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Biomedical subjects

R J Pierce

Publications and source records attributed to R J Pierce.

At least 109 records · Page 6Linked to original sources

Allergens of Schistosoma mansoni. I. Comparison of the IgE response in human and experimental infections towards characterized allergens from adult worm products.

The reaction of adult worm products of Schistosoma mansoni with IgE antibodies in infected human and Fischer rat sera has been studied using the Prausnitz-Küstner test and the radioallergosorbent test. Incubation of worms in water released most of the soluble material reacting with both rat and human sera in the radioallergosorbent test. Sera from infected Fischer rats recognized a fraction with pI 4.9-5.2 separated by preparative isoelectric focusing throughout the time course of infection, whereas human sera reacted with material focusing between pI 4.4 and 6.0. A peak of allergenic activity with an apparent molecular weight between 70,000 and 150,000 was obtained by gel filtration. Human bilharzian sera also reacted with material in the molecular weight range 12,000-25,000. Allergenic material bound specifically to concanavalin A-Sepharose, Lens culinaris agglutinin-Ultrogel, and wheat germ agglutinin-Ultrogel, but substantial allergenic activity was also present in unbound fractions.

Allergens↗

Antigenic properties of Schistosoma mansoni aminopeptidases: evolution during the development in mammalian hosts.

The involvement in the immunity to schistosomiasis of an aminopeptidase activity of schistosomula, 20-day-old and adult worms of Schistosoma mansoni has been studied. This activity, hydrolysing leucine-p-nitroanilide and alanine-p-nitroanilide at pH 7.4 was immunoprecipitated by various infected rat and human sera. These antigenic enzymes were expressed at day 28 after infection in the rat and seemed to be specific for the Schistosoma species. Several aminopeptidase activities were found after analysis by isoelectric focusing of the adult extract but only the pI 8.3 peak was antigenic. Three antigenic peaks were demonstrated after AcA 34 Ultrogel filtration. The biological relevance of these antigenic enzymes in schistosomiasis is discussed.

Aminopeptidases↗

Use of ipratropium bromide in patients with severe airways obstruction.

In ten adult patients with severe, partially reversible airflow obstruction due to asthma, with or without co-existent chronic bronchitis, the acute bronchodilator responses of ipratropium bromide (40 micrograms) and terbutaline (500 micrograms) from metered-dose inhalers, atropine methonitrate (2 mg) as a wet aerosol and placebo were compared in a double blind trial. Also the combination of ipratropium bromide and terbutaline aerosols was compared with both ipratropium and terbutaline alone in short-term and long-term studies. In the short-term study, all the drugs produced significant bronchodilatation compared with placebo. The responses to ipratropium bromide and terbutaline alone were not significantly different. The combination of ipratropium bromide with terbutaline did not produce significantly greater changes in the FEV1, SGaw or static lung volume than terbutaline alone. Atropine methonitrate however, produced significantly greater changes of the airway conductance (SGaw) and static lung volumes (TLC and RV) but not FEV1, when compared to ipratropium bromide. When administered over randomised periods of one month each there were no significant differences between the combination of ipratropium bromide and terbutaline and each drug alone in daily airflometer recordings, daily symptom scores or fortnightly spirometry and clinical assessment. It is concluded that ipratropium bromide, in the conventional dose of 40 microgramm by metered-dose inhaler produces safe, effective bronchodilatation. Its effect, however, did not significantly augment that of the beta adrenergic stimulant, terbutaline and was less than that of atropine methonitrate 2 mg by wet aerosol.

Aerosols↗

Comparison of intravenous and inhaled terbutaline in the treatment of asthma.

In a double-blind crossover controlled study, intravenous (IV) or nebulized terbutaline was given to eight patients with moderately severe asthma on two separate days. Four incremental doses of terbutaline were given by each route to establish a maximal effect. Both routes of administration produced significant increases increases in FEV1, FVC, PEFR, MEF50% single-breath TLC, and effective pulmonary blood flow. A decrease in slope of alveolar argon plateau was observed with both routes, but helium responsiveness showed variable changes with no significant or consistent effect seen. There was no significant difference between responses to incremental doses and maximal response apart from pulse rate, which rose during IV treatment. These results showed that the IV route had no advantage in terms of effectiveness or site of action over the inhaled route. Since IV treatment can produce systemic side effects, inhaled bronchodilator therapy should be used as the route of choice.

Adult↗

Single-exhalation method for study of lobar and segmental lung function by mass spectrometry in man.

A single-exhalation method, based on a modification of the conventional single-breath technique, was applied to study lung function in normal subjects during fiberoptic bronchoscopy. After a single inspiration of a test gas mixture (1% He, 1% C2H2, 0.07% C18O in air), the test gas concentrations were continuously monitored during subsequent slow exhalation, using a respiratory mass spectrometer that sampled either at the lips (Whole-lung test) or, through the bronchoscope, at various sites within the bronchial tree (Regional test). Changes in concentrations of the test gases with time allowed estimation of alveolar ventilation (Va), blood flow (Q), and diffusing capacity (DLCO), per unit accessible lung volume (Va). In the Whole-lung test, both DLCO and Q agreed closely with values obtained in the same subject by a rebreathing method. No differences were observed between the upright and the lateral decubitus positions. In teh Regional test, VA/VA, DLCO/VA and Q/VA were larger in the dependent than in the upper lung, when sampling was from the main bronchi in the lateral decubitus positions. Sampling from lobar bronchi in the upright position revealed an increase from top to bottom in VA/VA, DLCO/CA and Q/VA, this being most marked for Q. These results are compatible with the regional variations that have been shown by radioactive techniques and have been attributed to gravitational forces. The method appears to be suitable for the study of lobar and segmental lung function in patients with lung disease.

Bronchoscopy↗

Radiographic, scintigraphic, and gas-dilution estimates of individual lung and lobar volumes in man.

We describe a method of separately determining the volumes of the right and left lungs from conventional chest radiographs and of determining the volumes of individual lobes and pathological spaces, whenever their boundaries are visible radiologically or can be displayed scintigraphically--for example, during fibreoptic bronchoscopy. Scintigrams of individual lungs, lobes, and segments are obtained by deflecting a stream of air marked with 81m krypton down the suction channel of the bronchoscope into the appropriate bronchus during inspiration, followed by a breath-hold during which the image is recorded with a gamma camera. Both radiographic and scintigraphic methods have been validated by comparison with argon dilution estimates of individual lung and lobar volumes also obtained at bronchoscopy, and results for the three methods in normal subjects are presented. Used in conjunction with bronchoscopic soluble gas uptake studies, these volume measurements permit precise estimation of effective perfusion, tissue and water volume, and gas transfer at lobar and segmental level. Individual lung and lobar volumes can be used to quantify lung and lobar collapse and compression, mediastinal shift, regional ventilation and gas trapping, and phrenic paresis.

Adult↗

A comparative study of atropine methonitrate, salbutamol, and their combination in airways obstruction.

Dose-response relationships of the cholinergic antagonist, atropine methonitrate, and the beta-adrenergic agonist, salbutamol, were examined by cumulative dose techniques. A wet aerosol, 1.5 mg atropine methonitrate produced a maximum response. The response to 200 microgram of salbutamol from a pressurised aerosol was close to maximum. Secondly, the bronchodilator response of salbutamol microgram was compared with atropine methonitrate 2 mg and placebo in 18 asthmatic patients in a randomised crossover study. In 11 of them the bronchodilator response of the combination of salbutamol and atropine methonitrate was evaluated. Atropine methonitrate produced a similar peak bronchodilator effect to salbutamol, but its effect was more prolonged, the response being significantly greater at four and six hours than with salbutamol. The combination of drugs produced a significantly greater and more lasting bronchodilatation than either of the drugs alone. Despite mild side effects, atropine methonitrate, either alone or in combination with an adrenergic drug, appears to have a place in the treatment of sever reversible airway obstruction not adequately controlled by conventional treatment.

Aerosols↗

Estimation of lung volumes from chest radiographs using shape information.

The cross-sectional shapes of the chest and its contained structures have been assessed in post-mortem anatomical sections and from computerised tomographic scans in living subjects. These shapes are described by simple equations that can be used to increase the accuracy of measuring lung volumes from chest radiographs. Radiographic estimates of total lung capacity, using the equations, were compared with plethysmographic and single-breath helium dilution measurements in 35 normal subjects. The postures commonly used for taking chest radiographs were found, on average, to decrease total lung capacity (TLC) and to increase residual volume by about 200 ml when compared with the sitting positions used for the other two measurements (studies made in 18 of the subjects). After correction for this effect, the radiographic estimates of TLC, which measure the displacement volume of the lung, exceeded the plethysmographic estimates of contained gas volume by a mean of 720 ml, which was taken as the volume of tissue, blood, and water in the lungs. The single-breath dilution estimates of TLC fell short of the plethysmographic values by a mean of 480 ml, taken as the volume of contained gas that was inaccessible to helium in 10 seconds. The tomographic studies suggested that the radiographic technique of measuring lung displacement volumes has an accuracy of +/- 210 ml. The method is rapid and simple to use and has intra- and inter-observer variabilities of less than 1% and less than 5% respectively.

Helium↗

Urinary enzyme assays in toxicological studies in the rat and marmoset.

The relative merits of the automated, fluorimetric assay of urinary enzymes and cell exfoliation were compared with other commonly used tests for renal damage. Two types of nephrotoxic agent were used, causing crystal nephropathy and acute tubular necrosis respectively. Groups of marmosets were given one of two drugs known to cause crystal nephropathy. One agent caused intermittent increases in urinary enzyme excretion and an early increase in cell excretion which was not sustained. The second agent in contrast caused elevated cell and enzyme excretion, increasing throughout the period of administration. A nephrotoxic anti-tumour agent also caused increases in cell and enzyme excretion when given to marmosets. The early changes produced by this agent were studied using catheterised rats. Hourly samples of urine were collected and urinary beta-glycosidase excretion was found to give an early indication of renal damage, which correlated with albuminuria and glycosuria. The fluorimetric assay of urinary enzymes provides a sensitive, non-invasive test of nephrotoxicity.

Acetylglucosaminidase↗

Methods of studying lobar and segmental function of the lung in man.

Making the decision whether a patient with chest disease can undergo lung surgery may be easier if the anatomical extent of the disease and the functional effects of resection can be estimated. Although information can be gained by non-invasive physiological studies of lung function of a routine kind, these cannot define the anatomical extent of the disease or distinguish the relative influence of affected and unaffected parts as estimates of lung function. Whole lung ventilation and perfusion scans provide immediate topographic information but have limited resolution and anatomical accuracy, particularly when the architecture of the lung is disturbed by disease. Bronchoscopy gives direct visual information about the more central airways but little or none about the function of the areas they serve. This paper gives brief descriptions of a series of procedures which could help in assessing the feasibility of lung surgery. The size, shape and volumes of individual lungs and lobes can be estimated from plain chest radiographs. Corresponding information about individual segments, and about lobes not delineated by normal X-ray, can be obtained using radio-active krypton 81m and a gamma camera during otherwise routine fibreoptic bronchscopy segments can be determined by simple single-breath manoeuvres at bronchoscopy using a respiratory mass spectrometer. The radio-isotope and spectrometric tests can be obtained in the same breath. The spectrometric tests can be recorded from more than one part of the lung within the same breath. All of the procedures give information in terms of anatomical units of interest to the surgeon.

Adult↗

N-acetyl-beta-d-glucosaminidase in marmoset kidney, serum and urine.

N-Acetyl-beta-D-glucosaminidase activities were determined in homogenates of marmoset kidney, in serum and in urine by using the 4-methylumbelliferyl substrate. The enzyme activity was separated into several components by DEAE-cellulose ion-exchange chromatography, starch-gel electrophoresis and isoelectric focusing. The kidney contained two major forms of the enzyme, A and B, which had similar pH optima and Km values. The A-form bound to DEAE-cellulose at pH 6.8, migrated towards the anode on starch-gel electrophoresis and had a pI of 5.0. The B-form did not bind to DEAE-cellulose at pH 6.8, remained near the origin on starch-gel electrophoresis and had a pI of 7.64. The isoenzymes also differed in heat stability, the B-form being the more stable. Serum contained B-form activity and, in addition, two intermediate forms (I1 and I2) were loosely bound to DEAE-cellulose. The serum A-form activity was less firmly bound to DEAE-cellulose than was the tissue A-form and was designated As. Serum from a pregnant marmoset contained a form which may be analogous to the human P-isoenzyme. Urine contained only a small amount of B-form activity, the majority being present in the A-form. The kidney A- and B-forms both had mol.wts. of 96000--100000 and the activity was predominantly lysosomal. Partial purification of the kidney A isoenzyme was undertaken. Immunoprecipitation studies indicated a relationship between marmoset kidney A-form and human liver A-form activity.

Acetylglucosaminidase↗

The separation and characterization of marmoset kidney beta-D-galactosidase and beta-D-glucosidase.

beta-D-Galactosidase and beta-D-glucosidase activities were determined in homogenates of marmoset kidney by using the appropriate 4-methylumbelliferyl glycoside, beta-D-Galactosidase activity was separated into two main components by ion-exchange chromatography on DEAE-cellulose, starch-gel electrophoresis, isoelectric focusing and gel filtration on Sephadex G-200. One form designated A had a pI of 5.1, was loosely bound to DEAE-cellulose at pH7.0, remained near the origin on starch-gel electrophoresis at pH 7.0 and had an apparent molecular weight of 160000. The second beta-D-galactosidase component, designated B, was associated with the total beta-D-glucosidase activity, had a pI of 4.3, was firmly bound to DEAE-cellulose, migrated rapidly towards the anode on starch-gel electrophoresis and had an apparent molecular weight of 50000. The optimum pH values of beta-D-galactosidase A and B were 4.5 and 6.0 respectively. beta-D-Galactosidase A was activated by 0.1 M-NaC1 but the activity of the B form was inhibited by 1 M-NaC1 at pH 4.5. beta-D-galactosidase had a bimodal distribution, the A form being recovered in the lysosomal fraction whereas the B form was present in the soluble fraction, as was the major portion of the beta-D-glucosidase activity. The lysosomal and soluble forms were further characterized by DEAE-cellulose chromatography.

Animals↗