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F Fitzpatrick

Publications and source records attributed to F Fitzpatrick.

At least 19 recordsLinked to original sources
PubMed2001

Evaluation of ODS-AQ stationary phase for use in capillary electrochromatography.

The aim of this study was to evaluate the applicability of ODS-AQ packing material as a stationary phase in capillary electrochromatography (CEC). The electroosmotic flow created on an ODS-AQ stationary phase was measured at different mobile phase compositions and at different column temperatures. It was observed that the electroosmotic flow generated in the column increased by 50% when the temperature of the system was raised from 20 degrees C to 60 degrees C, while all other conditions were kept constant. The electroosmotic flow produced by the ODS-AQ stationary phase was found to be comparable to the flow generated in a column packed with Nucleosil bare-silica material. In addition, a set of polar compounds (D-lysergic acid diethylamide derivatives) was utilized to determine the influence of temperature and mobile phase composition on their chromatographic behavior on an ODS-AQ stationary phase in a CEC mode. A linear relationship between the solute retention factor and column temperatures was seen over the temperature range studied (20 degrees C to 60 degrees C). A quadratic function was used to describe the changes in the solute retention factors with variation of acetonitrile concentration in the mobile phase.

Chromatography, High Pressure Liquid↗
PubMed2001

Separation of peptides utilizing ultrahigh-temperature micellar electrokinetic chromatography.

The use of ultrahigh column temperatures, up to 110 degrees C, in micellar electrokinetic capillary chromatography was investigated. The number of plates generated per unit time increased from 0.22 to 12.8 plates/s for separations at 15 degrees C and 110 degrees C, respectively. Ultrahigh-temperature micellar electrokinetic capillary chromatography was used for the separation of cyclic undecapeptides (cyclosporins). A minimum resolution of 1.39 was calculated for a critical peak pair at 110 degrees C, which is more than a 50% increase over resolution generated at 40 degrees C. During a run time of more than 90 min at 110 degrees C and at pH 9.3, no sample degradation or solvent boiling was observed.

Acetonitriles↗
PubMed2000

High temperature and temperature programming in capillary electrochromatography.

In electrochromatography, solvent electrophoretic mobility and solute partitioning are temperature dependent processes. If temperature variations are controlled, solute selectivity and analysis times can be tailored. In this study the feasibility of temperature programming in capillary electrochromatography (CEC) was demonstrated using a reversed-phase CEC mode. The outcome of programmed separations was compared with isothermal, isocratic and isorheic (constant flow) separations. The combined effects of column temperature and mobile phase flow-rate changes during the separation run, resulted in up to a 50% reduction in the separation run time, without adversely affecting the quality of separation. For capillary electrochromatography, temperature programming may be a valuable alternative to solvent programming modes because of the great technical difficulties associated with carrying out solvent gradient elution.

Electrophoresis, Capillary↗
PubMed2000

Separation of D-lysergic acid diethylamide derivatives using micellar electrokinetic capillary chromatography.

By adjusting column temperature and applied electric field, a fast separation in micellar electrokinetic capillary chromatography was developed for the separation of D-lysergic acid diethylamide derivatives. A baseline separation of nine derivatives was accomplished with a run time of less than 12 min by utilizing elevated column temperature (60 degrees C) and an applied electric field of 387 V/cm. The number of plates generated per unit time for the separations completed at elevated temperatures was significantly higher when compared to separations at the same applied electric field but at lower temperatures (20 degrees C).

Chromatography, Micellar Electrokinetic Capillary↗
PubMed2000

A purpose built MRSA cohort unit.

The control of hospital-acquired infection, in particular methicillin-resistant Staphylococcus aureus (MRSA) remains a challenge. Our hospital has established a purpose built 11-bed cohort unit with on-site rehabilitation for care of patients colonized with MRSA, in an attempt to improve their quality of care. Prior to the opening of this unit a number of concerns were voiced and the aim of this study was to address these. First, to establish if patient cohorting reduces the likelihood of successful decolonization, second, to evaluate the risk of staff colonization, and finally to see if successful environmental control of MRSA is possible.A patient database was established detailing patient demographics, infection rates, eradication and reacquisition rates. Staff screening was performed weekly, at the start of a period of duty. Sixty environmental sites were screened before unit opening, at 48h, six weeks and at six months. There were 88 admissions in the first six months; 62 patients were colonized with MRSA, and 26 patients (10 surgical, 16 medical) had MRSA infections. Twenty-three of 88 patients (26%) were successfully decolonized, which compares favourably with an eradication rate of 20% for the rest of the hospital. Twenty staff members participated in weekly screening. Five staff members colonized with MRSA were detected and all were successfully decolonized. Environmental control was achieved with a combination of a daily detergent clean and a once weekly clean with phenolic disinfectant. Our preliminary data suggest that, despite cohorting patients colonized with MRSA, with proper education and supervised cleaning protocols, it is possible to control environmental MRSA load, successfully decolonize patients and limit the risk of staff colonization.

Carrier State↗
PubMed1999

High rate of human T lymphotropic virus type IIa infection in HIV type 1-infected intravenous drug abusers in Ireland.

Serological and molecular analyses of a cohort of HIV-1-infected intravenous drug abusers (IVDAs) (n = 103) in Dublin, Ireland have demonstrated that 15 of 103 (14.6%) were infected with HTLV-II, which is the highest infection rate yet recorded for any European country. Restriction fragment length polymorphism (RFLP) analysis of the env region of the provirus demonstrated that the infection involved only the HTLV-IIa subtype; the HTLV-IIb subtype was not detected. Phylogenetic analysis of the nucleotide sequences of the long terminal repeat (LTR) confirmed infection with the HTLV-IIa subtype, and demonstrated that the viruses clustered closely with HTLV-IIa isolates from North American IVDAs. Previous observations that IVDAs in southern Europe, specifically Spain and Italy, appear to be infected predominantly with the HTLV-IIb subtype, along with the present report and evidence that IVDAs in Sweden are infected with the HTLV-IIa subtype, suggest different origins of HTLV-II infection in Europe.

Adult↗
PubMed1996

Inhibition of 5-lipoxygenase-activating protein (FLAP) reduces pulmonary vascular reactivity and pulmonary hypertension in hypoxic rats.

Chronically elevated shear stress and inflammation are important in hypertensive lung vessel remodeling. We postulate that 5-lipoxygenase (5-LO) is a molecular determinant of these processes. Immunohistology localized the 5-LO to macrophages of normal and chronically hypoxic rat lungs and also to vascular endothelial cells in chronically hypoxic lungs only. In situ hybridization of normal and chronically hypoxic lungs demonstrated that 5-LO mRNA is expressed in macrophages. Rats hypoxic for 4 wk-developed pulmonary hypertension increased translocation of the lung 5-LO from the cytosol to the membrane fraction and increased levels of lung tissue 5-lipoxygenase-activating protein (FLAP). A FLAP ligand, 3-[l-(4-chlorobenzyl)-3-t-butyl-thio-t-isopropylindol-2-yl]-2,2- dimethylpropanoic acid (MK-886), inhibited the acute angiotensin II and hypoxia-induced pulmonary vasoconstriction in vitro and the development of chronic hypoxic pulmonary hypertension in rats in vivo. Mice bred with the deletion of the 5-LO enzyme (5-LO knockout) developed less right heart hypertrophy than age-matched 5-LO competent mice. Our results support the hypothesis that the 5-LO is involved in lung vascular tone regulation and in the development of chronic pulmonary hypertension in hypoxic rodent models.

5-Lipoxygenase-Activating Proteins↗
PubMed1993

Regulation of interleukin-1 receptor expression in mouse brain and pituitary by lipopolysaccharide and glucocorticoids.

Interleukin-1 (IL-1) receptors have been characterized in mouse pituitary and brain. Previous studies have demonstrated that IL-1 receptor density is high in the dentate gyrus in the hippocampus and that lipopolysaccharide (LPS) injection caused an 80% decrease in the number of hippocampal IL-1 receptors, while pituitary receptors in the anterior pituitary were unaffected. In order to investigate on the role of glucocorticoids (GC) in the control of IL-1 receptor expression in the brain and pituitary, the effect of stress, exogenous GC administration or adrenalectomy (ADX) on IL-1 receptor density was determined. Assays were achieved under basal and LPS-stimulated conditions by in situ quantitative autoradiography technique using human recombinant 125I-IL-1 alpha as a tracer. An increase of GC concentration in serum, following immobilization stress or dexamethasone (DEX) treatment (short and long term), did not modify, in the hippocampus, the density of IL-1 receptors under basal conditions or after peripheral LPS injection. On the contrary, ADX significantly decreased IL-1 receptor density in LPS-treated animals. In the anterior pituitary, a significant increase in the density of basal IL-1 receptors was observed 6 h following immobilization stress or after 7 days of DEX treatment while short-term DEX treatments are ineffective. In contrast to what was observed in the hippocampus, no changes in pituitary receptor densities were observed in ADX mice. These results indicate that hippocampal and pituitary IL-1 receptor expressions are differentially regulated by GC. Therefore, this report constitutes the first demonstration of an in vivo regulation of IL-2 receptors in the pituitary.

Adrenalectomy↗
PubMed1992

Glucocorticoids in the nonobese diabetic (NOD) mouse: basal serum levels, effect of endocrine manipulation and immobilization stress.

The NOD mouse is a recognized model for studying immunologically mediated insulin-dependent diabetes mellitus (IDDM). In most colonies, the disease appears with a greater preponderance in females than in males and castration alters the expression of the disease. The prevalence of diabetes may also vary depending upon environmental factors such as stress. Therefore, we measured in the NOD mouse serum glucocorticoid concentrations in basal and stress conditions. We observed in NOD as well as in C57BL/6 mice, taken as controls, a circadian rhythm of corticosterone, with females having higher values than males. After a single restraint stress, female and male NOD mice exhibit a comparable response, whereas after repeated stress, males respond significantly less than females, suggesting an adaptation phenomenon. In contrast, there is no difference in the pattern of corticosterone response of C57BL/6 females and males to both types of stress, but females always respond better than males. Moreover, whatever the stress considered, NOD mice generally exhibit a higher corticosterone response than C57BL/6 mice. The sexual dimorphism in diabetes expression in NOD mice may be related to the levels of corticosterone, a hyperglycemic hormone, in both basal and stress conditions. However, the understanding of corticosteroid effects in this model of type I IDDM is rather complex given their well known anti-inflammatory and immunosuppressive effects in other models of autoimmune diseases.

Adrenalectomy↗
PubMed1992

Biological activity and metabolism of 20-hydroxyeicosatetraenoic acid in the human platelet.

1. The cytochrome P-450 metabolite of arachidonic acid, 20-hydroxyeicosatetraenoic acid (20-HETE), was found to be a potent, dose-dependent inhibitor of platelet aggregation and inhibitor of thromboxane biosynthesis induced by arachidonic acid (IC50 5.2 +/- 1.5 microM), A23187 (IC50 16.2 +/- 5.4 microM), and U46619 (IC50 7.8 +/- 2.4 microM). 20-HETE did not inhibit thrombin-induced aggregation. 2. The human platelet metabolized 20-HETE to a series of novel metabolites formed by cyclo-oxygenase as well as lipoxygenase pathways. The structures of the metabolites were identified by mass spectrometry as 20-hydroxy-thromboxane B2, 12,17-dihydroxyheptadecatrienoic acid, 12,20-dihydroxyeicosatetraenoic acid, and 11,20-dihydroxyeicosatetraenoic acid. 3. The identification of the 11-hydroxy metabolite of 20-HETE suggests that 20-HETE is less efficiently cyclized to an endoperoxide intermediate by cyclo-oxygenase than is arachidonate. 4. Although some biological activity of 20-HETE may be related to competition with endogenous arachidonate for cyclo-oxygenase metabolism, the predominant mechanism of action of 20-HETE appears to be through antagonism of the prostaglandin H2/thromboxane A2 receptor.

Adult↗
PubMed1991

Sex steroids, glucocorticoids, stress and autoimmunity.

Interest in the field of neuroimmunoendocrinology is in full expansion. With regard to this, steroid influence on the immune system, in particular sex steroids and glucocorticoids, has been known for a long time. Sex steroids are part of the mechanism underlying the immune sexual dimorphism, as particularly emphasized in autoimmune diseases. Immunosuppressive and anti-inflammatory effects of glucocorticoids are now considered a physiological negative feedback loop to cytokines produced during an immune and/or inflammatory response. Psychosocial factors may play a role in the development of immunologically-mediated diseases, e.g. autoimmune diseases. The nonobese diabetic (NOD) mouse, that develops an immunologically-mediated insulin-dependent diabetes mellitus (IDDM) is an interesting model to study the role of endogenous steroids. Insulitis is present in both sexes, but diabetes has a strong preponderance in females. Hormonal alteration, such as castration, modulates the incidence of diabetes, whereas environmental factors, such as stress, accelerate the disease. In the present paper, we have reviewed the role of gender, sex steroid hormones, stress and glucocorticoids in autoimmunity as well as analyzed their different levels of actions and interrelationships, focusing particular attention on the immunologically-mediated IDDM of the NOD mouse.

Animals↗
PubMed1991

Influence of castration, alone or combined with thymectomy, on the development of diabetes in the nonobese diabetic mouse.

The nonobese diabetic (NOD) mouse is a recognized model for studying immunologically-mediated insulin-dependent diabetes mellitus. The disease appears with a greater preponderance in females than in males. Castration at weaning led to a significant increase in the prevalence of diabetes in NOD males, whereas a tendency to a decreased prevalence was observed in NOD females. Castration combined with thymectomy was found to further increase the prevalence of diabetes in NOD males, whereas in females castration reversed the effect of thymectomy. These results on changes in diabetes prevalence were corroborated by the degree of lymphocytic infiltration directed toward the pancreatic islets of Langerhans. Taken together these results indicate a direct relationship between the endocrine and immune systems, whereby orchidectomy has a deleterious effect on the immunopathogenesis of diabetes. In addition, we examined whether the distribution of lymphocyte subpopulations, mitogen reactivity, lymphokine production, and in vivo response to a thymus-dependent antigen, such as sheer red blood cell, were dependent or independent of the sex steroid environment.

Animals↗
PubMed1986

Leukotriene B4 and 20-hydroxyleukotriene B4 contract guinea-pig trachea strips in vitro.

In contrast to its established myotropic effect on guinea-pig lung parenchyma, the myotropic action of leukotriene B4 on the trachea is uncertain. Our characterization of its effects on the latter organ indicates that leukotriene B4 contracts guinea-pig trachea zig-zag strips in a concentration-dependent manner from 5 X 10(-9) to 5 X 10(-7) M. Leukotriene B4 was at least 10 times more potent than histamine, but 10 times less potent than leukotriene C4. Similar effects were evident with 20-hydroxyleukotriene B4; however, this metabolite contracted the trachea less forcefully. Tracheas developed tachyphylaxis after cumulative administration of leukotriene B4, but not 20-hydroxyleukotriene B4. The myotropic effect of leukotriene B4 was attributable to an indirect mechanism involving formation of cyclooxygenase metabolites of arachidonic acid. For example, the levels of prostaglandin E2 and prostaglandin F2 alpha released into the incubation medium correlated with the contractile response, and suppression of their biosynthesis with cyclooxygenase inhibitors eliminated that response. We conclude that myotropic effects of leukotriene B4 occur in central airways in addition to peripheral airways. The contribution of leukotriene B4 to tracheal bronchospasm is not necessarily negligible.

Animals↗
PubMed1985

Enzymatic hydration of leukotriene A4. Purification and characterization of a novel epoxide hydrolase from human erythrocytes.

Human erythrocytes contained a soluble cytosolic epoxide hydrolase for stereospecific enzymatic hydration of leukotriene A4 into leukotriene B4. The enzyme was purified 1100-fold, to apparent electrophoretic homogeneity, by conventional DEAE-Sephacel fractionation followed by high performance anion exchange and chromatofocusing procedures. Its characteristics include a molecular weight of 54,000 +/- 1,000, an isoelectric point 4.9 +/- 0.2, a Km apparent from 7 to 36 microM for enzymatic hydration of leukotriene A4, and a pH optimum ranging from 7 to 8. The enzyme was partially inactivated by its initial exposure to leukotriene A4. There was slow but detectable enzymatic hydration (pmol/min/mg) of certain arachidonic acid epoxides including (+/-)-14,15-oxido-5,8-11-eicosatrienoic acid and (+/-)-11,12-oxido-5,8,14-eicosatrienoic acid, but not others, including 5,6-oxido-8,11,14-eicosatrienoic acid. Human erythrocyte epoxide hydrolase did not hydrate either styrene oxide or trans-stilbene oxide. In terms of its physical properties and substrate preference for leukotriene A4, the erythrocyte enzyme differs from previously described versions of epoxide hydrolase. Human erythrocytes represent a novel source for an extrahepatic, cytosolic epoxide hydrolase with a potential physiological role.

8,11,14-Eicosatrienoic Acid↗