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Biomedical subjects

H O'Neill

Publications and source records attributed to H O'Neill.

At least 19 recordsLinked to original sources
PubMed1999

Review: dendritic cell immunotherapy for melanoma.

Melanoma is a particularly aggressive malignant tumour of the skin that is influenced by genetic, environmental and physiological elements. Since current therapy for melanoma is limited and associated with high toxicity and side effects, development of alternative approaches is imperative. The importance of dendritic cells (DCs) in immunity against tumours is now well established. DC immunotherapy for melanoma is possible but must be considered in terms of effectiveness and clinical viability. The source of DCs to be used in adoptive therapy as well as the nature and method of delivery of the priming antigen are important factors. The most suitable DC appears to be cells derived by culture from hemopoietic progenitor cells (HPC) in bone marrow or DC progenitors in peripheral blood. Generation of an effective anti-tumour immune response will be dependent upon the presentation of multiple melanoma-specific antigens by both major histocompatibility complex (MHC) class I and class II molecules and stimulation of both tumour-specific cytotoxic T lymphocytes (Tc) and T helper type 1 (Thl) cells. Different techniques for delivery of the priming antigen offer different advantages. DCs can be pulsed with peptide, protein or tumour cell lysate, transfected with viral vectors or naked nucleic acid and tumour/DC hybridomas can also be generated. Repeated antigen administration into neighbouring lymph nodes appears to be the most effective method for promoting a systemic anti-tumour response. Adjuvant therapies can also enhance immune responses and lead to total tumour clearance. The importance of DC immunotherapy in clinically different stages of disease will also be an important consideration.

Adjuvants, Immunologic↗
PubMed1999

Spleen stromal cells support haemopoiesis and in vitro growth of dendritic cells from bone marrow.

Long-term stroma-dependent cultures from murine spleen have been previously shown to support dendritic cell (DC) development in vitro. Secondary cultures have now been established using a splenic stromal cell layer overlaid with cells from different lymphoid sites. Cells resembling DCs can be generated in vitro from unfractionated murine lymphoid cells in the absence of added growth factors. Bone marrow (BM) cultures are the most successful but some cultures have been derived from spleen and thymus. Large numbers of mononuclear cells with dendritic morphology can be generated from BM within 2 weeks and cell production in many cultures has been maintained for at least 6 months. A significant proportion of cells binds antibodies specific for DC markers. No lymphoid cells, mast cells or granulocytes are detectable in culture by antibody and histochemical staining and light and electron microscopy. As with cells generated in primary cultures, cells grown in secondary cultures are equally potent stimulators of both syngeneic and allogeneic mixed lymphocyte reactions, confirming their function as antigen-presenting cells. They are also capable of endocytosing and presenting protein antigen to the D10.G4.1 Th2 clone and to unprimed T cells. This study confirmed the presence of DC precursors in multiple lymphoid sites which can be induced to proliferate in the presence of a spleen stromal cell monolayer. The secondary culture system provides an ideal in vitro model for investigation of the development of DC from different tissue sites. It also provides a stable and continuous resource of cells for further studies on DC development.

Animals↗
PubMed1998

Cloning and analysis of the genes for a novel electron-transferring flavoprotein from Megasphaera elsdenii. Expression and characterization of the recombinant protein.

The genes that encode the two different subunits of the novel electron-transferring flavoprotein (ETF) from Megasphaera elsdenii were identified by screening a partial genomic DNA library with a probe that was generated by amplification of genomic sequences using the polymerase chain reaction. The cloned genes are arranged in tandem with the coding sequence for the beta-subunit in the position 5' to the alpha-subunit coding sequence. Amino acid sequence analysis of the two subunits revealed that there are two possible dinucleotide-binding sites on the alpha-subunit and one on the beta-subunit. Comparison of M. elsdenii ETF amino acid sequence to other ETFs and ETF-like proteins indicates that while homology occurs with the mitochondrial ETF and bacterial ETFs, the greatest similarity is with the putative ETFs from clostridia and with fixAB gene products from nitrogen-fixing bacteria. The recombinant ETF was isolated from extracts of Escherichia coli. It is a heterodimer with subunits identical in size to the native protein. The isolated enzyme contains approximately 1 mol of FAD, but like the native protein it binds additional flavin to give a total of about 2 mol of FAD/dimer. It serves as an electron donor to butyryl-CoA dehydrogenase, and it also has NADH dehydrogenase activity.

Amino Acid Sequence↗
PubMed1993

Psychiatric morbidity in sentenced segregated HIV-positive prisoners.

In this comparative study with a control group of prisoners, psychiatric morbidity was measured in two groups of sentenced prisoners, each group completing the GHQ-30 and 21-item Beck Depression Inventory (BDI). Group 1 consisted of 40 segregated HIV-positive prisoners and group 2 a matched control group in the main prison who had no history of HIV seropositivity. All members of group 1 had a history of intravenous drug abuse. The mean GHQ-30 and BDI scores were significantly higher in group 1, and 90% of group 1 were psychiatric 'cases' compared with just over 42% of group 2. Levels of psychiatric morbidity present in a third group, consisting of HIV-positive prisoners who had not been segregated (prison authorities were unaware of their seropositivity) are an interesting pointer for further research.

Adult↗
PubMed1993

Adenovirus 12 and dermatitis herpetiformis.

Previous studies have shown that A-gliadin, a major gluten-derived peptide known to activate the gluten-sensitive enteropathy (GSE) of coeliac disease (CD), and the non-structural E1B peptide produced during early lytic gastrointestinal infection with human adenovirus type 12 (AD12) share an identical twelve amino acid sequence. It is suggested that immunological cross reactivity between these two peptides may play an important role in the pathogenesis of CD. As a milder but histologically identical GSE is found in the majority of patients with dermatitis herpetiformis (DH), a condition also thought to be caused by dietary gluten, we postulated that AD12 may also be involved in the pathogenesis of DH. To test this we assayed sera from 40 patients with DH and 18 healthy controls for AD12-neutralizing antibodies as evidence of past viral exposure. Detectable AD12 antibodies (titre of 13 or higher) were found in only 15% (6/40) of DH patients, compared with 27.8% (5/18) controls (not significant). These findings do not support a causative role for AD12 in the pathogenesis of DH.

Adenoviridae Infections↗
PubMed1992

Blunted prolactin responses to d-fenfluramine in sociopathy. Evidence for subsensitivity of central serotonergic function.

Using a neuroendocrine probe we studied nine male offenders in a forensic hospital, convicted of murder, with a diagnosis of antisocial personality disorder, who had been behaviourally 'quiescent' for varying periods and who had not recently been abusing drugs. Nine healthy age-matched men also participated. All subjects received 30 mg d-fenfluramine (d-FEN), a 5-HT releasing agent, orally, after an overnight fast, and serial samples for prolactin estimation were taken hourly for five hours. Responses were significantly impaired in the patients, suggesting a subsensitivity of certain 5-HT systems in antisocial personality disorder, regardless of recent or ongoing behavioural disturbance.

Adult↗
PubMed1989

Hepatitis B screening in a northern Irish mental handicap institution: relevance to hepatitis B vaccination.

The current DHSS guidelines on immunisation against hepatitis B in mental handicap hospitals recommend vaccination for personnel at risk directly involved in patient care (who may have direct contact with patients or their body fluids) and for new admissions into institutions where the incidence is known to be high. We report a serological survey of hepatitis B markers in over 99% of the residents of a large mental handicap hospital. Of 720 patients tested only one carried hepatitis surface antigen. This patient was anti-HBe positive. Only 4.5% of the residents carried any hepatitis marker. These results do not suggest the need for a local vaccination programme for patients or staff.

Cross Infection↗
PubMed1988

Difficulties in laser Doppler measurement of skin blood flow under applied external pressure.

During the course of a study of skin blood flow under applied external pressure, it became apparent that decreasing blood flow by loading the skin surface reveals problems that are fundamental to the method of laser Doppler flowmetry. These problems have to do with the fact that the laser Doppler is extremely sensitive to red cell motion of any kind, whether associated with the ordered red cell motion of blood flow or the random red cell motion associated with changes in temperature or vessel occlusion. This effect becomes increasingly important whenever blood flow is compromised (a situation of considerable clinical significance), since the random portion of the signal then becomes significant in comparison with the diminished blood flow. Experiments have been conducted in living animals and with stationary drops of blood which clearly show the importance of these effects with regard to the interpretation of laser Doppler signals. Significant laser Doppler flow signals were repeatedly observed after manipulations which could reasonably be expected to reduce blood flow to zero.

Animals↗
PubMed1985

Skin blood flow changes and tissue deformations produced by cylindrical indentors.

Since skin blood flow as a function of applied pressure depends on many factors, one may find different curves within each group of subjects, making separation of groups difficult. A dimensional analysis has been out which indicates that the percent decrease in skin blood flow associated with external loading is primarily a function of only three variables: the ratios of bone depth and bone diameter to indentor diameter, and percent compression of the tissue overlying the bone. The load itself is found to be unimportant. It is concluded that measurement of bone depth, bone diameter, and tissue deformation are more important than pressure measurements. Measurements of skin displacement and average indentor pressure for four male subjects indicate that tissue stiffness increases with age, regardless of disability, so that higher pressures are required to produce the same displacement in older subjects.

Adult↗
PubMed1984

Development and evaluation of a universal contoured cushion.

A new wheelchair seat cushion has been developed which reduces the ischaemia producing forces and redistributes them to the more tolerant areas of the posterior thighs and lateral gluteal muscles. The cushion is fabricated of foam materials and designed to stabilise the pelvis and promote proper spinal-pelvic alignment. Pressure measurements were recorded at the skin cushion interface for 66 subjects while seated on the cushion in their own wheelchair. The cushion was considered effective if maximum interface pressures recorded were: coccyx: less than 20 mmHg, ischii: less than 65 mmHg, trochanters: less than 70 mmHg, and posterior thighs: less than 80 mmHg. The cushion was considered ineffective if the interface pressure at any one location exceeded these criteria. The cushion was found effective for 52 of the subjects. The cushion was more effective (90 per cent versus 58 per cent) for subjects without certain skeletal deformities (pelvic obliquity, bony resections). Eighty-three per cent of the respondents who were followed on the cushion reported that they preferred the cushion to their previous cushions with improved posture, balance and comfort being the most commonly cited reasons. This study has shown the cushion to be a preferred alternative to other commercially available wheelchair cushions for those who are paraplegic.

Adult↗