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Biomedical subjects

B M Daly

Publications and source records attributed to B M Daly.

At least 19 recordsLinked to original sources
PubMed2003

Cytokine profiles in patients receiving wide-field + prostate boost radiotherapy (xRT) for adenocarcinoma of the prostate.

As a result of the association between ionizing irradiation and the induction of inflammatory and fibrogenic cytokines, circulating levels of IL-1alpha, macrophage colony stimulating factor (M-CSF) and TGFbeta were measured in a group of 37 patients who presented with well-defined adenocarcinoma of the prostate and were treated with wide-field pelvic (WFP) + prostate boost (PB) radiotherapy (xRT) according to RTOG protocols 94-08 and 94-13. First and foremost, patients with prostate cancer (PC) were found to have a significantly (p<0.05) elevated plasma level of the three cytokines prior to treatment. Moreover, during WFP + PB xRT, these circulating cytokine levels were further elevated, the elevation occurring in the form of cyclic waves; the concurrent waves of elevated IL-1alpha and M-CSF preceding that of TGFbeta. In addition to providing support for the existence of a humoral response to xRT in patients receiving WFP + PB xRT, the data demonstrated a significant correlation between the integral radiation dose (ID) and the temporal expression and magnitude of plasma IL-1alpha, M-CSF and TGFbeta levels in patients that had received 1-5 fractions (1.8-9Gy) of WFP + PB xRT. Thereafter, the appearance of elevated waves of cytokine expression in the patient's plasma continued independent of additional fractions of WFP + PB xRT.

Adenocarcinoma↗
PubMed2003

Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Subsurface oxidation of polyethylene.

Since the 1960s ultrahigh molecular weight polyethylene has been a primary bearing material in orthopedic prostheses. Most polyethylene components have been sterilized by exposure to gamma radiation, but in the presence of oxygen this promotes degradation and correlates with component failure in the body. To better understand the mechanism of degradation, we measured oxidation profiles for components shelf aged 5.8 and 10.9 years. Microtomed sections from each component were analyzed for ketones, which are the primary oxidation products, by FTIR spectroscopy. Maximum ketone concentrations in both cases were found several millimeters below the surface. We propose a model to explain the profiles. Alkyl radicals, which are uniformly generated in the polyethylene during irradiation, react with peroxyl radicals, which are produced by alkyl radicals with oxygen to form ketones. At the component surface ketone levels are low because high oxygen concentrations deplete alkyl radicals, creating an excess of peroxyl radicals. In the bulk material ketones are low because low oxygen concentrations limit the formation of peroxyl radicals. However, just below the surface the concentrations of alkyl and peroxyl radicals balance, promoting ketone production. A computer simulation that accounts for the coupling of these reactions with the diffusion of oxygen shows a good agreement with the measured profiles.

Biocompatible Materials↗
PubMed1997

Secondary cytokines interact in sequence with interleukin-1alpha (IL-1alpha) with or without macrophage colony-stimulating factor (M-CSF) to further accelerate granulopoietic recovery in myelosuppressed animals.

Interleukin-1alpha (IL-1), by itself, accelerates both granulopoietic and thrombopoietic recovery in the 5-fluorouracil (5-FU) myelosuppressed mouse (FUM). As a primary cytokine, IL-1 also interacts in concert with macrophage colony-stimulating factor (M-CSF) to synergistically enhance hematopoietic recovery in the FUM. As part of our continuing interest in cytokine sequencing, studies were carried out to determine whether the addition of several secondary cytokines (GM-CSF, IL-3, and IL-6) to IL-1 (+/-M-CSF) would further enhance the stimulatory effects of the primary cytokine(s) on hematopoietic recovery in FUM. Throughout these studies, IL-1 (+/-M-CSF) was administered for 2 days to the FUM, and the secondary cytokines were given either in concert (days 1 and 2) or in sequence (days 3-6) or both with the primary cytokine(s). Based on the magnitude of 7-day post-5-FU granulocyte recovery, the results demonstrated that the synergistic effects of IL-1 + M-CSF treatment on granulopoietic recovery in FUM could not be duplicated by substituting either IL-3, IL-6, or GM-CSF for M-CSF. Nonetheless, the secondary cytokines were observed to enhance the stimulatory effects of IL-1 under the following administration schedules: (1) 2 days of IL-1, followed by a sequential treatment (days 3-6) with either IL-3 or IL-6, (2) 2 days of IL-1 + GM-CSF followed by an additional 4 days of GM-CSF alone, and (3) 2 days of IL-1 + GM-CSF followed by 3-4 days of a combination of GM-CSF and either IL-3 or IL-6. Although these cytokine treatment schedules led to an enhanced granulocyte recovery (vs. IL-1 alone) in FUM, the day 7 granulocyte numbers never exceeded those observed after 2 days of IL-1 + M-CSF. Similarly, granulocyte recovery in FUM receiving 2 days of IL-1 + M-CSF followed by either GM-CSF or IL-3 also was significantly greater than that observed with IL-1 + M-CSF alone. In contrast, however, the sequential administration of IL-6 with IL-1 + M-CSF, unlike IL-1, failed to further enhance granulopoietic recovery, suggesting that there may be an antagonism between IL-6 and M-CSF in the FUM. In summary, therefore, the secondary cytokines were found to interact more effectively when they were administered in sequence, rather than in concert, with both IL-1 and IL-1 + M-CSF.

Animals↗
PubMed1991

Cyclosporin A in atopic dermatitis: therapeutic response is dissociated from effects on allergic reactions.

Fourteen patients with severe chronic atopic dermatitis were treated with cyclosporin A (CyA, Sandimmun; 5 mg/kg/day) for 7-16 weeks. All showed a marked clinical improvement and half could omit topical corticosteroid treatment during therapy. Adverse effects were minor, but two patients relapsed despite continued treatment. In the others, the disease recurred soon after stopping CyA. Serum IgE levels and prick-test responses were unchanged by CyA. Immediate and late-phase cutaneous responses to intradermal house dust mite antigen (HDM) were significantly increased during treatment; but a delayed response, present at 24 and 48 h, was unaffected. Four of six patients challenged with HDM patch tests to tape-stripped skin during treatment showed eczematous reactions at 48 h. Thus, cyclosporin A has a powerful therapeutic effect in atopic dermatitis but does not reduce allergic responses to inhalant antigens.

Adolescent↗
PubMed1991

[Cyclosporin A in atopic dermatitis: therapeutic effect and effect on allergic reactions are dissociated from each other].

Fourteen patients with severe chronic atopic dermatitis were treated with cyclosporin A (CyA, Sandimmun; 5 mg/kg/day) for 7-16 weeks. All showed a marked clinical improvement and half could omit topical corticosteroid treatment during therapy. Adverse effects were minor, but two patients relapsed despite continued treatment. In the others, the disease recurred soon after stopping CyA. Serum IgE levels and prick-test responses were unchanged by CyA. Immediate and late-phase cutaneous responses to intradermal house dust mite antigen (HDM) were significantly increased during treatment; but a delayed response, present at 24 and 48 h, was unaffected. Four of six patients challenged with HDM patch tests to tape-stripped skin during treatment showed eczematous reactions at 48 h. Thus, cyclosporin A has a powerful therapeutic effect in atopic dermatitis but does not reduce allergic responses to inhalant antigens.

Adolescent↗
PubMed1986

Effect of aspirin on pruritus.

The effect of 900 mg aspirin on persistent itch from chronic dermatoses other than urticaria (eight patients) and other causes (five patients) was measured subjectively using a 10 cm line and objectively as nocturnal scratch using limb meters. There was no change in itch or scratch and it is concluded that aspirin neither affects itch centrally by a pain related mechanism nor affects itch physiologically by cyclo-oxygenase inhibition in the skin.

Adolescent↗