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Biomedical subjects

D Joseph

Publications and source records attributed to D Joseph.

At least 91 records · Page 5Linked to original sources

Concepts of intraaortic balloon counterpulsation.

The concept of intraaortic balloon counterpulsation (IABC) was developed in the late 1960s, primarily for use in cardiogenic shock. Since that time, many published reports have documented the efficacy of this mechanical assist device in an expanding number of clinical situations. Research has shown that intraaortic balloon counterpulsation increases coronary flow velocity and decreases afterload, thus favorably affecting myocardial oxygen supply and demand. This article offers a review of the concepts and mechanics of IABC, as well as current indications and contraindications for use. The nurse must be able to recognize and address potential complications to ensure positive patient outcomes.

Contraindications↗

Role of interleukin-5 in enhanced migration of eosinophils from airways of immunized guinea-pigs.

1. Platelet activating factor (PAF), leukotriene B4 (LTB4) and interleukin-5 (IL-5) are potent chemoattractants for guinea-pig eosinophils, which may be involved in eosinophil recruitment and up-regulation in allergic diseases. Eosinophils from the bronchoalveolar lavage fluid (BALF) of ovalbumin-sensitized guinea-pigs were collected 24 h after antigen provocation and migration induced by PAF, LTB4 and rhIL-5 was studied. 2. Total BALF content and distribution of eosinophils were greater in immunized, ovalbumin-challenged guinea-pigs (5.0 +/- 0.8 x 10(6)/guinea-pig; 12 +/- 1%) than in immunized, saline-challenged animals (3.0 +/- 0.7 x 10(6)/guinea-pig; 7 +/- 1%). 3. The chemoattraction of eosinophils isolated on a metrizamide gradient was studied in micro-Boyden chambers, results being expressed as the number of migrating cells (mean +/- s.e. mean). PAF and LTB4-induced migration of eosinophils from immunized and OA-challenged guinea-pigs were significantly enhanced, as compared to immunized and saline-challenged animals (170 +/- 36 vs 35 +/- 9 migrating eosinophils for 10 nM PAF; 271 +/- 60 vs 110 +/- 19 for 1 nM LTB4). 4. The IL-5 antibody TRFK-5, in vivo, reduced eosinophil recruitment in BALF of antigen-challenged immunized animals as well as the enhanced responsiveness of eosinophils from the challenged animals, suggesting a role for IL-5 in the priming of eosinophils in vivo. 5. In contrast to TRFK-5, nedocromil sodium reduced to a similar extent eosinophil, macrophage and lymphocyte recruitment into the BALF of antigen-challenged, but failed to down-regulate the enhanced responsiveness of eosinophils from the challenged animals. 6. The increased eosinophil content in lungs from antigen-challenged guinea-pigs is thus selectively reduced by the anti-IL-5 antibody, which also attenuates the concomitant enhancement of the eosinophil responsiveness, supporting the concept that IL-5 is essential for recruitment and priming of eosinophils in vivo. In contrast, nedocromil sodium reduced non-selectively the total cell recruitment to the airways,but failed to attenuate the enhanced responsiveness of those eosinophils which migrated, indicating that its effects involve a different target.

Animals↗

Role of eosinophil activation in the bronchial reactivity of allergic guinea pigs.

Ovalbumin inhalation by sensitized guinea pigs induced a marked increase in the number of eosinophils (0.89 +/- 0.18 to 5.45 +/- 0.77 x 10(5)/ml, n = 10, p < 0.05) and elevations in the amounts of protein and eosinophil-derived major basic protein (MBP) (1,010.7 +/- 184.9 to 4,116.6 +/- 973.0 ng/ml, n = 10, p < 0.05) recovered by bronchoalveolar lavage (BAL). In contrast, no changes in the levels of eosinophil peroxidase (EPO) or in the sensitivity of the airways to bronchoconstriction induced by methacholine were detected. However, when ovalbumin-exposed guinea pigs received an intratracheal instillation of 1 microgram leukotriene (LT)B4 30 min prior to methacholine provocation, elevated levels of EPO and MBP in the BAL fluid and a marked bronchial hyperreactivity to methacholine were noted when compared with saline-challenged LTB4-injected animals (p < 0.05). In contrast, the intratracheal instillation of 1 or 3 micrograms platelet-activating factor (PAF) did not significantly modify the bronchial reactivity to methacholine or the levels of EPO and MBP. PAF and LTB4 induced similar enhancements in the amount of protein in BAL fluids from antigen-exposed guinea pigs, suggesting that increased endothelial/epithelial permeability does not account for hyperreactivity. A significant correlation between the levels of EPO or MBP and the intensity of the bronchial responsiveness to methacholine were shown in ovalbumin-challenged guinea pigs, irrespective of their subsequent treatment, i.e., either with PAF or with LTB4 or with their vehicle (r = 0.579, p = 0.0002 and r = 0.330, p = 0.049, n = 36 for EPO and MBP, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A novel structural basis for membrane association of a protein: construction of a chimeric soluble mutant of (S)-mandelate dehydrogenase from Pseudomonas putida.

The (S)-mandelate dehydrogenase (MDH) from Pseudomonas putida (ATCC 12633) is the only membrane-associated member of a homologous family of FMN-dependent, alpha-hydroxy acid dehydrogenases/oxidases that includes the structurally characterized glycolate oxidase from spinach (GOX). We have correlated the membrane association of MDH to a polypeptide segment in the interior of the primary sequence. This has been accomplished by construction of a chimeric enzyme in which the putative membrane-binding segment in MDH has been deleted and replaced with the corresponding segment from the soluble GOX. The resulting chimera, MDH-GOX, is soluble and retains partial catalytic activity (approximately 1%) using (S)-mandelate as substrate. In contrast, the activities of both the membrane-associated wild-type MDH and the soluble MDH-GOX are nearly the same when (S)-phenyllactate is used as substrate. To the best of our knowledge, this is the first example of a membrane-associated protein in which an internal polypeptide segment anchors the protein to the membrane.

Alcohol Oxidoreductases↗

Simulation analysis of triose phosphate isomerase: conformational transition and catalysis.

A theoretical approach is employed to study the catalysis of the dihydroxyacetone phosphate (DHAP) to D-glyceraldehyde 3-phosphate (GAP) reaction by the enzyme triose phosphate isomerase (TIM). The conformational change in a loop involved in protecting the active site from solvent is examined by use of X-ray data and molecular dynamics simulations. A mixed quantum-mechanics and molecular mechanics potential is used to determine the energy surface along the reaction path. The calculations address the role of the enzyme in lowering the barrier to reaction and provide a decomposition into specific residue contributions. To obtain a clearer understanding of the electronic effects, the polarization of the substrate carbonyl group by the active site residues is examined and compared with FTIR measurements on the wild-type and mutant forms of the enzyme.

Amino Acid Sequence↗

Activation of guinea pig eosinophils by human recombinant IL-5. Selective priming to platelet-activating factor-acether and interference of its antagonists.

The potential role of platelet-activating factor (PAF)-acether and of IL-5 as an eosinophil-proliferating, activating, and/or recruiting mediator in asthma led us to study the effects of human (h) rIL-5 (hrIL-5) and PAF-acether, alone or combined, on isolated guinea pig eosinophils. Two populations of eosinophils were separated from peritoneal lavages of polymyxin B-treated guinea pigs upon a discontinuous metrizamide gradient: one of low density (between 20 and 22% of metrizamide, purity: 63 +/- 3%, n = 27) and another of normal density (between 22 and 24% of metrizamide, purity: 87 +/- 2%, n = 16). Chemotactic activity was evaluated on a micro-Boyden chamber, results being expressed as the number of migrating eosinophils (mean +/- SEM) at 40 microns through a cellulose nitrate filter (3 microns pore size) in the presence of the agonist or of the solvent alone. hrIL-5 dose-dependently stimulated normodense eosinophil chemotaxis, reaching a peak at 500 ng/ml (98 +/- 21 migrating eosinophils, n = 5, p less than 0.05). These eosinophils also responded to PAF-acether and to LTB4 and not to FMLP, hrTNF alpha, and LPS. Eosinophil preincubation with hrIL-5 increased significantly the migration by PAF-acether (173 +/- 23 migrating eosinophils with PAF-acether 10 nM after preincubation with hrIL-5 500 ng/ml vs 69 +/- 10 after preincubation with buffer alone, p less than 0.01) and failed to enhance migration by LTB4 or to uncover an activity for FMLP. Migration by PAF-acether was antagonized when the cells were preincubated with the antagonists BN 52021 and WEB 2086, which also inhibited migration by hrIL-5. Eosinophils were auto-desensitized by and to PAF-acether or LTB4, but were not cross-desensitized to each other. Eosinophils desensitized to PAF-acether failed to migrate with hrIL-5, but those desensitized to LTB4 responded to hrIL-5 as controls. hrIL-5 failed to induce the elevation of intracellular free calcium concentration and superoxide anion generation from basal values, whereas preincubation of eosinophils with hrIL-5 induced a significant increase in the rise in intracellular free calcium concentration and in superoxide anion generation by 10 nM PAF-acether but not by LTB4. In conclusion, the in vivo eosinophil migration in allergy may involve hrIL-5, particularly associated to PAF-acether.

Animals↗

Studies of blood lead levels in children by proton-induced X-ray emission (PIXE).

Blood lead levels of children admitted to Sion Hospital, Bombay (India), from the adjoining Dharavi slum areas have been determined by proton-induced X-ray emission (PIXE). Blood samples were collected from 36 children with suspected lead poisoning and from 20 control children. The analysis showed that the lead concentration of the patients varied from 0.1 to 6.0 micrograms ml-1. In addition to lead, K, Ca, Fe, Cu, Zn, Se, Br and Rb were also detected simultaneously, of which the concentrations of Fe, Cu, Zn, Se, Rb and Pb were determined. The high blood lead levels of the children from this area may be ascribed to environmental pollution due to heavy vehicular traffic and industrial sources.

Anemia, Hypochromic↗

Accordion effect in tortuous right coronary arteries during percutaneous transluminal coronary angioplasty.

Coronary spasm and intimal dissection are well-known complications of coronary angioplasty with potentially serious consequences. Their treatments are different and need to be instituted quickly to prevent vessel closure. We report two cases of mechanical deformation caused by the angioplasty hardware masquerading as dissection or spasm during coronary angioplasty of tortuous native right coronary arteries.

Aged↗

LTB4, a potent chemotactic factor for purified guinea-pig eosinophils: interference of PAF-acether antagonists.

Two populations of eosinophils were separated upon a discontinuous metrizamide gradient from peritoneal lavages of polymyxin B-treated guinea-pigs. One population was of low density (between 20 and 22% of metrizamide, purity: 63 +/- 3%, n = 27) and another of normal density (between 22 and 24% of metrizamide, purity: 87 +/- 2%, n = 26). Responses to chemotactic stimuli were studied using a micro-Boyden chamber, results being expressed as the chemotactic index (CI, mean +/- S.E.M.), i.e. the ratio between the number of eosinophils migrating at 40 microns through a cellulose nitrate filter in the presence of the agonist and the number of cells migrating in the presence of the solvent alone. The normal density eosinophils responded more to LTB4 (CI = 19.4 +/- 4.6 with LTB4 10(-8) M; P less than 0.05; n = 9) than to PAF-acether (CI = 6.2 +/- 1.4 with PAF-acether 10(-8) M; P less than 0.05; n = 20). By contrast, low density eosinophils responded less intensely to LTB4 (CI = 7.6 +/- 1.8 with LTB4 10(-8) M; P less than 0.01; n = 6) and to PAF-acether (CI = 2.4 +/- 0.4 with PAF-acether 10(-8) M; P less than 0.05; n = 14). Guinea-pig eosinophils failed to migrate in response to FMLP and lyso PAF-acether.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Estimating left ventricular ejection fraction from two-dimensional echocardiograms: visual and computer-processed interpretations.

Digital echocardiography makes computer-processed estimates of ejection fraction feasible for clinical use but increases physician reading time. The practicabilities were examined by three novice fellows and four experienced attendings. Ejection fraction was visually estimated from playback of videotape or cine-loop displays. Ejection fraction was also estimated from single tracings of endocardium, digitized and applied to biplane Simpson's rule, and expressed in whole units. Differences between fellows' and attendings' visual estimates were close to 0 +/- 6.4 median standard deviation. The 95% confidence intervals for reproducing visual and computer-processed ejection fractions ranged from 15% to 46% of mean ejection fraction; for comparing the two methods, from 7% to 36%. Intraobserver reading errors varied widely and with one observer, systematically, and were independent of experience, but dependent on the quality of signals. Computer-processed readings of ejection fraction should be reserved for images of reasonable quality and for confirming visually estimated ejection fractions between the lower limits of normal (45%-50%) to moderately severely depressed (25%-30%), when accuracy is clinically relevant or when a serial change is at the confidence limits of the reader and needs verification.

Aged↗

Anatomy of a conformational change: hinged "lid" motion of the triosephosphate isomerase loop.

Triosephosphate isomerase (TIM) is used as a model system for the study of how a localized conformational change in a protein structure is produced and related to enzyme reactivity. An 11-residue loop region moves more than 7 angstroms and closes over the active site when substrate binds. The loop acts like a "lid" in that it moves rigidly and is attached by two hinges to the remainder of the protein. The nature of the motion appears to be built into the loop by conserved residues; the hinge regions, in contrast, are not conserved. Results of molecular dynamics calculations confirm the structural analysis and suggest a possible ligand-induced mechanism for loop closure.

Amino Acid Sequence↗

Transferable trimethoprim resistance of shigellae encountered in Vellore (south India).

Shigella flexneri and Sh. shigae which are the two most common shigellae encountered in Vellore (south India) were found to exhibit resistance to trimethoprim and trimethoprim-sulphamethoxazole. Eighty four per cent of this was high level resistance. Transfer studies conducted with these strains indicated that this high level resistance is plasmid mediated.

Drug Resistance, Microbial↗

Interference of the thromboxane antagonist SK&F 88046 with platelet activation and subsequent desensitization by arachidonic acid and the thromboxane mimetics U46619 and EP171.

We have investigated the effects of the thromboxane antagonist SK&F 88046 on human platelet activation and desensitization by arachidonic acid (AA) and by the thromboxane A2 mimetics U46619 or EP171. SK&F 88046 inhibited platelet aggregation and secretion induced by AA, U46619, EP171 and thrombin at low (0.05 U/ml) but not at a high (1 U/ml) concentrations. Platelet inhibition was reversed by washing the cells. Platelets pre-exposed to AA, U46619 or EP171 and then disaggregated with prostacyclin, washed and resuspended, failed to respond with aggregation or secretion to a second challenge by either agonist. In the presence of the endoperoxide/thromboxane receptor antagonist L636499 or of SK&F 88046, pre-exposure to AA, U46619 or EP171 failed to prevent subsequent responses to the related agonists. Our results suggest that SK&F 88046 is a selective antagonist of platelet activation and desensitization induced by TxA2 or prostaglandin endoperoxides and that it may have utility as an anti-platelet drug.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗