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Biomedical subjects

A Roberts

Publications and source records attributed to A Roberts.

At least 73 records · Page 4Linked to original sources
PubMed2001

Replication-competent or attenuated, nonpropagating vesicular stomatitis viruses expressing respiratory syncytial virus (RSV) antigens protect mice against RSV challenge.

Foreign glycoproteins expressed in recombinant vesicular stomatitis virus (VSV) can elicit specific and protective immunity in the mouse model. We have previously demonstrated the expression of respiratory syncytial virus (RSV) G (attachment) and F (fusion) glycoprotein genes in recombinant VSV. In this study, we demonstrate the expression of RSV F and G glycoproteins in attenuated, nonpropagating VSVs which lack the VSV G gene (VSVDeltaG) and the incorporation of these RSV proteins into recombinant virions. We also show that intranasal vaccination of mice with nondefective VSV recombinants expressing RSV G (VSV-RSV G) or RSV F (VSV-RSV F) elicited RSV-specific antibodies in serum (by enzyme-linked immunosorbent assay [ELISA]) as well as neutralizing antibodies to RSV and afford complete protection against RSV challenge. In contrast, VSVDeltaG-RSV F induced detectable serum antibodies to RSV by ELISA, but no detectable neutralizing antibodies, yet it still protected from RSV challenge. VSVDeltaG-RSV G failed to induce any detectable serum (by ELISA) or neutralizing antibodies and failed to protect from RSV challenge. The attenuated, nonpropagating VSVDeltaG-RSV F is a particularly attractive candidate for a live attenuated recombinant RSV vaccine.

Administration, Intranasal↗
PubMed2001

Ambient temperature modulates hypoxic-induced changes in rat body temperature and activity differentially.

When rats, acclimated to an ambient temperature (T(a)) of 29 degrees C, are exposed to 10% O(2) for 63 h, the circadian rhythms of body temperature (T(b)) and level of activity (L(a)) are abolished, T(b) falls to a hypothermic nadir followed by a climb to a hyperthermic peak, L(a) remains depressed (Bishop B, Silva G, Krasney J, Salloum A, Roberts A, Nakano H, Shucard D, Rifkin D, and Farkas G. Am J Physiol Regulatory Integrative Comp Physiol 279: R1378-R1389, 2000), and overt brain pathology is detected (Krasney JA, Farkas G, Shucard DW, Salloum AC, Silva G, Roberts A, Rifkin D, Bishop B, and Rubio A. Soc Neurosci Abstr 25: 581, 1999). To determine the role of T(a) in these hypoxic-induced responses, T(b) and L(a) data were detected by telemetry every 15 min for 48 h on air, followed by 63 h on 10% O(2) from rats acclimated to 25 or 21 degrees C. Magnitudes and rates of decline in T(b) after onset of hypoxia were inversely proportional to T(a), whereas magnitudes and rates of T(b) climb after the hypothermic nadir were directly proportional to T(a). No hyperthermia, so prominent at 29 degrees C, occurred at 25 or 21 degrees C. The hypoxic depression of L(a) was least at 21 degrees C and persisted throughout the hypoxia. In contrast, T(a) was a strong determinant of the magnitudes and time courses of the initial fall and subsequent rise in T(b). We propose that the absence of hyperthermia at 21 and 25 degrees C as well as a persisting hypothermia may protect the brain from overt pathology.

Abdomen↗
PubMed2001

Localized scleroderma in a 12-year-old girl presenting as gingival recession. A case report and literature review.

Scleroderma is a connective tissue disorder that displays considerable clinical heterogeneity. This case describes a 12-year-old girl who presented with a localized form of the disease. The consequences were a severe and progressive localized gingival recession affecting two maxillary incisors, a localized lip defect and scarring of the forehead. The case illustrates the difficulties in diagnosis and management of young patients with localized scleroderma.

Child↗
PubMed2001

A defect in HIV-1 transgenic murine macrophages results in deficient nitric oxide production.

HIV transgenic mice bearing multiple copies of a noninfectious (Deltagag/pol) proviral DNA were tested for the systemic production of nitric oxide (NO). Serum levels of NO metabolites were reduced about 50% in HIV transgenic mice compared with nontransgenic sibling mice. This difference persisted when NO production was induced with peritoneal injections of bacterial endotoxin (LPS). Peritoneal inflammatory macrophages, but not resident peritoneal macrophages, derived from HIV-1 transgenic mice and activated in vitro with LPS and IFN-gamma (or tumor necrosis factor alpha and IFN-gamma) also produced about 50% less NO than did macrophages harvested from nontransgenic littermates. Isogenic, transgenic mice bearing mutated nef or vpr genes had normal serum levels of NO metabolites and their macrophages produced normal levels of NO when stimulated. An explanation for the reduced NO response of HIV[Vpr+Nef+] macrophages was not apparent from measured levels of iNOS expression, viral gene expression, or arginase activity in activated macrophages. Inhibition of nitric oxide synthase (NOS) isoforms with L-NAME or aminoguanidine blocked time-dependent increases in HIV gene expression in activated macrophages cultured ex vivo. Inhibition with L-NAME occurred despite high levels of NO generated by iNOS, and exogenously supplied NO induced HIV gene expression only weakly, suggesting that cNOS had the greater influence on proviral gene induction. This system is presented as a model of HIV-1 proviral gene expression and dysfunction in macrophages.

Animals↗
PubMed2001

GALEN ten years on: tasks and supporting tools.

The GALEN technology has matured over more than a decade of use. We describe a set of software tools and associated methodologies that together are supporting ontological engineering in a production, rather than a research setting.

Artificial Intelligence↗
PubMed2001

Effects of water immersion on pulmonary function in asthmatics.

Immersion induces air trapping in the lungs, as does asthma. Consequently, when using diving apparatus, asthmatics may face greater risk than non-asthmatics of pulmonary barotrauma (PBT) during ascent. We studied the pulmonary airflows and closing capacities (CC = closing volume + residual volume) in subjects with exercise-induced asthma (A, n = 12) and in healthy controls (C, n = 11) under four conditions: dry and immersed, both before and after exercise (treadmill running, non-immersed). Immersed, both C and A had significant and equivalent reductions in vital capacity, FEV1, FEV1/FVC, and FEF25%-75%. Post-exercise and immersed, pulmonary airflows deteriorated further in A but were better in C: FEV1 (A, 3.6 +/- 0.8 liter vs. 3.3 +/- 0.8 liter, P = 0.001; C, 3.9 +/- 0.5 liter vs. 4.1 +/- 0.6 liter, P = 0.006), FEF25-75% (A, 3.5 +/- 1.0 liter x s(-1) vs. 3.0 +/- 0.8 liter x s(-1). P < 0.05; C, 4.0 +/- 0.9 liter x s(-1) vs. 4.3 +/- 0.9 liter x s(-1), P < 0.05). Therefore, in contrast to C, A subjects had reduced pulmonary airflows during immersion after exercise. Furthermore, A subjects more often had no closing volume phase IV when immersed after exercise than C (P = 0.005). Interpreting the absence of phase IV as indicative of more air trapping in the asthmatics during immersion after exercise would be consistent with the reductions in airflow.

Adult↗
PubMed2000

Early functional organization of spinal neurons in developing lower vertebrates.

The spinal neurons in the embryos and young larvae of two amphibians (Xenopus and Triturus) and two fish (Oryzias and Brachydanio) are described and compared. They can be placed into a limited number of common neuron classes: Rohon-Beard sensory, dorsolateral and dorsolateral commissural sensory interneurons, inhibitory ascending interneurons, two classes of inhibitory commissural interneuron, excitatory descending interneurons, motoneurons and possible sensory Kolmer-Agdhur neurons. In Triturus and other urodeles, there are also giant dorsolateral commissural sensory interneurons. The functions of the spinal neurons in simple flexion responses and swimming are considered in relation to evidence mainly from the Xenopus tadpole.

Amphibians↗
PubMed2000

Vergence provides veridical depth perception from horizontal retinal image disparities.

One useful source of depth information available to the human nervous system is present in the horizontal disparities that exist between the two retinal images (stereoscopic depth). The relationship between horizontal disparity and depth varies with viewing distance so that an interpreting signal is required if disparities are to yield useful information. One potentially useful interpreting signal is available from ocular vergence. A number of studies have concluded, however, that a vergence signal does not provide veridical stereoscopic depth. All of these studies required observers to make a range of judgements under conditions of uncertainty (often using random dot stimuli) and we suggest that the lack of veridicality arose because of a contraction bias: a general tendency to bias judgements towards the centre of the range of possible responses. We re-examined the role of ocular vergence in the maintenance of stereoscopic depth constancy for real three-dimensional objects. Our results question the conclusions reached by previous studies and suggest that vergence can provide a veridical interpretation of stereoscopic depth. Our results indicate that horizontal retinal image disparities are not interpreted by a 'higher order' signal (i.e. the 'perceived distance' of the fixation point). The results of the experiment have significant implications for models of depth processing from disparity.

Adolescent↗
PubMed2000

Plasma coenzyme Q(10) in children and adolescents undergoing doxorubicin therapy.

The objective of this study was to test the hypothesis that doxorubicin treatment for cancer in childhood and adolescence causes a dose-related decrease in the concentration of plasma coenzyme Q(10). The concentration of plasma coenzyme Q(10) was measured before and after administration of doxorubicin in six patients, and before and after chemotherapy in six patients undergoing treatments that did not include doxorubicin. There was a significant increase in the concentration of plasma coenzyme Q(10) in post-treatment samples compared to pre-treatment samples in patients treated with doxorubicin (P=0.008; n=32), whereas there were no significant changes in plasma coenzyme Q(10) concentrations in patients treated with chemotherapy that did not include doxorubicin. (P=0.770; n=30). We hypothesise that the increase in plasma coenzyme Q(10) that was observed in patients undergoing doxorubicin treatment is due to release of coenzyme Q(10) from apoptotic or necrotic cardiac tissue. We conclude that the cardiotoxicity due to doxorubicin therapy does not involve acute myocardial depletion of coenzyme Q(10).

Adolescent↗
PubMed2000

Psychiatric comorbidity in white and African-American illicit substance abusers: evidence for differential etiology.

Research on psychiatric comorbidity among opiate and cocaine addicts has consistently found African-Americans to report fewer symptoms of anxiety and affective disorders than Whites. The current article reviews the research on these racial differences, evaluates various interpretations of these differences, and discusses the limitations of past research. It is concluded that Whites and African-American addicts differ in their underlying reasons for abusing drugs. Drug addiction among Whites appears to be related largely to psychopathology, whereas Black drug abuse is best understood in terms of social and environmental factors. Treatment implications are also discussed.

Black or African American↗
PubMed2000

Sucralose metabolism and pharmacokinetics in man.

The metabolic and pharmacokinetic profile of sucralose was studied in human volunteers. Following a single oral dose of (14)C-sucralose (1mg/kg, 100 microCi) to eight male subjects, a mean of 14.5% (range 8.9 to 21.8%) of the radioactivity was excreted in urine and 78.3% (range 69.4 to 89.6%) in the faeces, within 5 days. The total recovery of radioactivity averaged 92.8%. Plasma concentrations of radioactivity were maximal at about 2 hours after dosing. The mean residence time (MRT) for sucralose was 18.8hr, while the effective half-life for the decline of plasma radioactivity was 13hr. Two volunteers given a higher oral dose (10mg/kg, 22.7 microCi) excreted a mean of 11.2% (9.6 and 12.7%) of the radioactivity in urine, and 85.5% (84.1 and 86.8%) in faeces over 5 days. The total recovery of radioactivity was 96.7%. The radiolabelled material present in faeces was essentially unchanged sucralose. Sucralose was the principal component in the urine together with two more polar components which accounted for only 2.6% of the administered dose (range 1.5 to 5.1% of dose); both metabolites possessed characteristics of glucuronide conjugates of sucralose.

Adult↗
PubMed2000

The metabolic fate of sucralose in rats.

The fate of sucralose was investigated in rats following single intravenous or oral doses of 2-1000mg/kg. Following intravenous administration (2-20mg/kg) approximately 80% of the dose was eliminated in urine with 9-16% in the faeces. In contrast, only about 5% of oral doses (10-1000mg/kg) was recovered in the urine, indicating that sucralose is poorly absorbed from the intestinal tract. After both intravenous and oral administration, the radioactivity excreted in urine and faeces was mainly unchanged sucralose. Two minor radioactive urinary components were observed, which together accounted for less than 1% of the administered dose. Rats which had been given high concentrations of sucralose (3%) in the diet for more than 18 months showed a similar metabolic profile, demonstrating that metabolic adaptation of the gut microflora or mammalian enzymes had not occurred during the treatment period.

Administration, Oral↗
PubMed2000

Combined alpha interferon and ribavirin for the treatment of hepatitis C in patients with hereditary bleeding disorders.

Patients with hereditary bleeding disorders who received non-virally inactivated plasma-derived clotting factor concentrates before the mid-1980s invariably became infected with hepatitis C virus (HCV). Therapy with interferon alpha (IFN-alpha) alone has been disappointing in this group. We conducted an open-label study, using a combination of IFN-alpha2b (3 million units three times per week) and ribavirin 1-1.2 g/d in 28 patients with hereditary bleeding disorders. Twenty-one of the 28 patients had liver biopsy-confirmed chronic hepatitis (median histological activity index 5; range 1-10) and all patients were HCV RNA positive by PCR. Virological response rate to therapy at 3 months was 82% (23 out of 28). Three HIV co-infected patients showed an early virological response with loss of HCV RNA, but two subsequently relapsed after 3 and 6 months of therapy. Four patients stopped treatment early (one at 4, one at 7 and two at 9 months) because of treatment-related side effects, although three of these have maintained a virological response. Seventeen patients completed the 48-week course. Twenty of the 28 (71%) treated have had a durable virological response with a median follow-up of 16 months (range 1-24). Combination therapy represents a significant advance in the treatment of hepatitis C in patients with hereditary bleeding disorders.

Adult↗
PubMed2000

Immunization with f-Met peptides induces immune reactivity against Mycobacterium tuberculosis.

OBJECTIVE: To determine whether synthetic peptides containing an amino terminal formyl-methionine residue and corresponding to the sequence of several proteins produced by Mycobacterium tuberculosis, would elicit an immune response in mice. DESIGN: Peptides corresponding to the amino termini of 8 M. tuberculosis proteins and initiating with formyl methionine residues were synthesized. The ability of these peptides to bind to the mouse non-classical MHC class I molecule H-2M3a was determined by flow microfluorimetry. These peptides were used to pulse dendritic cells that were then injected into normal mice. These mice were subsequently challenged with aerosolized M. tuberculosis and, 30 days later, the number of viable bacteria in the lungs was determined. RESULTS: Four of the 8 synthetic peptides bound to H-2M3a and stabilized its expression on the cell surface. Injection of mice with dendritic cells pulsed with H-2M3a binding peptides elicited non-MHC restricted cytotoxic T lymphocytes that killed peptide pulsed target cells and macrophages infected with M. tuberculosis. Immunization of mice with syngeneic dendritic cells pulsed in vitro with 2 of these peptides led to retardation of the growth of M. tuberculosis following aerosol challenge. CONCLUSION: Peptides that bind to non-polymorphic class I molecules can elicit immune reactivity directed towards M. tuberculosis.

Animals↗
PubMed2000

Evidence-based management of groin hernia in primary care--a systematic review.

BACKGROUND: National clinical guidelines on the surgical management of groin hernia have been published by the Royal College of Surgeons of England. There is also a need for guidance on the management of pre- and post-hernia repair patients in primary care, in areas such as diagnosis, referral and advice on recuperation. OBJECTIVE: The purpose of the present study was to determine best practice in primary care aspects of managing groin hernia in adults, by examination of the evidence base. METHOD: A systematic review of the available evidence was carried out, searching the major electronic databases: Medline, the Cochrane Library, Embase, Assia, Helmis, Cinahl and Psyclit. Key search terms were hern$, inguinal, femoral, groin, truss$, with searches limited to human adult subjects and the English language. RESULTS: Robust research on groin hernia is concerned almost exclusively with the in-patient surgical management of patients undergoing primary elective hernia repair. The areas with which this review was concerned, principally diagnosis, referral and advice about return to work, are areas in which it is more difficult to conduct robustly designed studies. Perhaps because of this, the evidence base on the non-surgical aspects of management is of poor methodological quality, being based primarily on expert opinion, reviews of clinical practice and experience, surveys, descriptive case studies and clinical audits. CONCLUSIONS: As the research in this area is generally of poor quality, strong conclusions are precluded, but it is possible to define best practice in some areas of care. In relation to diagnosis, GPs should distinguish correctly between a femoral and inguinal hernia because of the increased risks of strangulation and incarceration associated with the former. Due to clinical inaccuracy, the identification of whether a hernia is direct or indirect is not a good basis on which to base decision making regarding referral for elective repair. The risks associated with surgical repair are those of the normal range found for any procedure. Decisions about the fitness of patients for surgery in this instance are not procedure specific, and therefore the decisions about elective repair especially in older patients should be considered in terms of quality of life and patient choice rather than increased risks with surgical repair. Further research is required to address the gap in the evidence for the management of groin hernia within the primary care sector.

Adult↗
PubMed2000

The use of consensus to develop guidelines for the management of Helicobacter pylori infection in primary care. European Society for Primary Care Gastroenterology.

BACKGROUND: Guidelines are an increasingly important feature of clinical practice and have proliferated over the past decade. When the evidence base for effective practice is limited, guidelines have to derive from the opinions and experience of those with knowledge of the subject. The manner in which a group synthesizes its individual opinions, the consensus process, is central to the validity and applicability of the resulting recommendations. This paper considers the theoretical issues in consensus development and describes the consensus process used in developing the European Society for Primary Care Gastroenterology guidelines for the management of Helicobacter pylori in primary care. METHODS: A consensus development conference of 48 GPs from nine European countries used case scenarios to define clinical management strategies in dyspepsia and H.pylori infection. Structured data collection from this meeting allowed a quantitative measure of the extent of consensus to be produced. RESULTS: Specific recommendations were produced for 15 decision points relevant to the management of H.pylori infection in primary care. DISCUSSION: Consensus development is often utilized in the production of guidelines for clinical practice. Guideline appraisal instruments fail to examine in depth the methods used for this important part of the development process. We describe an approach to consensus development which contains a simple measure of the strength of consensus underlying each recommendation.

Anti-Bacterial Agents↗
PubMed2000

The management of Helicobacter pylori infection in primary care: a systematic review of the literature.

OBJECTIVE: The aim of the present study was to provide evidence from the literature to inform the production of guidelines by the European Society for Primary Care Gastroenterology (ESPCG) for the management of Helicobacter pylori infection in primary care. METHODS: A systematic review was conducted, searching MEDLINE, EMBASE and the Cochrane Library. The systematic review was designed to answer a number of question: the role of H.pylori in the aetiology of peptic ulcer disease (PUD), gastric cancer (GC), non-ulcer dyspepsia (NUD) and oesophagitis; non-invasive testing for H.pylori and post-treatment testing; eradication therapy; and cost issues. Selection of records concentrated on the highest quality studies, i.e. systematic reviews, meta-analyses and cost analyses. RESULTS: Helicobacter pylori infection is a causal factor in PUD and GC but not in NUD or oesophagitis. Serological tests and urea breath tests (UBTs) can be used for the detection of H.pylori, but UBT is the preferred choice for post-treatment testing. Proton pump inhibitor (PPI)-based triple regimens are the preferred eradication therapy. Eradication therapy is more cost-effective than long-term maintenance therapy. CONCLUSIONS: Strong evidence is available for answering questions on the aetiology of stomach ulcers and GU, eradication therapies and cost issues. Weaker evidence is available for answering the questions on the aetiology of NUD and non-invasive testing. No evidence is available for answering the question on the role of H.pylori in the aetiology of oesophagitis.

Anti-Bacterial Agents↗