Alison Rodriguez | PubMed Health

PubMed2006

The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly.

The heterodimeric tumor-suppressor complex BRCA1/BARD1 exhibits E3 ubiquitin ligase activity and participates in cell proliferation and chromosome stability control by incompletely defined mechanisms. Here we show that, in both mammalian cells and Xenopus egg extracts, BRCA1/BARD1 is required for mitotic spindle-pole assembly and for accumulation of TPX2, a major spindle organizer and Ran target, on spindle poles. This function is centrosome independent, operates downstream of Ran GTPase, and depends upon BRCA1/BARD1 E3 ubiquitin ligase activity. Xenopus BRCA1/BARD1 forms endogenous complexes with three spindle-pole proteins, TPX2, NuMA, and XRHAMM--a known TPX2 partner--and specifically attenuates XRHAMM function. These observations reveal a previously unrecognized function of BRCA1/BARD1 in mitotic spindle assembly that likely contributes to its role in chromosome stability control and tumor suppression.

Animals↗

PubMed2004

The startle test revisited.

OBJECTIVE: Our purpose was to the compare fetal heart reaction to external physical stimulation with the nonstress test (NST). STUDY DESIGN: This prospective study evaluates documentation of fetal heart rate accelerations by two methods. The standard NST was performed prior to the ultrasound evaluation. The NST results were unavailable to the ultrasonographer. M-mode ultrasound was used initially to detect a stable heart rate. Then the ultrasound transducer was used to stimulate fetal movement by indenting the uterus over the fetal small parts. A second fetal heart rate was determined within 15 seconds after stimulation. RESULTS: A total of 194 patients underwent 235 studies. The patient population included four sets of twins. When the NST was reactive, 151/216 had an ultrasound startle response of > or =15 beats per minute; however, all nonreactive NSTs were associated with an ultrasound response of 14 beats per minute or less (p<0.001). A receiver-operating characteristic curve comparing the ultrasound fetal response to the startle with the NST identified the area under the curve to be 0.948, consistent with high specificity and sensitivity. CONCLUSION: The fetal heart rate response to external stimulation identifies 67% of patients with a reactive NST.

Female↗