Evolution and development: Wnts in deep time.
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Animals↗
Biomedical subjects
G Freeman
Publications and source records attributed to G Freeman.
Integrated water cycle planning for towns in New South Wales, Australia.
Integration means different things to different people and as a consequence appears to only partially deliver on promised outcomes. For effective integrated water cycle management these outcomes should include improved water use efficiency, less waste, environmental sustainability, and provide secure and reliable supply to meet social and economic needs. The objective of integration is the management and combination of all these outcomes as part of a whole, so as to provide better outcomes than would be expected by managing the parts independently. Integration is also a consequence of the Water Reforms embarked on by the NSW State Government in 1995. The key goals of the reforms are clean and healthy rivers and groundwaters, and the establishment of more secure water entitlements for users. They are also essential for meeting the Council of Australian Government (COAG) water management strategies. The policies and guidelines that formed the NSW Water Reforms were the basis of the Water Management Act 2000 (NSW) (WMA) which is the legislative framework for water management in NSW. The NSW Department of Land and Water Conservation has developed an approach to integrated water cycle management for rural centres in NSW based on a catchment and policy context. This approach includes consideration of catchment wide needs and issues, environmental sustainability, government policy and community objectives in the development of an integrated water cycle plan. The approach provides for a transparent assessment of priorities and how to deal with them, and while specific to urban centres, could easily be expanded for use in the management of the whole of the catchment water cycle. Integration of the water cycle is expected to offer benefits to the local environment, community and economy. For instance, any unused proportion of an urban centre's water entitlement, or an offset against this entitlement created through returned flows (such as via good quality sewage effluent discharge to a river), can provide a surplus which is available to be traded on an annual basis. Further, improved demand management within an urban centre can be expected to result in a reduction in abstraction against the licence entitlement. This may result in the increased availability of in-stream water for environmental or other purposes and is expected to increase the economic value of returned water. Improved water use efficiencies are also expected to result in reduced capital works (and their associated costs) as the efficiency of service delivery and resource use improves. In this paper an example of the application of this process is provided and the outcomes discussed.
Conservation of Natural Resources↗
Cystoid macular oedema in uveitis: an unsolved problem.
Most papers on the subject of CMO associated with uveitis are retrospective, combine patients with different disease aetiologies, at different stages of evolution, and often describe patients who were previous treatment failures with other therapies besides the one under consideration. There are almost no prospective randomised double-masked controlled studies. This is perhaps in part due to the relative sparsity of uveitis patients seen by many uveitis centres. At the moment, treatment is largely empirical, based in large part on the studies, and others, quoted above. The need to regularly repeat courses of therapy, loss of efficacy of certain form of therapy after repeated use, and cumulative side-effects, all need to be taken into consideration when interpreting results and deciding upon the best approach to be adopted. The risks to the patient's well-being increase with the addition of systemic medication, and long-term steroid use can cause hypertension, induce or exacerbate diabetes, cause premature osteoporosis, cushingoid features, peptic ulceration and aseptic necrosis of the femoral head. Immunosuppressive drugs can be nephrotoxic, hepatotoxic, cause hypertension, gastric disturbances and excessive hair growth. The assessment of macular changes, both structurally and functionally, is the key aspect in understanding visual loss in CMO and also in predicting potential visualrecovery. The combined use of the various tools mentioned here, such as SLO, OCT and electrodiagnostic tests, may give us some of the necessary answers in this process. However, all these tests will need to be validated. A prospective analysis of CMO in cases of uveitis, especially if coupled with therapeutic intervention, will give us the opportunity to achieve this objective.
Humans↗
Aggressive retinal vasculitis in polyarteritis nodosa.
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Adult↗
Retinal toxicity due to Efavirenz.
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Adult↗
Regional specification during embryogenesis in the craniiform brachiopod Crania anomala.
A fate map has been constructed for the embryo of Crania. The animal half of the egg forms the ectodermal epithelium of the larva's apical lobe. The vegetal half of the egg forms endoderm, mesoderm, and the ectoderm of the mantle lobe. The vegetal pole is the site of gastrulation; this site becomes the posterior ventral region of the mantle lobe of the larva. The plane of the first cleavage goes through the animal-vegetal axis of the egg; it bears no relationship to the future plane of bilateral symmetry of the larva. The timing of regional specification was examined by isolating animal, vegetal, or meridional halves from oocytes, eggs, or embryos from prior to germinal vesicle breakdown through gastrulation. Animal halves isolated from oocytes formed either the epithelium of the apical lobe or a larva with all three germ layers. Animal halves isolated from unfertilized eggs and eight-cell embryos formed only apical lobe epithelium. Beginning at the blastula stage, animal halves formed mantle in addition to apical lobe epithelium. In animal halves isolated after gastrulation, the mantle lobe was always truncated. Vegetal halves isolated at all stages prior to gastrulation gastrulated and formed apical and mantle lobes with endoderm and mesoderm; however, the relative size of the apical lobe that formed decreased substantially when vegetal halves were isolated at later developmental stages. When meridional halves were isolated from unfertilized eggs and two- to four-cell embryos, both halves frequently formed normally proportioned larvae. Beginning at the blastula stage, a number of pairs frequently had a member that lacked dorsal setae on its mantle lobe while the other member of the pair formed setae, indicating that the dorsoventral axis had been set up. The process of regional specification in Crania is compared to those of Discinisca and Glottidia in the brachiopod subphylum Linguliformea and Phoronis in the phylum Phoronida.
Animals↗
Regional specification during embryogenesis in the inarticulate brachiopod Discinisca.
The process of embryogenesis is described for the inarticulate brachiopod Discinisca strigata of the family Discinidae. A fate map has been constructed for the early embryo. The animal half of the egg forms the dorsal ectoderm of the apical and mantle lobes. The vegetal half forms mesoderm and endoderm and is the site of gastrulation; it also forms the ectoderm of the ventral regions of the apical and mantle lobes of the larva. The plane of the first cleavage goes through the animal-vegetal axis of the egg along the future plane of bilateral symmetry of the larva. The timing of regional specification in these embryos was examined by isolating animal, vegetal, or lateral regions at different times from the 2-cell stage through gastrulation. Animal halves isolated at the 8-cell and blastula stages formed an epithelial vesicle and did not gastrulate. When these halves were isolated from blastulae they formed the cell types typical of apical and mantle lobes. Vegetal halves isolated at all stages gastrulated and formed a more or less normal larva; the only defect these larvae had was the lack of an apical tuft, which normally forms from cells at the animal pole of the embryo. When lateral isolates were created at all developmental stages, these halves gastrulated. Cuts which separated presumptive anterior and posterior regions generated isolates at the 4-cell and blastula stages that formed essentially normal larvae; however, at the midgastrula stage these halves formed primarily anterior or posterior structures indicating that regional specification had taken place along the anterior-posterior axis. The plane of the first cleavage, which predicts the plane of bilateral symmetry, can be shifted by either changing the cleavage pattern that generates the bilateral 16-cell blastomere configuration or by isolating embryo halves prior to, or during, the 16-cell stage. These results indicate that while the plane of the first cleavage predicts the axis of bilateral symmetry, the axis is not established until the fourth cleavage. The development of Discinisca is compared to development in the inarticulate brachiopod Glottidia of the family Lingulidae and to Phoronis in the phylum Phoronida.
Animals↗
Molecular characterisation of a NADH ubiquinone oxidoreductase subunit 5 from Schistosoma mansoni and inhibition of mitochondrial respiratory chain function by testosterone.
Complementary DNA, encoding the mitochondrial enzyme NADH-ubiquinone oxidoreductase subunit 5 (SmND5) of the human parasite Schistosoma mansoni was isolated by screening a S. mansoni cDNA library with a human androgen receptor (hAR) cDNA probe. The complete nucleotide and deduced aminoacid sequences of SmND5 were determined. Southern blot analysis revealed the occurrence of a single copy gene for SmND5 and by means of RT-PCR, it was shown that sex- and stage-specific expression of SmND5 occurred. In order to establish a functional relationship between the mitochondrial enzyme and the androgen receptor, the effects of testosterone were compared to those of classical respiratory chain inhibitors, using adult schistosome and beef heart submitochondrial particles. Physiological concentrations of testosterone were able to inhibit the maintenance of proton gradient across the mitochondrial membranes, as well as ATP synthesis. The steroid was found to be cytotoxic to the larvae, but not to adult schistosomes. A model is proposed to explain the observed in vivo testosterone-related differences in worm burdens, in experimental chronic infections.
Amino Acid Sequence↗
Calcium fluxes in hydrozoan embryos depend, in part, on exocytosis and fluid phase endocytosis.
In the hydrozoan Phialidium gregarium, the constitutive calcium influx of cleavage stage embryos in sea water is 1.96 +/- 0.75 x 10(-15) moles/embryo/minute. Treating embryos with 227 mM KCl in seawater briefly increases the calcium influx more than 100-fold, to 3.9 x 10(-13) mol/embryo/min. About 62% of the KCl-induced calcium influx is due to calcium flowing through voltage-sensitive calcium channels. This causes a marked intracellular calcium transient and secretion of intracellular vesicles. The other component (approximately 38%) of the calcium influx occurs via fluid phase endocytosis of the extracellular medium (detected using extracellular 3H-sucrose). KCl-treatment of 45Ca loaded embryos induces a 45Ca efflux which can reach peak fractional rates of 0.98/min, during which 55-75% (mean 66%) of the total 45Ca is lost. The KCl-induced calcium efflux is due, in part, to secretion because loaded 3H-sucrose is effluxed simultaneously. This pathway may be important for the calcium efflux necessary for long-term calcium homeostasis in cells.
Animals↗
Academic training for general practice.
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Education, Medical, Graduate↗
The London Academic Training Scheme (LATS): an evaluation.
BACKGROUND: A recognition of the inability of vocational training schemes (VTS) to teach all the skills needed for modern general practice, and the increasing unwillingness of vocationally trained doctors to commit to GP principal posts, has led to the promotion and piloting of post-VTS educational schemes. The London Academic Training Scheme (LATS) is a year's attachment to a University Department of General Practice in London, comprising seven academic and three clinical sessions. OBJECTIVE: We aimed to carry out an evaluation of the first 2 years of the LATS from the perspectives of the registrar, their departmental supervisor and the practice. METHODS: Data were collected by questionnaires, interviews and focus groups, at the beginning, during and at the end of the scheme. RESULTS: Results are available up to the midway point of the second (1996) intake. The registrars achieved confidence and success in research, with six publications in peer-referenced journals from the first cohort so far. Eight of this cohort were working in inner London 6 months later, seven in academic posts. The overwhelming career intention of the second cohort midway is to work in academic general practice in London. The registrars enjoyed their teaching opportunities and increased their confidence but would have liked more training and more time for teaching. All the supervisors identified positive effects on their departments, but some found the time commitment and the process of supervision challenging. Two out of the dozen practices involved with the first cohort had reservations about the attachment. The rest cited benefits in clinical care, involvement in research and time for their own development. CONCLUSION: The scheme fulfilled its immediate aims and is addressing the recruitment and retention of GPs in the inner city. Continuing follow-up is planned.
Education, Medical, Graduate↗
What future for continuity of care in general practice?
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Attitude of Health Personnel↗
Axis specification in animal development.
Axis specification is the first step in defining specific regions of the developing embryo. Embryos exploit asymmetries, either pre-existing in the egg or triggered by external cues, to establish embryonic axes. The axial information is then used to generate regional differences within the embryo. In this review, we discuss experiments in animals which address three questions: whether the unfertilized egg is constructed with pre-determined axes, what cues are used to specify the embryonic axes, and how these cues are interpreted to generate the initial regional differences within the embryo. Based on mapping the data onto an animal phylogeny, we then propose a scenario for how this primary developmental decision occurred in ancestral metazoans.
Animals↗
The role of localized cell surface-associated glycoproteins during fertilization in the hydrozoan Aequorea.
Hydrozoan eggs can be fertilized only at the site of polar body formation and first acquire this ability during second polar body formation. The eggs of Aequorea victoria form a discrete Triticum lectin binding moiety in the jelly coat near the first polar body as it is being given off and also a discrete concanavalin A binding moiety associated with the egg surface where the second polar body forms, which disappears immediately after fertilization. The germinal vesicle has an eccentric position in full grown Aequorea oocytes. The region of oocyte surface closest to the germinal vesicle is the site where the polar bodies normally form. When oocytes are centrifuged during oocyte maturation, the meiotic apparatus sometimes shifts to a different position with reference to the egg surface and polar bodies are given off at this new site. There is a corresponding shift in the position of the Triticum and concanavalin A lectin binding moieties, indicating that their formation is associated with local events occurring at the site of polar body formation. Treatment of Aequorea eggs with Triticum or concanavalin A causes a marked reduction in the ability of these eggs to be fertilized, suggesting that sugar-containing moieties, to which the lectins bind, play a role in fertilization. Removal of sugars on these moieties with mannosidase or N-acetylglucosaminidase, or the cleavage of the protein the sugars are attached to with trypsin, results in eggs that do not bind Triticum or concanavalin A and also show a marked reduction in the ability to be fertilized. These experiments suggest that the lectin binding moieties are glycoproteins.
Animals↗
B7-1 is superior to B7-2 costimulation in the induction and maintenance of T cell-mediated antileukemia immunity. Further evidence that B7-1 and B7-2 are functionally distinct.
Although intact, viable tumor cells rarely induce a clinically significant immune response in vivo, immunogenicity can be elicited by irradiated tumor cells that protect against subsequent challenge with wild-type intact viable tumor cells. Genetic modification of murine tumor cells, by transfection of cDNAs encoding either cytokines, MHC molecules, or costimulatory molecules, has been capable of inducing antitumor immunity. We and others have previously demonstrated that expression of the B7-1 costimulatory molecule, in either immunogenic or nonimmunogenic tumors, can protect against subsequent challenge with wild-type tumor cells. In this work, using a murine model of acute myeloid leukemia, we demonstrate that the B7-1 costimulatory molecule is superior to the B7-2 molecule in its capacity to protect against wild-type tumor challenge and eradicate minimal residual disease. These results provide compelling evidence that the B7-1 and B7-2 costimulatory signals are functionally distinct, thus resulting in clinically significant differences in the induction of antitumor immunity in vivo.
Animals↗
Inhibition of transplant rejection following treatment with anti-B7-2 and anti-B7-1 antibodies.
Antigen-specific T cell activation depends initially on the interaction of the T cell receptor (TCR) with peptide/MHC. In addition, a costimulatory signal, mediated by distinct cell surface accessory molecules, is required for complete T cell activation leading to lymphokine production and proliferation. CD28 has been implicated as the major receptor on T cells responsible for delivering the costimulatory signal. Although two distinct ligands for CD28, B7-1 and B7-2, have been identified on antigen-presenting cells (APC), the co-stimulatory role of each molecule during a physiological immune response remains unresolved. In the present study, the relative roles of B7-1 and B7-2 interactions were evaluated in an allogeneic pancreatic islet transplant setting. In isolation, anti-B7-2 mAbs and, to a much lesser degree, anti-B7-1 mAbs suppressed T cell proliferative responses to allogeneic islets or splenic APC in vitro. Maximal inhibition of the allogeneic response was observed using a combination of the anti-B7-1 and anti-B7-2 mAbs. Administration of anti-B7-2 but not anti-B7-1 mAbs prolonged C3H allograft survival in B6 recipients, with a combination of both mAbs significantly prolonging rejection beyond either mAb alone. The immunosuppressive effects of the in vivo mAb treatment were not manifested in in vitro analyses as T cells isolated from suppressed mice responded normally to allogeneic stimuli in terms of both proliferation and lymphokine production. However, combined mAb therapy in vivo selectively delayed CD4+ T lymphocyte infiltration into the graft. These data suggest that both B7-1 and B7-2 costimulatory molecules are active in vivo, although B7-2 plays a clearly dominant role in this allograft model. The mechanism of immune suppression in vivo remains unresolved but may occur at sites distinct from the allograft.
Abatacept↗
Preregistration house officers in general practice. Posts are purely educational.
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Education, Medical, Graduate↗
Regional specification during embryogenesis in the inarticulate brachiopod Glottidia.
A fate map has been constructed for the lingulid brachiopod Glottidia pyramidata. The animal half of the egg forms part of the apical lobe and the dorsal valve of the larva. The vegetal half of the egg forms mesoderm and endoderm and is the site of gastrulation; it also forms part of the apical lobe and the ventral valve of the larva. The plane of the first cleavage goes through the animal-vegetal axis of the egg along the future plane of bilateral symmetry of the larva. The timing of regional specification in these embryos was examined by isolating animal or vegetal, anterior or posterior, or lateral regions at different times from prior to fertilization through gastrulation. Animal halves isolated at all stages formed an epithelial vesicle and did not gastrulate. When these halves were isolated from unfertilized eggs or early cleavage stage embryos, they usually did not form an apical lobe or valve; however, when the halves were isolated at later developmental stages, these structures differentiated in a high frequency of cases. Vegetal halves were isolated at all stages gastrulated and formed a larva; however, when these halves were isolated at gastrulation they frequently lacked a dorsal valve. When lateral cuts were made along the animal-vegetal axis at all developmental stages, both halves gastrulated. When the cut was made perpendicular to the plane of the first cleavage from the four-cell stage on, one-half formed the anterior end and the other half formed the posterior end of the larva. These results suggest that there are localized determinants in the egg that specify the different regions of the larva, but there is also an inductive signal(s) from the vegetal region of the embryo that is necessary in order for cells that inherit a given determinant to differentiate. Embryogenesis in Glottidia is compared with articulate brachiopods and phoronids.
Animals↗