Search PubMed⌕ Search

Biomedical subjects

M Eldridge

Publications and source records attributed to M Eldridge.

At least 19 recordsLinked to original sources
PubMed2001

CD14-dependent airway neutrophil response to inhaled LPS: role of atopy.

BACKGROUND: Inhaled endotoxin (LPS) is associated with airway neutrophilic (PMN) inflammation in both asthmatic and control subjects, with asthmatic subjects demonstrating possibly higher sensitivity. CD14 is the principal receptor mediating LPS responses in vivo. It is unknown whether constitutive CD14 can predict the magnitude of the PMN response after LPS inhalation and whether atopy plays a role in this response. OBJECTIVE: We sought to examine associations between constitutive airway CD14 expression and LPS-induced PMNs after 5 microg of LPS inhalation and to examine associations between markers of atopy (eosinophils and eosinophil cationic protein) and CD14 expression and LPS-induced PMNs. METHODS: Ten atopic asthmatic subjects and 8 healthy control subjects inhaled 0.9% saline and LPS (Escherichia coli 026:B6, 5 microg) separated by 3 weeks. Induced sputum was collected at 24 hours before and 6 hours after inhalation. Induced sputum was analyzed for total and differential cell counts and soluble markers (soluble [s]CD14, eosinophil cationic protein, IL8, and total protein). Flow cytometry was used to analyze membrane-bound CD14 expression. RESULTS: Significant associations were found between the LPS-induced PMN response (PMNs per milligram of sputum) and both constitutive sCD14 (R = 0.7, P =.005) and membrane-bound CD14 (R = 0.9, P =.01). Asthmatic subjects demonstrated significantly higher levels of constitutive sCD14 compared with control subjects, and baseline eosinophils were significantly associated with baseline sCD14 (R = 0.7, P =.01) and LPS-induced PMNs (R = 0.6, P =.03). CONCLUSION: Constitutive airway CD14 expression can predict the magnitude of the PMN response after inhaled LPS. Atopy appears to play a role in the level of CD14 expression and may contribute to LPS sensitivity in asthmatic subjects.

Administration, Inhalation↗
PubMed2001

From molecular activities and processes to biological function.

This paper describes how biological function can be represented in terms of molecular activities and processes. It presents several key features of a data model that is based on a conceptual description of the network of interactions between molecular entities within the cell and between cells. This model is implemented in the aMAZE database that presently deals with information on metabolic pathways, gene regulation, sub- or supracellular locations, and transport. It is shown that this model constitutes a useful generalisation of data representations currently implemented in metabolic pathway databases, and that it can furthermore include multiple schemes for categorising and classifying molecular entities, activities, processes and localisations. In particular, we highlight the flexibility offered by our system in representing multiple molecular activities and their control, in viewing biological function at different levels of resolution and in updating this view as our knowledge evolves.

Animals↗
PubMed1996

Karyotype and nuclear DNA content of the Australian lungfish, Neoceratodus forsteri (Ceratodidae: Dipnoi).

The karyotype of the lungfish, Neoceratodus forsteri, is described as 2n = 54, comprising 3 pairs of very large metacentrics, 1 pair of large submetacentrics, 13 pairs of smaller acrocentrics, and 10 pairs of microchromosomes. In addition to centromeric constitutive heterochromatin, C-bands were located on the arms of almost all of the macrochromosomes. The nuclear DNA content of N. forsteri was confirmed as being high (98.6-111.9 pg/nucleus).

Animals↗
PubMed1995

Evidence for two distinct azurins in Alcaligenes xylosoxidans (NCIMB 11015): potential electron donors to nitrite reductase.

We have isolated two type 1 copper-containing proteins (M(r) approximately 13K) from Alcaligenes xylosoxidans (NCIMB 11015) grown under denitrifying conditions. Amino acid sequence analysis of these two proteins shows one to be the previously identified azurin (Ambler, 1971), which we shall call azurin I, and the other to be a related, but previously undescribed, blue copper protein which we show to also be an azurin and propose to call azurin II. Thus, NCIMB 11015 becomes the second system where two distinct azurins are found, the other being Methylomonas J (Ambler & Tobari, 1989). On isoelectric focusing, azurin I migrates very similarly to the previously identified azurin from this organism while azurin II migrates similarly to azurin purified from Alcaligenes denitrificans NCTC 8582. The sequence of azurin II is 33% different than the azurin I sequence but is only 11% different than the azurin from Alcaligenes denitrificans NCTC 8582. Optical spectra for the two proteins are very similar with epsilon mM values of 6.27 and 5.73 mM-1 cm-1 for azurin I and II, respectively, at lambda max approximately 620 nm. The 291 nm shoulder normally ascribed to the hydrophobic nature of tryptophan 48 is clearly observed in azurin I but is missing in azurin II. Amino acid analysis confirms that this tryptophan is missing in azurin II. Azurin I and azurin II show essentially the same redox potential of 305 +/- 10 mV at pH 7.5 and are equally effective electron donors to the purified dissimilatory nitrite reductase of Alc. xylosoxidans in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcaligenes↗
PubMed1994

Interleukin-1 beta and tumor necrosis factor-alpha synergistically induce NO synthase in rat vascular smooth muscle cells.

Cytokine-inducible nitric oxide (NO) production has been implicated in the pathogenesis of septic shock. The present study was designed to determine which cytokines induce expression of the NO synthase gene in rat aortic vascular smooth muscle cells (VSMC) in vitro and whether NO synthase gene expression is inducible in vivo. NO synthase mRNA appeared after 4-h exposure to interleukin-1 beta (IL-1 beta), and levels continued to increase up to 24 h. Levels of NO synthase transcripts were greatest in VSMC treated with IL-1 beta (1 nM), lower in VSMC treated with Escherichia coli lipopolysaccharide (LPS; 100 micrograms/ml), and just detectable in VSMC treated with tumor necrosis factor-alpha (TNF-alpha; 1 nM). IL-1 beta, TNF-alpha, and LPS each induced NO synthase activity, assessed by release of nitrite, conversion of L-arginine to L-citrulline, and increased levels of guanosine 3',5'-cyclic monophosphate, whereas IL-2, IL-6, and interferon-gamma were ineffective. IL-1 beta was more potent and effective than TNF-alpha; however, submaximal concentrations of TNF-alpha acted synergistically with IL-1 beta to induce NO synthase gene expression and activity. Inducible NO synthase mRNA was present in aorta from rats 6 h after treatment with LPS (5 mg/kg), but not at 24 h. Synergistic activation of NO synthase gene expression in VSMC by IL-1 beta and TNF-alpha may contribute to hypotension in sepsis.

Amino Acid Oxidoreductases↗
PubMed1991

Iron absorption in hypotransferrinemic mice.

We used a unique animal model, the hypotransferrinemic (Htx) mouse, to examine the role of transferrin (Tf) in gastrointestinal iron uptake. Despite the absence of Tf, Htx animals hyperabsorb iron. Transfusion of red blood cells sufficient to normalize the hematocrit and reticulocyte count resulted in a return of iron absorption to normal values. These studies indicate that Tf does not play an obligate role in iron absorption, either as a carrier or as a humoral signal regulating absorption. Transfer of plasma or whole blood from Htx mice or from other animal models of iron hyperabsorption to normal mice did not cause an increase in iron absorption in recipient animals. Using the plasma or blood transfer approach, we have been unable to detect a humoral regulator of gastrointestinal iron absorption.

Animals↗
PubMed1989

Effect of chest wall oscillation on mucus clearance: comparison of two vibrators.

This study was designed to investigate the effect of an experimental low-energy chest wall oscillator and of a commercial chest percussor on central airway mucociliary clearance. Five normal dogs were anesthetized, intubated, and placed supine in a trough to which the oscillator or percussor was mounted. Tracheal mucus velocity (TMV) was measured by radiopaque particle or charcoal spot movement. The commercial percussor (a fixed sinusoidal device) used at its minimum frequency of 40 Hz, produced a mean (+/- SE) maximum expiratory flow rate of 0.25 +/- 0.04 L/sec at the airway opening, and had no measurable effect on TMV. The experimental oscillator, when operated at a level sufficient to generate flows of 2-3 L/sec, and with an unbiased 13-Hz sine wave (estimated energy, 150 W), increased mean TMV to 204 +/- 13% of control (P less than 0.003); the percent increase was independent of baseline TMV. We conclude that moderate oscillatory power applied to the chest wall can enhance mucus clearance in central airways, but that currently available commercial percussors may not meet the mechanical requirements for this effect.

Animals↗
PubMed1988

Nedocromil sodium in allergen-induced bronchial responses and airway hyperresponsiveness in allergic sheep.

We examined the effects of nedocromil sodium, a new drug developed for the treatment of reversible obstructive airway disease, on allergen-induced early and late bronchial responses and the development of airway hyperresponsiveness 24 h after challenge in nine allergic sheep. On occasions greater than 2 wk apart the sheep were treated with 1) placebo aerosol (buffered saline) before and 3 h after antigen challenge, 2) an aerosol of nedocromil sodium (1 mg/kg in 3 ml buffered saline) before antigen challenge and placebo 3 h after challenge, and 3) placebo aerosol before and nedocromil sodium aerosol 3 h after challenge. Early and late bronchial responses were determined by measuring specific lung resistance (sRL) before and periodically after challenge. Airway responsiveness was assessed by determining from dose-response curves the carbachol concentration (in % wt/vol) that increased sRL to 5 cmH2O/s. In the placebo trial, antigen challenge resulted in early and late increases in sRL over a base line of 353 +/- 32 and 131 +/- 17% (SE), respectively. Both early and late increases in sRL were blocked (P less than 0.05) when the sheep were pretreated with nedocromil sodium. When nedocromil was given after the early response, the late response was reduced significantly. Eight of nine sheep developed airway hyperresponsiveness 24 h after antigen challenge. In these eight sheep, carbachol concentration before antigen challenge was 2.6 +/- 0.3%, 24 h later carbachol concentration was significantly lower (1.8 +/- 0.3%). Both nedocromil sodium treatments blocked (P less than 0.05) this antigen-induced airway hyperresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1987

Nitrogenase of Klebsiella pneumoniae. Rhodanese-catalysed restoration of activity of the inactive 2Fe species of the Fe protein.

The inactive 2Fe species of the Fe protein of the nitrogenase of Klebsiella pneumoniae was generated by treating oxidized Fe protein (Kp2) with MgATP and chelator. Incubation of the 2Fe species of Kp2 with the sulphurtransferase rhodanese in the presence of thiosulphate, ferric citrate and reduced lipoate reproducibly restored activity. The extent of restoration of activity depended on the molar ratio of 2Fe Kp2 to rhodanese and was time-dependent. Re-activation did not occur in the reaction mixture lacking rhodanese.

Enzyme Activation↗
PubMed1987

Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis.

Genetically hypotransferrinemic mice accumulate iron in the liver and pancreas. A similar pattern of tissue iron accumulation occurs in humans with hereditary hemochromatosis. In both disorders, there is a decreased plasma concentration of apotransferrin. To test the hypothesis that nontransferrin-bound iron exists and is cleared by the parenchymal tissues, the tissue distribution of 59Fe was studied in animals lacking apotransferrin. Two groups of animals were used: normal rats and mice whose transferrin had been saturated by an intravenous injection of nonradiolabeled iron, and mice with congenital hypotransferrinemia. In control animals, injected 59Fe was found primarily in the bone marrow and spleen. In the transferrin iron-saturated animals, injected 59Fe accumulated in the liver and pancreas. Gastrointestinally absorbed iron in hypotransferrinemic or transferrin iron-saturated mice was deposited in the liver. This indicates that newly absorbed iron is released from mucosal cells not bound to transferrin. Clearance studies demonstrated that transferrin-bound 59Fe was removed from the circulation of rats with a half-time of 50 min. In transferrin iron-saturated animals, injected 59Fe was removed with a half-time of less than 30 s. Analysis of the distribution of 59Fe in serum samples by polyacrylamide gel electrophoresis demonstrated the presence of 59Fe not bound to transferrin. These results demonstrate the existence of and an uptake system for non-transferrin-bound iron. These observations support the hypothesis that parenchymal iron overload is a consequence of reduced concentrations of apotransferrin.

Animals↗
PubMed1984

Effect of patent ductus arteriosus on lower extremity blood flow velocity patterns in preterm infants.

We used a 20-MHz, range-gated, pulsed Doppler device to measure noninvasively femoral artery blood flow velocity patterns in 24 preterm infants with patent ductus arteriosus (PDA). Mean spatial flow velocity and its temporal average were recorded by illumination of the entire flow stream. Peak systolic forward flow velocity (Vs), peak diastolic retrograde flow velocity (VD), mean flow velocity (Vf), and the peak to peak-mean velocity ratio, (VS-VD)/Vf, were determined serially in each patient. The changes in the femoral flow velocity pattern preceded or coincided with other evidence of ductal left to right shunting. Prior to PDA closure, (VS-VD)/Vf averaged 14.1 and Vf averaged 4.4 cm/sec; after ductal closure, (VS-VD)/Vf fell to 3.7 (P less than .001) and Vf rose to 9.1 cm/sec, more than twice the preclosure value (P less than .001). Large diastolic reverse flow velocity vectors and low mean velocity correlated with large left to right PDA shunts estimated from other methods of assessment. The noninvasive femoral artery Doppler approach detects patency of the ductus early in life, reflects left to right shunting in diastole, and emphasizes the impact of the PDA on systemic blood flow.

Blood Flow Velocity↗
PubMed1982

Noninvasive pulsed Doppler determination of cardiac output in neonates and children.

Mean blood flow velocity (VAo) in the ascending aorta was measured noninvasively in 33 children, ages 3 days to 17 years, by pulsed Doppler technique at the time of cardiac catheterization. Measurements were made from a suprasternal approach with a portable, range-gated device. The ascending aortic diameter was determined echocardiographically and aortic cross sectional area calculated (A = pi d2/4 cm2). Aortic flow (QAo) was computed from Doppler recordings: QAo (ml/minute) = VAo (cm/second) X A (cm2) X 60 (second/minute). Values were compared with cardiac outputs determined according to the Fick principle, using measured oxygen consumption calculated oxygen capacity, and oxygen saturation. Subjects with aortic valve abnormalities or left ventricular outflow tract obstruction were excluded from study. Agreement between the two methods was excellent (linear regression r = 0.98, slope = 1.07, y-intercept = -4.5 ml, range 403 to 5.540 ml/minute). The Doppler technique is a quick, noninvasive, and accurate method of determining ascending aortic blood flow in neonates and children.

Adolescent↗
PubMed1981

Hemodynamics after microsurgical anastomosis: the effects of topical lidocaine.

The hemodynamics in the femoral arteries of 30 rats were measured with a 20-MHz pulsed Doppler velocity meter (PUDVM) in an attempt to define the changes resulting from anastomosis and to assess the effects of 1% lidocaine on those changes. Control values were obtained, the arteries were severed and anastomosed, and either physiologic saline or 1% lidocaine was applied topically to the vessels in a randomized blind study. Velocity measurements, derivations of vessel lumen diameters, and calculations of blood flow then were made with the velocity meter at intervals of 1,2,3,5, and 10 minutes after the addition of the experimental fluid. The measurements obtained indicated that calculated blood flow through the anastomoses was reduced 36% at the 10-minute interval in the group treated with physiologic saline but only 5% in the group treated with 1% lidocaine. These results demonstrate that microsurgical anastomosis adversely effects normal hemodynamic variables, but these effects are minimized by the application of a bolus of 1% lidocaine, a topical vasodilator. These results also suggest that the 20-MHz PUDVM has sufficient resolution and sensitivity to provide the measurements of blood velocity necessary for reproducible calculations of blood flow distal to a microsurgical anastomosis in small vessels.

Animals↗
PubMedDate not supplied

Representing and analysing molecular and cellular function using the computer.

Determining the biological function of a myriad of genes, and understanding how they interact to yield a living cell, is the major challenge of the post genome-sequencing era. The complexity of biological systems is such that this cannot be envisaged without the help of powerful computer systems capable of representing and analysing the intricate networks of physical and functional interactions between the different cellular components. In this review we try to provide the reader with an appreciation of where we stand in this regard. We discuss some of the inherent problems in describing the different facets of biological function, give an overview of how information on function is currently represented in the major biological databases, and describe different systems for organising and categorising the functions of gene products. In a second part, we present a new general data model, currently under development, which describes information on molecular function and cellular processes in a rigorous manner. The model is capable of representing a large variety of biochemical processes, including metabolic pathways, regulation of gene expression and signal transduction. It also incorporates taxonomies for categorising molecular entities, interactions and processes, and it offers means of viewing the information at different levels of resolution, and dealing with incomplete knowledge. The data model has been implemented in the database on protein function and cellular processes 'aMAZE' (http://www.ebi.ac.uk/research/pfbp/), which presently covers metabolic pathways and their regulation. Several tools for querying, displaying, and performing analyses on such pathways are briefly described in order to illustrate the practical applications enabled by the model.

Cell Physiological Phenomena↗