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Biomedical subjects

A Roberts

Publications and source records attributed to A Roberts.

At least 19 recordsLinked to original sources
PubMed1999

Motoneurons of the axial swimming muscles in hatchling Xenopus tadpoles: features, distribution, and central synapses.

Xenopus tadpole motoneurons make cholinergic synapses within the spinal cord. This excitation changes with longitudinal position and contributes to the excitation that controls motor activity and its longitudinal spread during swimming. To explore the anatomic constraints on this excitation, backfilling has been used to examine the anatomy and distribution of the whole population of spinal motoneurons, to define the extent of their central axons and to find where they make synapses. Motoneuron features show considerable variation but do not allow their separation into primary and secondary. Most motoneurons have descending central axons and it is likely that central synapses are made from these axons as longitudinal dendritic extent is very limited. Motoneuron density reaches a broad plateau over the mid-trunk region at 12-13 per 100 microm. Soma size does not change with longitudinal position, but the dorsoventral extent of the dendrites decreases caudally, whereas the central axon length increases. Motoneuron distribution data were used to estimate the longitudinal distribution of central motoneuron axons. This has a broad plateau at 12-14 per 100 microm over much of the trunk and only decreases significantly caudal to the anus. This distribution correlates with cholinergic excitation during swimming. Transmission electron microscopy of motoneurons backfilled with horseradish peroxidase was used to show that central motoneuron axons make en passant synapses with motoneuron dendrites and the dendrites of other unstained neurons. By using measures of synapse frequency and total dendrite length, trunk motoneurons are estimated to each receive 100-200 synapses.

Acetylcholine↗
PubMed1999

Teaching hospitals. University challenge.

The position of large teaching hospitals in the NHS is being challenged by changing patterns of medical education and the expansion of services offered by acute hospitals. The clinical activity of teaching hospitals is now similar to that of district general hospitals. The future of teaching hospitals may lie in becoming centres of research excellence.

Clinical Clerkship↗
PubMed1999

Role of elevated plasma transforming growth factor-beta1 levels in wound healing.

Transforming growth factor (TGF)-beta1 plays a central role in wound healing. Wounds treated with neutralizing antibody to TGF-beta1 have a lower inflammatory response, reduced early extracellular matrix deposition, and reduced later cutaneous scarring, indicating the importance of local tissue TGF-beta1. By contrast, increasing the local, tissue levels of TGF-beta1 increases the early extracellular matrix deposition but does not alter scar formation. Increased levels of plasma TGF-beta1 correlate with increased fibrogenesis in the lung, kidneys, and liver. The aim of the present study was to investigate the role of elevated systemic levels of TGF-beta1 on wound healing. We used transgenic mice that express high levels of active TGF-beta1 and have elevated plasma levels of TGF-beta1 and wild-type mice of the same strain as controls. Incisional wounds and subcutaneously implanted polyvinyl alcohol (PVA) sponges were analyzed. Surprisingly, cutaneous wounds in transgenic, TGF-beta1-overexpressing mice healed with reduced scarring accompanied by an increase in the immunostaining for TGF-beta3 and TGF-beta-receptor RII and a decrease in immunostaining for TGF-beta1 compared with wounds in control mice. By contrast, the PVA sponges showed the opposite response, with PVA sponges from transgenic mice demonstrating an enhanced rate of cellular influx and matrix deposition into the sponges accompanied by an increase in the immunostaining for all three TGF-beta isoforms and their receptors compared with PVA sponges from control mice. Together, the data demonstrate that increased circulating levels of TGF-beta1 do not always result in increased expression or activity in selected target tissues such as the skin. The two wound models, subcutaneously implanted PVA sponges and cutaneous incisional wounds, differ significantly in terms of host response patterns. Finally, the data reinforce our previous observations that the relative ratios of the three TGF-beta isoforms is critical for control of scarring.

Animals↗
PubMed1999

Liver function tests and glucose and lipid metabolism in growth-restricted fetuses.

OBJECTIVE: To assess hematologic and biochemical blood variables in growth-restricted fetuses and relate them to biophysical measurements. METHODS: Blood was sampled from 22 growth-restricted fetuses. All had normal karyotypes and no congenital infections. Venous pH, partial pressure of oxygen, hematocrit, glucose, uric acid, urea, creatinine, total protein, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase, amylase, pseudocholinesterase, creatinine kinase, triglycerides, and cholesterol were measured and compared with our reference range. RESULTS: Ultrasound measurements of abdominal circumference correlated with fetal pH (r = 0.64), partial pressure of oxygen (r = 0.52), glucose (r = 0.67), total bilirubin (r = -0.54), lactic dehydrogenase (r = -0.48), and triglyceride levels (r = -0.65). Compared with fetuses with present end-diastolic velocities in the umbilical artery, the eight with absent end-diastolic velocities had lower pH (median z score -4.31), partial pressure of oxygen (median z score = -2.39), glucose (median z score = -2.01), and cholesterol (median z score = -2.34), and higher gamma-glutamyltransferase (median z score = 2.43), lactic dehydrogenase (median z score = 3.75), urea (median z score = 1.33), creatinine (median z score = 1.23), and triglyceride levels (median z score = 1.71). Only triglycerides correlated with abdominal circumference, independent of Doppler results. CONCLUSION: Growth-restricted fetuses with absent end-diastolic velocities in the umbilical artery had more marked acidemia, hypoxemia, hypoglycemia, and abnormal liver function than those with end-diastolic velocities. Triglyceride levels were inversely related to fetal size independent of Doppler results. High triglyceride levels might reset fetal homeostatic mechanisms, leading to disturbances of lipid metabolism in later life.

Acid-Base Equilibrium↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗