Redesign and genetic dissection of the rhabdoviruses.
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Animals↗
Biomedical subjects
A Roberts
Publications and source records attributed to A Roberts.
The risk and protective functions of perceived family and peer microsystems among urban adolescents in poverty.
Utilized a pattern-based approach to discover the different constellations of perceived social transactions separately for family and peer systems and explored the risk and protective functions of these microsystem profiles for both depression and antisocial behavior among a sample of ethnically and racially diverse urban adolescents living in poverty. Measures of perceived social support, involvement and hassles with family and peers, as well as perceived social acceptance and peers' values were entered into two sets of iterative cluster analyses to identify distinct profiles of family and peer transactions. From each of the perceived family and peer transactional analyses, six replicated profiles emerged. Several of the profiles were consistent with expectations from prior literature such as Enmeshing families and Rejecting peer networks, while others were novel and intriguing such as Entangling peers. Family profiles were consistent in their risk and protective associations for both depression and antisocial behavior, while the peer profiles varied in their effects for each developmental outcome. For example, the Rejecting peer profile placed adolescents at increased risk for depression but protected them from antisocial behavior. Implications for future research and preventive intervention are discussed.
Adolescent↗
A longitudinal ethics curriculum for medical students and generalist residents at the Medical College of Georgia.
Medical ethics is an important instructional area for both the undergraduate student pursuing a generalist education and generalist residents. With the support of a Generalist Physician Initiative (GPI) award from The Robert Wood Johnson Foundation, the Medical College of Georgia has implemented a longitudinal experience in clinical ethics spanning the four undergraduate years to make this area more meaningful and clinically relevant. This report outlines the structure and content of this four-year curriculum, which has been developed and implemented in a stepwise fashion since 1996. Course themes and students' activities during the four years are described. Since 1997, a shared curriculum in ethics--developed for residents in internal medicine, family medicine, and pediatric generalist programs--has been provided in combined interdepartmental conferences as part of a broader interdepartmental generalist curriculum. Early evaluation findings and plans for future evaluation programs are also described.
Curriculum↗
Modulation of Rubisco Activity during the Diurnal Phases of the Crassulacean Acid Metabolism Plant Kalanchoë daigremontiana.
The regulation of Rubisco activity was investigated under high, constant photosynthetic photon flux density during the diurnal phases of Crassulacean acid metabolism in Kalanchoë daigremontiana Hamet et Perr. During phase I, a significant period of nocturnal, C(4)-mediated CO(2) fixation was observed, with the generated malic acid being decarboxylated the following day (phase III). Two periods of daytime atmospheric CO(2) fixation occurred at the beginning (phase II, C(4)-C(3) carboxylation) and end (phase IV, C(3)-C(4) carboxylation) of the day. During the 1st h of the photoperiod, when phosphoenolpyruvate carboxylase was still active, the highest rates of atmospheric CO(2) uptake were observed, coincident with the lowest rates of electron transport and minimal Rubisco activity. Over the next 1 to 2 h of phase II, carbamylation increased rapidly during an initial period of decarboxylation. Maximal carbamylation (70%-80%) was reached 2 h into phase III and was maintained under conditions of elevated CO(2) resulting from malic acid decarboxylation. Initial and total Rubisco activity increased throughout phase III, with maximal activity achieved 9 h into the photoperiod at the beginning of phase IV, as atmospheric CO(2) uptake recommenced. We suggest that the increased enzyme activity supports assimilation under CO(2)-limited conditions at the start of phase IV. The data indicate that Rubisco activity is modulated in-line with intracellular CO(2) supply during the daytime phases of Crassulacean acid metabolism.
Journal Article↗
Mini-allografts' for haematological malignancies: an alternative to conventional myeloablative marrow transplantation.
BACKGROUND: Considerable morbidity and mortality are consequences of the myeloablative chemoradiotherapy utilised in conventional allogeneic marrow transplantation. This has generally restricted such potentially curative treatment to patients <50-55 years with normal organ function. Recent studies suggest that purine-analogue based non-myeloablative regimens are sufficiently immunosuppressive to facilitate allogeneic donor cell engraftment. AIM: To review the outcome of HLA-compatible sibling allogeneic peripheral blood progenitor cell (PBPC) transplants using fludarabine-based conditioning in patients ineligible for a conventional transplant, with emphasis on engraftment, graft vs host disease (GVHD) and graft vs tumour effects. METHODS: Eleven patients (nine > or = 47 years age) with advanced haematological malignancies received one of three different fludarabine-based chemotherapy followed by infusion of granulocyte colony-stimulating factor mobilised PBPC. Cyclosporin-methotrexate was used as GVHD prophylaxis. RESULTS: Two patients died early; minimal non-haematological toxicity apart from mucositis occurred in the other nine. Eight of the nine evaluable patients had evidence of durable donor cell engraftment in preference to recipient cells. Acute GVHD (> or = grade 2) occurred in seven of eight patients with donor engraftment who survived beyond two months. Four patients are alive in complete remission 8-28 months post-transplant; another is alive in probable remission at four months. CONCLUSIONS: Fludarabine-based non myeloablative chemotherapy facilitates rapid engraftment of allogeneic donor cells, which produce powerful GVHD and graft vs tumour effects. This approach has the potential to extend the applicability of allogeneic stem cell transplants to patients traditionally regarded as too old or sick for conventional marrow transplants.
Adult↗
Administration of low-dose aspirin to mothers with small for gestational age fetuses and abnormal umbilical Doppler studies to increase birthweight: a randomised double-blind controlled trial.
OBJECTIVE: To determine whether antenatal treatment (for > or = 14 days) with 100 mg aspirin daily, given to mothers with small for gestational age fetuses and abnormal umbilical Doppler, will increase birthweight. DESIGN: Randomised, double-blind placebo controlled trial. SETTING: A tertiary referral centre. PARTICIPANTS: Ninety-nine women, of whom 65 were treated for > or = 14 days (32 with aspirin and 33 with placebo) and comprised the study group. The entry criteria were: singleton pregnancy with ultrasound evidence of a small for gestational age fetus (abdominal circumference < 10%); previous anatomy scan < 20 weeks and no evidence of fetal abnormality; gestation between 24 and 36 weeks; umbilical artery Doppler resistance index > 95% for gestation; no previous aspirin treatment in pregnancy; and no contra-indication to aspirin treatment. RESULTS: The mean duration of treatment was 30 days for aspirin treated, and 29 for placebo. No difference was found in birthweight or other measures of fetal growth or newborn morbidity between those treated with aspirin or placebo. Compliance, assessed by thromboxane B2 analysis, showed almost complete suppression of thromboxane B2 in aspirin treated women. CONCLUSION: Low-dose aspirin did not increase birthweight in pregnancies where the fetus has abnormal umbilical Doppler and is thought to be small for gestational age.
Adult↗
Molecular characterization and human T-cell responses to a member of a novel Mycobacterium tuberculosis mtb39 gene family.
We have used expression screening of a genomic Mycobacterium tuberculosis library with tuberculosis (TB) patient sera to identify novel genes that may be used diagnostically or in the development of a TB vaccine. Using this strategy, we have cloned a novel gene, termed mtb39a, that encodes a 39-kDa protein. Molecular characterization revealed that mtb39a is a member of a family of three highly related genes that are conserved among strains of M. tuberculosis and Mycobacterium bovis BCG but not in other mycobacterial species tested. Immunoblot analysis demonstrated the presence of Mtb39A in M. tuberculosis lysate but not in culture filtrate proteins (CFP), indicating that it is not a secreted antigen. This conclusion is strengthened by the observation that a human T-cell clone specific for purified recombinant Mtb39A protein recognized autologous dendritic cells infected with TB or pulsed with purified protein derivative (PPD) but did not respond to M. tuberculosis CFP. Purified recombinant Mtb39A elicited strong T-cell proliferative and gamma interferon responses in peripheral blood mononuclear cells from 9 of 12 PPD-positive individuals tested, and overlapping peptides were used to identify a minimum of 10 distinct T-cell epitopes. Additionally, mice immunized with mtb39a DNA have shown increased protection from M. tuberculosis challenge, as indicated by a reduction of bacterial load. The human T-cell responses and initial animal studies provide support for further evaluation of this antigen as a possible component of a subunit vaccine for M.tuberculosis.
Adolescent↗
Attenuated vesicular stomatitis viruses as vaccine vectors.
We showed previously that a single intranasal vaccination of mice with a recombinant vesicular stomatitis virus (VSV) expressing an influenza virus hemagglutinin (HA) protein provided complete protection from lethal challenge with influenza virus (A. Roberts, E. Kretzschmar, A. S. Perkins, J. Forman, R. Price, L. Buonocore, Y. Kawaoka, and J. K. Rose, J. Virol. 72:4704-4711, 1998). Because some pathogenesis was associated with the vector itself, in the present study we generated new VSV vectors expressing HA which are completely attenuated for pathogenesis in the mouse model. The first vector has a truncation of the cytoplasmic domain of the VSV G protein and expresses influenza virus HA (CT1-HA). This nonpathogenic vector provides complete protection from lethal influenza virus challenge after intranasal administration. A second vector with VSV G deleted and expressing HA (DeltaG-HA) is also protective and nonpathogenic and has the advantage of not inducing neutralizing antibodies to the vector itself.
Animals↗
A possible pathway connecting the photosensitive pineal eye to the swimming central pattern generator in young Xenopus laevis tadpoles.
The pineal eye of young Xenopus laevis tadpoles mediates a swimming response to dimming. Our aim was to define pathways that allow pineal photoreceptors to influence the swimming central pattern generator (CPG) in the hindbrain and spinal cord. Retrograde filling with horseradish peroxidase (HRP) and carboxyfluorescein showed that: (1) pineal ganglion cells do not project to the hindbrain, and (2) diencephalic/mesencephalic descending (D/MD) neurons, which could be contacted by pineal ganglion cell axons, do project to the hindbrain. Lesion experiments demonstrated that ganglion cell axons form ipsilateral and contralateral connections, either of which is sufficient to mediate a swimming response. Latency measurements suggest that the contralateral pathway is stronger than the ipsilateral one. Multiple unit recordings from the midbrain in the region of the D/MD neurons showed short latency activity in response to dimming or a brief current pulse to pineal axons. This activity could last for many seconds after the stimulus. Pharmacological experiments showed that it depended on synaptic excitation and suggested that the ganglion cell transmitter is glutamate. If pineal ganglion cells excite midbrain D/MD neurons on both sides of the brain, the D/MD neuron projections to the hindbrain could excite the swimming CPG and initiate swimming.
Animals↗
Biomechanics of judicial hanging: a case report.
A prisoner in Washington State in the United States of America appealed against sentence of death by hanging on the grounds that it was 'cruel and unusual' and hence contravened the Eighth Amendment of the US Constitution. The man weighed 184 kg (406 lb) and it was suggested that the 'drop' proposed to effect judicial hanging might result in decapitation. This hypothesis was tested by applying simple biodynamic principles to the available data from past hangings. It was concluded that decapitation was a significant possibility.
Adult↗
A longitudinal evaluation of a communication skills programme.
Communication is an essential component of palliative care, but patients and their families are often dissatisfied with their interactions with health professionals. Communication difficulties are also a recognized stress factor among health professionals. Education and training, however, are said to improve communication skills. A communication skills training programme for 110 nurses has demonstrated statistically significant improvements in the nurses' skills, but no long-term effect was evaluated. This paper presents the results of the long-term follow-up study. Of the 110 nurses contacted, 20% refused to participate, 45% agreed and 35% did not respond; 33 nurses returned usable data. The mean length of time since completing the original study was 2.5 years. Since completion of the original course there was no statistically significant deterioration or improvement in eight of the nine areas of assessment skills evaluated. In the area of psychological assessment there was a statistically significant improvement, and overall the nurses maintained their skills and improved in this area. The results suggest that over time the nurses became more confident in the emotional areas of care as a result of the training. The two key elements of the training were audio-tape recordings and feedback, which raised self-awareness, and experiential workshops covering ways of handling difficult situations. Whether a similar training effect could be achieved by a short 3-5 day course on communication skills needs addressing, because the integrated training skills course evaluated here is costly. Preliminary evidence suggests that the 3-5-day course may not be as effective, so the increased costs associated with the integrated training skills course may be wisely spent if it improves the quality of nurse-patient interaction as evidence here suggests.
Adult↗
Malunion in the lower limb. A nomogram to predict the effects of osteotomy.
Nomograms derived from mathematical analysis indicate that the level of malunion is the most important determinant of changes in the moment arm of the knee, the plane of the ankle and alterations in limb length. Testing in five patients undergoing reconstruction showed a mean error of postoperative limb length of 2.2 mm (SD 0.8 mm), knee moment arm of 4.7 mm (SD 3.3 mm) and ankle angle of 2.6 degrees (SD 2.3 degrees). These nomograms provide the information required when assessing whether a particular degree of angulation may be accepted.
Algorithms↗
A comparison of three risk assessment scales.
Nurses often use pressure sore risk assessment tools without clearly understanding their underlying principles. Comparing different tools can help to determine which are of most value to nurses. Assessment tools can aid decision-making and give objective credibility to practice.
Humans↗
Central circuits controlling locomotion in young frog tadpoles.
The young Xenopus tadpole is a very simple vertebrate that can swim. We have examined its behavior and neuroanatomy, and used immobilized tadpoles to study the initiation, production, coordination, and termination of the swimming motor pattern. We will outline the sensory pathways that control swimming behavior and the mainly spinal circuits that produce the underlying motor output. Our recent work has analyzed the glycinergic, glutamatergic, cholinergic, and electrotonic synaptic input to spinal neurons during swimming. This has led us to study the nonlinear summation of excitatory synaptic inputs to small neurons. We then analyzed the different components of excitation during swimming to ask which components control frequency, and to map the longitudinal distribution of the components along the spinal cord. The central axonal projection patterns of spinal interneurons and motoneurons have been defined in order to try to account for the longitudinal distribution of synaptic drive during swimming.
Animals↗
Axon projections of reciprocal inhibitory interneurons in the spinal cord of young Xenopus tadpoles and implications for the pattern of inhibition during swimming and struggling.
We have examined the morphology and longitudinal axon projections of a population of spinal commissural interneurons in young Xenopus tadpoles. We aimed to define how the distribution of axons of the whole population constrains the longitudinal distribution of the inhibition they mediate. Forty-three neurons at different positions were filled intracellularly with biocytin and processed with avidin-conjugated horseradish peroxidase. Soma size did not vary longitudinally and only one ipsilateral axon was found. Contralateral axons ascended, descended, or usually branched to do both. Total axon length and the extent of dendritic arborisation decreased caudally. The distributions of ascending and descending axon lengths were different; there were more long ascending (mean 737 +/- standard deviation 365 microm) than long descending (447 +/- 431 microm) axons. We used the axon length distribution data with existing data on the distribution of commissural interneuron somata to calculate the overall longitudinal density of these inhibitory axons. Axon numbers showed a clear rostrocaudal gradient. Axon length distributions were then incorporated into a simple spatiotemporal model of the forms of inhibition during swimming and struggling motor patterns. The model predicts that the peak of inhibition on each cycle will decrease from head to tail in both motor patterns, a feature already confirmed physiologically for swimming. It also supports a previous proposal that ascending inhibition during struggling shortens cycle period by shortening rostral motor bursts, whereas descending inhibition could delay subsequent burst onset.
Animals↗
Non-linear summation of excitatory synaptic inputs to small neurones: a case study in spinal motoneurones of the young Xenopus tadpole.
1. We examined the steady-state summation of postsynaptic potentials (PSPs) in small, electrotonically compact neurones with short dendrites, using a one-compartment electrical equivalent model of the passive membrane with conductances to represent chemical synapses and electrotonic junctional connections to neighbouring neurones. 2. Our model shows that PSP summation is non-linear and for small depolarizations is mainly determined by the increase in total neurone conductance due to the opening of synaptic channels. At bigger depolarizations the change in synaptic driving force becomes an equally important cause of non-linearity. 3. Non-linear summation of AMPA-mediated PSPs was measured experimentally when two monosynaptic pathways to motoneurones were stimulated. The conductances underlying these PSPs were calculated relative to the resting neurone conductance using our model. These conductance ratios were hardly affected by the size of electrotonic coupling conductances. The non-linearity in PSP summation could be predicted by the model provided that the depolarizations remained negative to potentials at which voltage-dependent channels open. 4. The model was used to estimate the relative contributions of glutamatergic, cholinergic and electrotonic excitation to EPSPs measured in Xenopus tadpole spinal motoneurones during swimming. Estimates of synaptic conductances and electrotonic coupling to other motoneurones suggest that ligand-gated conductance mediated by glutamate may be twice that due to acetylcholine. 5. We conclude that in small electrotonically compact motoneurones of the Xenopus tadpole, our simple model can predict the non-linearity in PSP summation and may allow the conductances of different synaptic inputs to be compared. Furthermore, excitatory synaptic conductances can increase the resting neurone conductance significantly and limit depolarization. Our general model may also be applicable to other small neurones.
Animals↗
Longitudinal distribution of components of excitatory synaptic input to motoneurones during swimming in young Xenopus tadpoles: experiments with antagonists.
1. Recent studies have revealed that the excitatory synaptic input to spinal motoneurones during fictive swimming in Xenopus tadpoles has three main components: glutamatergic (Glu) from premotor excitatory interneurones, nicotinic cholinergic (nACh) from more rostral motoneurones, and electrotonic coupling from neighbouring motoneurones. During swimming, these components sum to produce two kinds of excitation: phasic excitation (EPSPs) underlying spikes, and tonic depolarization. 2. We have investigated the longitudinal distribution of these excitatory synaptic inputs to presumed motoneurones at different positions along the spinal cord using intracellular recording techniques. Different antagonists (10 microM dihydro-beta-erythroidine (DHbetaE) for nicotinic ACh receptors (nAChRs), 2 mM kynurenate (Kyn) for glutamate receptors (GluRs), and 100 microM Cd2+ for all chemical synapses) were microperfused very locally to unmask the relative contributions of these components to the total excitatory drive, and their distribution along the spinal cord during swimming. 3. If the potentials remaining when all chemical components were blocked by Cd2+ were subtracted from potentials recorded after blocking nAChRs and GluRs with DHbetaE plus Kyn, a small unidentified component was observed. This component was blocked by the specific AMPA antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (NBQX, 5 microM), so is glutamate mediated. 4. We used the potential measurements to calculate the relative synaptic conductances of the different synaptic inputs, and conclude that: (a) there is a rostral-caudal gradient in input during EPSPs and tonic depolarization; (b) the glutamatergic component accounts for most of the excitation, and decreases caudally; (c) cholinergic and electrotonic components are relatively constant in different positions along the spinal cord; and (d) these two components provide an increasing proportion of the input in more caudal neurones. 5. We propose that the glutamate components of excitation are fundamental to rhythm generation in the brainstem and rostral cord, while the electrotonic and cholinergic components ensure that the central pattern generator activates motoneurones effectively in all parts of the spinal cord.
Animals↗