Most psychiatrists oppose plans for new mental health act.
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Attitude of Health Personnel↗
Biomedical subjects
M J Crawford
Publications and source records attributed to M J Crawford.
Subcellular localization of acetyl-CoA carboxylase in the apicomplexan parasite Toxoplasma gondii.
Apicomplexan parasites such as Toxoplasma gondii contain a primitive plastid, the apicoplast, whose genome consists of a 35-kb circular DNA related to the plastid DNA of plants. Plants synthesize fatty acids in their plastids. The first committed step in fatty acid synthesis is catalyzed by acetyl-CoA carboxylase (ACC). This enzyme is encoded in the nucleus, synthesized in the cytosol, and transported into the plastid. In the present work, two genes encoding ACC from T. gondii were cloned and the gene structure was determined. Both ORFs encode multidomain proteins, each with an N-terminal extension, compared with the cytosolic ACCs from plants. The N-terminal extension of one isozyme, ACC1, was shown to target green fluorescent protein to the apicoplast of T. gondii. In addition, the apicoplast contains a biotinylated protein, consistent with the assertion that ACC1 is localized there. The second ACC in T. gondii appears to be cytosolic. T. gondii mitochondria also contain a biotinylated protein, probably pyruvate carboxylase. These results confirm the essential nature of the apicoplast and explain the inhibition of parasite growth in cultured cells by herbicides targeting ACC.
Acetyl-CoA Carboxylase↗
Bcl-2 overexpression protects photooxidative stress-induced apoptosis of photoreceptor cells via NF-kappaB preservation.
We recently showed that photooxidative stress on cultured photoreceptor cells results in down-modulation of NF-kappaB activity which then leads to apoptosis of cultured 661W photoreceptor cells. In an effort to further delineate the mechanism of photoreceptor cell death, we sought to determine the effects of Bcl-2 overexpression on cell survivability. Wild-type 661W cells were transfected with the plasmid construct pSFFV-neo-Bcl-2 and several clones were isolated. All clones demonstrated increased Bcl-2 mRNA and protein levels, with the B4 clone exhibiting the greatest enhancement. On exposure to visible light the B4 cells were protected from undergoing apoptosis when compared with the mock transfected cells, as ascertained by TUNEL apoptosis assay and formazan based estimation of cell viability. The Bcl-2 overexpressing cells also maintained a higher Bcl-2/Bax ratio, suggesting that this ratio is important in protection from photooxidative stress. Electrophoretic mobility shift assays for NF-kappaB demonstrated higher activity in both nuclear and cytosolic fractions of the B4 photoreceptors compared with the 661W wild-type cells at all light exposure time points. Furthermore, the findings of the gel shift assays were further supported by immunocytochemistry for NF-kappaB which revealed that protein levels of the RelA subunit of NF-kappaB were protected in the nucleus as well as in the cytoplasm of Bcl-2 overexpressing B4 cells exposed to light compared to the 661W cells. These results suggest that Bcl-2 overexpression protects NF-kappaB protein levels and activity in the nucleus, indicating that preservation of NF-kappaB binding activity in the nucleus may be essential for photoreceptor cells to survive photooxidative damage induced apoptosis.
Animals↗
British psychiatry in the 20th century--observations from a psychiatric journal.
In order to investigate change and continuity in the concerns and practices of psychiatry in Britain during the 20th century we examined contents of the British Journal of Psychiatry. Specifically we sought to examine the paradigms used by psychiatry to conceptualize mental illness during this time. Back issues of the journal for 1 year at the mid-point of each decade were examined. We undertook a quantitative analysis categorising each article in terms of its form and content and a qualitative analysis in order to summarise the subjects that were covered. The results show that there has been continuous interest in biological aspects and treatments of mental illness with relatively little coverage of psychoanalysis or social psychiatry. Little support was found for the suggestion that major shifts have occurred in the explanatory paradigms used by psychiatry over the century. Modern interest in biological psychiatry is therefore not a new departure, but appears rather as the continuation of a long-standing inclination. The decline of the asylum-based system of care has been accompanied by a broadening in the scope of psychiatric concerns with a greater emphasis on milder mental disorders such as neurosis and depression.
Bibliometrics↗
xPitx1 plays a role in specifying cement gland and head during early Xenopus development.
Xenopus Pitx1 is a homeobox gene whose family members are structurally and functionally conserved in organisms as diverse as Drosophila, chick, mouse, human, and frog. Present as a maternal transcript, the gene is zygotically expressed during gastrulation in a dorsal streak of cells. This streak restricts to a small circular domain underlying the center of presumptive neural plate. Shortly thereafter, a crescent of expression develops at the border of anterior neural ectoderm, and as the central plate domain diminishes, the crescent coalesces to define the presumptive cement gland. Expression remains high throughout cement gland development, and subsequently expands to include ectodermal cells involved in stomodeal invagination. During early organogenesis, expression ensues in developing eye, posterior lateral mesoderm, and first branchial arch derivatives. Ectopic expression of xPitx1 causes head deformities including enlarged cement gland, ectopic cement glands, and posterior deformities or, in extreme cases, inhibition of recognizable structures posterior to the cement gland. Expression of markers such as XCG-1, xOtx2, xPax6, neuralbeta tubulin, and xTwist suggest that increases in cement gland and lower mandibular size are likely at the expense of other head tissues. Paradoxically, overexpression is sufficient to partially rescue embryos that are axially perturbed by ultraviolet irradiation or retinoic acid administration. Ectopic expression of xPitx1 in ectodermal explants directly promotes cement gland development as there was no evidence that mesodermal or neural tissue was present in explants.
Amino Acid Sequence↗
Xenopus adenine nucleotide translocase mRNA exhibits specific and dynamic patterns of expression during development.
We report the isolation and characterization of the Xenopus homolog to human T1 ANT (adenine nucleotide translocase). The 1290-nucleotide sequence contains initiation and termination signals, and encodes a conceptual protein of 298 amino acids. The sequence shares high amino acid identity with the mammalian adenine translocases. The transcript is present in unfertilized eggs, and it is expressed at higher levels during formation of the antero-posterior dorsal axis in embryos. Although low levels are expressed constitutively except in endodermal cells, adenine nucleotide translocase (ANT) expression is dynamically regulated during neurulation. At this stage, expression in ectoderm rapidly diminishes as the neural folds form, and then ANT expression increases slightly in mesoderm. At the culmination of neurulation, the neural tube briefly expresses ANT, and thereafter its expression predominates in the somitic mesoderm and also the chordoneural hinge. In addition, ANT expression is particularly high in the prosencephalon, the mesencephalon, the branchial arches, eye, and the otic vesicle. Treatment of embryos with retinoic acid has the effect of diminishing constitutive expression of ANT, but microinjection studies demonstrate that immediate and local repression cannot be induced in dorsal structures.
Amino Acid Sequence↗
The plastid of Toxoplasma gondii is divided by association with the centrosomes.
Apicomplexan parasites harbor a single nonphotosynthetic plastid, the apicoplast, which is essential for parasite survival. Exploiting Toxoplasma gondii as an accessible system for cell biological analysis and molecular genetic manipulation, we have studied how these parasites ensure that the plastid and its 35-kb circular genome are faithfully segregated during cell division. Parasite organelles were labeled by recombinant expression of fluorescent proteins targeted to the plastid and the nucleus, and time-lapse video microscopy was used to image labeled organelles throughout the cell cycle. Apicoplast division is tightly associated with nuclear and cell division and is characterized by an elongated, dumbbell-shaped intermediate. The plastid genome is divided early in this process, associating with the ends of the elongated organelle. A centrin-specific antibody demonstrates that the ends of dividing apicoplast are closely linked to the centrosomes. Treatment with dinitroaniline herbicides (which disrupt microtubule organization) leads to the formation of multiple spindles and large reticulate plastids studded with centrosomes. The mitotic spindle and the pellicle of the forming daughter cells appear to generate the force required for apicoplast division in Toxoplasma gondii. These observations are discussed in the context of autonomous and FtsZ-dependent division of plastids in plants and algae.
Aniline Compounds↗
Kinematic analysis of shot-putting performed by wheelchair athletes of different medical classes.
The aim of this study was to identify those kinematic characteristics that are most closely related to an athlete's medical classification and measured distance of a put. Two S-VHS camcorders (60 fields per second) were used to record the performance of 17 males of different classes. Each participant performed six trials and the best trial for each was selected for analysis. Three-dimensional kinematics of the shot and upper body segments at the instant of release and during the forward thrust (delivery) were determined. The average speeds and angles of the shot at release for different classes (5.3-7.8 m x s(-1) and 21.2 to 34.4 degrees, respectively) were smaller than those exhibited by elite male able-bodied throwers. The height of the shot at release, the angular speed of the upper arm at release, the range of motion of the shoulder girdle during the delivery, and the average angular speeds of the trunk, shoulder girdle and upper arm during the delivery, were all significantly correlated with both the classification and measured distance (P < 0.05). The results indicate the importance of achieving a high average angular speed for each upper body segment during the delivery.
Acceleration↗
Concerns over reform of the Mental Health Act.
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Attitude of Health Personnel↗
Photo-oxidative stress down-modulates the activity of nuclear factor-kappaB via involvement of caspase-1, leading to apoptosis of photoreceptor cells.
The mechanisms of photoreceptor cell death via apoptosis, in retinal dystrophies, are largely not understood. In the present report we show that visible light exposure of mouse cultured 661W photoreceptor cells at 4.5 milliwatt/cm2 caused a significant increase in oxidative damage of 661W cells, leading to apoptosis of these cells. These cells show constitutive expression of nuclear factor-kappaB (NF-kappaB), and light exposure of photoreceptor cells results in lowering of NF-kappaB levels in both the nuclear and cytosolic fractions in a time-dependent manner. Immunoblot analysis of IkappaBalpha and p50, and p65 (RelA) subunits of NF-kappaB, suggested that photo-oxidative stress results in their depletion. Immunocytochemical studies using antibody to RelA subunit of NF-kappaB further revealed the presence of this subunit constitutively both in the nucleus and cytoplasm of the 661W cells. Upon exposure to photo-oxidative stress, a depletion of the cytoplasmic and nuclear RelA subunit was observed. The depletion of NF-kappaB appears to be mediated through involvement of caspase-1. Furthermore, transfection of these cells with a dominant negative mutant IkappaBalpha greatly enhanced the kinetics of down modulation of NF-kappaB, resulting in a faster photo-oxidative stress-induced apoptosis. Taken together, these studies show that the presence of NF-kappaB RelA subunit in the nucleus is essential for protection of photoreceptor cells against apoptosis mediated by an oxidative pathway.
Animals↗
A national target for reducing suicide. Suicide in older people must be reduced.
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Aged↗
Transport and trafficking: Toxoplasma as a model for Plasmodium.
Like Plasmodium, the protozoan parasite Toxoplasma gondii is a member of the phylum Apicomplexa, and an obligate intracellular pathogen. Unlike Plasmodium, however, Toxoplasma is highly amenable to experimental manipulation in the laboratory. The development of molecular transformation protocols for T. gondii has provided both scientific precedent and practical selectable markers for Plasmodium. Beyond the feasibility of molecular biological experimentation now possible in both systems, the high frequency of stable transformation in Toxoplasma allows this parasite to be used for molecular genetic analysis. The ability to control homologous vs. non-homologous recombination in T. gondii permits gene knockouts/allelic replacements at previously cloned loci, and saturation insertional mutagenesis of the entire parasite genome (and cloning of the tagged loci). T. gondii also exhibits unusual ultrastructural clarity, facilitating cell biological analysis. The accessibility of Toxoplasma as an experimental system allows this parasite to be used as a surrogate for asking many questions that cannot easily be addressed in Plasmodium itself. T. gondii also serves as a model system for genetic exploration of parasite biology and host-parasite interactions. Success stories include: biochemical analysis of antifolate resistance mechanisms; pharmacological studies on the mechanisms of macrolide activity; genetic identification of nucleobase/nucleoside transporters and metabolic pathways; and cell biological characterization of the apicomplexan plastid. As with any model system, not all questions of interest to malariologists can be addressed in Toxoplasma; differentiating between sensible and foolish questions requires familiarity with the biological similarities and differences of these systems.
Animals↗
Increasing rates of suicide in young men in England during the 1980s: the importance of social context.
Attempts to explain rising rates of suicide among young men in Britain and elsewhere during the 1980's have identified the characteristics of those people who kill themselves. Little, however, is known about the impact that changes in social context may have had on changing rates of suicide during this time. Changes in aggregate levels of unemployment, poverty, marriage and the proportion of adults living alone during the 1980s were derived from data collected in the UK National Census of 1981 and 1991. In an ecological analysis these changes were compared with changes in age-adjusted rates of suicide in men aged 15 to 44, in 364 county districts of England between the beginning and end of the 1980s. Areas experiencing the lowest increase in rates of suicide were those that experienced the smallest rise in the proportion of people living alone, the greatest increase in unemployment and highest levels of social deprivation. In addition to investigating the effect that characteristics of people have in determining the risk of suicide in individuals who kill themselves, further attention needs to be paid to the impact that social context may have on mediating these risks.
Adolescent↗
Origin, targeting, and function of the apicomplexan plastid.
The discovery of a plastid in Plasmodium, Toxoplasma and related protozoan parasites provides a satisfying resolution to several long-standing mysteries: the mechanism of action for various surprisingly effective antibiotics; the subcellular location of an enigmatic 35 kb episomal DNA; and the nature of an unusual intracellular structure containing multiple membranes. The apicomplexan plastid highlights the importance of lateral genetic transfer in evolution and provides an accessible system for the investigation of protein targeting to secondary endosymbiotic organelles. Combining molecular genetic identification of targeting signals with whole genome analysis promises to yield a complete picture of organellar metabolic pathways and new targets for drug design.
Animals↗
Not listening to patients--the use and misuse of patient satisfaction studies.
Demand for the development of health services that are responsive to the views of users has led to a growing interest in the measurement of patient satisfaction. Initial reluctance to seek the views of users of mental health services focused on a debate about whether or not mentally disordered patients were able to make 'valid' comments about their treatment. More recently the development of questionnaires that claim to 'reliably measure' the views of patients have coincided with a greater acceptance of the role that such studies can play. However, it is argued that the use of these quantitative and often simplistic methods underestimate the dissatisfaction of many patients. Further exploration of the differing expectations of users and providers of services and a degree of willingness in both parties to change is required if services are to be developed that better meet the needs of patients.
Health Care Surveys↗
Regulation of the Salmonella typhimurium flavohemoglobin gene. A new pathway for bacterial gene expression in response to nitric oxide.
Flavohemoglobins, a family of two-domain proteins with homology to vertebrate hemoglobins, are found in a variety of prokaryotic and eukaryotic microorganisms. Recent studies suggest a role for these proteins in nitrogen oxide metabolism. We now show that nitric oxide donors positively regulate a chromosomal flavohemoglobin (hmp)/lacZ operon fusion in Salmonella typhimurium. hmp gene expression in the presence of NO. is independent of the SoxS, OxyR, and FNR transcription factors and instead relies on inactivation of the iron-dependent Fur repressor. Other Fur-repressed promoters in S. typhimurium are also activated by an NO. donor. In contrast to the wild-type strain, an hmp- mutant requires markedly lower concentrations of NO to induce the hmp/lacZ fusion, whereas its response to iron chelation is equivalent to wild type. These data unveil a new pathway for NO-dependent gene expression in S. typhimurium.
2,2'-Dipyridyl↗
Does initial management affect the rate of repetition of deliberate self harm? cohort study.
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Cohort Studies↗
Role for the Salmonella flavohemoglobin in protection from nitric oxide.
Hemoglobin homologs are being identified in an expanding number of unicellular prokaryotic and eukaryotic organisms. Many of these hemoglobins are twodomain proteins that possess a flavin-containing reductase in their C terminus. Determination of a function for these flavohemoglobins has been elusive. A Salmonella typhimurium strain harboring a deletion in the flavohemoglobin gene shows no difference in growth under oxidative stress conditions but displays an increased sensitivity to acidified nitrite and S-nitrosothiols, both of which produce nitric oxide. The effect is seen aerobically or anaerobically, indicating that oxygen is not required for flavohemoglobin function. These results suggest a role for the bacterial flavohemoglobins that is independent of oxygen metabolism and provide evidence for a bacterial route of protection from nitric oxide that is distinct from oxidative stress responses.
Bacterial Proteins↗