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Biomedical subjects

C Mooney

Publications and source records attributed to C Mooney.

36 records · Page 2Linked to original sources
PubMed1991

Neutrophil activation by Helicobacter pylori.

Helicobacter pylori infection of the stomach is accompanied by a persistent polymorphonuclear leukocyte (PMNL) infiltrate of the mucosa. The aim of this work was to study the activation of human PMNL by substances produced by H pylori. Filtered H pylori conditioned media stimulated a significant PMNL oxidative burst (p less than 0.002). This was equal to 26% of the maximal response stimulated by the PMNL chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 mumol/l). The response to FMLP was prolonged by the combined presence of complement inactivated human anti-H pylori plasma and conditioned medium (p less than 0.002). High pressure liquid chromatography of an extract of conditioned medium showed a fraction that stimulated PMNL, eluted, and antigenically cross reacted with FMLP. Washed H pylori cells, and those opsonised with complement inactivated human anti-H pylori plasma, did not induce a significant oxidative burst. Opsonized H pylori, however, prolonged the oxidative burst induced by FMLP (p less than 0.02). In conclusion, H pylori synthesizes and secretes a substance, probably FMLP, that may account for the PMNL accumulation that accompanies H pylori infections. Immune complexes composed of H pylori antigen and specific antibody potentiate the PMNL oxidative burst. This combination of H pylori derived products, and host PMNL and antibodies, may be involved in the mucosal damage observed in H pylori associated gastritis.

Antibodies, Bacterial↗
PubMed1987

Prescribing digoxin in geriatric units--exercise and redistribution of drug.

In subjects capable of normal everyday activity, exercise has been shown to lower the serum digoxin concentration by increasing uptake into skeletal muscle. A randomized cross-over study of the effect on the serum digoxin concentration of treatments consisting of rest for, or exercise during, 30 min was carried out in 20 elderly patients undergoing rehabilitation. In one patient exercise was associated with a marked (40%) reduction in the serum digoxin concentration. In the remainder there was a very small, but statistically significant, fall in concentration in the exercise as compared with the rest period. Unexpectedly low serum digoxin concentrations in in-patients of geriatric units, may occasionally be an artefact due to temporary redistribution of digoxin.

Aged↗
PubMed1985

Assay of anti-cancer drugs in tissue culture: relationship of relapse free interval (RFI) and in vitro chemosensitivity in patients with malignant cerebral glioma.

One hundred and seventeen patients with cerebral glioma (Kernohan grades III and IV) were treated with adjuvant chemotherapy using procarbazine (PCB), CCNU and vincristine (VCR) following whole head irradiation. Cell cultures were prepared from 40 patients in this series and their sensitivity to each cytotoxic drug was assessed in a mictotitration assay with 35 S-methionine incorporation as the end point. Twenty-two of forty (55%) patients responded to PCB and/or CCNU in vitro, and sensitivity to these drugs was linked with increased RFI, whilst sensitivity to VCR was not. The RFI of patients who had responded to PCB or CCNU in vitro was significantly longer than the RFI of patients whose tumours failed to respond in vitro or patients who had not been tested. There was no difference in sex ratio, extent of operation, radiation dose and degree of steroid cover between responders, non-responders and untested groups. Grade III tumours tended to be more sensitive in vitro than grade IV tumours. The age of patients also influenced in vitro chemosensitivity. Patients with chemosensitive tumours in vitro tended to be younger than patients with insensitive tumours in vitro. Further statistical analysis, taking into account these prognostic factors, indicated an association between chemosensitivity in vitro and RFI.

Adult↗
PubMed1983

The use of buccal partitioning as a model of drug absorption interactions.

Bioavailability describes both the rate and extent of drug absorption. The buccal absorption technique is a useful method for the examination of changed extent of drug absorption resulting from drug absorption interactions. The present work examined the usefulness of drug recovery profiles (after buccal absorption) in evaluating the rate of drug absorption. Recovery data, in the case of propranolol, did not change markedly after marked changes in the drug absorption rate, indicating that recovery profiles are a poor monitoring tool for changed absorption rates. The rate of drug absorption can be found using the buccal absorption method; however, this involves several different experiments on different days and, also, data must be found by measuring the drug in the absorption solution which also contains the interactant. The latter agent may interfere with drug assay procedures. The present work involved the model drug propranolol. Other drugs perhaps may behave differently.

Absorption↗
PubMed1980

The action of human and rabbit serum phospholipase A2 on Escherichia coli phospholipids.

We have compared the properties of phospholipase A (E.C. 3.1.1.4) activity in whole human and rabbit serum toward the phospholipids of Escherichia coli. Using as substrate E. coli labeled during growth with either [1-(14)C]-palmitic acid or [1-(14)C]oleic acid, and then autoclaved to inactivate E. coli phospholipases and to render the labeled phospholipids accessible to exogenous phospholipases, we show that the deacylating activity in both human and rabbit serum is almost exclusively of the A(2) type. Rabbit serum is at least 20-fold more active than human serum. Activity in both sera is maximal at physiological Ca(2+) concentrations (2 mM) and is abolished by ethylenediaminetetraacetic acid. To examine hydrolysis of intact (unautoclaved) E. coli treated with 25% serum, use was made of a phospholipase A-deficient E. coli strain (E. coli S17), thereby eliminating the possible contribution of bacterial phospholipases to degradation. Human and rabbit serum are about equally bactericidal toward E. coli and cause comparable structural damage. However, only rabbit serum produces substantial hydrolysis of the phospholipids of intact E. coli S17. Heated (56 degrees C, 30 min) rabbit serum is non-bactericidal and retains phospholipase A(2) activity toward autoclaved, but not intact E. coli. The ability of heated serum to degrade phospholipids of intact E. coli S17 is restored, however, by adding 25% normal human serum, which is bactericidal. In this combination, doses of heated rabbit serum containing as much phospholipase A(2) activity (toward autoclaved E. coli) as is present in 25% unheated rabbit serum, produce roughly the same extent of hydrolysis of intact E. coli as does normal rabbit serum alone. Low doses with a phospholipase A(2) activity comparable to that of normal human serum elicit little or no hydrolysis. These findings indicate that hydrolysis of the phospholipids of intact E. coli S17 by serum occurs when: 1) the serum is bactericidal, and 2) when sufficient phospholipase A(2) is present. The difference in phospholipid hydrolysis that accompanies killing of E. coli by human or rabbit serum appears to reflect, therefore, the different amounts of phospholipase A(2) activity in the two sera. Phospholipid degradation is not required for the bactericidal action of serum. Bacterial phospholipid breakdown may be important, however, in the overall destruction and digestion of invading bacteria by the host.-Kaplan-Harris, L., J. Weiss, C. Mooney, S. Beckerdite-Quagliata, and P. Elsbach. The action of human and rabbit serum phospholipase A(2) on Escherichia coli phospholipids.

Animals↗
PubMed1978

A comparison of the disturbingness of behaviors related to learning disability and emotional disturbance.

Behaviors thought to be characteristic of emotional disturbance or learning disabilities were investigated through ratings of teachers with regard to the relative disturbingness of the behaviors. Obtained differences suggested that behaviors characteristic of emotional disturbance were rated as more disturbing than those of learning disabilities; differences within sets of characteristic behaviors were also indicated. Results are discussed with regard to implications for teacher expectancies and labeling research.

Adult↗
PubMed1975

Altered phospholipid metabolism in Escherichia coli accompanying killing by disrupted granulocytes.

The effect of bactericidal concentrations of disrupted rabbit granulocytes and of partially purified granulocyte fractions on phospholipid metabolism by Escherichia coli has been investigated. Previous studies in this laboratory have shown that, during and after killing of E. coli by granulocytes, bacterial macromolecular synthesis continues. Similarly, despite almost complete loss of viability within 15 min, incorporation of [1-(14)C]palmitate, [2-(14)C]glycerol, and [1-(14)C]acetate into E. coli phospholipids, in the presence of granulocyte preparations, remains the same as in control E. coli populations for at least 1 h. Incorporation of [1-(14)C]oleate into E. coli phospholipids is actually stimulated during the first 60 min of incubation in the presence of granulocyte preparations (more than twofold at 30 min and 40% at 60 min). With all labeled lipid precursors, bactericidal granulocyte preparations cause a relative increase in the labeling of E. coli cardiolipin, with a corresponding drop in labeled phosphatidyl-glycerol. Labeled lyso-compounds accumulate in the presence of granulocyte preparations when [1-(14)C]palmitate, but not when [1-(14)C]oleate is the labeled precursor. Since oleate occurs mainly in the 2-acyl position of E. coli phospholipids, whereas at least 50% of palmitate occurs in the 1 position, it appears that a phospholipase A(2) acts on the E. coli phospholipids. These various effects are also seen when E. coli are exposed to highly purified granulocyte preparations that possess potent bactericidal and phospholipase A(2) activities. We speculate that this phospholipase A(2) in the granulocyte preparations stimulates oleate but not palmitate incorporation by initiating increased turnover of the fatty acid in the 2-acyl position of E. coli phospholipids, causing formation of 1-acyl lyso-compounds likely to be preferentially reacylated with unsaturated fatty acids.

Acetates↗
PubMed1974

Early and discrete changes in permeability of Escherichia coli and certain other gram-negative bacteria during killing by granulocytes.

Rapid killing of Escherichia coli by intact or disrupted rabbit granulocytes or by granulocyte fractions was found to be accompanied by an equally rapid increase in permeability of the E.coli envelope. This increase in permeability was detected by determining entry of substances that normally do not cross E.coli's permeability barrier, namely actinomycin D and o-nitrophenyl-beta-D-galactopyranoside (ONPG), a substrate for cytoplasmic beta-galactosidase. Because E.coli continue to incorporate radioactively labeled precursors into bacterial RNA and protein for at least 1 h, despite rapid killing by granulocytes, entry of actinomycin D could be measured by its inhibitory effect on macromolecular synthesis. Entry was evident within minutes after exposure to granulocytes or granulocyte fractions and is independent of pH over a range of 6.5-9.0. The effect of disrupted granulocytes or partially purified fractions on susceptibility of E.coli to actinomycin D and entry of ONPG is dose dependent. That the entry of actinomycin D and ONPG was not caused by gross destruction of the envelope is indicated by two sets of observations: (a) net influx of (42)K was maintained for at least 15 min, even though efflux of potassium was immediately accelerated upon addition of bactericidal concentrations of granulocyte fractions; (b) beta-galactosidase did not leak out of E.coli under conditions that produce maximal inhibition by actinomycin D. Different species of gram-negative bacteria exhibited different susceptibilities to the bactericidal and permeability effects of granulocyte fractions. Thus, three strains of E.coli and one strain of Salmonella typhimurium were highly susceptible to both the bactericidal and the permeability enhancing effects of granulocyte fractions, whereas two strains of Serratia marcescens and one strain of Pseudomonas aeruginosa were resistant to both effects. Another strain of P. aeruginosa was rendered susceptible to actinomycin D without being killed and two strains of S. typhimurium remained insensitive to actinomycin D while being killed by granulocytes.

Animals↗
PubMedDate not supplied

Targeting assessments of magnetic resonance imaging in suspected multiple sclerosis.

Decision-analytic methods can be valuable for targeting research in technology assessment. They can indicate whether further evaluation of a technology is warranted, and if so, which variables are key determinants of its clinical utility and cost-effectiveness. This approach was tested on a salient issue--whether magnetic resonance imaging (MR) should be used in evaluating patients with mild neurologic symptoms who might have multiple sclerosis (MS). The authors developed a decision-analytic model to assess the expected utility and costs associated with immediately using MR in this situation, compared with waiting for further symptoms to emerge before testing. Sensitivity analyses demonstrated that priorities for technology assessment research include estimating the value of information to patients in resolving uncertainty, evaluating the impact on patients of being labeled with a diagnosis of MS, and measuring the test characteristics of MR.

Adult↗
PubMedDate not supplied

The accuracy of magnetic resonance imaging in patients with suspected multiple sclerosis. The Rochester-Toronto Magnetic Resonance Imaging Study Group.

OBJECTIVE: To design and implement a methodologically rigorous study to examine the accuracy of magnetic resonance imaging (MRI) in a patient population clinically suspected of having multiple sclerosis (MS). DESIGN AND SETTING: Three hundred three patients, who were referred to two university medical centers because of the suspicion of MS, underwent MRI of the head and double-dose, contrast-enhanced computed tomography (CT) of the head. The images were read by two observers individually and without knowledge of the clinical course or final diagnosis. Patients were followed up for at least 6 months and reevaluated clinically with subsequent neurological examination. Final diagnosis (MS or not MS) was made by a panel of neurologists on the basis of the clinical findings at presentation, those that developed during follow-up, and other diagnostic tests. The results of the imaging procedures were excluded to avoid incorporation bias. Diagnostic accuracy was assessed using receiver-operating characteristic analysis and likelihood ratios. RESULTS: Magnetic resonance imaging of the head was considerably more accurate than CT in diagnosing MS. The area under the receiver-operating characteristic curve for MS was 0.82 (compared with 0.52 for CT) indicating that MRI was a good but not definitively accurate test for MS. A "definite MS" reading on an MRI of the head was specific for MS (likelihood ratio, 24.9) and essentially established the diagnosis, especially in patients clinically designated as "probable MS" before testing. However, MRI of the head was negative for MS in 25% and equivocal in 40% of the patients considered to have MS by the diagnostic review committee (sensitivity, 58%). CONCLUSIONS: Magnetic resonance imaging of the head provided assistance in the diagnosis of MS when lesions were visualized. Its ability far exceeded imaging with double-contrast CT. The sensitivity and, therefore, the predictive value of a negative MRI result for MS were, however, not sufficiently high for a normal MRI to be used to conclusively exclude the diagnosis of MS.

Adolescent↗