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Biomedical subjects

A Rae

Publications and source records attributed to A Rae.

At least 19 recordsLinked to original sources
PubMed2003

Maternal phenylketonuria in Western Australia: pregnancy outcomes and developmental outcomes in offspring.

OBJECTIVE: To examine the outcomes of phenylketonuric (PKU) pregnancies in Western Australia including birth characteristics and cognitive and behavioural outcomes in offspring. METHODS: A cross-sectional study of women and their offspring who were identified from the Western Australian Maternal PKU Program (WAMPKUP) from 1991 to 2000 was carried out. Cognitive assessments (K-BIT or Griffiths scales) were conducted on women and their children, and behavioural assessments (CBCL) were conducted on the children. RESULTS: Thirty pregnancies by nine women were registered on the WAMPKUP between 1991 and 2000. There were 16 live births, with one preterm delivery at 32 weeks. There were no congenital abnormalities. Five of the nine mothers and their nine children (aged 18 months-10 years) participated in developmental assessments. A linear relationship was shown between lower maternal IQ scores and later attainment of metabolic control in pregnancy (rs = -0.828; P = 0.01). There was significant correlation between lower offspring IQ scores and later attainment of metabolic control in pregnancy (rs = -0.734; P = 0.02). Correlation between maternal and offspring cognitive scores was not significant. Four of nine (44%) children rated in the clinical range for behavioural problems. Compared to children with no behavioural difficulties, these children had lower cognitive abilities (P = 0.05) and maternal metabolic control during pregnancy was poor (P = 0.05). CONCLUSIONS: Poor metabolic control in pregnancy is associated with poorer cognitive outcomes and increased behavioural difficulties in offspring of mothers with PKU. The results have implications for the implementation of appropriate dietary measures before conception in PKU pregnancies, and indicate a need for the establishment of multidisciplinary teams to follow up individuals with PKU to communicate the importance of pregnancy planning, to manage PKU pregnancies, and to follow up the offspring.

Child Behavior↗
PubMed2001

Protection against vertical transmission in bovine neosporosis.

In this study we were interested to determine whether infection of cattle prior to pregnancy would afford any protection to the foetus if the dams were challenged with Neospora caninum at mid-gestation. The experiment comprised four groups of cattle: group 1, uninfected controls; group 2, inoculated with N. caninum tachyzoites 6 weeks prior to mating and then challenged with N. caninum at mid-gestation; group 3, naive cattle challenged with N. caninum at mid-gestation and group 4 were infected with N. caninum prior to mating and left unchallenged throughout pregnancy. Positive cell-mediated and humoral immune responses to N. caninum were recorded in groups 2 and 4 prior to pregnancy and in groups 2, 3 and 4 following challenge at mid-gestation. However there was a marked down regulation of the cell-mediated immune response in all groups around mid-gestation. There was a significant increase in rectal temperature response in animals in group 3 compared to group 2 following challenge but no other clinical symptoms of disease were recorded and all cattle proceeded to calving. At calving, pre-colostral blood samples were negative for antibodies to N. caninum in all the calves born to dams in groups 1, 2 and 4. In contrast, all the calves born to dams in group 3 had high levels of specific antibody to N. caninum indicating that they had been exposed to the parasite in utero. At post-mortem N. caninum DNA was detected in CNS, thymus and placental cotyledon samples in calves from group 3. All tissue samples from calves in the other 3 groups were negative for N. caninum DNA with the exception of one calf from group 2 where specific DNA was detected in a sample of spinal cord. These results suggest that the immune response generated in the dams in group 2 prior to pregnancy had protected against vertical transmission of the parasite following challenge at mid-gestation.

Animals↗
PubMed2001

A previous infection with Toxoplasma gondii does not protect against a challenge with Neospora caninum in pregnant sheep.

Sheep immunized with Toxoplasma gondii (Toxovax) prior to pregnancy were tested for their ability to withstand a challenge at 90 days gestation with 107 Neospora caninum (NC1) tachyzoites. The antibody responses in sheep following immunization with T. gondii were specific for T. gondii whereas peripheral blood mononuclear cells responded to both T. gondii and N. caninum antigen in vitro. This suggested that there was induction of crossreactive immune recognition in the sheep, at least at the cellular level. Following challenge of sheep at mid-gestation with N. caninum, no febrile responses were recorded in the group of sheep which had previously received Toxovax while significant febrile responses were recorded in the group of sheep which received N. caninum challenge alone. Antibody responses to N. caninum developed in all sheep following N. caninum challenge and antibody responses to T. gondii were boosted in the group of sheep which had previously been immunized with Toxovax. No antibodies to T. gondii were observed in the sheep which received the N. caninum challenge alone. Peripheral blood mononuclear cells from both groups of sheep responded to T. gondii and N. caninum antigen in vitro and interferon gamma was present in the cell-free supernatant from activated cells. However despite evidence of the induction of crossreactive immunity between T. gondii and N. caninum, this was not sufficient to prevent foetal death. The group of sheep which had received Toxovax prior to pregnancy and the group of sheep which only received the N. caninum challenge experienced 100% foetal death compared with 0% in the unchallenged control group. Vaccination prior to pregnancy with Toxovax did protect against foetal death following oral challenge at 90 days with 2000 T. gondii oocysts which caused 100% foetal death in a control challenge group.

Animals↗
PubMed2001

Plasmacytoid dendritic cells are highly susceptible to human immunodeficiency virus type 1 infection and release infectious virus.

Plasmacytoid dendritic cells (pcDC) and myeloid dendritic cells (myDC) are shown to express CD4 and low levels of CCR5 and CXCR4, but only myDC express DC SIGN, a C-type lectin that binds human immunodeficiency virus but does not mediate virus entry. Both DC types were more susceptible to infection with a macrophage than a lymphotropic strain of human immunodeficiency virus type 1, but pcDC were more readily infected than myDC.

CD4 Antigens↗
PubMed2000

A randomised controlled trial of dietary energy restriction in the management of obese women with gestational diabetes.

A randomised controlled trial was designed to determine the effect of moderate 30% maternal dietary energy restriction on the requirement for maternal insulin therapy and the incidence of macrosomia in gestational diabetes. Although the control group restricted their intake to a level similar to that of the intervention group (6,845 kiloJoules (kJ) versus 6,579 kJ), the resulting cohort could not identify any adverse effect of energy restriction in pregnancy. Energy restriction did not alter the frequency of insulin therapy (17.5% in the intervention group and 16.9% in the control group). Mean birthweight (3,461 g in the intervention group and 3,267 g in the control group) was not affected. There was a trend in the intervention group towards later gestational age at commencement of insulin therapy (33 weeks versus 31 weeks) and lower maximum daily insulin dose (23 units versus 60 units) which did not reach statistical significance. Energy restriction did not cause an increase in ketonemia.

3-Hydroxybutyric Acid↗
PubMed2000

Neosporosis. Aspects of epidemiology and host immune response.

Neospora caninum is a recently recognized protozoan parasite which has been described as causing a neuromuscular paralysis in dogs and is emerging as a major cause of bovine infertility and abortion worldwide. The parasite is known to infect a range of warm blooded animals but the disease predominates in dogs and cattle. It is not yet known if N. caninum can infect and cause disease in people. The dog has recently been identified as the definitive host and the parasite may be transmitted through the ingestion of oocysts or congenitally from mother to fetus. N. caninum is known to infect red foxes (Vulpes vulpes) and coyotes (Canis latrans) and the role of wildlife species as reservoirs of infection requires further investigation. Little is known about the range of parasite genotypes within the environment or the variation in virulence between different strains. RAPD-PCR analysis of geographically distinct bovine and canine isolates has revealed little genetic variation. Epidemiological studies from different areas of the world have investigated the importance of N. caninum as an abortifacient agent and longitudinal studies have shown the high rate (approximately 80%) of congenital transmission within infected herds. Information on the rates of repeat abortion due to neosporosis are less well defined however current estimates put this at 5% suggesting that cattle may develop some form of protective immunity against N. caninum-induced abortion. Diagnosis of the disease is based upon detection of the parasite in the tissues, most commonly using immunohistochemistry with additional information provided by serology. However, although positive fetal serology is a strong indicator of exposure to the parasite, care should be taken in the interpretation of maternal serology. As we understand more about the epidemiology of neosporosis we are also better able to interpret the results of diagnostic tests. The mere presence of the parasite does not necessarily infer that this was the primary cause of abortion. CD4+ T-cells, interferon gamma and macrophages have all been found to significantly inhibit multiplication of N. caninum tachyzoites. The nature of a protective immune response and its modulation in the pregnant animal is discussed.

Animals↗
PubMed2000

A three year review of injuries to professional footballers (1995-98) and comparison with previous observations (1990-93).

A prospective study over a three year period (1995-8) of footballers' injuries in first team players was undertaken in a similar fashion to a previous study (1990-3). During the present study the Club had a major cup success and appeared to have a younger squad with less major injury and subsequent time out of action. As a result of the earlier paper it would appear that some lessons and observations may have been put into action and helped produce a more consistent standard for the club. Increasing recognition of the need to reduce and monitor the levels and types of injuries seems now to be established.

Adult↗
PubMed2000

The cellular basis of immune induction at mucosal surfaces by DNA vaccination.

The nasal mucosa provides a simple, non-invasive route to deliver DNA encoding the gene of interest to stimulate mucosal and systemic immune responses. However, unlike the intradermal or intramuscular routes for plasmid DNA (pDNA) delivery, immune responsiveness to antigen exposure at the respiratory mucosa is tightly regulated, consistent with the balance between active immunity and non-responsiveness to pathogenic or inert environmental antigens. We have characterised the antigen presenting cell types, their distribution and activation status following nasal vaccination with pDNA-cytofectin complexes encoding model antigens. We demonstrate that nasal immunisation is associated with expression of the encoded protein in a small population of dendritic cells and macrophages at the site of pDNA delivery, in the draining lymph nodes (LN) and in the spleen. Antigen expression by nasal dendritic cells was associated with up-regulation of surface MHC class II and CD86 expression and functional activation of T-lymphocytes. The results highlight the potential of intranasal vaccination with pDNA, provided the activation / costimulatory requirements for an active immune response are achieved.

Administration, Intranasal↗
PubMed1999

Activation of the mitogen-activated protein kinase pathway by a Gq/11-coupled muscarinic receptor is independent of receptor internalization.

A number of recent studies have demonstrated an essential role for receptor endocytosis in the activation of the mitogen-activated protein (MAP) kinases, Erk-1 and Erk-2 (extracellular activated protein kinases 1 and 2), by growth factor receptors and the G-protein coupled beta2-adrenergic receptor. Because ligand-mediated receptor endocytosis and activation of the MAP kinase pathway are common phenomena among G-protein coupled receptors, it has been suggested that the essential role of endocytosis in MAP kinase activation identified for the beta2-adrenergic receptor may be universal for all G-protein coupled receptors (Daaka,Y., Luttrell, L. M., Ahn, S., Della Rocca, G. J., Ferguson, S. S. G., Caron, M. G., and Lefkowitz, R. J. (1998) J. Biol. Chem. 273, 685-688). We tested this hypothesis using the Gq/11-coupled m3-muscarinic receptor expressed in Chinese hamster ovary cells and an m3-muscarinic receptor mutant that does not undergo endocytosis. We demonstrate that inhibition of endocytosis by concanavalin A and cytochalasin D does not affect the ability of the wild type m3-muscarinic receptor to activate Erk-1/2. Furthermore, the mutant m3-muscarinic receptor that is unable to undergo endocytosis, activates the MAP kinase pathway in an identical manner to the wild type receptor. We conclude that receptor endocytosis is not universally essential for MAP kinase activation by G-protein coupled receptors. We discuss the possibility that the differential roles played by endocytosis in MAP kinase activation between various receptor subtypes may be linked to the mechanism of upstream activation of Raf-1.

Animals↗
PubMed1995

A review of injuries to professional footballers in a premier football team (1990-93).

A prospective study of injuries sustained by first team professional foot-ballers either in training or in competition was undertaken over a 3 year period. These were injuries which resulted in loss of availability for playing. In a total of 27 players, 94 significant injuries occurred resulting in 364 weeks "out of action". 79% of these injuries were sustained in matches. Midfield players suffered the most injuries (39%). A prospective study in Heart of Midlothian Football Club's first team players over a 3 year period 1990-3 revealed that significant injuries resulting in loss of availability for playing occurred in 27 players. The majority of injuries occurred in match play (79%) with the average time "out of action" per player being 13 weeks (overall total = 364 weeks). Midfield players suffered the most injuries (39%) and the most common anatomical site of injury was the thigh followed by the knee. Muscle and ligament injuries were the commonest soft tissue problem. 6% of injuries were skeletal. Players older than 26 years of age appeared to be more prone to injury. No good correlation could be found between the number of games played and increased likelihood of injuries.

Adult↗
PubMed1994

A single allele from the polymorphic CCG rich sequence immediately 3' to the unstable CAG trinucleotide in the IT15 cDNA shows almost complete disequilibrium with Huntington's disease chromosomes in the Scottish population.

The CCG rich sequence immediately 3' to the CAG repeat that is expanded in Huntington's disease (HD) has recently been shown to be polymorphic with at least 4 alleles differing by multiples of 3 bp being found in the normal population. We have studied the allele distribution in 180 HD families resident in Scotland and have found very strong evidence for disequilibrium in this population. For the 131 families where phase was unambiguously determined, 130 were shown to have a CCG repeat allele of 176 bp cosegregating with the HD chromosome. This observation is significantly different to the normal population distribution where 31% of people have an allele of 185 bp. The evidence for and against a possible founder effect in the Scottish HD population is discussed. We propose the hypothesis that we may have identified a region of the IT15 gene that is critical in Huntington's disease.

Alleles↗
PubMed1994

Laparoscopic Ileogastrostomy for Morbid Obesity.

This paper describes the technique of laparoscopic ileogastrostomy which we developed during the summer of 1993. The procedure is identical to that of our 'open' ileogastrostomy except that it is performed laparoscopically. The aim of the surgery is to increase ambulation of the patient, while reducing pain, morbidity, and the chance of apnea (due to impaired breathing in the first 24 h following conventional surgery), by carrying out surgery for the morbidly obese person through a laparoscope. This form of laparoscopic surgery may be completed within 4 h and, as our staff gains more experience with laparoscopic ileogastrostomy, we expect patient stays to be 2-3 days in length. Pulmonary function tests at 24 h show a great advantage in favor of the laparoscopic approach. Response of the medical team to this procedure was that it was more time-consuming and demanding than open surgery.

Journal Article↗