Search PubMed⌕ Search

Biomedical subjects

G O'Donoghue

Publications and source records attributed to G O'Donoghue.

10 recordsLinked to original sources
PubMed1998

Dendritic cells pulsed with CEA peptide induce CEA-specific CTL with restricted TCR repertoire.

The human carcinoembryonic antigen (CEA), which is expressed in several cancer types is a potential target for antigen-specific immunotherapy. In this study, we show that dendritic cells (DC) pulsed with an HLA class I restricted CEA cytotoxic T lymphocyte (CTL) peptide epitope can stimulate T cells to kill CEA peptide loaded T2 target cells as well as CEA expressing tumor lines in the presence of interleukin-7 (IL-7) in an HLA-restricted manner. This has been demonstrated for carcinoma patients as well as healthy donors. The DC-CEA + IL-7 stimulated cultures contained predominantly CD3+CD8+CD56- cells indicative of MHC class I restricted CTL. In addition, DC-CEA + IL-7 stimulated cells showed higher levels of CD69 expression compared with cells stimulated with IL-7 alone, implying an activated phenotype. When the T-cell receptor (TCR) from CTL cultures stimulated with DC-CEA + IL-7 was analyzed, an oligoclonal pattern of expression was found for certain V beta subfamilies compared with the polyclonal patterns shown by IL-7 or phytohemagglutinin stimulated T cells from the same donors. This TCR restriction appeared to be maintained and enhanced after additional rounds of restimulation with DC-CEA + IL-7. The association between cytotoxicity and TCR restriction suggests that TCR analysis may be useful as an in vitro indicator to monitor alterations in the T-cell population in response to antigen-specific immunotherapies.

Amino Acid Sequence↗
PubMed1998

Cochlear implants in children: an analysis of use over a three-year period.

OBJECTIVE: This study aimed to determine whether children continue to wear their cochlear implant systems 1 and 3 years after implantation. STUDY DESIGN: The design was a prospective study based on the analysis of forced-choice questionnaires on implant use completed independently by parents and teachers. SETTING: The study was performed at a dedicated pediatric cochlear implant program in a tertiary referral center in the United Kingdom. PATIENTS: All 85 consecutively implanted children who had reached the 1-year interval after implantation and 37 children who had reached the 3-year assessment interval after implantation participated. The patients represented all socioeconomic status groups, the entire range of educational settings, and often lived at a considerable distance from the implant center. MAIN OUTCOME MEASURES: Parents and local teachers were asked to describe implant use in the following categories: 1) all of the time; 2) most of the time; 3) some of the time; and 4) none of the time. RESULTS: One year after implantation, parents and teachers, respectively, rated 79 (93%) and 82 (96%) children as full-time users (category 1). Parents rated six children (7%) as users most of the time (category 2), and teachers rated three children (4%) as users most of the time. No child was rated as an occasional or nonuser (category 3 or 4). At 3 years after implantation, 33 (89%) and 34 (95%) children were rated as full-time users (category 1) by parents and teachers, respectively. Parents judged four children (11%) and teachers rated two children (5%) to be users most of the time (category 2). Again, no child was rated in category 3 or 4 as an occasional or nonuser. CONCLUSIONS: The majority of implanted children use their implant systems all of the time over a 3-year period after implantation when selected appropriately and given appropriate follow-up.

Child↗
PubMed1995

Children who could benefit from a cochlear implant: a European estimate of projected numbers, cost and relevant characteristics.

The incidence of profound hearing impairment by the age of 5, derived from a number of retrospective studies in the UK (population about 58 million; birth rate 14/1000), is estimated to be about 300 per annual birth cohort in the 1990s. This estimate includes 80 children who might be expected to acquire deafness in those first 5 years. Projected to Europe as a whole (population 511 million; birth rate 12/1000) this would mean a population who should be considered as potential cochlear implant patients of some 2268 children, given a variety of assumptions. At a take-up rate of 25% for both congenital and acquired cases of profound hearing impairment this would imply a European-wide expenditure of the order of 17 pounds m/p.a. on hardware and associated rehabilitation programmes. The need for such programmes is explored, in the context of strategies of early identification of hearing impairments.

Child↗
PubMed1985

Otomycosis--a continuing problem.

The microbiology of 12,174 symptomatic ears presenting over an eight-year period to one hospital was examined in detail. 1,061 cases of fungal infection were found. The incidence and pattern of these fungi and the accompanying bacteria, in cases of mixed infection, do not appear to have been affected by the widespread use of powerful topically-applied antibiotic/steroid preparations over more than two decades. Otomycosis remains an uncommon, often overlooked but important cause of morbidity in a temperate climate.

Adolescent↗
PubMed1980

Palmar primary hyperhidrosis in children.

Palmar Primary Hyperhidrosis, though an uncommon problem in the paediatric age group, is an unpleasant and socially disabling one for the affected child. Although the condition occurring in adults has been extensively documented, little, if any, attention has been given to the problem in children. We describe the clinical presentation of four such patients who presented in our unit over the past 4 yr. All had an upper dorsal sympathectomy performed with excellent results.

Adolescent↗
PubMedDate not supplied

Transgene expression in dendritic cells to induce antigen-specific cytotoxic T cells in healthy donors.

Immunization with specific tumor-associated antigen (Ag) (TAA)-pulsed dendritic cells (DC) has proven to be efficacious in a variety of animal models and is being investigated for the treatment of cancer patients. Use of DC pulsed with specific peptides or transfected with TAA genes has been a focused area of investigation for the induction of potent tumor and viral immune responses. In this study we demonstrate transgene expression, including expression of the MART-1 gene, in DC transfected with plasmid DNA and cationic liposome complexes. These transiently transfected DC, derived from healthy donor monocytes cultured with granulocyte macrophage colony-stimulating factor and interleukin-4, express the transgene and can stimulate naive CD8+ T cells to elicit an antitumor immune response. These cytotoxic T lymphocytes (CTL) were capable of recognizing both known and unknown TAA epitopes and were able to exhibit cytolytic activity against human histocompatibility leukocyte Ag-matched tumor cells expressing the Ag. In addition to their cytolytic function, the CTL displayed an oligoclonal T-cell receptor repertoire, indicating that the presented Ag induced alterations in the T-cell population. The ability to induce tumor-specific CTL in vitro using gene-modified DC transiently expressing TAAs demonstrates the potential use of these Ag-presenting cells to generate future in vivo cancer vaccine strategies.

Antigens, Neoplasm↗