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Biomedical subjects

J Dodd

Publications and source records attributed to J Dodd.

At least 19 recordsLinked to original sources
PubMed2006

RNA polymerase II elongation factors Spt4p and Spt5p play roles in transcription elongation by RNA polymerase I and rRNA processing.

Previous investigations into the mechanisms that control RNA Polymerase (Pol) I transcription have primarily focused on the process of transcription initiation, thus little is known regarding postinitiation steps in the transcription cycle. Spt4p and Spt5p are conserved throughout eukaryotes, and they affect elongation by Pol II. We have found that these two proteins copurify with Pol I and associate with the rDNA in vivo. Disruption of the gene for Spt4p resulted in a modest decrease in growth and rRNA synthesis rates at the permissive temperature, 30 degrees C. Furthermore, biochemical and EM analyses showed clear defects in rRNA processing. These data suggest that Spt4p, Spt5p, and, potentially, other regulators of Pol I transcription elongation play important roles in coupling rRNA transcription to its processing and ribosome assembly.

Chromosomal Proteins, Non-Histone↗
PubMed2004

Treatment for women with postpartum iron deficiency anaemia.

BACKGROUND: Postpartum anaemia is associated with breathlessness, tiredness, palpitations and maternal infections. Blood transfusions or iron supplementation have been used in the treatment of iron deficiency anaemia. Recently other anaemia treatments, in particular erythropoietin therapy, have also been used. OBJECTIVES: To assess the clinical effects of treatments for postpartum anaemia, including oral, intravenous or subcutaneous iron/folate supplementation and erythropoietin administration, and blood transfusion. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (30 May 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to March 2003), EMBASE (1980 to March 2003), Current Contents and ACP Journal Club (from inception to March 2003). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing therapy for postpartum iron deficiency anaemia (oral, intravenous or subcutaneous administration of iron, folate, erythropoietin or blood transfusion) with placebo, another treatment or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Six included RCTs involving 411 women described treatment with erythropoietin or iron as their primary interventions. No RCTs were identified that assessed treatment with blood transfusion. Few outcomes relating to clinical maternal and neonatal factors were reported: studies focused largely on surrogate outcomes such as haematological indices. Overall, the methodological quality of the included RCTs was reasonable; however, their usefulness in this review is restricted by the interventions and outcomes reported. When compared with iron therapy only, erythropoietin increased the likelihood of lactation at discharge from hospital (1 RCT, n = 40; relative risk (RR) 1.90, 95% confidence interval (CI) 1.21 to 2.98). No apparent effect on need for blood transfusions was found, when erythropoietin plus iron was compared to treatment with iron only (2 RCTs, n = 100; RR 0.20, 95% CI 0.01 to 3.92), although the RCTs may have been of insufficient size to rule out important clinical differences. Haematological indices (haemoglobin and haemocrit) showed some increases when erythropoietin was compared to iron only, iron and folate, but not when compared with placebo. REVIEWERS' CONCLUSIONS: There is some limited evidence of favourable outcomes for treatment of postpartum anaemia with erythropoietin. However, most of the available literature focuses on laboratory haematological indices, rather than clinical outcomes. Further high-quality trials assessing the treatment of postpartum anaemia with iron supplementation and blood transfusions are required. Future trials may also examine the significance of the severity of anaemia in relation to treatment, and an iron-rich diet as an intervention.

Anemia, Iron-Deficiency↗
PubMed2001

Two-kaon correlations in central Pb+Pb collisions at 158 a GeV/c.

Two-particle interferometry of positive kaons is studied in Pb+Pb collisions at mean transverse momenta approximately 0.25 and 0.91 GeV/c. A three-dimensional analysis was applied to the lower p(T) data, while a two-dimensional analysis was used for the higher p(T) data. We find that the source-size parameters are consistent with the m(T) scaling curve observed in pion-correlation measurements in the same collisions, and that the duration time of kaon emission is consistent with zero within the experimental sensitivity.

Journal Article↗
PubMed2001

Petrol sniffing in a pregnant Aboriginal population: a review of maternal and neonatal outcomes.

The study's aim was to determine if petrol sniffing during pregnancy is associated with adverse maternal and neonatal outcomes at the Alice Springs Hospital. The study design was a retrospective case note review. The subjects were Aboriginal women who delivered at the Alice Springs Hospital between July 1991 and September 1999 where petrol sniffing was identified on the discharge coding; 14 women with 21 pregnancies were identified. One hundred and eleven nulliparous Aboriginal women who delivered at hospital between July 1998 and June 1999, with singleton gestation in cephalic presentation, were identified from the birth register and used as the control group. We found that women identified as petrol sniffers during pregnancy presented later for antenatal care, had fewer antenatal visits, lower booking haemoglobin and weighed less at booking when compared with non-petrol-sniffing women. Women who sniffed petrol during pregnancy were more likely to have one or more sexually transmitted diseases identified during the pregnancy; to use other substances during pregnancy; to be colonised with group B Streptococcus; to have meconium stained liquor prior to delivery; and to have a still-birth. Infants born to petrol-sniffing mothers were more likely to have birthweight less than 2,500 g; to have Apgar scores of less than 7 at 5 minutes; to require admission to the neonatal unit; and to be placed in foster care or for adoption. We concluded that the pregnancy complicated by petrol sniffing should be recognised as one at increased risk of adverse outcome, necessitating increased antenatal surveillance. However, as with other substances abused, it is extremely difficult to determine the role played by the substance per se, and that of the lifestyle associated with the abuse behaviour.

Adolescent↗
PubMed2000

Antideuteron production in 158A GeV/c Pb + Pb collisions

The invariant cross section as a function of transverse momentum for antideuterons produced in 158A GeV/c per nucleon Pb+Pb central collisions has been measured by the NA44 experiment at CERN. This measurement, together with a measurement of antiprotons, allows for the determination of the antideuteron coalescence parameter. The extracted coalescence radius is found to agree with the deuteron coalescence radius and radii determined from two particle correlations.

Journal Article↗
PubMed2000

Use of cues by Lipophrys pholis L. (Teleostei, Blenniidae) in learning the position of a refuge.

The ability of Lipophrys pholis to remember the position of a refuge was tested in an artificial habitat under the influence of different visual clues. L. pholis learned the position of the refuge in the presence of a clue consisting only of a small black screen. They responded to this clue by moving towards it and pressing themselves up against it. Lego towers and a white screen clue did not provoke such a response. In a further experiment L. pholis continued to respond to the black screen in this way when the screen was moved to another location further from the refuge. After 12 days L. pholis learned to use the black screen in its new position as an indirect clue and navigate to the refuge directly without first approaching the black screen. These results suggested that when placed in a novel habitat the immediate reaction of L. pholis is to move quickly towards the first dark area they see but, with experience, they can use the position of large objects around them to navigate quickly and efficiently to a refuge.

Journal Article↗
PubMed2000

Paradoxical vocal cord motion causing stridor after thyroidectomy.

Two women developed stridor immediately after thyroidectomy as a result of paradoxical vocal cord motion. In both cases the cord function showed a normal pattern during vocalisation but paradoxical movement was seen at laryngoscopy during tidal breathing. The abnormality improved in both patients over time with speech therapy. Whilst the syndrome of paradoxical vocal cord motion is classically thought to have a largely psychological aetiology, subtle interference with laryngeal innervation at surgery is more likely to have been the cause in these cases.

Adult↗
PubMed1999

The cost of research: an analysis of Auckland Healthcare's research activity.

AIM: Research informs clinical practice. It may also increase the cost of health service delivery, especially in an academic medical centre, where there is a greater concentration of research activity. Data on the cost of research in New Zealand Hospital and Health Services, particularly those providing teaching and other academic opportunities, are scarce. This article describes a method for collecting and analysing data related to research activities at Auckland Healthcare, New Zealand's largest Hospital and Health Service and, in association with the Auckland School of Medicine, the largest clinical research facility. METHOD: During the 1996/1997 financial year, 190 research projects received Auckland Healthcare management approval. The nature, purposes, and budget for each project were recorded on a dedicated database. The financial data excluded the University-funded components of research. RESULTS: Data presented for the 1996/1997 financial year reveal the volume, nature and cost of research for Auckland Healthcare. The budgeted external revenue was $1.6M, with 52% coming from commercial sponsors. Interestingly, 8% of the research projects during this period were budgeted to generate savings to the cost of standard clinical care. This was achieved primarily through the sponsorship of pharmaceuticals in commercial clinical trials. When these revenues and savings are deducted, the net budgeted cost of research at Auckland Healthcare in the 1996/1997 financial year was $86 572, or only 0.02% of total cost. CONCLUSION: The Ministry of Health and the Health Funding Authority are voicing concern over the diversion of clinical care funding for research in Hospital and Health Services. While these concerns might be philosophically challenged on the grounds that sound research informs best clinical practice, it is also clear from these results that the net cost of research at Auckland Healthcare is indeed very small.

Budgets↗
PubMed1999

BMPs as mediators of roof plate repulsion of commissural neurons.

During spinal cord development, commissural (C) neurons, located near the dorsal midline, send axons ventrally and across the floor plate (FP). The trajectory of these axons toward the FP is guided in part by netrins. The mechanisms that guide the early phase of C axon extension, however, have not been resolved. We show that the roof plate (RP) expresses a diffusible activity that repels C axons and orients their growth within the dorsal spinal cord. Bone morphogenetic proteins (BMPs) appear to act as RP-derived chemorepellents that guide the early trajectory of the axons of C neurons in the developing spinal cord: BMP7 mimics the RP repellent activity for C axons in vitro, can act directly to collapse C growth cones, and appears to serve an essential function in RP repulsion of C axons.

Animals↗
PubMed1999

Endometrial balloon ablation under local analgesia and intravenous sedation.

We report a series of women (n = 16) with menorrhagia undergoing endometrial balloon ablation under local analgesia with light sedation. Ten women had significant, coexistent medical problems. The median duration of the procedure was 8.6 minutes (range 8.47-9.5 minutes). Postoperative assessment included pain scores assessed by linear analogue scale; requirement for opiate analgesia; length of postoperative stay and patient satisfaction with the procedure. The minimum postoperative follow-up was 6 months. The procedure was well-tolerated and in 80% of cases either no postoperative analgesia or simple analgesia only was required. Two women were admitted overnight, 1 for social reasons and the other for pain control. Three women ages 44, 54 and 55 years were amenorrhoeic at 6 months; 8 women were still menstruating but satisfied with the outcome and 5 women are seeking further treatment for menorrhagia. While the longer-term efficacy of the procedure remains to be established these results indicate that endometrial balloon ablation under local analgesia and light sedation, a simple and acceptable technique, may be a suitable alternative to more difficult procedures such as rollerball ablation. This is most likely to be the case in appropriately selected women who are willing to accept a reduction in menstrual flow rather than amenorrhoea as the treatment outcome. The main disadvantage of balloon ablation is the cost of the disposable balloons and the need for a dedicated electrosurgical unit.

Adult↗
PubMed1999

Differential patterning of ventral midline cells by axial mesoderm is regulated by BMP7 and chordin.

Ventral midline cells in the neural tube have distinct properties at different rostrocaudal levels, apparently in response to differential signalling by axial mesoderm. Floor plate cells are induced by sonic hedgehog (SHH) secreted from the notochord whereas ventral midline cells of the rostral diencephalon (RDVM cells) appear to be induced by the dual actions of SHH and bone morphogenetic protein 7 (BMP7) from prechordal mesoderm. We have examined the cellular and molecular events that govern the program of differentiation of RDVM cells under the influence of the axial mesoderm. By fate mapping, we show that prospective RDVM cells migrate rostrally within the neural plate, passing over rostral notochord before establishing register with prechordal mesoderm at stage 7. Despite the co-expression of SHH and BMP7 by rostral notochord, prospective RDVM cells appear to be specified initially as caudal ventral midline neurectodermal cells and to acquire RDVM properties only at stage 7. We provide evidence that the signalling properties of axial mesoderm over this period are regulated by the BMP antagonist, chordin. Chordin is expressed throughout the axial mesoderm as it extends, but is downregulated in prechordal mesoderm coincident with the onset of RDVM cell differentiation. Addition of chordin to conjugate explant cultures of prechordal mesoderm and neural tissue prevents the rostralization of ventral midline cells by prechordal mesoderm. Chordin may thus act to refine the patterning of the ventral midline along the rostrocaudal axis.

Animals↗
PubMed1999

Stromal cells mediate retinoid-dependent functions essential for renal development.

The essential role of vitamin A and its metabolites, retinoids, in kidney development has been demonstrated in vitamin A deficiency and gene targeting studies. Retinoids signal via nuclear transcription factors belonging to the retinoic acid receptor (RAR) and retinoid X receptor (RXR) families. Inactivation of RARaplpha and RARbeta2 receptors together, but not singly, resulted in renal malformations, suggesting that within a given renal cell type, their concerted function is required for renal morphogenesis. At birth, RARalpha beta2(-) mutants displayed small kidneys, containing few ureteric bud branches, reduced numbers of nephrons and lacking the nephrogenic zone where new nephrons are continuously added. These observations have prompted us to investigate the role of RARalpha and RARbeta2 in renal development in detail. We have found that within the embryonic kidney, RARalpha and RARbeta2 are colocalized in stromal cells, but not in other renal cell types, suggesting that stromal cells mediate retinoid-dependent functions essential for renal development. Analysis of RARalpha beta2(-) mutant kidneys at embryonic stages revealed that nephrons were formed and revealed no changes in the intensity or distribution of molecular markers specific for different metanephric mesenchymal cell types. In contrast the development of the collecting duct system was greatly impaired in RARalpha beta2(-) mutant kidneys. Fewer ureteric bud branches were present, and ureteric bud ends were positioned abnormally, at a distance from the renal capsule. Analysis of genes important for ureteric bud morphogenesis revealed that the proto-oncogene c-ret was downregulated. Our results suggest that RARalpha and RARbeta2 are required for generating stromal cell signals that maintain c-ret expression in the embryonic kidney. Since c-ret signaling is required for ureteric bud morphogenesis, loss of c-ret expression is a likely cause of impaired ureteric bud branching in RARalpha beta2(-) mutants.

Animals↗
PubMed1997

Cooperation of BMP7 and SHH in the induction of forebrain ventral midline cells by prechordal mesoderm.

Ventral midline cells at different rostrocaudal levels of the central nervous system exhibit distinct properties but share the ability to pattern the dorsoventral axis of the neural tube. We show here that ventral midline cells acquire distinct identities in response to the different signaling activities of underlying mesoderm. Signals from prechordal mesoderm control the differentiation of rostral diencephalic ventral midline cells, whereas notochord induces floor plate cells caudally. Sonic hedgehog (SHH) is expressed throughout axial mesoderm and is required for the induction of both rostral diencephalic ventral midline cells and floor plate. However, prechordal mesoderm also expresses BMP7 whose function is required coordinately with SHH to induce rostral diencephalic ventral midline cells. BMP7 acts directly on neural cells, modifying their response to SHH so that they differentiate into rostral diencephalic ventral midline cells rather than floor plate cells. Our results suggest a model whereby axial mesoderm both induces the differentiation of overlying neural cells and controls the rostrocaudal character of the ventral midline of the neural tube.

Animals↗
PubMed1997

Outcomes of induced labour.

We report a review of maternal and neonatal outcomes of labour in 1,405 pregnancies managed during a 12-month period. This included all singleton pregnancies of greater than 20 weeks' gestation, excluding women antenatally assigned for Caesarean delivery. Labour was induced in 313 cases (22.3%), and records were available for review in 311 of these. We classified the indications for induction according to the Australian Council of Healthcare Standards (ACHS)/RACOG list of 'defined' indications in Obstetric Clinical Indicator number 1. In 165 cases (53.7%) labour was induced for defined indications. There was no significant difference in the rates of instrumental vaginal delivery, Caesarean delivery or adverse neonatal outcome (admission to neonatal nursery in the first 24 hours of life; 5 minute Apgar score of < 7) between women who laboured spontaneously and those induced for 'nondefined' indications. However, labours induced for 'defined' indications had a significantly increased rate of these outcomes.

Adult↗
PubMed1997

Misexpression of Cwnt8C in the mouse induces an ectopic embryonic axis and causes a truncation of the anterior neuroectoderm.

Transgenic embryos expressing Cwnt8C under the control of the human beta-actin promoter exhibit duplicated axes or a severely dorsalised phenotype. Although the transgene was introduced into fertilised eggs all duplications occurred within a single amnion and, therefore, arose from the production of more than one primitive streak at the time of gastrulation. Morphological examination and the expression of diagnostic markers in transgenic embryos suggested that ectopic Cwnt8C expression produced only incomplete axis duplication: axes were always fused anteriorly, there was a reduction in tissue rostral to the anterior limit of the notochord, and no duplicated expression domain of the forebrain marker Hesx1 was observed. Anterior truncations were evident in dorsalised transgenic embryos containing a single axis. These results are discussed in the light of the effects of ectopic Xwnt8 in Xenopus embryos, where its early expression leads to complete axis duplication but expression after the mid-blastula transition causes anterior truncation. It is proposed that while ectopic Cwnt8C in the mouse embryo can duplicate the primitive streak and node this only produces incomplete axis duplication because specification of the anterior aspect of the axis, as opposed to maintenance of anterior character, is established by interaction with anterior primitive endoderm rather than primitive streak derivatives.

Actins↗
PubMed1997

Misexpression of chick Vg1 in the marginal zone induces primitive streak formation.

In the chick embryo, the primitive streak is the first axial structure to develop. The initiation of primitive streak formation in the posterior area pellucida is influenced by the adjacent posterior marginal zone (PMZ). We show here that chick Vg1 (cVg1), a member of the TGFbeta family of signalling molecules whose homolog in Xenopus is implicated in mesoderm induction, is expressed in the PMZ of prestreak embryos. Ectopic expression of cVg1 protein in the marginal zone chick blastoderms directs the formation of a secondary primitive streak, which subsequently develops into an ectopic embryo. We have used cell marking techniques to show that cells that contribute to the ectopic primitive streak change fate, acquiring two distinct properties of primitive streak cells, defined by gene expression and cell movements. Furthermore, naive epiblast explants exposed to cVg1 protein in vitro acquire axial mesodermal properties. Together, these results show that cVg1 can mediate ectopic axis formation in the chick by inducing new cell fates and they permit the analysis of distinct events that occur during primitive streak formation.

Animals↗