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Biomedical subjects

B Storey

Publications and source records attributed to B Storey.

At least 19 recordsLinked to original sources
PubMed2001

Regulation of oxygen sensing in peripheral arterial chemoreceptors.

The carotid bodies are a small pair of highly vascularized and well perfused organs located at each carotid artery bifurcation, strategically situated to sense oxygen in arterial blood as it leaves the heart. Carotid body glomus cells are identified as the primary oxygen sensors, which respond to changes in blood P(O(2)) within milliseconds. Acute hypoxia causes a rapid increase in carotid sinus nerve (CSN) activity, providing afferent signals to the respiratory center in the brainstem. Glomus cells secrete numerous neurotransmitters that modulate CSN firing rates. This review will discuss major hypotheses that have emerged regarding acute oxygen sensing by glomus cells. In contrast, chronic responses to hypoxia are much slower, involving cytosolic reactions that take place over several minutes and nuclear reactions which occur over several hours. Converging concepts from different areas of research in oxygen sensing cells and tissues (including the carotid body) have been combined to describe molecular and biochemical changes that take place in the carotid body with chronic hypoxia. These include oxygen dependent proteolytic processes in the cytosol and gene transcription in the nucleus. In addition, cellular and nuclear responses to chronic hypoxia will be discussed.

Animals↗
PubMed2000

The metabolic hypothesis revisited.

High levels of CO are used to mimic the stimulatory response of the CSN initiated by hypoxia. Using light of different wavelengths we show that the stimulatory effects of high CO can be pinpointed to the cytochrome c oxidase in the mitochondrial respiratory chain. This supports the metabolic theory of oxygen sensing in the mitochondria.

Animals↗
PubMed1997

c-Jun NH2-terminal kinase regulation of the apoptotic response of small cell lung cancer cells to ultraviolet radiation.

Exposure of cultured small cell lung cancer (SCLC) cells to UV radiation induces apoptosis. We observed that the UV sensitivity of a panel of SCLC lines and the activation of c-Jun NH2-terminal kinases (JNKs) by UV in the individual SCLC lines, assessed by binding and phosphorylation of glutathione S-transferase (GST)-c-Jun fusion proteins, ranged widely. In fact, increased JNK activity in this assay was closely correlated with decreased sensitivity to apoptosis following UV irradiation. Increased JNK activity was also detected in anti-JNK1 immune complexes collected from UV-irradiated SCLC cells, although the level of activity was similar among the various SCLC lines and correlated poorly with UV sensitivity. Immunoblot analysis of JNK polypeptides that bound to GST-c-Jun revealed at least two JNK polypeptides, one of which appeared only in extracts from UV-irradiated SCLC. To test the role of JNKs in UV-induced apoptosis, nonphosphorylatable mutants of JNK1 or JNK2 in which the phosphorylation site Thr-Pro-Tyr is changed to Ala-Pro-Phe (JNK-APF) and are predicted to behave as competitive inhibitors were stably expressed in SCLC. Expression of JNK1-APF or JNK2-APF significantly reduced UV-stimulated JNK activity. However, JNK1-APF markedly increased the resistance of the cells to UV-induced apoptosis, while JNK2-APF did not influence SCLC sensitivity to UV. The findings suggest that UV-stimulated JNK1 activation promotes UV-induced SCLC apoptosis, while a JNK isoform that is variably activated among the SCLC lines may signal a UV-protective response. We hypothesize that integration of distinct JNK activities dictates the relative responsiveness of SCLC to UV and ionizing radiation.

Apoptosis↗
PubMed1996

Discordant signal transduction and growth inhibition of small cell lung carcinomas induced by expression of GTPase-deficient G alpha 16.

Small cell lung carcinoma (SCLC) accounts for 20-25% of primary lung cancers and is rapidly growing, widely metastatic, and rarely curable. Autocrine stimulation of multiple G protein-coupled neuropeptide receptor systems contributes to the transformed growth of SCLC. The ability of neuropeptide receptors to stimulate phospholipase C and mobilize intracellular Ca2+ indicates that Gq family members of heterotrimeric G proteins are a convergence point mediating autocrine signaling by multiple neuropeptides in SCLC. Expression of a GTPase-deficient, constitutive active form of an alpha q family member, alpha 16Q212L, in SCLC markedly inhibited growth of the cells in soft agar and tumor formation in nude mice. SCLC lines expressing alpha 16Q212L exhibited 2-4-fold elevated basal phospholipase C activity, but neuropeptide and hormone-regulated intracellular Ca2+ mobilization was nearly abolished. The data suggest that Ca2+ mobilization is an obligatory signal in neuropeptide-stimulated growth of SCLC. In addition, the proline-directed c-Jun NH2-terminal kinases/stress-activated protein kinases, which are members of the mitogen-activated protein kinase family, were stimulated approximately 2-fold in parental SCLC in response to exogenous neuropeptides and muscarinic agonists and were constitutively activated to the same degree in alpha 16Q212L-expressing SCLC. Thus, alpha 16Q212L expression induced desensitizaton of neuropeptide-stimulated Ca2+ signaling and persistent activation of the c-Jun NH2-terminal kinase/stress-activated protein kinase pathway. We propose that the induction of discordant signaling by selective perturbation of receptor-regulated effector systems leads to the inhibition of SCLC cell growth.

Amino Acid Sequence↗
PubMed1996

GTPase-deficient G alpha 16 and G alpha q induce PC12 cell differentiation and persistent activation of cJun NH2-terminal kinases.

Persistent stimulation of specific protein kinase pathways has been proposed as a key feature of receptor tyrosine kinases and intracellular oncoproteins that signal neuronal differentiation of rat pheochromocytoma (PC12) cells. Among the protein serine/threonine kinases identified to date, the p42/44 mitogen-activated protein (MAP) kinases have been highlighted for their potential role in signalling PC12 cell differentiation. We report here that retrovirus-mediated expression of GTPase-deficient, constitutively active forms of the heterotrimeric Gq family members, G alpha qQ209L and G alpha 16Q212L, in PC12 cells induces neuronal differentiation as indicated by neurite outgrowth and the increased expression of voltage-dependent sodium channels. Differentiation was not observed after cellular expression of GTPase-deficient forms of alpha i2 or alpha 0, indicating selectivity for the Gq family of G proteins. As predicted, overexpression of alpha qQ209L and alpha 16Q212L constitutively elevated basal phospholipase C activity approximately 10-fold in PC12 cells. Significantly, little or no p42/44 MAP kinase activity was detected in PC12 cells differentiated with alpha 16Q212L or alpha qQ209L, although these proteins were strongly activated following expression of constitutively active cRaf-1. Rather, a persistent threefold activation of the cJun NH2-terminal kinases (JNKs) was observed in PC12 cells expressing alpha qQ209L and alpha 16Q212L. This level of JNK activation was similar to that achieved with nerve growth factor, a strong inducer of PC12 cell differentiation. Supportive of a role for JNK activation in PC12 cell differentiation, retrovirus-mediated overexpression of cJun, a JNK target, in PC12 cells induced neurite outgrowth. The results define a p42/44 MAP kinase-independent mechanism for differentiation of PC12 cells and suggest that persistent activation of the JNK members of the proline-directed protein kinase family by GTPase-deficient G alpha q and G alpha 16 subunits is sufficient to induce differentiation of PC12 cells.

Animals↗
PubMed1995

Mitogen-activated protein kinase activation is insufficient for growth factor receptor-mediated PC12 cell differentiation.

When expressed in PC12 cells, the platelet-derived growth factor beta receptor (beta PDGF-R) mediates cell differentiation. Mutational analysis of the beta PDGF-R indicated that persistent receptor stimulation of the Ras/Raf/mitogen-activated protein (MAP) kinase pathway alone was insufficient to sustain PC12 cell differentiation. PDGF receptor activation of signal pathways involving p60c-src or the persistent regulation of phospholipase C gamma was required for PC12 cell differentiation. beta PDGF-R regulation of phosphatidylinositol 3-kinase, the GTPase-activating protein of Ras, and the tyrosine phosphatase, Syp, was not required for PC12 cell differentiation. In contrast to overexpression of oncoproteins involved in regulating the MAP kinase pathway, growth factor receptor-mediated differentiation of PC12 cells requires the integration of other signals with the Ras/Raf/MAP kinase pathway.

Animals↗
PubMed1991

Possible causes linking asphyxia, thick meconium and respiratory distress.

The cause of fetal distress and neonatal respiratory distress (RD) in association with meconium-stained liquor is not always clear. To clarify this, a prospective study was undertaken in a tertiary referral maternity hospital for 1 year. In all infants born after meconium-stained liquor who developed RD, evidence was sought for 1) fetal distress (from the cardiotocograph (CTG), the cord blood pH, the Apgar score and the asphyxial complications in the neonate) 2) causes of fetal distress (including maternal risk factors, fetal infection and fetal malnutrition) 3) causes of respiratory distress (including meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn (PPHN) and infection). Of 4,026 livebirths, 717 (17.8%) had meconium-stained liquor and 44 term and 5 preterm infants developed RD. In the 44 term infants, there was frequent evidence of fetal distress possibly caused by previously unrecognized factors such as fetal malnutrition with reduced neonatal skinfold thickness in 35% triceps and 41% subscapular measurements, and histological chorioamnionitis (CA) in 74%. The cause for respiratory distress was identified in only 48% of infants, and included clinical evidence of PPHN (41%), MAS (16%) and infection (2%). However in preterm infants, 80% had definite or suspected infection. The findings indicate that fetal distress is common in infants who develop respiratory distress after meconium-stained liquor. A role for histological CA and reduced nutrition in the fetus, as factors contributing to the vulnerability of the term infant to intrapartum fetal distress, is suggested.

Apgar Score↗
PubMed1985

The early development of head control in preterm infants.

This study documents the longitudinal development of head control in 104 infants born at 25-33 weeks gestation. Protective side turning of the head was found to have a developmental sequence of reducing spinal extension. In the 93 infants with normal motor outcome, individual differences in the rate of development correlated with caudo-cephalic muscle development (P less than 0.001, r = 0.5) but not with the length of extra-uterine experience. As a group, the 11 infants with later motor handicap showed a persistence of the early form of movement at 35-39 weeks post-menstrual age, without a significant correlation with the ratio of upper-lower limb muscle development. Head control, supine to sitting, in the infants with normal motor outcome showed variations in the rate of preterm development. The infants born at less than 31 weeks showed significantly higher scores at 33-35 weeks post-menstrual age than those born at 31-33 weeks (P less than 0.01). There was no difference at later ages. The spinal extension movement accompanying protective side turning of the head is age specific to the preterm infant. Individual rates of normal preterm development can be evaluated by longitudinal standardised examination. As a group, the infants with subsequent abnormal motor development showed delay at preterm age but this was not individually significant.

Cerebral Palsy↗
PubMed1985

Combined renal and pancreatic dysplasia in the newborn.

A term female infant with early onset respiratory distress and pneumothorax died on day 20 with renal failure. Autopsy revealed dysplastic kidneys with occasional cortical cysts. The pancreas showed focal dysplasia with cysts and dilated ducts lying in primitive mesenchyme. A mild chronic inflammatory infiltrate was present in the dysplastic areas of kidneys and pancreas. The abnormalities in the affected organs were similar to those in two siblings described by Ivemark et al. in 1959 and designated "familial dysplasia of kidneys, liver and pancreas". Relationships to subsequently reported cases, including some with major congenital malformations, and the validity of this dysplastic triad as a disease entity are examined.

Female↗
PubMed1980

Incidence of the respiratory distress syndrome in infants of diabetic mothers--perinatal influences.

This survey of 73 infants of insulin dependent (ID) diabetic mothers and 70 infants of gestational diabetics (GD) born at King George V Memorial Hospital between January, 1968 and December, 1975, showed that all 12 babies with RDS were from the ID group. RDS was the cause of all 6 neonatal deaths and together with the 5 stillbirths gave this high risk group a 15% mortality rate. Since no deaths occurred in the GD group, the overall mortality was 8%. In the 6 years, 1970-1975, RDS occurred 21 times more often in babies of ID mothers than in control babies born to non-diabetics. Babies born to ID mothers were of significantly lower mean gestational age than those born to the GD mothers. Within the ID group, those babies with RDS were of significantly lower gestation than those without and the mean gestation was similar to control babies with RDS. Provided the diabetes is controlled and fetal welfare ensured, later delivery, following documentation of lung maturity, may lower the incidence of RDS and therefore perinatal mortality and morbidity.

Diabetes Complications↗
PubMed1977

Neonates at risk. Screening for deafness--practical or not?

Over a six-year period, 3,507 neonates in King George V Memorial Hospital, classified as being at risk for deafness, were screened for hearing. Although 144 failed to respond in the nurseries, 88 of them were cleared at a later test. The remainder, whether suspect, untraceable or still to return, would all be outside the neonatal period by now. No sensorineural impairment of hearing was detected in all neonates in the programme.

Australia↗
PubMed1976

Perinatal implications of the respiratory distress syndrome.

Major advances in the prevention and treatment of the respiratory distress syndrome (RDS) have occurred. Since 1970 there has been a fall in the mortality rate but not in the incidence. Persistence of the disorder could be partly accounted for by the increasing practice of elective delivery in normal pregnancies. In 1974 and 1975, 28 (25%) of babies with RDS were delivered this way and six died. The major problem appeared to be mistaken gestational age.

Australia↗