surgical procedure logging. Procedural data were uploaded via the Internet to a central database. Survey data were collected regarding previous computer use as well as previous procedure logging methods. MAIN OUTCOME MEASURE: Utilization of the procedure logging system. RESULTS: After a 5-month pilot period, 38% of surgical residents were using the procedure-logging program successfully and on a regular basis. Program use was higher among more junior trainees. Analysis of the database provided valuable information on individual trainees, hospital programs and supervising surgeons, data that would assist in program development. CONCLUSIONS: Hand-held devices can be implemented in a large division of general surgery to provide a reference database and a procedure-logging platform. However, user acceptance is not uniform and continued training and support are necessary to increase acceptance. The procedure database provides important information for optimizing trainees' educational experience.

Attitude to Computers↗

PubMedDate not supplied

Handheld computing in medicine.

Handheld computers have become a valuable and popular tool in various fields of medicine. A systematic review of articles was undertaken to summarize the current literature regarding the use of handheld devices in medicine. A variety of articles were identified, and relevant information for various medical fields was summarized. The literature search covered general information about handheld devices, the use of these devices to access medical literature, electronic pharmacopoeias, patient tracking, medical education, research, business management, e-prescribing, patient confidentiality, and costs as well as specialty-specific uses for personal digital assistants (PDAs). The authors concluded that only a small number of articles provide evidence-based information about the use of PDAs in medicine. The majority of articles provide descriptive information, which is nevertheless of value. This article aims to increase the awareness among physicians about the potential roles for handheld computers in medicine and to encourage the further evaluation of their use.

Biomedical Research↗