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J Buckley

Publications and source records attributed to J Buckley.

At least 19 recordsLinked to original sources

Different Mg to Fe ratios in the mixed metal MgFe hydroxy-carbonate compounds and the effect on phosphate binding compared with established phosphate binders.

Due to the side effects of the current oral phosphate binders, there is a need for effective alternatives. A number of mixed metal hydroxy-carbonate compounds (MMHCs) based on Mg and Fe have recently been established as effective phosphate binders. We have now carried out further studies on the MMHCs with different ratios of Mg(2+):Fe(3+) in different forms to assess for phosphate binding efficacy and ionic release in aqueous solution and food slurries. The compounds that provide the most promise are those with Mg(2+):Fe(3+) ratios of 2:1 and 4:1 in the unaged/dry form. Their phosphate binding efficacy was compared with a wide range of established phosphate binders, such as aluminum hydroxide [Al(OH)(3)], calcium carbonate (CaCO(3)), calcium acetate (CaAc(2)), magnesium hydroxide [Mg(OH)(2)], and lanthanum carbonate [La(2)(CO(3))(3)] in various food slurries. The results showed that the MgFe compounds were much more effective (on a weight for weight basis) than the established binders, and their properties were relatively pH independent. Calcium compounds (CaCO(3) and CaAc(2)) were ineffective under the experimental conditions. Mg(OH)(2) was effective at low pH but not at pHs greater than 5.0, and also released two- to threefold more magnesium than the MgFe compounds. Al(OH)(3) showed some degree of efficacy, but the binding capacity was, at best, less than 50% of the MMHCs. La(2)(CO(3))(3) required at least a 10-fold increase in weight to give comparable binding to the MMHCs. In conclusion, MgFe hydroxy-carbonate compounds are effective phosphate binders and may provide a better alternative to both existing and emerging binders for combating hyperphosphataemia.

Binding Sites↗

Cephalosporin-resistant pneumococcal pneumonia: does it, affect outcome?

STUDY OBJECTIVES: Penicillin resistance has been reported in various studies to have no impact on the outcome of pneumococcal pneumonia. However, the importance of cephalosporin resistance has not been systematically studied. We conducted an analysis of patients with high-level cephalosporin-resistant Streptococcus pneumoniae pneumonia (H-CRSPP). DESIGN: Retrospective matched, case-control study. SETTING: Two inner-city academic hospitals. PATIENTS: Twenty-six patients with H-CRSPP admitted to the hospital between 1995 and 1999 were identified. Each patient was matched with two controls with cephalosporin-sensitive but oxacillin-resistant pneumococcal pneumonia admitted during the same time period. Matching was done based on pneumonia severity of illness index (PSI) and for other factors. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We evaluated a number of outcomes including mortality length of stay in the hospital, and time to respond to treatment. Patients with H-CRSPP took longer to respond to treatment (6.5 +/- 0.9 days vs 4.1 +/- 0.7 days, P=0.05) and had a longer length of stay in hospital (15.4 +/- 2.2 days vs 92 +/- 1.6 days, P=0.02). None of the other outcomes were different between the two groups. CONCLUSIONS: Overall, we have found that the presence of cephalosporin resistance does impact the course of pneumococcal pneumonia.

Adult↗

Iodinated contrast media induce neutrophil apoptosis through a mitochondrial and caspase mediated pathway.

Iodinated contrast media (ICM) can induce apoptosis (programmed cell death) in renal, myocardial and endothelial cells. Following intravascular injection, circulating immune cells are exposed to high concentrations of ICM. As neutrophils constitutively undergo apoptosis we hypothesized that ICM may adversely affect neutrophil survival. Our aim was to investigate the effect of ICM on neutrophil apoptosis. Neutrophils were isolated from healthy subjects and cultured in vitro with ionic (diatrizoate and ioxaglate) and non-ionic (iohexol and iotrolan) ICM. The effect of ICM on neutrophil apoptosis in both unstimulated and lipopolysaccharide-stimulated neutrophils was determined by annexin V flow cytometry. The influence of physicochemical properties of the different ICM on apoptosis of neutrophils was also studied. We further investigated the effects of ICM on key intracellular signal pathways, including p38 mitogen-activated protein kinase (MAPK) by Western blotting, and mitochondrial depolarization and caspase activity by flow cytometry. Isoiodine concentrations (20 mg ml(-1)) of ionic (diatrizoate 69.6+/-2.9%; ioxaglate 58.9+/-2.0%) and non-ionic (iohexol 57.3+/-2.9%; iotrolan 57.1+/-2.6%) ICM significantly induced neutrophil apoptosis over control levels (47.7+/-1.4%). The apoptotic effect of ICM was influenced by their chemical structure, with ionic ICM having a more significant (p<0.01) apoptotic effect than non-ionic ICM (p<0.05). Furthermore, ICM reversed the anti-apoptotic effect of lipopolysaccharide (1000 ng ml(-1)) treated neutrophils to control levels (23.0+/-3.5% to 61.2+/-5.3%; n=4; p<0.05). These agents induce apoptosis through a p38 MAPK independent pathway that results in mitochondrial depolarization, and is dependent on caspase activation. As neutrophils play a central role in host response to infection and injury, ICM, through induction of neutrophil apoptosis, could have a significant deleterious effect on host immune defence and resolution of an inflammatory response.

Adult↗

Continued raw milk consumption on farms: why?

The potential dangers associated with drinking unpasteurized milk have been highlighted over recent years. Nevertheless, the vast majority of Irish farming families persist in the practice. This qualitative study was undertaken to ascertain the reasons why. It was found that farmers generally believe their milk to be risk free on the basis of 'routine' test results. They also believe it to be of better quality than pasteurised milk, in addition to being the cheaper option. Adherence to tradition is another factor. The targeting of a more informed, credible public health message which takes account of commonly held, and understandable, views among the farming community is proposed.

Agriculture↗

Loss of heterozygosity in childhood de novo acute myelogenous leukemia.

A genome-wide screening for loss of heterozygosity (LOH), a marker for possible involvement of tumor suppressor genes, was conducted in 53 children with de novo acute myelogenous leukemia (AML). A total of 177 highly polymorphic microsatellite repeat markers were used in locus-specific polymerase chain reactions. This comprehensive allelotyping employed flow-sorted cells from diagnostic samples and whole-genome amplification of DNA from small, highly purified samples. Nineteen regions of allelic loss in 17 patients (32%) were detected on chromosome arms 1q, 3q, 5q, 7q (n = 2), 9q (n = 4), 11p (n = 2), 12p (n = 3), 13q (n = 2), 16q, 19q, and Y. The study revealed a degree of allelic loss underestimated by routine cytogenetic analysis, which failed to detect 9 of these LOH events. There was no evidence of LOH by intragenic markers for p53, Nf1, or CBFA2/AML1. Most lymphocytes lacked the deletions, which were detected only in the leukemic myeloid blast population. Analysis of patients' clinical and biologic characteristics indicated that the presence of LOH was associated with a white blood cell count of 20 x 10(9)/L or higher but was not correlated with a shorter overall survival. The relatively low rate of LOH observed in this study compared with findings in solid tumors and in pediatric acute lymphoblastic leukemia and adult AML suggests that tumor suppressor genes are either infrequently involved in the development of pediatric de novo AML or are inactivated by such means as methylation and point mutations. Additional study is needed to determine whether these regions of LOH harbor tumor suppressor genes and whether specific regions of LOH correlate with clinical characteristics. (Blood. 2001;98:1188-1194)

Adolescent↗

Prospective study of omental transposition in patients with chronic spinal injury.

OBJECTIVES: This prospective study was designed to assess the effects of omental transposition in patients with a chronic spinal injury. METHODS: Neurological status was established to be stable and multiple baseline across patient studies were done preoperatively and repeated postoperatively. Assessments included activities of daily living (ADL), functional ability, degree of spasticity, motor power, sensation, pain perception, urodynamic studies, electromyography, sensory evoked potentials (SEPs), and infrared thermography to measure peripheral and general skin vascular responses. Each patient had MRI. Assessments were done at 3, 6, and 12 months after omental transposition in 17 patients. RESULTS: The detailed assessments failed to show significant improvement, although some patients showed minor objective and subjective change in some categories. Neurological deterioration occurred in one patient. There were 20 surgical complications including urinary tract infection, deep vein thrombosis, wound infection, and incisional hernia. CONCLUSIONS: Omental transposition has not been shown to improve neurological function in 17 patients with chronic spinal cord injury, and continued use of this operation in this situation is not supported by this study. Further advances in spinal cord repair may utilise the pedicled omental graft to provide an alternative vascular supply, but its current use should be limited to experimental models.

Activities of Daily Living↗

How I lost my eye.

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Anecdotes as Topic↗

Identification of the principal circulating metabolite of a synthetic 5,4'-diaminoflavone (NSC 686288), an antitumor agent, in the rat.

During the course of our study to develop analytical methodology for quantitating the investigative antitumor agent 5-amino-2-(4-amino-3-fluorophenyl)-6,8-difluoro-7-methyl-4H-1-benzopyran -4-one (DAF; NSC 686288) in plasma, a significant concentration of a metabolite was observed in a post-dosed rat. The results of electron-ionization (EI) mass spectrometric analysis of the metabolite suggested that N-acetylation had occurred, but, interestingly, that only one of the compound's two primary amino groups had been transformed. Comparing the mass spectra and gas chromatographic retention times of a mono-acetylated sample of DAF and that of the metabolite showed both to be the same. A retro-Diels-Alder (RDA) fragmentation of the B ring of DAF results in formation of two abundant product ions, each retaining one of the amino groups. The EI mass spectrum of mono-N-acetamido-d3 DAF shows loss of ketene-d2, leading to formation of an -NHD group. The ensuing RDA fragmentation easily identifies which of the two product ions contains the deuterium, thereby allowing us to assign the site of N-acetylation as the amino group on ring C (the 4' position) of DAF.

Acetylation↗

A study to assess inducible nitric oxide synthase expression in oral lichen planus.

Nitric oxide (NO) has been implicated in a variety of diseases but has not been previously studied in oral lichen planus (OLP). Since OLP has a complex immunogenesis with abundant macrophage infiltration, this study determined by immunohistochemistry whether or not the expression of the inducible form of nitric oxide synthase (iNOS) was increased in this condition relative to normal mucosa. Thirty cases of OLP and 10 normal buccal mucosa biopsies were studied utilising primary antibodies to iNOS and CD68, a myelomonocytic marker. iNOS activity was additionally assessed using a [(14-)C]-labelled arginine to citrulline assay. CD68 expression was significantly increased in the cellular infiltrate of all 30 cases of OLP compared with normal mucosa (P<0.009). Although iNOS staining was seen in a minority of cells in nine cases, this was not statistically significant when compared with the absent staining in normal oral mucosa (P=0.26). Furthermore, the minimal iNOS activity found in OLP was similar to that in normal mucosa. We conclude that expression of iNOS by macrophages is downregulated in OLP and discuss the possible reasons for this finding.

Adult↗

Are myoepithelial cells responsible for the widespread expression of inducible nitric oxide synthase in pleomorphic adenoma? An immunohistochemical study.

Many of the actions of nitric oxide (NO) are still poorly understood. Recently, it has been shown that the inducible isoform of the enzyme nitric oxide synthase, iNOS, is expressed in both salivary ducts and pleomorphic adenoma. The current immunohistochemistry study determined whether or not this distribution correlated with smooth muscle actin (SMA) expression, thereby suggesting the expression by myoepithelial cells in both sites. Twenty cases of histologically confirmed pleomorphic adenoma, the sections of which contained adjacent normal salivary gland tissue, were stained for iNOS and smooth muscle actin (clone 1A4). The salivary ducts of all cases were stained intensely by both antibodies, with smooth muscle actin staining also being noted around acini in the normal gland parenchyma. Moderate or heavy staining for iNOS was found in all specimens of pleomorphic adenoma, with smooth muscle actin being distributed in a similar manner in 19 cases. Smooth muscle actin, but not iNOS, was also noted in blood vessels of both normal glands and tumours. The correlation between iNOS and SMA in pleomorphic adenoma was significant (P<0.001). The presence of iNOS in normal salivary ducts and pleomorphic adenoma is most likely due to expression by myoepithelial cells.

Actins↗

Expression of nitric oxide synthase in pleomorphic adenomas of the parotid.

The actions of nitric oxide (NO) in the pathology of solid tumours are complicated and many are poorly understood because NO has both inhibitory and tumour-promoting activities. In the current study we aimed to find out immunohistochemically whether the expression of both the inducible (iNOS) and endothelial (eNOS) forms of the enzyme nitric oxide synthase (NOS) were changed in pleomorphic adenomas of the parotid compared with normal salivary tissue. There was a significant difference in staining for iNOS between the tumour and normal salivary tissue, with tumour epithelial cells being stained in 29 cases of the 30 cases studied (P< 0.0001). The luminal cells of the salivary ducts also stained, but not the normal salivary tissue. Immunohistochemistry for the eNOS isoenzyme showed moderate staining of the tumour epithelium in only three specimens. There was also mild staining in the salivary duct cells of the normal glandular tissue and in endothelium of blood vessels in both tumour and normal glandular tissue in the same 29 cases.

Adenoma, Pleomorphic↗

Molecular characterization of Irish Salmonella enterica serotype typhimurium: detection of class I integrons and assessment of genetic relationships by DNA amplification fingerprinting.

Salmonella enterica is among the principal etiological agents of food-borne illness in humans. Increasing antimicrobial resistance in S. enterica is a cause for worldwide concern. There is concern at present in relation to the increasing incidence of human infection with antimicrobial agent-resistant strains of S. enterica serotype Typhimurium, in particular of phage type DT104. Integrons appear to play an important role in the dissemination of antimicrobial resistance genes in many Enterobacteriaceae including S. enterica. In this study the antimicrobial susceptibilities and phage types of 74 randomly collected strains of S. enterica serotype Typhimurium from the Cork region of southern Ireland, obtained from human, animal (clinical), and food sources, were determined. Each strain was examined for integrons and typed by DNA amplification fingerprinting (DAF). Phage type DT104 predominated (n = 48). Phage types DT104b (n = 3), -193 (n = 9), -195 (n = 6), -208 (n = 3), -204a (n = 2), PT U302 (n = 1), and two nontypeable strains accounted for the remainder. All S. enterica serotype Typhimurium DT104 strains were resistant to ampicillin, chloramphenicol, streptomycin, Sulfonamide Duplex, and tetracycline, and one strain was additionally resistant to trimethoprim. All DT104 strains but one were of a uniform DAF type (designated DAF-I) and showed a uniform pattern of integrons (designated IP-I). The DT104b and PT U302 strains also exhibited the same resistance phenotype, and both had the DAF-I and IP-I patterns. The DAF-I pattern was also observed in a single DT193 strain in which no integrons were detectable. Greater diversity of antibiograms and DAF and IP patterns among non-DT104 phage types was observed. These data indicate a remarkable degree of homogeneity at a molecular level among contemporary isolates of S. enterica serotype Typhimurium DT104 from animal, human, and food sources in this region.

Animals↗

Analysis of 2-(3-methyl-4-aminophenyl)-benzothiazole (NSC 674495) in plasma by gas chromatography with mass-selective detection.

Certain naturally occurring isoflavonoids have been shown to inhibit protein-tyrosine kinases, and this has led to investigations of ring-modified structural analogs. Most recently, 2-(3-methyl-4-aminophenyl)-benzothiazole (MAB: NSC 674495) was shown to possess significant activity against certain breast cell cancer lines in vitro and in vivo. Our efforts thus focussed on developing a simple and sensitive method for quantitating MAB in plasma using GC-MS. The GC-MS assay was found to be linear over the range of 0.050 to 5.0 microg/ml, and was applied to monitor the plasma concentration of MAB in a rat dosed with 25 mg/kg as a 1 min intravenous infusion. Plasma was collected at intervals from 3 through 180 min, and concentrations of MAB were determined. Non-linear regression analysis of the plasma concentration-time data revealed that levels declined from a maximum at 3 min of 18 microg/ml to 1 microg/ml at 3 h in a biphasic manner. In another investigation, significant plasma concentrations of a major metabolite was detected and determined to be mono-N-acetylated MAB.

Aniline Compounds↗

The Golgi apparatus plays a significant role in the maintenance of Ca2+ homeostasis in the vps33Delta vacuolar biogenesis mutant of Saccharomyces cerevisiae.

The vacuole is the major site of intracellular Ca2+ storage in yeast and functions to maintain cytosolic Ca2+ levels within a narrow physiological range. In this study, we examined how cellular Ca2+ homeostasis is maintained in a vps33Delta vacuolar biogenesis mutant. We found that growth of the vps33Delta strain was sensitive to high or low extracellular Ca2+. This strain could not properly regulate cytosolic Ca2+ levels and was able to retain only a small fraction of its total cellular Ca2+ in a nonexchangeable intracellular pool. Surprisingly, the vps33Delta strain contained more total cellular Ca2+ than the wild type strain. Because most cellular Ca2+ is normally found within the vacuole, this suggested that other intracellular compartments compensated for the reduced capacity to store Ca2+ within the vacuole of this strain. To test this hypothesis, we examined the contribution of the Golgi-localized Ca2+ ATPase Pmr1p in the maintenance of cellular Ca2+ homeostasis. We found that a vps33Delta/pmr1Delta strain was hypersensitive to high extracellular Ca2+. In addition, certain combinations of mutations effecting both vacuolar and Golgi Ca2+ transport resulted in synthetic lethality. These results indicate that the Golgi apparatus plays a significant role in maintaining Ca2+ homeostasis when vacuolar biogenesis is compromised.

Adenosine Triphosphatases↗

Health surveillance of cattle in the vicinity of a chemical industrial complex.

Following allegations of environmental contamination, a scheme for the surveillance of animal health on dairy farms in the vicinity of a large complex of chemical industries in the region of Cork harbour was initiated in 1991. Multidisciplinary investigations were undertaken as a result of unusual incidents of animal ill-health or decreased productivity, and an explosion and fire at one of the industrial plants. There was no evidence that exposure to environmental pollutants caused variations in either productivity or the incidence of disease. Many incidents which might have been linked with environmental pollution were found to have other causes. A broad database of animal disease incidence, productivity and blood composition has been established, and a bank of tissues taken from animals submitted for routine slaughter has been frozen, so that they may be analysed for toxins if required. The main difficulty encountered during the study was inadequate disclosure of information by some herd owners.

Animal Welfare↗

Informed consent in the Childrens Cancer Group: results of preliminary research.

BACKGROUND: Informed consent is critical to the ethical conduct of pediatric cancer clinical research. Research regarding such consent has been limited. METHODS: After conducting a background survey of institutional practice from principal investigators (PIs) at 113 Childrens Cancer Group (CCG) centers, the authors obtained more detailed data regarding informed consent from 23 parents of children recently enrolled in CCG research trials and from 23 clinician-investigators at 5 CCG institutions. RESULTS: Approximately 73% of PIs responded to the background survey, providing context in which to interpret the more detailed information. Parents reported that they found the informed consent process helpful, although somewhat confusing. Satisfaction with informed consent was not related to ethnicity or education level. Parents found discussion with staff more helpful than the consent document, and the majority reported that the amount of information conveyed was appropriate. Although only 3 parents (13%) reported that too much information was given, nearly 50% of the investigators believed too much information usually is provided. All investigators believed that patients benefit from participation in CCG studies; the majority recommend that the child be enrolled on study, and the majority believe the major obstacle to good informed consent is parents' "state of shock." CONCLUSIONS: Parents expressed general satisfaction with the consent process. By contrast, clinician responses indicate dissatisfaction with the informed consent process. Future research must include more centers and larger numbers of parents of children who we enrolled as well as those who declined to participate in CCG studies, examine consent in minority subgroups, and further investigate the role of clinician-investigators and their interaction with parents and children during the informed consent process.

Adult↗