LAWRENCE LONGO

..Ovine CAs at 95 GD appeared morphologically immature and poorly equipped to respond to major hemodynamic adjustments with maturation...

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..This essay considers Osler's scholarship as evidenced in his historical and biographical writings, and some lessons that we might learn from his endeavours...

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..In addition, phosphorylated CPI-17 may regulate Ca(2+) sensitivity by interacting with caldesmon and reversing its inhibitory effect on myosin ATPase...

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..This may have important implications in the regulation of cerebral blood flow in the developing organism...

..We suggest that maternal O2 administration can have an important effect in ameliorating nonreassuring fetal status, and perhaps be of value in instances of mothers who smoke heavily or with cardiopulmonary disease...

..Chronic hypoxia suppresses uterine artery sensitivity to cortisol, which may play an important role in the adaptation of uterine vascular tone and blood flow in response to chronic stress of hypoxia during pregnancy...

..We conclude that in fetal and adult ovine cerebral arteries, alpha(2)-AR appear to be chiefly prejunctional. Nonetheless, the fetal cerebral arteries appear to have a significant component of postjunctional alpha(2)-AR...

..The latter may play a key role in the pathophysiologic disorders associated with acclimatization to high altitude...

..We speculate that in fetal CA alpha(1B)-AR and alpha(1D)-AR subtypes may be a critical factor associated with cerebrovascular growth and function...

..In addition, despite differences in several variables, the fetus at high altitude showed evidence of successful acclimatization, supporting the hypothesis that such fetuses demonstrate no compromise in cerebral oxygenation...

..The greater cerebral myogenic response in P14 compared with adult MCA appears to be due to greater pressure-induced increases in [Ca(2+)](i), rather than enhanced augmentation of myofilament calcium sensitivity...

..The study was undertaken to determine to what extent a 10-minute total umbilical cord occlusion affects autoregulation of cerebral blood flow and cerebral heat production in the fetus...

..In addition, the results suggest that pregnancy increases type 2 11 beta-hydroxysteroid dehydrogenase activity in the UA...

..In contrast, ERK attenuates the thin filament regulatory pathway and suppresses contractions independent of changes in LC20 phosphorylation in the uterine artery...

..In response to hypercapnia in high-altitude, acclimatized, long-term hypoxic fetal sheep, the response of CBF and cerebral oxygenation did not differ significantly from that of low-altitude controls...

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..However, the PKC-mediated thin-filament regulatory pathway is upregulated, resulting in increased baseline Ca(2+) sensitivity in the uterine artery during pregnancy at high altitude...

..In addition, PKC plays an important role in the regulation of basal Ca2+ sensitivity, which is downregulated during pregnancy...

..Overall, the present study demonstrates an important maturational shift from RhoA/ROCK-mediated to CPI-17/caldesmon-mediated PKC-induced contractile response in ovine cerebral arteries...

..Hypercapnia favored cerebral tissue oxygenation of the fetal brain; and cortical tPo2 and sagittal sinus [HbO2] complement or support one another as indices of cerebral oxygenation under hypercapnic conditions...

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..The findings suggest an augmented nitrite reductase activity of fetal hemoglobin and that the production of nitrite may participate in the regulation of vascular NO homeostasis in the fetus...

..In addition, the relatively constant expression levels of alpha-actin and cyclophilin A with development, suggest that these are useful internal standards for studies of cytosolic protein expression...

..Flow compensations in acute hypoxia are not adequate to sustain O(2) delivery, and other compensations, including reduced metabolic rate, are possible...

..These results also support the hypothesis of significant developmental differences with maturation from fetus to adult...

..In addition, ERK1/2-dependent phosphorylation of caldesmon(Ser789) was not necessary for PDBu-induced contraction and appears not to be involved in the reversal of caldesmon's inhibitory effect on actin-myosin ATPase...

..In addition to highlighting independent regulation of various elements of the signal transduction cascade, the studies demonstrate the potential for LTH to program the fetus for cerebrovascular and other disease as an adult...

..They specifically highlight the significant differences in acclimatization responses between the fetus and adult...

..Overall, the results of this study demonstrate selective adaptations in receptor-mediated Ca(2+) signaling, but not in cellular Ca(2+) homeostasis...

..The authors speculate that for a fetus that may be otherwise compromised, this increase in CMRO(2) with decreased cortical tPO(2) could present a problem...

..We tested the hypothesis that supplemental CO2 can enhance the effect of maternal oxygen administration on fetal cerebral oxygenation...

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..For the normoxic fetus, CBF was closely related to ECoG state, but this association was less evident during acute hypoxia. We speculate that, in the otherwise stressed fetus, acute hypoxia may further compromise cerebral oxygenation...

..Lower Ca0 and Kd values in BK channels of fetal myocytes can be explained by a greater extent of channel phosphorylation of fetal than adult myocytes...

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..e., the calcium set points) at 0 mV were 8.8 and 4.7 microM for adult and fetal myocytes, respectively. Thus the increased BKCa current density in fetal myocytes appears to result from a lower calcium set point...

..We speculate that these changes have important implications in the regulation of cerebral blood flow in the developing organism...

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..In addition, these findings suggest that the functional stoichiometry of CAPAKs varies significantly during development and that such variation may be a hitherto unrecognized mechanism of ion channel regulation...

..The early years of the American Gynecological Club represent a somewhat idyllic and bygone era in medicine and obstetrics and gynecology...

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..In the current study, we tested the hypothesis that antenatal maternal low protein diet (MLPD) leads to epigenetic changes and alterations in gene expression of brain RAS of the mouse fetus...

..The risk of late fetal or neonatal death from increased Hb(CO) from diffusion testing is considerably less than the risk of death from all causes reported by the Centers for Disease Control, and is therefore considered "minimal risk"...

..Our data indicate that EGFR plays a role in fetal ovine pulmonary vascular remodeling following long-term fetal hypoxia and that inhibition of EGFR signaling may ameliorate hypoxia-induced pulmonary vascular remodeling...

..Further analysis has demonstrated that several functional classes are up- and down-regulated at specific time points in placental development. These changes may have significant implications for placental development in the human...

..The observation that hypoxia upregulates reactive oxygen species metabolism, in conjunction with DNA methylation enzymes, suggests that hypoxia may contribute to long-term epigenetic changes in stressed fetal tissues and organs...

..Increased ROCK activity may inhibit PKG action through increased phosphorylation of MYPT1 at Thr696 and Thr850...

..Also, except for the spleen where there is a high expression of HO-1 under normal conditions, tissue HO activity is correlated with the expression of HO-2, the constitutive isozyme...

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..These findings suggest that increased PAF-R protein expression and increased PAF binding contribute to pulmonary vascular remodeling in these animals and may predispose them to persistent pulmonary hypertension after birth...

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..We will quantify the relation of fetal oxygen levels to placental diffusing capacity, and the relation of fetal oxygenation to severity of maternal exercise. ..

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..Overall, these studies will form a basis for gene or other therapy for the prevention and/or amelioration of these disorders. ..

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