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S Robson

Publications and source records attributed to S Robson.

At least 19 recordsLinked to original sources
PubMed2001

Disordered cellular migration and angiogenesis in cd39-null mice.

BACKGROUND: Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39 is the major ectonucleotidase of endothelial cells and monocytes and catalyzes phosphohydrolysis of extracellular nucleoside diphosphates (NDP) and triphosphates (NTP, eg, ATP and UTP). Deletion of cd39 causes perturbations in the hydrolysis of NTP and NDP in the vasculature. Activation of P2 receptors appears to influence endothelial cell chemotactic and mitogenic responses in vitro. Therefore, aberrant regulation of nucleotide P2 receptors may influence angiogenesis in cd39-null mice. Methods and Results- In control mice, implanted Matrigel plugs containing growth factors were rapidly populated by monocyte/macrophages, endothelial cells, and pericytes, with the development of new vessels over days. In cd39-null mice, migrating cells were completely confined to the tissue-Matrigel interface in a clearly stratified manner. Absolute failure of new vessel ingrowth was consistently observed in the mutant mice. Linked to these findings, chemotaxis of cd39-null monocyte/macrophages to nucleotides was impaired in vitro. This abnormality was associated with desensitization of nucleotide receptor P2Y-mediated signaling pathways. CONCLUSIONS: Our findings demonstrate a role for NTPDase1 and phosphohydrolysis of extracellular nucleotides in the regulation of the cellular infiltration and new vessel growth in a model of angiogenesis.

Acid Anhydride Hydrolases↗
PubMed2001

Vesicle-associated proteins and transmitter release from sympathetic ganglionic boutons.

A method is reported for introducing peptides derived from SNARE proteins that control exocytosis of vesicles at boutons formed by sympathetic ganglion cells in tissue culture. These peptides were coupled to the DNA binding domain of the Drosophila transcription factor antennapedia, called penetratin. This facilitated the passage of peptides across the bouton membrane. FM1-43 was used to monitor the exocytosis of transmitter from depolarized boutons after their exposure to the penetratin-peptide sequences IETRHNEIIKLETSIRELHD of syntaxin and KGFLSSLFGGSSK of alpha-SNAP, both of which blocked secretion, whereas the peptide sequences SELDDRA-DALQAGASQFETSAAKLKRK of synaptobrevin did not. This report introduces a readily applicable method for determining the effect of different peptide sequences of vesicle-associated proteins on secretion at vertebrate boutons and presents an account of the effects of a selection of such peptides on exocytosis.

Amino Acid Sequence↗
PubMed2001

Subsequent birth outcomes after an unexplained stillbirth: preliminary population-based retrospective cohort study.

The objective of this study was to determine whether women who have experienced an unexplained stillbirth have a higher risk of adverse perinatal outcomes in subsequent births. We compared 316 subsequent births to women with a previous unexplained stillbirth, with 3160 births to women with no previous history of stillbirth, matched by year of birth, in the period 1987-1997, from the South Australian perinatal database, using logistic regression analysis. There was no increase in the rate of stillbirth and no statistically significant increase in the rate of perinatal death (OR 1.62 [95%CI 0.63-4.20]) or neonatal death, although larger studies are needed to confirm this. However, after adjusting for age, parity, and hospital category of birth, women who had a previous stillbirth had increased incidences in subsequent births of abnormal glucose tolerance or gestational diabetes (a fourfold increase); induction of labour and elective Caesarean section; fetal distress and postpartum haemorrhage; and forceps and emergency Caesarean delivery and preterm birth, which were independent of induction of labour. Gestational age at birth and birthweight were also significantly reduced, suggesting a need for close monitoring of their future pregnancies.

Adult↗
PubMed2001

Micromovements at the aortic aneurysm neck measured during open surgery with close-range photogrammetry: implications for aortic endografts.

PURPOSE: To describe the motion of abdominal aortic aneurysm (AAA) as a first step toward determining if stent-graft migration may be due to propulsive movements at the neck. METHOD: In an initial laboratory validation test, a silicone AAA model was imaged with a stereo-pair configuration of calibrated digital cameras using retro-reflective and ink dot surface targets. This technique was then applied to 4 aneurysm necks imaged at open surgery. In each case the paired images were measured and analyzed to produce sequences of accurate three-dimensional (3-D) surface models of the anterior aspect of the aortic neck. Engineering techniques were used to visualize and identify differences between the generated surfaces, allowing changes in shape of the aortic wall to be determined. RESULTS: The correlation between stereoscopic digital imaging with electronic caliper measurements of linear dimensions was accurate, irrespective of the type of surface targets used (r2 = 0.98). The AAA neck demonstrated complex 3-D movements that ranged from 1.0 to 1.5 mm in the radial direction to 0.6 to 1.0 mm along the longitudinal axis, with a 0.44 to 0.59-mm rotational component (p < 0.05). CONCLUSIONS: This pilot study raises questions about the validity of accepted models of arterial wall movements and compliance in which rotation has not been described. The technique used to measure dynamic neck morphology appears promising as a means to further define the mechanical parameters of the human aorta, which may assist in designing stent-grafts.

Aged↗
PubMed2000

SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development.

SRY, SOX9, and DAX1 are key genes in human sex determination, by virtue of their associated male-to-female sex reversal phenotypes when mutated (SRY, SOX9) or over-expressed (DAX1). During human sex determination, SRY is expressed in 46,XY gonads coincident with sex cord formation, but also persists as nuclear protein within Sertoli cells at 18 weeks gestation. High-level SOX9 expression in the sex cords of the testis parallels that seen during mouse development, however in humans, SOX9 transcripts also are detected in the developing ovary. Low-level DAX1 expression predates peak SRY expression by at least 10 days, and persists in Sertoli cells throughout the entire sex determination period. In Dosage Sensitive Sex reversal, the anti-testis properties of DAX1 over-expression could act prior to the peak effects of SRY and continue during the period of SOX9 expression. These findings highlight expression differences for the SRY, SOX9, and DAX1 genes during sex determination in humans and mice. These results provide a direct framework for future investigation into the mechanisms underlying normal and abnormal human sex determination.

Animals↗
PubMed2000

Human-mouse differences in the embryonic expression patterns of developmental control genes and disease genes.

Our understanding of early human development has been impeded by the general difficulty in obtaining suitable samples for study. As a result, and because of the extraordinarily high degree of evolutionary conservation of many developmentally important genes and developmental pathways, great reliance has been placed on extrapolation from animal models of development, principally the mouse. However, the strong evolutionary conservation of coding sequence for developmentally important genes does not necessarily mean that their expression patterns are as highly conserved. The very recent availability of human embryonic samples for gene expression studies has now permitted for the first time an assessment of the degree to which we can confidently extrapolate from studies of rodent gene expression patterns. We have found significant human-mouse differences in embryonic expression patterns for a variety of genes. We present detailed data for two illustrative examples. Wnt7a, a very highly conserved gene known to be important in early development, shows significant differences in spatial and temporal expression patterns in the developing brain (midbrain, telencephalon) of man and mice. CAPN3, the locus for LGMD2A limb girdle muscular dystrophy, and its mouse orthologue differ extensively in expression in embryonic heart, lens and smooth muscle. Our study also shows how molecular analyses, while providing explanations for the observed differences, can be important in providing insights into mammalian evolution.

5' Untranslated Regions↗
PubMed2000

Management of vaginal agenesis: review of 10 years practice at a tertiary referral centre.

Vaginal agenesis is an uncommon congenital anomaly, and is often associated with agenesis of the uterus and fallopian tubes. Recent reports suggest that non-surgical methods to create a neovagina offer advantages when assisted reproductive treatments are used in the adult life of these women. We have reviewed the management of 39 women with congenital vaginal agenesis to assess the outcomes of neovaginal creation. In 25 women with total Müllerian agenesis, creation of a neovagina using progressive perineal dilatation alone was very successful in women motivated by a sexual relationship.

Adolescent↗
PubMed2000

Prenatal diagnosis of congenital heart disease in the northern region of England: benefits of a training programme for obstetric ultrasonographers.

OBJECTIVE: To examine the results of fetal cardiac scanning and audit the changes in performance resulting from the introduction of a training programme for obstetric ultrasonographers. METHODS: Using the database of the Northern Regional Congenital Abnormality Survey (NORCAS), fetuses with complex or significant congenital heart disease (CCHD) diagnosed prenatally in 1994 were identified. A simple programme of centralised and local training was instituted in 1995 by the department of paediatric cardiology to teach obstetric ultrasonographers in district general hospital maternity departments to identify congenital heart malformations. The results of the training programme were assessed by comparing the 1994 identification rate of CCHD with the rates for 1996 and 1997. RESULTS: Birth rate fell during the study from 35,026 in 1994 to 32,874 in 1997. Registration of CCHD also fell, from 115 in 1994 to 87 in 1997. Prenatal recognition of CCHD rose from 17% in 1994 to 30% in 1995 and 36% in 1996. In 1997 it fell slightly to 26.9%. The total number of scans did not change much year on year, but the number of parents choosing termination increased significantly (from 22.7% to 57%). CONCLUSIONS: A simple training programme for obstetric ultrasonographers increased their ability to detect serious congenital heart disease at a routine 18-20 week anomaly scan. With a termination rate of more than 50%, the incidence of CCHD in the population fell from 3.3/1000 to 2.6/1000 live births. This audit, conducted within a stable population using ascertainment by a well established fetal malformation registry, suggests that prenatal diagnosis may have a significant effect on the incidence of complex or serious congenital cardiac malformations.

Abortion, Therapeutic↗
PubMed1999

The neurodevelopmental outcome of term infants with different intrauterine growth characteristics.

The objective of this study was to test the hypothesis that neurodevelopmental outcome would differ between two groups of small-for-gestational age infants born at term showing different in utero growth characteristics during the third trimester. The design was a prospective cohort study done at a tertiary referral centre. The 76 subjects who fulfilled the inclusion criteria had an estimated fetal weight below the 10th centile for their gestation. Subsequent to enrolment, repeat ultrasound scans were performed weekly to determine growth velocity. Twenty-three infants whose change in fetal abdominal circumference between first and last scan was greater than -1.5 standard deviation scores (SDS) were assigned to the intrauterine growth retardation group (IUGR) while 53 infants whose fetal abdominal circumference changed less than 1.5 SDS were assigned to the small-for-gestational-age (SGA) group. Ten infants with normal intrauterine growth were enrolled as controls. Following delivery all infants had a neurological examination and a cranial ultrasound scan. At 1 year, 75 infants (87%) were traced and reassessed (49 SGA, 18 IUGR and eight controls) with a neurological examination and a developmental assessment. At birth, impairments were found in 27 (51%) of the SGA, 13 (57%) of the IUGR groups and one (10%) of the controls. At 1 year, 18 (37%) of the SGA subjects, six (33%) of the IUGR subjects and one (13%) of the control infant were impaired, including three (6%) of the SGA subjects and one (6%) of the IUGR subjects who were disabled. We conclude that in term fetuses with an estimated birthweight below the 10th centile for their gestation, the pattern of growth in the third trimester does not affect outcome at 1 year. In spite of optimum obstetric management, nearly one-third of the combined SGA and IUGR term fetuses had suffered some, albeit minor, neurological damage.

Apgar Score↗
PubMed1999

Expression of steroidogenic factor 1 and Wilms' tumour 1 during early human gonadal development and sex determination.

The transcription factors SF-1 and WT1 play pivotal roles in mammalian gonadal development and sexual differentiation. In human embryos, both SF-1 and WT1 are expressed when the indifferent gonadal ridge first forms at 32 days post-ovulation. As the sex cords develop - providing morphological evidence of testis differentiation - SF-1 localises predominantly to developing Sertoli cells in the sex cords, whereas WT1 retains a broader pattern of expression. Later, SF-1 localises predominantly to steroidogenic Leydig cells, and WT1 localises to the sex cords. In the ovary, SF-1 and WT1 transcripts persist in the gonadal ridge from the earliest developmental stages throughout the critical period of sex determination. These studies, which delineate for the first time the sequential expression profiles of SF-1 and WT1 during human gonadal development, provide a framework for understanding human sex reversal phenotypes associated with their mutations.

DNA-Binding Proteins↗
PubMed1999

Registrar experience in vaginal breech delivery. How much is occurring?

The debate surrounding the safety of vaginal breech delivery compared to Caesarean delivery may be close to resolution, with a large randomized trial underway. However, trends in the management of vaginal breech delivery over recent years have led to suggestions that training in the technique of such deliveries may be inadequate. We have attempted to quantify the level of training in vaginal breech delivery available to registrars. This was accomplished by surveying obstetric training schemes in comparable regions of England and South Australia. Our findings suggest that registrar exposure to this important obstetric skill may be insufficient to guarantee expertise.

Breech Presentation↗
PubMed1999

Have Kielland forceps reached their 'use by' date?

Kielland forceps have long been used in Australian hospitals for rotation and delivery from occipitolateral and occipitoposterior positions. We have studied the pattern and use of these forceps in our hospital, and conducted a statewide survey of obstetric trainees about their experience with Kielland forceps. We conclude that current obstetric training programmes are unlikely to provide registrars with sufficient skill in their safe use.

Clinical Competence↗
PubMed1998

A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis.

Partial absence of the sacrum is a rare congenital defect which also occurs as an autosomal dominant trait; association with anterior meningocoele, presacral teratoma and anorectal abnormalities constitutes the Currarino triad (MIM 176450). Malformation at the caudal end of the developing notochord at approximately Carnegie stage 7 (16 post-ovulatory days), which results in aberrant secondary neurulation, can explain the observed pattern of anomalies. We previously reported linkage to 7q36 markers in two dominantly inherited sacral agenesis families. We now present data refining the initial subchromosomal localization in several additional hereditary sacral agenesis (HSA) families. We excluded several candidate genes before identifying patient-specific mutations in a homeobox gene, HLXB9, which was previously reported to map to 1q41-q42.1 and to be expressed in lymphoid and pancreatic tissues.

Base Sequence↗