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Biomedical subjects

S Carroll

Publications and source records attributed to S Carroll.

At least 73 records · Page 4Linked to original sources

Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic.

The TGF-beta (transforming growth factor-beta)-related signalling proteins, including Decapentaplegic (Dpp) in Drosophila-and bone morphogenic proteins and activin in vertebrates, affect the growth and patterning of a great variety of structures. However, the mechanisms by which these ligands regulate gene expression are not understood. Activation of complexes of type I with type II receptors results in the phosphorylation and nuclear localization of members of the SMAD protein family, which are thought to act as co-activators of transcription, perhaps in conjunction with sequence-specific cofactors. Here we show that the amino-terminal domain of the Drosophila Mothers against dpp protein (Mad), a mediator of Dpp signalling, possesses a sequence-specific DNA-binding activity that becomes apparent when carboxy-terminal residues are removed. Mad binds to and is required for the activation of an enhancer within the vestigial wing-patterning gene in cells across the entire developing wing blade. Mad also binds to Dpp-response elements in other genes. These results suggest that Dpp signalling regulates gene expression by activating Mad binding to target gene enhancers.

Animals↗

Challenges to clinical deployment of upper limb neuroprostheses.

The technology for functional neuromuscular stimulation (FNS) as a means of providing upper limb function to people with tetraplegia has been under development by three clinical research groups for almost two decades. This paper presents the current status of the clinical trials of three FNS systems: a noninvasive system built into a cosmetic forearm splint, a 30-channel percutaneous system, and an 8-channel implantable system. The complexity of FNS systems and the unique characteristics of the individuals to whom they are applied combine to create many clinical and technical challenges that must be addressed before the devices can be deployed. The emerging challenges to widespread clinical introduction of FNS systems for hand and arm function are identified and analyzed. In addition to the demands of designed and conducting the clinical trials to satisfy regulatory requirements, the lack of knowledge, skepticism, and the complacency on the part of potential FNS recipients, as well as of rehabilitation professionals, must be overcome through education and careful consideration of economic and societal factors in the design of clinical systems.

Arm↗

Pre-term pre-labour amniorrhexis.

In pregnancies complicated by pre-term pre-labour aminorrhexis, there is a risk of intra-uterine infection, which is associated with maternal and perinatal mortality and morbidity. The causes of neonatal death in pregnancies with aminorrhexis are prematurity, pulmonary hypoplasia and sepsis. In the management of pregnancies with pre-term pre-labour amniorrhexis, it is essential to distinguish between those with and without intra-uterine infection. If there is no infection at presentation, it is unlikely that this will develop, and in such cases there is no benefit from hospitalization, bed rest, prophylactic tocolytics or antibiotics. The group with evidence of intra-uterine infection go into spontaneous labour within a few days of amniorrhexis; in this group, the main determinant for the appropriate management is the gestational age at amniorrhexis.

Anti-Inflammatory Agents↗

The development of crustacean limbs and the evolution of arthropods.

Arthropods exhibit great diversity in the position, number, morphology, and function of their limbs. The evolutionary relations among limb types and among the arthropod groups that bear them (insects, crustaceans, myriapods, and chelicerates) are controversial. Here, the use of molecular probes, including an antibody to proteins encoded by arthropod and vertebrate Distal-less (Dll and Dlx) genes, provided evidence that common genetic mechanisms underlie the development of all arthropod limbs and their branches and that all arthropods derive from a common ancestor. However, differences between crustacean and insect body plans were found to correlate with differences in the deployment of particular homeotic genes and in the ways that these genes regulate limb development.

Amino Acid Sequence↗

Homeotic genes and diversification of the insect body plan.

The homeotic genes regulate segmental identity by repressing the formation of or influencing the morphology of segmental structures during development. The specific roles these genes have played in the generation of insect diversity are discussed relative to abdominal limb formation and to the evolution of wings as novel repeated structures. Other recent findings discussed suggest possible 'homeotic' origins for the non-homeotic genes found within the homeotic complexes of higher insects.

Animals↗

Exhaled nitric oxide concentration and amniotic fluid nitrite concentration during pregnancy.

We have assessed fetal and maternal nitric oxide (NO) production in pregnancy. Exhaled NO and amniotic fluid nitrite concentrations were measured by chemiluminescence between 10 and 42 weeks of pregnancy. Exhaled NO concentrations did not alter significantly during gestation. In contrast, there was a significant change in mean amniotic fluid nitrite concentration in late pregnancy (P < 0.001). The finding of decreased amniotic nitrite concentrations after 37 weeks of gestation support the hypothesis that reduced NO production may contribute to increased uterine activity in late pregnancy.

Adolescent↗

Evolution of homeotic gene regulation and function in flies and butterflies.

It has been proposed that the evolution of homeotic genes parallels, and to some degree directs, the evolution of segment diversity in the myriapod-insect lineage. But the discovery of discrete Antennapedia complex (ANT-C) and bithorax complex (BX-C) gene members in crustacea, chelicerates, annelids and various insects, as well as in vertebrates, indicates that the expansion and diversification of homeotic genes preceded the diversification of arthropods and insects. How, then, have these genes influenced the evolution of body plans? To address this question, we now examine homeotic gene expression and regulation in butterflies (Lepidoptera), which, unlike flies, possess larval abdominal limbs and two pairs of wings. We show that the difference in larval limb number between these insects results from striking changes in BX-C gene regulation in the butterfly abdomen, and we deduce that the wing-patterning genes regulated by Ultrabithorax have diverged in the course of butterfly and fly evolution. These findings have general implications for the role of homeotic genes in animal evolution.

Amino Acid Sequence↗

Conservation of wingless patterning functions in the short-germ embryos of Tribolium castaneum.

During embryogenesis, all insects reach a conserved, or phylotypic, stage at which all future segments are present. Different insects, however, arrive at this stage by overtly different pathways. In the long-germ insect Drosophila melanogaster, segmentation of the entire embryo occurs nearly simultaneously and results from the action of a cascade of transcriptional regulatory factors that operate in the acellular environment of the syncytial blastoderm. In short-germ insects, segmentation occurs in an anterior-to-posterior sequence, within a cellular environment, and might then be dependent on intercellular signalling. To compare the molecular mechanisms of segmentation, we have isolated a homologue of the Drosophila wingless gene, a mediator of cell-cell communications, from the short-germ beetle Tribolium castaneum. The principal features of wingless expression patterns in Drosophila are conserved in Tribolium, including its early deployment in rostral and caudal domains in the blastoderm, its segmental iteration in cells immediately anterior to cells expressing the engrailed gene, and its later restriction to a ventral sector of the developing appendages.

Amino Acid Sequence↗

Diurnal variation of mood and neuropsychological function in major depression with melancholia.

20 DSM-III-R melancholics with clinically evident diurnal symptoms and 20 controls were assessed with a battery of neuropsychological tests, a test of maximum voluntary hand-grip, and neuroendocrine measures of hypothalamic-pituitary-adrenal axis function morning and evening in a 24-h period, using a balanced design. The morning pattern of neuropsychological impairment in the melancholics was comprehensive, affecting attention and concentration/working memory, episodic memory, reaction time and, strikingly, the speed of simultaneous match to sample, which was performed more slowly than the version of the task delayed to 0 or 4 s. The melancholics were significantly weaker than controls, on a measure of maximal voluntary contraction. Significantly improved neuropsychological function was seen in the melancholic patients in the evening, in line with diurnal improvement in mood; there was also a large increase in strength. Slowing on the digit symbol substitution test, the simultaneous match to sample task, total errors on the match to sample and hand-grip remained impaired in the evening compared to controls; other neuropsychological measures were no longer statistically different from control values which were often worsened. Neuroendocrine measures showed significantly raised levels of cortisol and ACTH morning and evening in the melancholics. Morning cortisol in the melancholics correlated with the diurnal improvement in neuropsychological functioning. The results have implications for the timing of neuropsychological assessment in major depression. Indices of neuropsychological and motor function may be as reliable quantitative estimates of illness severity as subjective estimates of mood.

Adrenocorticotropic Hormone↗

A central 5-HT2 receptor mechanism plays a key role in the proestrous surge of luteinizing hormone in the rat.

The role of serotonin (5-HT) in generating the spontaneous preovulatory surge of luteinizing hormone (LH) has been investigated by studying the effect of ketanserin (a mixed 5-HT2/alpha 1 adrenoreceptor antagonist); the selective 5-HT2 receptor antagonist, ritanserin; and the selective alpha 1 adrenoreceptor antagonist, prazosin, on the plasma concentrations of LH during the afternoon of proestrus in conscious Wistar rats. Sequential blood samples for hormone estimation were taken through intra-atrial cannulae previously implanted under halothane anesthesia. All three drugs blocked the LH surge; ketanserin, but not ritanserin or prazosin, also blocked basal LH release. These results provide the first robust evidence for the fact that a 5-HT2 receptor as well as an alpha 1 adrenoreceptor mechanism is involved in the LH surge generator.

Animals↗

Blood culture in the first 6 months of life for the diagnosis of vertically transmitted human immunodeficiency virus infection. The Women and Infants Transmission Study Group.

Serial blood cultures over the first 6 months of life in 310 infants with vertical exposure to human immunodeficiency virus (HIV) in the Women and Infants Transmission Study were analyzed to determine their value for early diagnosis of HIV infection. Cultures were done at 0-7 days and 1, 2, 4, and 6 months of age: 55 infants were infected. Blood culture sensitivity in infected children was 24% (7/29) during the first week of life and 85%, 91%, 82%, and 88%, respectively, at 1, 2, 4, and 6 months. The sensitivity, specificity, and positive and negative predictive values of a single culture between 1 and 6 months of age were, respectively, 86.9%, 99.6%, 97.9%, and 97.5%. Two negative cultures between 1 and 6 months of age defined an uninfected infant with a specificity of 99.2%-100.0%. Blood culture done between 1 and 6 months of age in children of HIV-positive mothers is a sensitive and specific test for HIV infection, with high positive and negative predictive values.

Blood↗

Morphing: a new graphics tool for animating confocal images.

The application of morphing to the display of developmental processes is described. This new graphics tool imparts the dynamic aspects of time-lapse microscopy to a series of fixed and stained images of a developing system. The technique is illustrated using confocal images of wing imaginal discs of Drosophila. It is anticipated that morphing can be applied not only to the display and analysis of developing systems but also to the elucidation of evolutionary relationships between species and to comparative anatomy.

Animals↗

The elevation of plasma beta-endorphin levels in major depression.

Day-time plasma beta-endorphin/beta-lipotrophic hormone (beta-ENDO/beta-LPH), ACTH and cortisol have been determined in 26 patients with major depression and 25 controls. beta-ENDO/beta-LPH and cortisol were significantly elevated in patients, while ACTH was not. Cortisol levels were significantly negatively correlated with age in controls as were beta-ENDO/beta-LPH and ACTH. In patients, by contrast, cortisol levels were positively, albeit not significantly, related to age. Peptide levels were not related to age in the patient group. Instead, beta-ENDO/beta-LPH was negatively correlated with clinical ratings of symptom severity in patients and positively associated with an acute psychosocial precipitant. The findings cast further light on beta-ENDO/beta-LPH as a measure of hypothalamic-pituitary over activity in depressive illness. A negative association with symptom severity suggests that beta-ENDO/beta-LPH responses are, like those of ACTH, down-regulated in the course of depressive illness.

Adrenocorticotropic Hormone↗

H+ countertransport and electrogenicity of the sarcoplasmic reticulum Ca2+ pump in reconstituted proteoliposomes.

The Ca2+ transport adenosine triphosphatase of sarcoplasmic reticulum was reconstituted in unilamellar liposomes prepared by reverse-phase evaporation. The size of the resulting proteoliposomes was similar to that of native sarcoplasmic reticulum vesicles, but their protein content was much lower, with a protein/lipid ratio (wt/wt) of 1:40-160, as compared with 1:1 in the native membrane. The proteoliposomes sustained adenosine triphosphate-dependent Ca2+ uptake at rates proportional to the protein content (1-2 mumol Ca2+/mg protein/min), reaching asymptotic levels corresponding to a lumenal calcium concentration of 10-20 mM. The low permeability of the proteoliposomes permitted direct demonstration of Ca2+/H+ countertransport and electrogenicity by parallel measurements in the same experimental system. Countertransport of one H+ per one Ca2+ was demonstrated, and inhibition of the Ca2+ pump by lumenal alkalinization was relieved by the H+ ionophore carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone. Consistent with the countertransport stoichiometry, net positive charge displacement was produced by Ca2+ transport, as revealed by a rapid oxonol VI absorption rise. The initial rise and the following steady-state level of oxonol absorption were highest when SO4(2-) was the prevalent anion and lowest in the presence of the lipophilic anion SCN-. The influence of anions was attributed to potential driven counterion compensation. The absorption rise was rapidly collapsed by addition of valinomycin in the presence of K+. Experimentation with Ca2+ and H+ ionophores was consistent with a primary role of Ca2+ and H+ in net charge displacement. The estimated value of the steady-state electrical potential observed under optimal conditions was approximately 50 mV and was accounted for by the estimated charge transfer associated with Ca2+ and H+ countertransport under the same conditions.

Adenosine Triphosphate↗

A national survey to assess current use of computerised information systems in obstetrics.

OBJECTIVE: To ascertain the number and type of obstetric computer systems (OCS) in Great Britain, and to ascertain user satisfaction with these systems. DESIGN: A postal questionnaire was circulated to every consultant obstetrician in Great Britain at the beginning of 1992. MAIN OUTCOME MEASURES: Information was sought on the hardware, software and uses of obstetric computer systems. Satisfaction with, benefits and problems of the system were also assessed. RESULTS: There was an 87.5% response rate. Of the 264 units questioned, 100 units reported that they had a computer system. Sixty-five units used terminals connected to a mainframe or minicomputer and 17 used stand-alone personal computers (PCs). Local area networks (LANs) were used in 19 units and wide area network (WANs) in 22 units. Software varied from commercial turnkey systems to in-house systems. The quoted annual running cost ranged from 50 pounds to 48,000 pounds. Most units were satisfied with their system. Problems included slow operating times, unreliability, user unfriendliness, deficiencies in training and inadequate customer support services. CONCLUSIONS: Obstetric computer systems are now coming into widespread use. Despite problems, the use of such systems is likely to increase. This survey establishes a database for those units who are considering acquiring or changing their computer system for the purpose of audit or research.

Attitude to Computers↗

Spirituality and purpose in life in alcoholism recovery.

This study examines the relationship between spirituality and recovery from alcoholism. Spirituality was defined as the extent of practice of Alcoholics Anonymous Steps 11 and 12 and was measured by a Step Questionnaire developed by the researcher. Step 11 suggests prayer and meditation and Step 12 suggests assistance of other alcoholics. Expressed degree of purpose in life was also seen as a reflection of spirituality. It was postulated that the extent to which Steps 11 and 12 were practiced would be positively correlated with the extent of purpose in life reported by 100 Alcoholics Anonymous members. The major findings of this study are significant positive correlations between practice of Step 11 and purpose in life scores (r = .59, p < .001) and between Step 11 and length of sobriety (r = .25, p < .01). Number of Alcoholics Anonymous meetings attended was significantly correlated with purpose in life scores (r = .24, p < .01) and length of sobriety (r = .25, p < .01). These findings suggest that a sense of purpose in life increases with continuing sobriety and practice of the spiritual principles of Alcoholics Anonymous.

Adult↗