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Biomedical subjects

A O'Connor

Publications and source records attributed to A O'Connor.

At least 73 records · Page 4Linked to original sources

Measurement of allergen-specific IgD and correlation with allergen-specific IgE.

A new method for the measurement of allergen-specific IgD (as-IgD) was developed by modifying the ImmunoCAP assay (Pharmacia), and amplification of the signal with a goat anti-human/rabbit anti-goat detection system. The assay was sensitive enough to measure as-IgD in serum samples. The specificity of the assay was examined using inhibition tests with excess corresponding and non-corresponding allergens. For the different allergens inhibition rates between 56% (house dust mite) and 88% (cat) could be achieved. Non-corresponding allergens did not inhibit the as-IgD binding. Total IgE and allergen-specific IgE (as-IgE) was measured using the ImmunoCAP system. Total IgD was measured using a sandwich ELISA. As-IgD was measured in serum samples from 51 atopic and 23 non-atopic subjects, and the correlation with as-IgE was examined. As-IgD was detected in both atopics and non-atopics but at higher levels in atopics. As-IgD against birch pollen and timothy pollen allergen was found to be increased in atopics with IgE directed against these allergens compared to atopics without IgE against these allergens (P < 0.02 and P < 0.03). As-IgD against birch pollen allergen was higher in atopics with IgE specific to this allergen than in non-atopics (P < 0.02). In contrast to total IgE and total IgD, significant correlations were observed between as-IgD and as-IgE against timothy pollen (r = 0.34, P < 0.04), birch pollen (r = 0.38, P < 0.05) and cat dander allergen (r = 0.52, P < 0.01). The observed correlations between as-IgD and IgE suggest that IgD and IgE may be similarly regulated, and thus the measurement of as-IgD may give further insight into the regulation of IgE.

Adolescent↗

Dysphagia associated with pharyngoesophageal segment dysfunction.

This paper deals with pharyngoesophageal segment dysfunction in swallowing. The mechanisms of normal opening of the PE segment is discussed. Problems in evaluation of the PE segment are presented. Examples of various etiologies of PE segment dysfunction are discussed.

Central Nervous System Diseases↗

Dysphagia secondary to head and neck cancer surgery.

This paper deals with swallowing abnormalities associated with the resection of cancers of the head and neck. The different sites of resection and the effects on swallowing as documented by modified barium swallow and manofluorography are described. Recommendations are made for the most functional types of reconstruction based upon the experience of the senior author.

Deglutition Disorders↗

Measurement of membrane bound IgD and IgM on B lymphocytes.

An assay system for the determination of the membrane bound IgD (mIgD) and IgM (mIgM) on B lymphocytes was developed by the combination of two new ELISA methods with the results of flow cytometry after labeling with specific antibodies. The mIgD and mIgM of B lymphocytes were prepared by incubating mononuclear cells (MNCs) in Tween 20 containing buffer and repeated freeze/thaw cycles. Optimal results were achieved with 0.2-0.4% Tween 20 and two freezing cycles. With biotin-streptavidin amplification the sensitivity of the ELISA was 30 microU/ml for IgD and 0.5 ng/ml for IgM. In healthy persons 3.5 +/- 0.5 mU mIgD were detected on 10(6) IgD+ cells and 57.1 +/- 5.9 ng mIgM on 10(6) IgM+ cells. The mIgD/mIgM ratio was 0.065 +/- 0.005 mU/ng. The developed ELISA systems utilize only commercially available reagents and therefore provide a convenient reproducible tool for determining membrane bound IgD and IgM on B lymphocytes.

Adult↗

Isolation and properties of YCK2, a Saccharomyces cerevisiae homolog of casein kinase-1.

A soluble fragment of YCK2, a casein kinase-1 isoform from Saccharomyces cerevisiae, has been purified and characterized in vitro. The procedure enriches enzyme activity to a final specific activity of 4.7 mumol min-1 mg-1 (when assayed with casein as substrate). Structural analysis reveals that the preparation arises from N-terminal modification and C-terminal proteolysis of the initially synthesized 546-residue protein, consisting of residues 2-495 +/- 1. Kinetic analysis demonstrates that YCK2 is similar to casein kinase-1 isolated from other organisms in its inability to use GTP as nucleotide substrate, in its sensitivity to heparin and ribofuranosyl-benzimidazole inhibitors, and in its peptide substrate selectivity. The enzyme is unusual, however, in that it is insensitive to the potent mammalian casein kinase-1 inhibitor N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide.

Amino Acid Sequence↗

Cyclobutane pyrimidine dimers in UV-DNA induce release of soluble mediators that activate the human immunodeficiency virus promoter.

Ultraviolet (UV) irradiation of human cells induced expression of a stably maintained fusion gene consisting of the human immunodeficiency virus long terminal repeat promoter controlling the bacterial chloramphenicol acetyltransferase gene. Two experiments demonstrated that DNA damage can initiate induction: UV induction was greater in DNA repair-deficient cells from a xeroderma pigmentosum patient than in repair-proficient cells, and transfection of UV-irradiated DNA into unirradiated cells activated gene expression. Increased repair of cyclobutane pyrimidine dimers by T4 endonuclease V abrogated viral gene activation, suggesting that dimers in DNA are one signal leading to increased gene expression. This signal was spread from UV-irradiated cells to unirradiated cells by co-cultivation, implicating the release of soluble factors. Irradiation of cells from DNA repair-deficiency diseases resulted in greater release of soluble factors than irradiation of cells from unaffected individuals. These results suggest that UV-induced cyclobutane pyrimidine dimers can activate the human immunodeficiency virus promoter at least in part by a signal-transduction pathway that includes secretion of soluble mediators.

Cell Line, Transformed↗

Psychiatric morbidity in sentenced segregated HIV-positive prisoners.

In this comparative study with a control group of prisoners, psychiatric morbidity was measured in two groups of sentenced prisoners, each group completing the GHQ-30 and 21-item Beck Depression Inventory (BDI). Group 1 consisted of 40 segregated HIV-positive prisoners and group 2 a matched control group in the main prison who had no history of HIV seropositivity. All members of group 1 had a history of intravenous drug abuse. The mean GHQ-30 and BDI scores were significantly higher in group 1, and 90% of group 1 were psychiatric 'cases' compared with just over 42% of group 2. Levels of psychiatric morbidity present in a third group, consisting of HIV-positive prisoners who had not been segregated (prison authorities were unaware of their seropositivity) are an interesting pointer for further research.

Adult↗

The effects of benzene and hydroquinone on myeloid differentiation of HL-60 promyelocytic leukemia cells.

Chronic exposure of humans to benzene (BZ) affects hematopoietic progenitor cells in intermediate stages of differentiation which can lead to aplastic anemia and/or acute myelogenous leukemia and some of its variant forms. We studied the effects of BZ and hydroquinone (HQ), a toxic bone marrow metabolite, on the human HL-60 promyelocytic leukemic cell line. Because the HL-60 cell is bipotential and can be induced to differentiate to monocytes or granulocytes it has been used in many studies as a surrogate for the granulocyte/macrophage committed cell, GM-CFU. Treatment of HL-60 cells with BZ specifically induced differentiation along the granulocytic lineage as measured by morphology, induction of superoxide production and chloroacetate esterase activity and the appearance of the L12-2 surface antigen. Differentiation was induced via the activation of protein kinase C and the phosphorylation of several proteins known to be involved in HL-60 cell differentiation. Subsequent to kinase C activation, arachidonic acid was released from membrane phospholipids and the 5-lipoxygenase pathway was activated for the production of leukotriene D4 (LTD4) required for granulocytic differentiation. BZ induction of granulopoiesis was prevented by preincubation of HL-60 cells with inhibitors of protein kinase C, 5-lipoxygenase, gamma-glutamyl transpeptidase required for the conversion of LTC4 to LTD4, or LTD4 receptor antagonists. Treatment of HL-60 cells with tetraphorbol myristate acetate (TPA), 1 alpha, 25-dihydroxyvitamin D3 (1,25-(OH2)D3) or interleukin-1 (IL-1) induced HL-60 cells to differentiate to monocytes/macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonate 5-Lipoxygenase↗

Regulation of beta-adrenergic receptors on endothelial cells in culture.

This study aimed to determine the density of vascular beta-adrenergic receptors in cultured endothelial cells and to study the regulation of endothelial receptors after exposure to catecholamines and the ACE inhibitors, lisinopril and ramiprilat. Membranes from bovine aortic endothelial cells (BAEC) and bovine pulmonary artery endothelial cells (BPAEC) showed saturable binding of the radioligand [125I]iodocyanopindolol (ICYP). The beta-receptor density and binding affinity were comparable in both types of endothelial cells. Isoproterenol induced significant down-regulation of beta-receptors (-50%; P < 0.01). Incubation (24h) with the ACE inhibitors lisinopril 10(-5) M (+28.8%; P < 0.05) and ramiprilat 10(-5) M (+33.7%, P < 0.09) augmented the beta-receptor density in BAEC, but lower ACE inhibitor doses had no affect. Incubation with lisinopril 10(-5) M for 24 h resulted in significantly lower cAMP baseline levels, but did not affect cAMP concentrations after stimulation with isoproterenol. These results indicate that down-regulation of endothelial beta-receptors occurs during prolonged exposure to beta-stimulation, and that high concentrations of ACE inhibitors may affect the density of endothelial beta-receptors.

Angiotensin-Converting Enzyme Inhibitors↗

Comparison between MAGIC LITE- and CAP-system: two automated specific IgE antibody assays.

The MAGIC LITE system, a newly developed immunochemiluminometric assay for specific and total IgE antibody using paramagnetic particles coupled with standardized allergens as solid phase, was compared to the CAP system, a recently introduced immunoassay based on a cellulose polymer encased in a capsule. A total of 357 serum samples of patients with suspected inhalant allergies and a positive skin prick test (SPT) to common allergens (birch, timothy-grass, mugwort, cat dander, Dermatophagoides pteronyssinus, Alternaria) were investigated. Fifty SPT negative subjects served as controls (total number of tests in each assay = 1600). Both assays were highly precise (overall intra-assay and inter-assay coefficients of variation were 2.9% and 4.5% in MAGIC LITE, 4.7% and 5.5% in CAP) and showed excellent linearity (mean r2 of eightfold log2 serum dilutions were 99.7% and 99.3% in MAGIC LITE and CAP). Good correlations were found between the absolute specific IgE antibody values detected by both methods (correlation coefficient r: birth 0.86, grass 0.93, mugwort 0.96, cat 0.91, D. pteronyssinus 0.73, Alternaria 0.90). Excellent specificity (greater than or equal to 98%) occurred in both assays and with all allergens, and sensitivity was related to the allergen (MAGIC LITE/CAP): birch 91%/89%, grass 83%/90%, mugwort 50%/69%, cat 83%/83%, D. pteronyssinus 72%/78%, Alternaria 75%/81%. Our results indicate that both in vitro tests are useful tools for the detection of specific IgE antibody.

Allergens↗

Comparison of the Phadebas RAST with the Pharmacia CAP system for insect venom.

Determination of specific IgE by RAST is a well-established method in the diagnosis of immediate allergic reactions. In this study, we have compared the RAST with the ImmunoCAP, a novel test system which is based on a new type of solid phase. A total of 123 sera from 111 insect venom-allergic patients (74% female) were investigated. All patients had their diagnosis confirmed on the basis of their history and skin tests with insect venom. The patients' age showed a mean +/- S of 44.2 +/- 14.6 years. The total serum IgE levels ranged from 4-1712 kU/l, with a median of 108 kU/l. The results of specific IgE, as determined by RAST and CAP, showed a significantly higher sensitivity, by almost one class, with the CAP compared with the RAST system. The quotient of specific IgE to total IgE, determined with the CAP system, could not be shown to be an expression of sensitization, compared with the severity of sting reactions (Müller classification (16)). A conversion factor for vespid venom RAST to CAP was calculated from the present data by subtracting the RAST from the CAP values. The mean delta value +/- SD was found to be 0.9 +/- 0.65, with a range from -0.8 to 2.7 and a median of 0.9. The data clearly show the differences between RAST and CAP-RAST classes, indicating that the CAP-system has a higher sensitivity and that patients with a low level sensitization are missed by the RAST method.

Adolescent↗

XYY genotype and crime: 2 cases.

The presence of 47, XYY genotype has stimulated much debate as to whether these men are more likely to indulge in criminal and violent behaviour than 46, XY males. Two cases of XYY men who had committed murder are described, and the current literature regarding criminality and psychopathology in XYY males is reviewed. It is important that Forensic Psychiatrists with XYY patients are aware of these issues as the link between XYY genotype and criminality may be raised in court.

Adult↗

Blunted prolactin responses to d-fenfluramine in sociopathy. Evidence for subsensitivity of central serotonergic function.

Using a neuroendocrine probe we studied nine male offenders in a forensic hospital, convicted of murder, with a diagnosis of antisocial personality disorder, who had been behaviourally 'quiescent' for varying periods and who had not recently been abusing drugs. Nine healthy age-matched men also participated. All subjects received 30 mg d-fenfluramine (d-FEN), a 5-HT releasing agent, orally, after an overnight fast, and serial samples for prolactin estimation were taken hourly for five hours. Responses were significantly impaired in the patients, suggesting a subsensitivity of certain 5-HT systems in antisocial personality disorder, regardless of recent or ongoing behavioural disturbance.

Adult↗

IgE-mediated inhalant allergy in inhabitants of a building infested by the rice weevil (Sitophilus oryzae).

The rice weevil (Sitophilus oryzae) is known as a stored product pest. Occupants living in a factory used previously as a granary and known to be contaminated by the rice weevil developed rhinitis and asthma. To study the role of the potential insect allergens, extracts were prepared from whole body and a grain dust of the rice and grain weevil (Sitophilus granarius). The extracts were coupled to cyanogen bromide-activated paper disks. Skin prick tests (SPT) were performed using common inhalant allergens as well as the insect allergen preparations. In cases of a positive SPT, specific serum IgE to the insect products was measured. Histamine release studies with peripheral leukocytes (HR) and studies using immunoblot techniques were performed. Fifteen of 39 subjects living in the infested rooms demonstrated positive SPT to the extracts of insect origin. Histamine equivalent wheal size induced by the whole body extract of the rice weevil required 3-160 micrograms protein/mL. Five of 15 subjects (with positive SPTs) had elevated specific IgE-levels to the insect material. RAST-inhibition studies indicated cross allergenicity between rice and grain weevils, and also between the frass of both beetles. Five of 15 subjects were positive in the HR assay (Ag30, allergen concentration for 30% HR for the whole body extract: range, 10(-3) to 400 micrograms protein/mL, maximum release: 26% to 89%). IgE binding was detected after SDS-PAGE by immunoblot techniques at different locations: 35-38, 54, 67, 70, and > 94 kD.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Community health service utilisation and needs in an elderly population.

This study was carried out to determine community health service utilisation and needs of an elderly population living in a geographically defined area of Dublin. A random sample of 208 persons was taken from the 11,852 elderly persons living in the area. Activities of daily living and cognitive function were assessed in the person's own home. Whilst the community health services provided were less than comprehensive, they were targeted to those most in need; the very elderly, those living alone, and persons with a mental or physical disability. Objectively assessed need for further services far outweighed the demand for such services. Studies such as this are essential if the elderly are to receive their fair share of services in a demand based health service.

Aged↗

Concentrations of immunoactive inhibin in serum during human pregnancy: evidence for an ovarian contribution.

Immunoactive inhibin (ir-inhibin) concentrations in maternal serum during normal human pregnancy have been established in two separate studies employing cross-sectional and longitudinal sampling regimes. Ir-inhibin concentrations rose from the mid-luteal phase (geometric mean + 95% confidence intervals 1.490 (1.086-2.028) U mL-1) to peak at week 11 of gestation (3.77 (3.26-4.35) U mL-1), declined to a plateau from 14 to 25 weeks with means ranging from 1.8 to 2.3 U mL-1, and subsequently rose slowly to a peak of 6.53 U mL-1 at 41 weeks. In the longitudinal study, similar results were obtained and no differences were found in maternal inhibin levels in women carrying male or female fetuses. Paired cord blood and maternal samples showed no significant difference in ir-inhibin concentrations irrespective of the sex of the fetus. However, in all such pregnancies amniotic fluid ir-inhibin levels were 2-3 fold greater than maternal or fetal levels raising the possibility that the amnion may secrete inhibin. In 12 women without functional ovaries in whom a singleton pregnancy was achieved by donation of oocytes and in vitro fertilization, the ir-inhibin levels showed a similar pattern in the first trimester of pregnancy but the concentrations achieved were markedly lower (peak 1.1 U mL-1 at 9 weeks). In five women from the group in whom samples were available late in gestation, three showed greater than normal levels and two had subnormal levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗

Circulating immunoreactive inhibin, gonadotropin, and prolactin levels during pregnancy, lactation, and postweaning estrous cycle in the rat.

Serum inhibin levels were measured by heterologous RIA during pregnancy, lactation, and the post-weaning estrous cycle in the rat and correlated with changes in serum FSH and LH and prolactin. Blood was serially collected by cardiac puncture under light ether anesthesia from adult Sprague-Dawley rats on alternate days throughout the experimental period. For the first 8 days of pregnancy, immunoreactive inhibin levels remained high, then gradually decreased to reach a nadir at Day 16, and subsequently rose steeply until parturition. The pattern of serum immunoreactive inhibin levels during early pregnancy does not support a corpus luteum source and the dramatic rise from Day 16 to Day 22 correlates with the recommencement of follicular development in the ovary. Inhibin levels decreased rapidly on the day after birth and were suppressed until Day 8 of lactation, slowly increasing thereafter to reach a plateau from Day 14 until weaning (Day 22.5 of lactation). These changes in inhibin levels positively correlated with LH and FSH and negatively with prolactin, and are consistent with an ovarian source for inhibin associated with the recommencement of follicular development resulting from the diminution of the suckling stimulus. Immediately after weaning, serum immunoreactive inhibin levels showed a 4-day cyclic pattern corresponding to the estrous cycle identified by vaginal smear. Inhibin levels peaked on the day of proestrus, reached a nadir on the day of estrus, and rose slowly during metestrus and diestrus to a new peak at proestrus. Serum FSH levels showed an inverse correlation to inhibin levels consistent with a feedback relationship with inhibin.

Animals↗