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Biomedical subjects

M B Bradley

Publications and source records attributed to M B Bradley.

8 recordsLinked to original sources
PubMed2004

Outcomes of unrelated cord blood transplantation in pediatric recipients.

We report results of unrelated cord blood transplants (UCBT) in 29 pediatric recipients in one center and the risk factors associated with survival. Median age: 9 years (0.5-20); diagnosis: ALL (9), AML (4), CML (1), HD (3), HLH (1), NHL (3), NBL (2); B-thal (1), FA (1), FEL (1), Krabbe (1), WAS (1), SAA (1); median follow-up: 11 months; conditioning: total body irradiation (TBI)-ablative (14), chemotherapy-ablative (6) and reduced intensity chemotherapy (9); GVHD prophylaxis: MMF/FK506 (18), cyclosporin A (CsA)+steroids+/-MMF (7) or CsA+methotrexate (MTX) (4); median total nucleated cells (TNC): 3.8 x 10(7)/kg (1.1-11); median CD34+: 2.3 x 10(5)/kg (0.2-9.9); and HLA match: 2 (6/6), 5 (5/6), 22 (4/6). Neutrophil engraftment by cumulative incidence curves 63% (median 28 (95% confidence interval (CI) 18-32)). Probability of >/=grade II acute graft-versus-host disease (aGVHD) by day +60 27%, >/=grade III aGVHD 20% and chronic graft-versus-host disease 3%. Estimated 1-year overall survival (OS) 46% (95% CI 30-71) and standard risk 60% (95% CI 29-100%). Variables associated with improved survival by multivariate analysis include non-TBI-ablative conditioning (P=0.024), CD34+/kg (P=0.038) and gender (P=0.048). These results suggest that CD34/kg cell dose and non-TBI-ablative conditioning may be important variables influencing OS following UCBT in pediatric recipients. Given the small number of patients, these results should be viewed cautiously.

Adolescent↗
PubMed2003

A comparison of ex vivo expanded DCs derived from cord blood and mobilized adult peripheral blood plastic-adherent mononuclear cells: decreased alloreactivity of cord blood DCs.

BACKGROUND: Cord blood (CB) has been used as an alternative source of transplantable allogeneic stem cells for a variety of malignant and non-malignant diseases. However, we have demonstrated delayed recovery of T- and B-cell function, and T-cell subsets post unrelated CB transplantation (UCBT), and deficiencies of CB mononuclear cells (MNC) in producing cytokines, including G-CSF, GM-CSF, M-CSF, IL-12, and IL-15. In this study we have investigated the ex vivo generation of DC from CB versus mobilized adult peripheral blood (APB) for later use as adoptive cellular immunotherapy. METHODS: CB and APB-adherent MNC were cultured in serum-free media with GM-CSF IL-4, FLT-3 ligand, tumor growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha) for 7 days. Morphology, phenotype, immunohistochemistry, clonogenic activity, and alloreactivity in MLR were evaluated. RESULTS: CB and APB monocyte-derived ex vivo expanded DC expressed similar DC markers CD83 (31.27+ 11.7% versus 34.0+ 5.2%, CB versus APB), CD1a (23.4+ 4.2% versus 27.6+ 6.3%), and CD80 (21.97+ 12.01% versus 27.7+ 5.95). Immunohistochemistry showed that cells with DC morphology expressed CDla but not CD14. Neither FLT-3 ligand nor TGF-fl enhanced DC expansion. Addition of 10% autologous plasma to CB cultures promoted greater cell survival and a 150% increase in CDla + /CD80+ cell recovery. CB DC were 62% as effective stimulators of adult allogeneic T-cels as APB DC (p < .05) in allogeneic MLR. DISCUSSION: While phenotypically similar, CB and APB DC have differential potency in allogeneic MLR, which may account for the difference in GvHD and infection incidence and severity between UCBT and allogeneic stem cell transplantation, and may require a different approach for adoptive cellular immunotherapy. The mechanism(s) associated with these differences require further elucidation.

Adult↗
PubMed1998

Highly polarized HLA class II antigen processing and presentation by human intestinal epithelial cells.

The high concentration of foreign antigen in the lumen of the gastrointestinal tract is separated from the underlying lymphocytes by a single cell layer of polarized epithelium. Intestinal epithelial cells can express HLA class II antigens and may function as antigen-presenting cells to CD4(+) T cells within the intestinal mucosa. Using tetanus toxoid specific and HLA-DR-restricted T lymphocytes, we show that polarized intestinal epithelial cells directed to express HLA-DR molecules are able to initiate class II processing only after internalization of antigen from their apical surface. Coexpression of the class II transactivator CIITA in these cells, which stimulates highly efficient class II processing without the characteristic decline in barrier function seen in polarized monolayers treated with the proinflammatory cytokine gamma-IFN, facilitates antigen processing from the basolateral surface. In both cases, peptide presentation to T cells via class II molecules was restricted to the basolateral surface. These data indicate a highly polarized functional architecture for antigen processing and presentation by intestinal epithelial cells, and suggest that the functional outcome of antigen processing by the intestinal epithelium is both dependent on the cellular surface at which the foreign antigen is internalized and by the underlying degree of mucosal inflammation.

Anti-Bacterial Agents↗
PubMed1998

Choice of sugar-free medicines by a sample of dentists, doctors and pharmacists in Northern Ireland: the views of parents and health professionals.

OBJECTIVE: To determine the sources of learning and the levels of support concerning sugar-free medicines by doctors and pharmacists, to examine the provision of choice from the viewpoints of professionals and the parents, and to test the sugar-free status of medication in tests of prescribing. DESIGN: Samples of health professionals comprising 47 general medical practitioners, (87% response rate) 29 pharmacists (94%) and 25 general dental practitioners (100%) completed closed questionnaires as did 209 parents (72%) of 4-year-old children. SETTING: Newry and Mourne Health Trust Area, Northern Ireland. OUTCOME MEASURES: Proportions of respondents citing various learning sources and the levels of support for the use of sugar-free medicines were obtained and the proportions of doctors and pharmacists claiming to offer various frequencies of choice were compared to the proportions of parents recalling receiving such choices. Test prescriptions were examined and the sugar-free status of the prescribed medication was determined. RESULTS: Markedly different sources of learning were cited by different groups. Ninety per cent of pharmacists and 88% of dentists believed that medication should be in sugar-free form in all cases, while only 66% of doctors thought so. Forty three per cent of doctors claimed to always offer a choice while 17% of parents recalled receiving this. The equivalent figures for pharmacists and parents were 69% and 11%. The majority of test prescriptions by doctors and dentists were for sugar containing medicines.

Attitude of Health Personnel↗
PubMed1997

Correction of defective expression in MHC class II deficiency (bare lymphocyte syndrome) cells by retroviral transduction of CIITA.

Retrovirus-mediated gene transfer was used to restore expression to MHC class II-negative patient cells from complementation group A(II) of MHC class II immunodeficiency or bare lymphocyte syndrome (BLS). The cells of these patients do not transcribe MHC class II genes due to a defect in the trans-acting factor, CIITA. We constructed a vector, pGAG/Ii-CIITA, with the MHC class II-associated invariant chain promoter driving CIITA expression. Cocultivation with the virus producer line was consistently shown to be the optimal method for infection of all cell types. The induction of MHC class II expression after virus infection was rapid, and high levels of expression were achieved in cell lines within 1 wk of infection. In addition, expression was easily detectable even in peripheral blood cells of a BLS patient within a few days. Cell lines maintained in vitro for several months remained positive, and the proportion of cells with surface expression of DR was correlated with the number of integrated proviruses. Moreover, transduced B lymphoblastoid cell lines readily established tumors in CB17-scid/scid mice, and the MHC class II-positive cells demonstrated a clear competitive advantage in vivo. Ultimately, we hope to use this transduction system to restore normal immune function to a BLS patient for which no other therapeutic option currently exists.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1994

The effect of participating in a functional electrical stimulation exercise program on affect in people with spinal cord injuries.

Functional electrical stimulation (FES) is a technology that is increasingly being used in the acute and post rehabilitation of people with spinal cord injuries. Though there has been considerable interest in the potential psychological effects of FES, little research has been done in this area. This study examined the effect of participation in an FES exercise program on affect in 37 persons with spinal cord injury. The effect of the subjects' expectations is also examined. Results indicate significant changes in negative affective status but no significant changes in positive affect. In particular, the results show increases in depression and hostility in subjects in the treatment group who had unrealistic expectations for the FES program. It is important to identify and monitor FES participants who have unrealistic expectations.

Adult↗
PubMed1992

Hyperbaric oxygen toxicity: role of thromboxane.

Exposing rabbits for 1 h to 100% O2 at 4 atm barometric pressure markedly increases the concentration of thromboxane B2 in alveolar lavage fluid [1,809 +/- 92 vs. 99 +/- 24 (SE) pg/ml, P less than 0.001], pulmonary arterial pressure (110 +/- 17 vs. 10 +/- 1 mmHg, P less than 0.001), lung weight gain (14.6 +/- 3.7 vs. 0.6 +/- 0.4 g/20 min, P less than 0.01), and transfer rates for aerosolized 99mTc-labeled diethylenetriamine pentaacetate (500 mol wt; 40 +/- 14 vs. 3 +/- 1 x 10(-3)/min, P less than 0.01) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt; 10 +/- 3 vs. 1 +/- 1 x 10(-4)/min, P less than 0.01). Pretreatment with the antioxidant butylated hydroxyanisole (BHA) entirely prevents the pulmonary hypertension and lung injury. In addition, BHA blocks the increase in alveolar thromboxane B2 caused by hyperbaric O2 (10 and 45 pg/ml lavage fluid, n = 2). Combined therapy with polyethylene glycol- (PEG) conjugated superoxide dismutase (SOD) and PEG-catalase also completely eliminates the pulmonary hypertension, pulmonary edema, and increase in transfer rate for the aerosolized compounds. In contrast, combined treatment with unconjugated SOD and catalase does not reduce the pulmonary damage. Because of the striking increase in pulmonary arterial pressure to greater than 100 mmHg, we tested the hypothesis that thromboxane causes the hypertension and thus contributes to the lung injury. Indomethacin and UK 37,248-01 (4-[2-(1H-imidazol-1-yl)-ethoxy]benzoic acid hydrochloride, an inhibitor of thromboxane synthase, completely eliminate the pulmonary hypertension and edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗