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A Roberts

Publications and source records attributed to A Roberts.

At least 145 records · Page 8Linked to original sources
PubMed1997

The African polio vaccine-acquired immune deficiency syndrome connection.

Seroepidemiological, clinical and molecular findings suggest that the acquired immune deficiency syndrome virus human immunodeficiency virus-1 was introduced into the human species at the time (late 1950s) and in the geographic area (Zaire) in which millions of Africans were vaccinated with attenuated poliomyelitis virus strains that were produced in kidney tissue obtained from monkeys. Since monkeys not only harbor viruses that are remarkably similar to and genetically related to human immunodeficiency virus-1, but also served as tissue donors for the African polio vaccine, it is reasonable to suspect that a then non-detectable monkey virus with human-1-like properties was unknowingly co-cultured with the attenuated poliovirus virus and subsequently administered to the vaccinees. The possibility of such a polio vaccine-acquired immune deficiency syndrome connection is a reminder of the unpredictable danger of artifically crossing natural species-barriers in biomedical laboratories.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Cloning and expression of human V-genes derived from phage display libraries as fully assembled human anti-TNF alpha monoclonal antibodies.

BACKGROUND: With the advent of phage antibody libraries, access to completely human antibody fragments is feasible, either by direct selection from human antibody libraries, or by guided selection. After selection, Fabs and scFvs may need to be expressed as complete antibodies in mammalian cells for further characterisation, or if effector functions are required. OBJECTIVES: To rebuild and express the human anti-TNF alpha antibody Fab-P3A2 (isolated as a Fab fragment from phage display libraries by guided selection) as a fully assembled, functional human antibody (gamma-1, lambda) in Sp2/0 myeloma cells, and to perform preliminary characterisation studies of the secreted IgG1 molecule. A further objective was to investigate the kinetics of human antibody production and the stability of antibody secretion in transfectomas cultured in various media formulations. STUDY DESIGN: A tripartite strategy was employed for cloning heavy chain gene (VH)-P3 and light chain gene V lambda-A2-C lambda into mammalian cell expression vectors p alpha Lys-30 and p alpha Lys-17 respectively. The cell line P3A2.B5 was isolated after co-transfection of Sp2/0 mouse myelomas with the constructs, expanded and weaned into a protein free medium. Fully assembled Ig-P3A2 antibody was purified by Protein A affinity chromatography and characterised with respect to size of antibody chains, and affinity for human TNF alpha. Stability of secretion was investigated by extended serial sub-culture and analysis of P3A2.B5 sub-clones. Strategies of media enrichment were tested for any effect on antibody productivity by selected P3A2.B5 sub-clones. RESULTS: The cell line P3A2.B5 secreted an assembled, human antibody Ig-P3A2, with heavy and light chains of molecular weight 55 and 28 KD respectively. Equilibrium capture studies showed Ig-P3A2 to have a dissociation constant of approximately 1.5 x 10(-8) M. The mean specific productivity of the cell line increased from 1.2 pg/cell/day to 7.8 pg/cell/day by a combination of medium enrichment and serum reduction. Prolonged serial sub-culture of P3A2.B5 showed the cell line to be unstable with respect to antibody secretion. CONCLUSIONS: We have outlined a method for expression of human V genes as assembled antibodies in Sp2/0 myeloma cells. A cloning strategy for the stable expression of scFv or Fab genes isolated from phage display libraries as assembled human antibodies of the IgGl subclass in Sp2/0 myeloma cells has been described. For maximising specific productivity of antibody-producing cell lines, supplementation of culture media with glucose, glutamine and amino acids increases antibody yield significantly compared to that in conventional media, indicating the latter is stoichiometrically limiting for production purposes.

Animals↗
PubMed1997

Interaction between piloting and beacon homing by rats in a swimming pool.

In three experiments, rats in a swimming pool were trained to find a submerged platform with a beacon attached to it. For some rats this beacon unambiguously identified the location of the platform; for others the beacon was made ambiguous by placement of an identical beacon in a different part of the pool. Test trials, in the absence of the platform and the beacons, revealed more persistent searching near the original location of the platform if the beacon attached to the platform had been ambiguous. These results show that learning about the location of the platform, with regard to cues that lie beyond the pool, is influenced by the extent to which an animal can find the platform by relying on other cues. The final experiment shows that this interaction between cues is influenced by an animal's prior experience.

Animals↗
PubMed1997

Linkage analysis of candidate regions for coeliac disease genes.

A strong HLA association is seen in coeliac disease [specifically to the DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account for the increased risk seen in relatives of affected cases. One or more genes at HLA-unlinked loci also predispose to coeliac disease and are probably stronger determinants of disease susceptibility than HLA. A recent study has proposed a number of candidate regions on chromosomes 6p23 (distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3, 19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked susceptibility gene. We have examined these regions in 28 coeliac disease families by linkage analysis. There was excess sharing of chromosome 6p markers, but no support for a predisposition locus telomeric to HLA. No significant evidence in favour of linkage to coeliac disease was obtained for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or 22cen. There was, however, excess sharing close to D15S642. The maximum non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac disease to chromosome 15q26 is not strong, the well established association between coeliac disease and insulin dependent diabetes mellitus, together with the mapping of an IDDM susceptibility locus (IDDM3) to chromosome 15q26, provide indirect support for this as a candidate locus conferring susceptibility to coeliac disease in some families.

Celiac Disease↗
PubMed1997

Brain 5-HT function in obsessive-compulsive disorder. Prolactin responses to d-fenfluramine.

BACKGROUND: Drugs that potentiate brain serotonin (5-HT) neurotransmission are effective in the treatment of obsessive-compulsive disorder (OCD), but it is unclear whether disturbances in brain 5-HT function play a role in the pathophysiology of OCD. METHOD: We studied the prolactin response to the selective 5-HT releasing agent d-fenfluramine in 14 non-depressed, drug-free OCD patients, and 14 healthy controls matched for age and gender. RESULTS: The prolactin response to d-fenfluramine was significantly increased in OCD patients compared with controls. CONCLUSIONS: The disparate results of studies of 5-HT neuroendocrine function in OCD make it unlikely that disturbances of brain 5-HT function play a central role in the pathophysiology of OCD. Increased brain 5-HT neurotransmission in non-depressed OCD subjects may represent an adaptive neurobehavioural mechanism which can be amplified to therapeutic advantage by treatment with 5-HT potentiating drugs.

Adult↗
PubMed1997

Drugs used for pain relief in palliative care.

Nurses have a vital role in assessing, monitoring and evaluating pain. Pain control should be based on a logical step-by-step approach. Morphine is not a panacea; adjuvant drugs are often required. While drug therapy is an important aspect of pain control, management must encompass an holistic approach.

Analgesics↗
PubMed1996

Lay people's attitudes to treatment of depression: results of opinion poll for Defeat Depression Campaign just before its launch.

OBJECTIVE: To investigate the attitudes of the general public towards depression before the Defeat Depression Campaign of the Royal Colleges of Psychiatrists and General Practitioners; these results form the baseline to assess the change in attitudes brought about by the campaign. DESIGN: Group discussions generated data for initial qualitative research. The quantitative survey comprised a doorstep survey of 2003 people in 143 places around the United Kingdom. RESULTS: The lay public in general seemed to be sympathetic to those with depression but reluctant to consult. Most (1704 (85%)) believed counselling to be effective but were against antidepressants. Many subjects (1563 (78%)) regarded antidepressants as addictive. CONCLUSIONS: Although people are sympathetic towards those with depression, they may project their prejudices about depression on to the medical profession. Doctors have an important role in educating the public about depression and the rationale for antidepressant treatment. In particular, patients should know that dependence is not a problem with antidepressants.

Antidepressive Agents↗
PubMed1996

In vitro selection of a high affinity antibody to oestradiol using a phage display human antibody library.

We have isolated a monoclonal antibody binding to oestradiol with high affinity (3.7 nM), and exhibiting a better than 1000-fold selectivity in binding to other steroids. A high affinity antibody with good specificity is essential for the accurate determination of circulating oestradiol levels. To date, conventional hybridoma technology has not yielded a reagent of sufficiently high affinity and specificity for this ligand. The aim of this study was to investigate whether such a reagent was accessible through the engineering of antibodies on the surface of filamentous phage. Antibodies were isolated from a large repertoire of single chain Fv fragments (scFv) derived from non-immunised human donors, with selection and screening procedures biased to favour those binding to free oestradiol. This resulted in an antibody with nanomolar affinity for oestradiol, while affinities for related steroids are in the micromolar range. The relative lack of reactivity for steroids substituted at either end of the molecule suggests that this antibody is unique among anti-steroid monoclonal antibodies in lacking a 'blind-spot'. Our results demonstrate that phage display can provide solutions to problems that have so far proved intractable using conventional hybridoma technology.

Antibodies, Monoclonal↗
PubMed1996

Selenium deficiency and miscarriage: a possible link?

OBJECTIVE: To investigate a possible relationship between a deficiency in serum selenium concentration and first trimester miscarriage. DESIGN: An observational study. SETTING: A teaching hospital in South Wales. PARTICIPANTS AND METHODS: Serum selenium, albumin and total protein concentration were measured in 40 women admitted with first trimester nonrecurrent miscarriage. The results were compared with an equal number of age-matched nonpregnant healthy volunteers, and also from 40 pregnant women attending the antenatal clinic for booking in the first trimester. RESULTS: A reduction in serum selenium normally occurs in the first trimester of pregnancies that progress to term. However, a further statistically highly significant decrease in serum selenium was observed in those women who miscarried. CONCLUSION: Further studies are required to assess the potential benefits of selenium supplements.

Abortion, Spontaneous↗
PubMed1996

The representation of ethnic minorities at genetic clinics in Birmingham.

A study of the ethnic distribution of families attending genetic clinics in Birmingham has shown a deficit of Afro-Caribbean and Pakistani families. The former may be because of a deficiency of autosomal recessive diseases other than sickle cell disease, but the numbers are too small to be certain of this. The deficit of Pakistani families is probably for a variety of causes, such as a poorer attendance rate at clinics unless there is some encouragement, and a lack of awareness of, or interest in, genetic issues.

Adolescent↗
PubMed1996

Retreatment of patients surviving cancer-free 2 or more years after initial treatment of small cell lung cancer.

STUDY OBJECTIVE: To assess the outcome after retreatment of patients with small cell lung cancer (SCLC) who redevelop small cell cancer (SCC) 2 or more years after initial therapy. DESIGN: Retrospective analysis. SETTING: Single government institution: the National Cancer Institute. PATIENTS: Twenty patients who redeveloped SCC among 65 patients who survived 2 or more years after starting treatment for their initial cancer. MEASUREMENTS: The response rate of patients after retreatment, the survival duration from the time of redevelopment of SCC, and the toxicities of retreatment. RESULTS: Twenty patients redeveloped SCC: 18 with a relapse and 2 with a second primary cancer. Sixteen received treatment after they redeveloped SCLC while four did not. Eleven patients were retreated with chemotherapy alone, two patients received chemotherapy plus chest radiotherapy, one patient received radiotherapy alone, one patient underwent lobectomy, and one patient was treated with a monoclonal antibody followed by chemotherapy. Nine of 16 patients (56%) treated after they redeveloped SCLC had an objective response (3 complete and 6 partial). The median survival of all 20 patients after they redeveloped SCC was 3.9 months (range, 0 to 46 months). The median survival of the patients who were retreated was 6.5 months (range, 1 to 46 months). CONCLUSIONS: Patients who suffer relapses with SCLC 2 or more years from diagnosis are candidates for retreatment.

Adult↗
PubMed1996

Central synapses of spinal motoneurons innervating the trunk swimming muscles of Xenopus laevis embryos.

Our aim was to investigate the presence and nature of central motoneuron synapses within the Xenopus embryo spinal cord. Motoneurons in the rostral trunk were back-filled by applying HRP to the segmented axial swimming muscles on one side of the body. After fixation and DAB processing 4 embryos were selected where many motoneurons were filled and the level of staining was suitable for transmission electron microscopy. Thin transverse sections of the spinal cord showed that central HRP-filled motoneuron processes formed the presynaptic element of chemical synaptic junctions and also made gap junctions with other axons. We discuss the possible role of these synapses in mediating positive feedback excitation to sustain swimming after brief sensory stimulation.

Animals↗
PubMed1995

Make an application for flexible (part time) training.

Part time training posts are advertised in the BMJ each year in August or September in an advertisement placed by the Department of Health. Although the advertisement is placed by the department and manpower approvals are allocated centrally, each region runs its own scheme, and the first person to approach is the regional postgraduate dean (most regions have an assistant dean responsible for flexible training). If an application is successful then part time trainees are interviewed by the same appointments committee as full time applicants and they are judged by the same criteria. Manpower approval is granted to applicants who reach the same standard as full time applicants, but there may be a waiting list if there are more suitable applicants than training places available. The next stage is to gain educational approval from the relevant higher training committee for the proposed training programme, followed by funding from the region.

Female↗
PubMed1995

Cholinergic and electrical synapses between synergistic spinal motoneurones in the Xenopus laevis embryo.

1. To investigate central motoneurone synapses within the spinal cord of a simple vertebrate, the Xenopus embryo, simultaneous intracellular recordings were made from fifty-five pairs of spinal motoneurones. 2. Chemical synapses were found between seventeen out of thirty-five pairs on the same side of the spinal cord. Current-evoked spikes in the presynaptic neurone led to fast depolarizing postsynaptic potentials (PSPs) in the postsynaptic neurone at latencies of 0.5-1.5 ms. The PSPs had an average amplitude of 7 mV, a rise time of 8 ms and a half-fall time of 18 ms. 3. The presynaptic motoneurone was always the more rostral of the pair. No excitatory connections were found which crossed the cord. The fast PSPs were blocked by 10 microM mecamylamine but not by 1 mM kynurenic acid, so were mediated by nicotinic acetylcholine receptors (nAChRs). These are the first unitary excitatory postsynaptic potentials (EPSPs) mediated by nAChRs recorded intracellularly within the vertebrate central nervous system. 4. Bidirectional electrical synapses were found between five pairs of motoneurones. All these pairs were on the same side of the spinal cord and less than 70 microns apart. Each neurone responded in a graded manner to either hyperpolarizing or depolarizing current injected into the other. 5. Since motoneurones are rhythmically active during swimming, both chemical and electrical synapses will add to the fast on-cycle excitation underlying spiking activity in other motoneurones. This may increase the reliability and local synchrony of synergistic motoneurone firing during locomotion.

Animals↗