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W O'Connell

Publications and source records attributed to W O'Connell.

At least 19 recordsLinked to original sources
PubMed2001

Identification of Legionella pneumophila rcp, a pagP-like gene that confers resistance to cationic antimicrobial peptides and promotes intracellular infection.

In the course of characterizing a locus involved in heme utilization, we identified a Legionella pneumophila gene predicted to encode a protein with homology to the product of the Salmonella enterica serovar Typhimurium pagP gene. In Salmonella, pagP increases resistance to the bactericidal effects of cationic antimicrobial peptides (CAMPs). Mutants with insertions in the L. pneumophila pagP-like gene were generated and showed decreased resistance to different structural classes of CAMPs compared to the wild type; hence, this gene was designated rcp for resistance to cationic antimicrobial peptides. Furthermore, Legionella CAMP resistance was induced by growth in low-magnesium medium. To determine whether rcp had any role in intracellular survival, mutants were tested in the two most relevant host cells for Legionnaires' disease, i.e., amoebae and macrophages. These mutants exhibited a 1,000-fold-decreased recovery during a Hartmannella vermiformis coculture. Complementation of the infectivity defect could be achieved by introduction of a plasmid containing the intact rcp gene. Mutations in rcp consistently reduced both the numbers of bacteria recovered during intracellular infection and their cytopathic capacity for U937 macrophages. The rcp mutant was also more defective for lung colonization of A/J mice. Growth of rcp mutants in buffered yeast extract broth was identical to that of the wild type, indicating that the observed differences in numbers of bacteria recovered from host cells were not due to a generalized growth defect. However, in low-Mg(2+) medium, the rcp mutant was impaired in stationary-phase survival. This is the first demonstration of a pagP-like gene, involved in resistance to CAMPs, being required for intracellular infection and virulence.

Amino Acid Sequence↗
PubMed2000

Heterogeneous sympathetic innervation influences local myocardial repolarization in normally perfused rabbit hearts.

BACKGROUND: Heterogeneity of sympathetic innervation is thought to contribute to the potential for fatal arrhythmia. However, little is known about the effects of heterogeneous innervation on repolarization. METHODS AND RESULTS: To assess this relationship, we measured activation recovery intervals (ARIs) from 64 epicardial sites in 11 rabbits studied 2 weeks after regional denervation produced by phenol and 4 sham-operated rabbits. ARI results were compared with the distribution of sympathetic innervation measured from 3D reconstructions of serial autoradiographs of [(125)I]metaiodobenzylguanidine and (99m)Tc-sestamibi. ARIs were recorded during baseline sinus rhythm, norepinephrine (NE) infusion (0.1 microg. kg(-1). min(-1)), and left stellate ganglion stimulation (SS). NE shortened ARI in 98% of electrodes in the denervated region. The degree of ARI shortening and dispersion increased (P<0.001 and P<0.01, respectively) as denervation became more severe. SS shortened ARI in 30% of electrodes in the denervated area, with increased shortening and dispersion related to increased severity of denervation (P<0.01). SS prolonged ARI in 70% of electrodes in the denervated area, with no correlation with severity of denervation. CONCLUSIONS: The magnitude and dispersion of local repolarization responses are related to the severity of denervation, as well as the type of stimulation: neural (SS) versus humoral (NE). The differences may relate to the concentration of NE released.

3-Iodobenzylguanidine↗
PubMed1996

Legionella pneumophila mutants that are defective for iron acquisition and assimilation and intracellular infection.

Legionella pneumophila, a parasite of macrophages and protozoa, requires iron for optimal extracellular and intracellular growth. However, its mechanisms of iron acquisition remain uncharacterized. Using mini-Tn10 mutagenesis, we isolated 17 unique L. pneumophila strains which appeared to be defective for iron acquisition and assimilation. Eleven of these mutants were both sensitive to the iron chelator ethylenediamine di(o-hydroxyphenylacetic acid) and resistant to streptonigrin, an antibiotic whose lethal effect requires high levels of intracellular iron. Six mutants were also defective for the infection of macrophage-like U937 cells. Although none were altered in entry, mutants generally exhibited prolonged lag phases and in some cases replicated at slower rates. Overall, the reduced recoveries of mutants, relative to that of the wild type, ranged from 3- to 1,000-fold. Strain NU216, the mutant displaying the most severe lag phase and the slowest rate of replication, was studied further. Importantly, within U937 cells, NU216 was approximately 100-fold more sensitive than the wild type was to treatment with the Fe3+ chelator deferoxamine, indicating that it is defective for intracellular iron acquisition and assimilation. Furthermore, this strain was unable to mediate any cytopathic effect and was impaired for infectivity of an amoebal host. Taken together, the isolation of these mutants offers genetic proof that iron acquisition and assimilation are critical for intracellular infection by L. pneumophila.

DNA Transposable Elements↗
PubMed1995

Detection of mip-like sequences and Mip-related proteins within the family Rickettsiaceae.

The Mip surface protein, a prokaryotic analog of the FK506-binding proteins, enhances the ability of Legionella pneumophila to infect macrophages and protozoa. Using mip-specific probes and low-stringency Southern hybridizations, we have detected DNA sequences homologous to mip within Coxiella burnetii and Rochalimaea quintana. Using specific anti-Mip antisera and immunoblot analysis, we also detected Mip-related proteins within these bacteria as well as within Rickettsia and Ehrlichia species. These data suggest that Mip-related proteins have broad significance for host-parasite interactions. However, they also indicate that care must be exercised when using mip probes or anti-Mip antibodies for the detection of Legionella organisms in water or clinical samples.

Bacterial Proteins↗
PubMed1993

Basal interventricular septal thallium-201 defects: real or artifact?

Misinterpretation of reversible defects at the base of the interventricular septum is perhaps among the greatest single causes of false positive TI-201 myocardial perfusion images. This is a report of a patient with angiographically documented ischemia at the base of the septum and corresponding reversible defects as seen using TI-201 imaging. Illustrated are two different forms of malalignment artifact that duplicate this patient's findings in a patient with normal perfusion.

Aged↗
PubMed1989

Clot lysis by gastric juice: an in vitro study.

Gastric juice from patients with peptic ulcer disease and from patients with no upper gastrointestinal abnormality was studied in order to assess its effect on a formed fibrin clot. In both groups of patients gastric juice caused a marked increase in fibrinolysis as evidenced by a shortening of the euglobulin clot lysis time. This plasmin mediated fibrinolytic activity was found to be heat labile and only present in an acid environment. Addition of tranexamic acid or sucralfate to gastric juice almost completely reversed this effect, whereas pepstatin was only partially effective. It is probable that acid dependent proteases other than pepsin are responsible for the marked fibrinolysis. The ulcer healing agent sucralfate might be useful in those patients at risk of bleeding or rebleeding from active peptic ulcer disease.

Fibrinolysis↗
PubMed1988

Apolipoproteins of the orotic acid fatty liver: implications for the biogenesis of plasma lipoproteins.

Rats fed orotic acid develop fatty livers characterized by triglyceride-laden, membrane-bounded vesicles designated "liposomes." We have measured the levels of apolipoproteins in isolated liposomes and other subcellular fractions by SDS-polyacrylamide gel electrophoresis, electrotransfer, and immunodecoration. Apolipoproteins Bh, Bl, E, and C appear to cofractionate; for these proteins, the liposomal pool represents a large portion of their total intracellular mass. However, liposomes are deficient in both variants of apoB relative to apoE and apoC when compared with rat plasma very low density lipoprotein (VLDL). Albumin and apolipoproteins A-I and A-IV are also found in liposomes, but this organelle represents a minor fraction of their total intracellular mass. The liposomal apolipoproteins show varying degrees of association with cisternal lipid and with organelle membranes. Orotic acid may selectively block VLDL production at the level of particle assembly or transorganellar movement. We conclude that liposomal contents probably represent exaggerated accumulations of VLDL assembly intermediates, and that the intracellular partitioning of high density lipoprotein-destined from VLDL-destined components occurs at an early stage in particle biogenesis. Moreover, some unique structural feature of apoB may effect movement of VLDL assembly intermediates through secretory organelles.

Animals↗
PubMed1986

Quantitation of regional myocardial function by cine computed tomography: pharmacologic changes in wall thickness.

To determine the capability of high speed computed transmission tomography to quantitate regional wall thickening dynamics over a wide range of physiologic states, left ventricular wall thickening was studied in nine anesthetized mongrel dogs in the control state and during separate infusions of dobutamine (10 micrograms/kg per min) and phenylephrine (25 micrograms/kg per min). After an intravenous bolus of contrast medium the heart was imaged from base to apex with serial transverse images in eight short-axis cine computed tomographic planes. In each dog during each experimental condition, 50 ms scans spanning the cardiac cycle were acquired at each anatomic level. Left ventricular epicardial and endocardial boundaries were identified on end-diastolic and end-systolic images at the equatorial left ventricular planes by an objective threshold contour method validated in a series of experiments performed on ex vivo anatomic specimens. End-diastolic and end-systolic frames were automatically realigned by superposition of epicardial centers of gravity and then rotated using a cross correlation function. The left ventricular wall thickness was measured manually at 16 points around the circumference by two independent observers. For the group of dogs the average percent wall thickening was 40.5 +/- 28.2% and varied among segments from 18 to 70% in the control state. After dobutamine was administered, significant increases in heart rate and cardiac output (p less than or equal to 0.01) were accompanied by an increase in the average wall thickening (73.6 +/- 51.2%; p less than or equal to 0.001) in the left ventricle; the average wall thickening among segments ranged from 46 to 97%. After phenylephrine administration, significant increases in mean blood pressure and cardiac output (p less than or equal to 0.01) were noted along with a significant increase in average left ventricular wall thickening (60.3 +/- 52.5%; p less than or equal to 0.001). Despite an overall increase in the percent wall thickening, no statistically significant changes in segmental contraction pattern between control and drug intervention states were observed. The wall thickness measurements were highly reproducible between the two independent readers (reliability coefficient = 0.99). Cine computed tomography-derived measurements can potentially be used for quantitative assessment of left ventricular wall thickening dynamics of a single heartbeat during acute interventions, such as the administration of drugs.

Animals↗
PubMed1985

Interaction of "supplementary" scintigraphic indicators of ischemia and stress electrocardiography in the diagnosis of multivessel coronary disease.

Lung uptake, ventricular cavitary dilation and basal myocardial uptake represent abnormalities that have been associated with myocardial ischemia on stress thallium-201 images, but that are supplementary to the conventional assessment of perfusion distribution. These "supplementary" indicators of ischemia were related to the coronary distribution of perfusion abnormalities, the results of electrocardiographic stress testing and to the findings on coronary angiography in 73 patients. Forty patients had multivessel coronary disease; 19 of these had three vessel disease. Perfusion abnormalities were seen in 39 of these 40 patients but were indicative of multivessel coronary disease in only 28 and of three vessel disease in only 6. However, supplementary indicators were present in 33 of 40 patients with multivessel disease and in 15 of 19 with three vessel disease. Furthermore, they were seen in 16 of 22 patients with multivessel disease in whom conventional perfusion abnormalities underestimated the extent of disease, but in only 4 of 12 patients in whom the extent of disease was overestimated. The presence of either perfusion abnormalities in a multivessel distribution or supplementary indicators identified 38 (95%) of 40 patients with multivessel disease. A markedly positive electrocardiographic treadmill test was a less sensitive indicator of multivessel disease, appearing in only 15 of 40 patients. However, it was present in only 4 of 33 patients without multivessel coronary disease and was more specific for that diagnosis than were supplementary scintigraphic indicators (88 versus 67%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

The etiology and implications of dense cavitary "photopenia" on myocardial perfusion scintigraphy.

Dense cavitary "photopenia" was observed on 21 of 200 consecutive stress perfusion scintigrams. A prominent finding in many cases, it sometimes occupied only a portion of the region overlying the ventricular cavity, was often seen in some projections and not others, and was frequently adjacent to myocardial perfusion defects. To distinguish an etiology among reduced cavitary radioactivity, relatively increased background radioactivity, or reduced radioactivity in overlying myocardium, quantitative analysis of cavitary, lung and myocardial radioactivity was performed in patients with dense cavitary "photopenia," with and without lung uptake, and compared with results from studies showing increased lung uptake without cavitary photopenia and with normal studies. The results showed that dense cavitary photopenia was related to reduced radioactivity in overlying myocardium. Correlative imaging studies performed with echocardiography and contrast ventriculography confirmed this relationship to myocardial scar in 15 of 21 patients in whom associated akinesis or dyskinesis was seen. Hence, dense cavitary photopenia on stress perfusion scintigraphy is due to a dense myocardial perfusion abnormality, and is often indicative of related scar and an associated severe contraction abnormality.

Adult↗
PubMed1984

Phase image characterization of localized and generalized left ventricular contraction abnormalities.

To evaluate their phase image characteristics, 61 patients with varying left ventricular contraction abnormalities were studied. In 16 normal patients, the left ventricular phase image revealed a homogeneous pattern, a narrow bell-shaped histogram and an orderly spatial progression of phase angle (phi). In 16 patients with segmental abnormalities, the left ventricular phase image showed a region of uniformly delayed phase angle corresponding to the site of segmental abnormality, a discrete secondary histogram peak and a discontinuous, but orderly, spatial progression of phase angle. The mean phase angle (phi) (23.6 +/- 15.7 degrees) and its standard deviation (17.6 +/- 7.2 degrees) differed from the normal group (7.6 +/- 11.1 degrees, p less than 0.002 and 8.9 +/- 2.8 degrees, p less than 0.001). The percent of end-diastolic volume involved in the segmental abnormality, calculated using phase data in 13 of these and in 11 additional patients with a left ventricular aneurysm on ventriculography, correlated well with the percent akinetic segment on scintigraphic (r = 0.78) and angiographic (r = 0.84) study. In 18 patients with generalized abnormalities, the left ventricular phase image revealed multiple regions of inhomogeneous phase angle, a grossly irregular histogram and a disorderly spatial progression of phase angle. The mean phase angle (56.4 +/- 23.9 degrees) and standard deviation (27.3 +/- 7.1 degrees) differed from values in the normal group and from patients with segmental contraction abnormalities (both p less than 0.001). The mean phase angle and its standard deviation in scattered regions with abnormally prolonged phase angle differed significantly from abnormal regions in patients with segmental abnormalities (both p less than 0.001). These patterns of left ventricular phase angle demonstrate characteristics that may help differentiate between ventricles with segmental and generalized contraction abnormalities. Their relation to underlying pathophysiology and potential clinical implications should be considered.

Adult↗
PubMed1984

Phase image evaluation of patients with ventricular pre-excitation syndromes.

To localize bypass pathways, left and right ventricular regions were analyzed at rest by phase image analysis in 18 patients with ventricular pre-excitation syndromes. These were compared with image findings in 18 normal subjects. In each of 17 patients with pre-excitation, the site localized on electrophysiologic study correlated closely with the region of earliest ventricular phase angle. This site could be objectively separated from that in normal subjects in each of eight patients with an active left-sided pathway and in both patients with a right-sided pathway. Those with a septal pathway revealed earliest septal phase angle, but could not be separated from normal subjects. In the eight patients with an active left bypass tract, the onset, upstroke and peak of the left ventricular phase histogram preceded those of the right ventricular histogram. Those with a left-sided pathway demonstrated a mean left ventricular phase angle, a difference between mean left and mean right ventricular phase angle and a difference between earliest left and right ventricular phase angles which was significantly less than that in normal subjects (p less than 0.05). These variables presented characteristic converse changes in those with a right-sided pathway. Sequential phase changes in 10 studies suggested "fusion" of normal septal with lateral bypass fronts. Electrocardiographic and electrophysiologic localization of the bypass pathway agreed in only 8 of 14 patients with a recognized delta wave. The phase image represents a new, noninvasive method of evaluating ventricular pre-excitation. The method may provide useful information complementary to that of electrocardiographic and electrophysiologic analysis.

Adolescent↗
PubMed1984

A new method with high sensitivity and specificity for localization of abnormal parathyroid glands.

A novel method for localization of abnormal parathyroid glands involving color-processing of nuclear scintigrams of the neck after injection of Thallium-201 and Technetium pertechnetate is presented with surgical correlation. Preoperative localization of single parathyroid adenomas was successful in 88% of previously unoperated patients and in 85.7% of those with adenomas not located at previous surgery. Eighty-three per cent of glands with secondary hyperplasia, 66% of glands with primary hyperplasia, and one carcinoma were localized. No abnormal studies were seen in non-hyperparathyroid hypercalcemia, and no false positive studies were seen. Localization appeared related to larger adenomas (300-5000 mg), although one of 60 mg was localized. Color-comparison dual-isotype scintigraphy was useful for localization of parathyroid adenomas and hyperplastic glands and exceeded the reported sensitivity of either ultrasonography or computerized tomography. It deserves wider evaluation in preoperative management of at least hyperparathyroidism of the primary or persistent types.

Adenoma↗
PubMed1982

Are regions of ischaemia detected on stress perfusion scintigraphy predictive of sites of subsequent myocardial infarction?

To determine the relation between scintigraphic regions of stress-induced ischaemia and subsequent myocardial infarction, a select group of 21 patients was investigated. Each patient had undergone stress perfusion scintigraphy before myocardial infarction was recorded. After acute infarction, thallium-201 perfusion scintigraphy was performed in 16 patients (76%) and 99mTc (stannous) pyrophosphate in 14 patients (67%). All patients had at least one post-myocardial infarction scintigram and nine (42%) had both perfusion scintigraphy and infarct imaging. Nineteen patients (90%) had scintigraphic evidence of stress-induced ischaemia pre-infarction. Scintigraphic regions of infarction were compared with regions of previously demonstrated stress-induced ischaemia. In 11 patients (53%) the myocardial infarction was more extensive; in one of these patients, reimaged one week before myocardial infarction, and in four others (19%) there were matching defects; in three patients (14%) the infarction was less extensive, and in two patients (9%) the infarction was less extensive but also involved regions not previously shown to develop ischaemia. In the final patient (5%) there was no match. Stress perfusion scintigraphy was generally abnormal before acute infarction in this group of patients. Acute infarction frequently involved regions previously shown to develop stress-induced ischaemia, though these often underestimated the extent of myocardium at risk.

Aged↗
PubMed1982

The phase image: its relationship to patterns of contraction and conduction.

To determine the relationship of phase changes and abnormalities of ventricular contraction and conduction, we performed phase image analysis of blood pool scintigrams in 29 patients. Eleven patients had no evidence of blood pool contraction or ECG conduction abnormalities, four had contraction abnormalities, seven had abnormal conduction and seven had abnormalities of both variables. The phase delay generally related to the degree of contraction abnormality. The mean phase delay in hypokinetic segments differed from that in normokinetic segments in the same patient (p less than 0.025), the phase delay of akinetic and dyskinetic segments differed from that in normokinetic segments (p less than 0.001) and the phase delay in dyskinetic segments differed from that in akinetic segments (p less than 0.005), but there was a significant overlap in the phase delay in normal and hypokinetic segments. Also, in patients with conduction abnormalities, the minimal associated regional phase delay presented a phase dispersion and a pattern of contraction consistent with the pattern of conduction and different from normal. A single study performed both at rest and with stress demonstrated the effect of heart rate on phase assessment and confirmed the independent effects of contraction and conduction on phase delay. Acquisition and analytic methods should add significantly to the resolution of the phase method.

Arrhythmias, Cardiac↗