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Biomedical subjects

N Logan

Publications and source records attributed to N Logan.

8 recordsLinked to original sources
PubMed2006

A functionally distinct member of the DP family of E2F subunits.

E2F transcription factors regulate genes involved in cell-cycle progression. In mammalian cells, physiological E2F exists as an E2F/DP heterodimer. Currently, eight E2F and two DP subunits have been characterized. We report here the characterization of a new member of the DP family, DP-4. While DP-4 exhibits certain similarities with members of the DP family, it also possesses a number of significant differences. Thus, DP-4 forms a heterodimer with E2F subunits, binds to the E2F site and associates with pocket proteins including pRb. In contrast to DP-1, however, DP-4/E2F-1 complexes exhibit reduced DNA binding activity. Furthermore, DP-4 interferes with E2F-1-dependent transcription and delays cell-cycle progression. These results highlight an emerging complexity in the DP family of E2F subunits, and suggest that DP-4 may endow E2F heterodimers with distinct transcription properties.

Amino Acid Sequence↗
PubMed2004

Differential regulation of caspase-3 by pharmacological and developmental stimuli as demonstrated using humanised caspase-3 mice.

Caspase-3 is a potential therapeutic target for a number of degenerative diseases. However the development of specific caspase-3 inhibitors has been hampered by inter-species differences and the high degree of homology shared by different caspases. To circumvent these issues, we have produced and characterised a humanised caspase-3 mouse line (possessing one copy of the human gene with both copies of the murine gene disrupted) by crossing human caspase-3 transgenic mice with nullizygous caspase-3 knock-out mice. Humanised mice appeared normal and survived to adulthood. Analysis of the human gene revealed that human pro-caspase-3 was expressed in the same tissues as its murine counterpart. However humanised mice retained the hypercellularity of frontal cortex seen in their knock-out parental line and there was no biochemical evidence of human protein processing during naturally occurring neuronal death taking place during brain development. In contrast, the human protein was cleaved by the mouse machinery following anti-Fas treatment of adult mice. These data suggest that there is a fundamental difference between the activation pathways leading to caspase-3 cleavage during naturally occurring cell death in development/embryogenesis and following an apoptotic stimulus in the adult.

Animals↗
PubMed2004

Mice overexpressing human caspase 3 appear phenotypically normal but exhibit increased apoptosis and larger lesion volumes in response to transient focal cerebral ischaemia.

Caspase 3 activation has been implicated in cell death following a number of neurodegenerative insults. To determine whether caspase genes can affect the susceptibility of cells to neurodegeneration, a transgenic mouse line was created, expressing human caspase 3 under control of its own promoter. The human gene was regulated by the murine homeostatic machinery and human procaspase 3 was expressed in the same tissues as mouse caspase 3. These novel transgenic mice appeared phenotypically and developmentally normal and survived in excess of 2 years. Behavioural assessment using the 5-choice serial reaction time task found no differences from wild-type littermates. Caspase activity was found to be tightly regulated under physiological conditions, however, significantly larger lesions were obtained when transgenic mice were subjected to focal cerebral ischaemia/reperfusion injury compared to wild-type littermates. These data demonstrate that mice overexpressing human caspase 3 are essentially normal, however, they have increased susceptibility to degenerative insults.

Animals↗
PubMed2000

Resting heart rate definition and its effect on apparent levels of physical activity in young children.

PURPOSE: Heart rate monitoring is widely used to measure physical activity in children, but it may be dependent on the definition of resting heart rate used and the protocol used to measure or derive resting heart rate (RHR). The aim of this study was to determine the effect of RHR definition on activity levels assessed by PAHR-25 (% time at >25% of RHR), PAHR-50 (% time at >50% of RHR), and activity heart rate (AHR; mean HR minus RHR). METHODS: Minute-to-minute heart rates were measured over 3 d in 20 healthy preschool children aged 3-4 yr. Resting heart rate was measured for 5 min after a 10-min rest and was also derived from the following different but commonly used protocols: 1) mean of lowest heart rate plus all heart rates within three beats; 2) mean of lowest 5; 3) lowest 10; 4) lowest 50. This gave five different definitions of RHR. Differences in RHR and in the derived indices of activity among definitions were tested for agreement using a Bland-Altman analysis, and by rank order correlation. RESULTS: Differences in RHR among all definitions were statistically significant. These resulted in significant differences in apparent physical activity levels: PAHR-25 varied 10-50% depending on the protocol used to define RHR; PAHR-50 varied by 16-65% as a function of the protocol used to define RHR. However, the different definitions of RHR had no significant influence on physical activity level when children were rank ordered. CONCLUSION: Choice of method for defining RHR has a profound effect on the apparent level of activity of children. This does not alter the relative assessment of activity by rank order. A consensus definition of RHR is desirable if comparisons of activity levels between samples or populations are to be made and if the adequacy of physical activity levels is to be assessed using heart rate.

Body Height↗
PubMed1982

Hypnosis in dental education: a survey of U.S. dental schools, 1980.

This paper reports the results of a 1980 survey of the teaching of hypnosis in U.S. dental schools. Responses were received from 60 dental schools. Information was obtained on hypnosis education in both the predoctoral and postdoctoral curriculums, including what is being taught, how hypnosis education is structured in the curriculum, who is teaching hypnosis, the number of students receiving hypnosis education, and attitudes and policies about hypnosis education. Results of this survey were compared to previous surveys by Parrish (1973) and Scott (1977, for the United Kingdom). The survey reveals a gradual increase in the number of U.S. dental schools teaching hypnosis.

Curriculum↗