Biomedical subjects

S Tyrrell

Publications and source records attributed to S Tyrrell.

At least 19 recordsLinked to original sources

PubMed1992

Effects of ciliary neurotrophic factor (CNTF) and depolarization on neuropeptide expression in cultured sympathetic neurons.

We examined the effects of ciliary neurotrophic factor (CNTF) and depolarization, two environmental signals that influence noradrenergic and cholinergic function, on neuropeptide expression by cultured sympathetic neurons. Sciatic nerve extract, a rich source of CNTF, increased levels of vasoactive intestinal peptide (VIP), substance P, and somatostatin severalfold while significantly reducing levels of neuropeptide Y (NPY). No change was observed in the levels of leu-enkephalin (L-Enk). These effects were abolished by immunoprecipitation of CNTF-like molecules from the extract with an antiserum raised against recombinant CNTF, and recombinant CNTF caused changes in neuropeptide levels similar to those of sciatic nerve extract. Alterations in neuropeptide levels by CNTF were dose-dependent, with maximal induction at concentrations of 5-25 ng/ml. Peptide levels were altered after only 3 days of CNTF exposure and continued to change for 14 days. Depolarization of sympathetic neuron cultures with elevated potassium elicited a different spectrum of effects; it increased VIP and NPY content but did not alter substance P, somatostatin, or L-Enk. Depolarization is known to block cholinergic induction in response to heart cell conditioned medium and we found that it blocked the induction of choline acetyltransferase (ChAT) and peptides by recombinant cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF). In contrast, it did not antagonize the effects of CNTF on either ChAT activity or neuropeptide expression. Thus, while CNTF has effects on neurotransmitter properties similar to those previously reported for CDF/LIF, the actions of these two factors are differentially modulated by depolarization, suggesting that the mechanisms of cholinergic and neuropeptide induction for the two factors differ. In addition, in contrast to CDF/LIF, CNTF did not alter levels of ChAT, VIP, substance P, or somatostatin in cultured dorsal root ganglion neurons. These observations indicate that CNTF and depolarization affect the expression of neuropeptides by sympathetic neurons and provide evidence for an overlapping yet distinct spectrum of actions of the two neuronal differentiation factors, CNTF and CDF/LIF.

Animals↗

PubMed1992

Tyrosine hydroxylase and neuropeptide Y are increased in ciliary ganglia of sympathectomized rats.

We have examined the expression of tyrosine hydroxylase and neuropeptide Y in ciliary ganglia of normal adult rats and of adult rats in which the environment of these neurons was altered by sympathectomy at birth. Following neonatal 6-hydroxydopamine treatment, the proportion of tyrosine hydroxylase-immunoreactive and neuropeptide Y-immunoreactive neurons in ciliary ganglia was significantly increased. In ciliary neurons of both control and sympathectomized rats, neuropeptide Y immunoreactivity was preferentially co-localized with tyrosine hydroxylase. Immunoblot analysis confirmed the presence of tyrosine hydroxylase and its increase following sympathectomy. In situ hybridization studies revealed that many ciliary neurons contain mRNA for tyrosine hydroxylase and for neuropeptide Y. Like tyrosine hydroxylase immunoreactivity, the number of ciliary neurons containing tyrosine hydroxylase mRNA and the amount of mRNA per cell were increased in 6-hydroxydopamine-treated rats. In contrast, neuropeptide Y mRNA levels were the same in control and 6-hydroxydopamine-treated rats. Nerve growth factor is a candidate for mediating the effects of sympathectomy and most ciliary neurons in control and sympathectomized rats expressed immunoreactivity for the low-affinity nerve growth factor receptor. In addition, ciliary neurons from 6-hydroxydopamine-treated animals possessed increased nerve growth factor receptor immunoreactivity. These studies indicate that both tyrosine hydroxylase and neuropeptide Y in the ciliary ganglion are regulated by alterations in their environment. Their expression was enhanced by chemical sympathectomy which does not affect ciliary neurons directly but, rather, removes sympathetic innervation of shared targets, including the iris. In situ hybridization analysis suggests that the increased tyrosine hydroxylase and neuropeptide Y levels result from different mechanisms and provides evidence that neuropeptide levels can be regulated without changes in mRNA levels.

Animals↗

PubMed1990

Distribution and projection pattern of motoneurons that innervate hindlimb muscles in the quail.

We characterized the motoneuron pool positions and projection patterns in the embryonic quail hindlimb and compared them to those in the chick to determine the degree of similarity and to form a baseline for future chimeric experiments. We find that the most similar parameters of pool position correlate with the major axonal pathway choices. First, the medial-lateral pool position, which is highly conserved among birds and mammals, is identical in the quail and chick and correlates with the dorsal-ventral pathway choice, the first and least plastic of the choices within the limb. Second, although quail pools were known to be compressed into seven rather than eight segments, we show that the map of pools is compressed about a central point (segment three) that preserves the spatial relationships between anterior pools and the crural plexus, and between posterior pools and the sciatic plexus. Access to guidance cues that are restricted to each plexus region is thus maintained between species. Third, pool position along the anterior-posterior axis is the least similar parameter between species. In fact, the entire lumbosacral motor complex may shift by +/- half a segment in individual quail. Despite the consequent differences in segmental projections, the specific projection pattern within each quail hindlimb is identical to that in the chick. There is no need to preserve the exact segmental pattern either phylogenetically or during development, because motoneurons accommodate to modest variations in their position along the anterior-posterior axis by sorting out at the limb base. The contrast between variable segmental and constant limb projections also demonstrates that neither the specification nor the precise projection of motoneurons is dependent upon the specification or development of somites.

Animals↗

PubMed1989

Umbilical artery Doppler velocimetry as a predictor of fetal hypoxia and acidosis at birth.

We studied the relationship between preoperative umbilical artery Doppler waveforms and umbilical vein pO2 and pH at elective cesarean section. An absence of end-diastolic velocities had a strong statistical association with hypoxia and acidosis, and was an accurate clinical test for hypoxia (sensitivity 78%, specificity 98%, positive predictive value 88%, and negative predictive value 98%) and acidosis (sensitivity 90%, specificity 92%, positive predictive value 53%, and negative predictive value 100%). It was also a clinically sensitive indicator of perinatal morbidity and mortality. Most fetuses with no end-diastolic velocities were growth-retarded, but the reverse was not true. The absence of end-diastolic velocities also divided both mature and immature fetuses into high- and low-risk groups for hypoxia and acidosis. In the presence of end-diastolic velocities, only very high S/D ratios (above 4.5) have any association with hypoxia. As a noninvasive test of fetal umbilical vein pO2 and pH, umbilical artery Doppler performs well.

Acidosis↗

PubMed1988

Should maternal alpha-fetoprotein estimation be carried out in centers where ultrasound screening is routine? A sensitivity analysis approach.

We describe a case of small, open spina bifida that was detected on the basis of maternal serum alpha-fetoprotein levels but consistently missed on careful ultrasound examination. This prompted us to reexamine the policy (adopted by an increasing number of departments) of relying exclusively on ultrasound examination for the detection of spinal lesions. In this article we therefore analyze the number of additional cases of spina bifida that could be detected by offering maternal serum alpha-fetoprotein screening in addition to a routine ultrasound examination. Our calculations are made on the basis of published assessments of the performance of these tests and on the assumptions about test independence. We test our conclusions against a wide variety of test performance values in a detailed sensitivity analysis. The final decision to carry out maternal serum alpha-fetoprotein testing is a value judgment, but this decision should be based on realistic numeric estimates of the potential benefits and hazards of this procedure.

Adolescent↗

PubMed1988

Sinuatrial disease causing persistent fetal bradycardia: intrauterine detection and management.

We report a case of sustained sinus bradycardia, detected at 32 weeks gestation and confirmed by echocardiography, where emergency caesarian section was avoided by demonstration of normal intrauterine cord blood pH and oxygen tension. Delivery at 37 weeks produced a healthy girl who required no resuscitation. The bradycardia persisted and, in the absence of structural heart disease, was attributed to sinuatrial disease. Persistent fetal sinus bradycardia is not necessarily an indication for urgent delivery.

Adult↗

PubMed1987