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Biomedical subjects

A L Abbott

Publications and source records attributed to A L Abbott.

10 recordsLinked to original sources

Calcium and the control of mammalian cortical granule exocytosis.

At fertilization, the release of intracellular calcium is necessary and sufficient for most, if not virtually all, of the major events of egg activation that are responsible for the onset of embryonic development. In mammalian eggs, repetitive calcium oscillations stimulate egg activation events through calcium-dependent effectors, such as calmodulin, protein kinases, and specific proteins involved in exocytosis. One of the earliest calcium-dependent events is the exocytosis of cortical granules (CGs), a secretory event resulting in the block to polyspermy and the prevention of triploidy. Emerging studies suggest that CG release in mature eggs is dependent upon calcium-dependent proteins similar to those in somatic cells employed to undergo calcium-regulated exocytosis. In contrast, pre-ovulatory oocytes are incompetent to undergo CG exocytosis due to deficiencies in the ability to release and respond to increases in intracellular calcium. The development of competence to release and respond to calcium is relevant to both animal and human in vitro fertilization programs that largely utilize ovarian oocytes not all of which are fully activation competent.

Adaptor Proteins, Signal Transducing↗

Dextran reduces embolic signals after carotid endarterectomy.

One hundred fifty patients undergoing carotid endarterectomy were randomly assigned to receive intravenous 10% dextran 40 or placebo. Transcranial Doppler monitoring of the ipsilateral middle cerebral artery 0 to 1 hour postoperatively detected embolic signals in 57% of placebo and 42% of dextran patients, with overall embolic signal counts 46% less for dextran (p = 0.052). Two to 3 hours postoperatively, embolic signals were present in 45% of placebo and 27% of dextran patients, with embolic signal counts 64% less for dextran (p = 0.040). We conclude that dextran reduces embolic signals within 3 hours of CEA.

Aged↗

Infant motor development and equipment use in the home.

Forty-three mother-infant dyads were recruited to determine the relationship between both total equipment use and the use of individual pieces of equipment and infant motor development. At 8 months of age, total and individual equipment use was determined by parental survey and infant motor development was assessed using the Alberta Infant Motor Scale. Statistically significant correlations were found for the relationships between total equipment use and infant motor development (r = -0.50, P = 0.001) and individual pieces of equipment [exersaucer (r = -0.58, P = 0.001), highchair (r = -0.32, P = 0.04), and infant seat (r = -0.32, P = 0.03)] and infant motor development. These findings suggest that infants who have high equipment use tend to score lower on infant motor development or that infants who have low equipment use tend to score higher on infant motor development. Limitations of this cross-sectional study make it difficult to determine causality between these constructs. If equipment use is found to be causally related to infant motor development and predictive of later motor development in a future prospective study, parental education emphasizing the moderate use of equipment within the home environment might be warranted.

Child Development↗

Identification of a translocation deficiency in cortical granule secretion in preovulatory mouse oocytes.

Preovulatory, germinal vesicle (GV)-stage mouse oocytes are unable to undergo normal cortical granule (CG) secretion. Full secretory competence is observed by metaphase II (MII) of meiosis and involves the development of calcium response mechanisms. To identify the deficient or inhibited step in CG secretion, preovulatory GV-stage oocytes were stimulated and tested for their ability to undergo translocation, docking, and/or fusion. The mean CG distance to the plasma membrane was not reduced in fertilized or sperm fraction-injected, GV-stage oocytes relative to that in control GV-stage oocytes. In addition, analysis of individual CG distances to the plasma membrane indicated no subpopulation of CGs competent to translocate. Further analysis demonstrated that secretory incompetence likely is not due to a lack of proximity of CGs to the egg's primary calcium store, the endoplasmic reticulum. Calcium/calmodulin-dependent protein kinase II (CaMKII), which is reportedly involved in secretory granule translocation and secretion in many cells, including eggs, was investigated. A 60-kDa CaMKII isoform detected by Western blot analysis increased 150% during oocyte maturation. The CaMKII activity assays indicated that MII-stage eggs correspondingly have 110% more maximal activity than GV-stage oocytes. These data demonstrate that the primary secretory deficiency is due to a failure of CG translocation, and that a maturation-associated increase in CaMKII correlates with the acquisition of secretory competence and the ability of the egg to undergo normal activation.

Animals↗

Incompetence of preovulatory mouse oocytes to undergo cortical granule exocytosis following induced calcium oscillations.

Immature oocytes of many species are incompetent to undergo cortical granule (CG) exocytosis upon fertilization. In mouse eggs, CG exocytosis is dependent primarily on an inositol 1,4,5-trisphosphate (IP3)-mediated elevation of intracellular calcium ([Ca2+]i). While deficiencies upstream of [Ca2+]i release are known, this study examined whether downstream deficiencies also contribute to the incompetence of preovulatory mouse oocytes to release CGs. The experimental strategy was to bypass upstream deficiencies by inducing normal, fertilization-like [Ca2+]i oscillations in fully grown, germinal vesicle (GV) stage oocytes and determine if the extent of CG exocytosis was restored to levels observed in mature, metaphase II (MII)-stage eggs. Because IP3 does not stimulate a normal Ca2+ response in GV-stage oocytes, three alternate methods were used to induce oscillations: thimerosal treatment, electroporation, and sperm factor injection. Long-lasting oscillations from thimerosal treatment resulted in 64 and 10% mean CG release at the MII and GV stages, respectively (P < 0.001). Three electrical pulses induced mean [Ca2+]i elevations of approximately 730 and 650 nM in MII- and GV-stage oocytes, respectively, and 31% CG release in MII-stage eggs and 9% in GV-stage oocytes (P < 0.001). Sperm factor microinjection resulted in 86% CG release in MII-stage eggs, while similarly treated GV-stage oocytes exhibited < 1% CG release (P < 0.001). Taken together, these results demonstrate a deficiency downstream of [Ca2+]i release which is developmentally regulated in the 12 h prior to ovulation.

Animals↗

In vitro culture retards spontaneous activation of cell cycle progression and cortical granule exocytosis that normally occur in in vivo unfertilized mouse eggs.

We have previously demonstrated that metaphase II-arrested eggs recovered from oviducts at increasing times after hCG administration display a time-dependent spontaneous entry into anaphase, as well as release of cortical granules (CGs) and the associated modifications of the zona pellucida (ZP), a decrease in histone H1 and mitogen-activated protein kinase activities, and the recruitment of maternal mRNAs [Xu et al., Biol Reprod 1997; 57:743-750). These changes are correlated with the time-dependent increase in susceptibility of these eggs to undergo parthenogenetic activation. We report here the effect of culture of ovulated eggs, retrieved 13 or 16 h post-hCG administration and cultured in vitro for various periods of time, on the aforementioned parameters of egg activation and cell cycle resumption. In contrast to extended residence of the eggs in the oviduct, culture in vitro retarded cell cycle events associated with completion of the second meiotic reduction and inhibited CG release and the associated modifications of the ZP, as well as the recruitment of maternal mRNAs. The retardation or inhibition of these changes during in vitro culture resulted in eggs that were less susceptible to parthenogenetic activation than eggs that resided in the oviduct for comparable time periods. Results of these experiments indicate that egg culture in vitro (which likely occurs under suboptimal conditions) inhibits, rather than accelerates, the progression into the interphase-like state as compared to that seen in eggs residing in the oviduct for increasing periods of time. These results also suggest that, for studies focused on in vitro fertilization or egg activation, the ovulated eggs should be placed under appropriate in vitro conditions as soon as possible.

Animals↗

Medicaid managed care in Texas. What have we learned from the pilots?

Texas has a plan for statewide implmentation of Medicaid managed care by 2001. This article presents evidence from initial demonstration projects, which were implemented in 1993. The 1st-year experience is described and preliminary effects are examined in terms of reactions of clients and providers and changes in utilization patterns and costs of care. Results of the evaluation indicate implementation difficulties with several operational aspects of managed care, variable effects in terms of client and provider reaction to the reform, and little or no change in utilization patterns, but significant cost-savings to the state. Because of the implementation difficulties identified by the evaluation and the mixed results regarding effects, further research is recommended to determine the potential benefit of this reform.

Child↗