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Biomedical subjects

R J Pierce

Publications and source records attributed to R J Pierce.

At least 55 records · Page 3Linked to original sources
PubMed1993

Cloning of the gene encoding a Schistosoma mansoni antigen homologous to human Ro/SS-A autoantigen.

A cDNA library was constructed from the mRNA of adult worms of Schistomsoma mansoni in the expression vector lambda gt11 and screened with a rabbit antiserum raised against a 60-65-kDa electroeluted adult worm fraction. Two overlapping clones were selected and a partial nucleotide sequence was deduced (1172 bp). The full-length sequence was obtained by the amplification of the 5' end of first strand cDNA using PCR. The overall mRNA size was 1335 nt including a 25 nt 5' non-coding region and a 131 nt untranslated region with the poly(A) tail. The predicted amino acid sequence of 393 aa (45 kDa) has 52% identity with the human Ro/SS-A autoantigen, which is considered to be the human calreticulin. As for the human Ro/SS-A, the protein encoded by the cDNA described here contains a hydrophobic leader sequence and a carboxyl terminal sequence, HDEL consensus signal sequence for retention in the ER. An antiserum raised against the fusion protein of one clone recognized a 58-kDa antigen in homogenates of cercariae and of adult worms. The expression of the protein in the pGEX-2T fusion system allowed us to show the presence of specific antibodies in S. mansoni infected patients' sera and in the sera of patients with systemic lupus erythematosus, reflecting a cross-immunoreactivity between the S. mansoni protein and the human calreticulin autoantigen.

Amino Acid Sequence↗
PubMed1992

Nebuhaler versus wet aerosol for domiciliary bronchodilator therapy. A multi-centre clinical comparison.

OBJECTIVE: To compare the clinical effectiveness and patient acceptance of a large spacer device (Nebuhaler) for delivery of metered dose aerosol (MDI) terbutaline with nebulised wet aerosol terbutaline. DESIGN: Randomised open crossover study over two sequential four week treatment periods, following a two week run-in. SETTING: Multi-centre including five adult thoracic units and three paediatric centres throughout Australia. PATIENTS: Thirty-eight adults and 23 children with clinical asthma and reversible airflow obstruction (increase in forced expiratory volume in one second [FEV1] of greater than or equal to 15% in response to inhaled bronchodilator) entered the study proper. Six adults and one child withdrew. INTERVENTIONS: Terbutaline was administered four times daily via Nebuhaler/MDI or nebuliser. Clinical assessment with spirometry and peak flow readings was made after run-in and at the end of each treatment period. Patients recorded on diary cards daily peak expiratory flow rates and symptom scores and comparisons of these results for each treatment period were made. At the completion of the study patients answered a treatment preference questionnaire. RESULTS: No differences were found between the two treatment periods in diary card peak flow recordings and symptom score data, and in clinical assessment of spirometry and peak expiratory flow rates. There were also no differences between spirometry and peak flow values recorded at the clinic at randomisation and at the end of each treatment period, suggesting stable basal airflow obstruction over the period of the study. Thirty-two per cent of adults and 52% of children preferred the Nebuhaler/MDI combination, mainly because of convenience of use. Treatment preference was not related to any measured index of lung function. CONCLUSIONS: MDI terbutaline delivered via Nebuhaler provides clinical benefit similar to that of wet aerosol terbutaline in the long-term domiciliary management of patients with stable airflow obstruction.

Adult↗
PubMed1992

Crystallization and preliminary X-ray diffraction studies of a protective cloned 28 kDa glutathione S-transferase from Schistosoma mansoni.

Crystals of the recombinant 28 kDa glutathione S-transferase from Schistosoma mansoni have been obtained by the hanging-drop method of vapor diffusion from ammonium sulfate solutions. The successful crystallization of this enzyme required the presence of a reducing agent and S-hexylglutathione. The crystals belong to the cubic space group P4(1)32 (or P4(3)32), with unit cell dimensions a = 122.6 A and contain one molecule in the asymmetric unit. The crystals diffract to at least 2.8 A resolution and are suitable for X-ray crystallographic structure analysis.

Animals↗
PubMed1992

Immunity after treatment of human schistosomiasis: association between IgE antibodies to adult worm antigens and resistance to reinfection.

Previous studies in school children have demonstrated the slow development with age of resistance to reinfection after chemotherapy of Schistosoma mansoni infections, and have indicated that inappropriate ("blocking") antibody responses prevent the expression of immunity in young children. The present study was designed to investigate further the nature of the protective responses, by serological studies on a group of 151 S. mansoni-infected individuals resident in an endemic area in Machakos District, Kenya. Antibody levels against various antigens in blood samples before treatment were related to intensity of previous infections; antibodies in blood samples taken 6 months after treatment were related to cumulative reinfection rates over the following 30 months. IgE against an adult-worm antigen preparation correlated positively with age and negatively with reinfection. In contrast, IgE antibodies against other life-cycle stages showed either no relationship or the reverse correlation. Furthermore, antibodies of other isotypes against adult-worm antigens showed no correlations with reinfection. The correlation with IgE could be demonstrated for different preparations of adult worms, including a periodate-treated preparation presumptively depleted of carbohydrate epitopes. For both the intact and the periodate-treated preparations, multiple regression analysis of the results for children less than or equal to 16 years old demonstrated an IgE effect after allowing for age, although this effect was not observed in a previously studied group of school children. Western blot analysis of the adult-worm preparation revealed a limited set of antigens recognized by IgE, among which an antigen of 22 kDa was prominent. The qualitative presence of IgE against this antigen could also be shown to be related to a lack of subsequent reinfection.

Adolescent↗
PubMed1992

Inter-species variation of schistosome 28-kDa glutathione S-transferases.

The 28-kDa glutathione S-transferase from Schistosoma mansoni (Sm28GST) is a candidate vaccine antigen. To evaluate the antigenic and phylogenetic variations between the 28-kDa GSTs from 4 species of schistosome, we have cloned and sequenced the 28-kDa GSTs from Schistosoma haematobium (Sh28GST) and Schistosoma bovis (Sb28GST). Sb28GST and Sh28GST are more similar to each other (97%) than to Sm28GST (90%) and particularly to the 28-kDa GST from Schistosoma japonicum (Sj28GST, 77%). Antisera directed against the major Sm28GST epitopes revealed differences in the recognition of the 28-kDa GSTs from the other schistosome species suggesting that these regions have been subjected to evolutionary pressure. The consequences of such species-specific epitopes on the development of a multi-species anti-schistosome vaccine are discussed.

Amino Acid Sequence↗
PubMed1992

Chronic persistent cough: use of ipratropium bromide in undiagnosed cases following upper respiratory tract infection.

The clinical effects of inhaled ipratropium bromide were studied in 14 non-smoking patients with persistent post-viral infective cough employing a controlled double-blind, cross-over trial. Patients were selected if they demonstrated no apparent underlying cause for their persistent cough after appropriate radiological and respiratory function tests including methacholine reactivity and bronchoscopic examination. Inhaled ipratropium bromide (320 micrograms day-1) produced significantly less day and night time cough (P < 0.05) with overall clinical improvement in 12 cases, five of whom had total resolution of their cough. We conclude that ipratropium bromide is an effective treatment in non-smoking adults with protracted cough following clinical upper respiratory tract infection.

Administration, Inhalation↗
PubMed1992

Vaccine strategies against schistosomiasis.

In this review the authors analyze the effector and regulatory mechanisms in the immune response to schistosomiasis. To study these mechanisms two animal models were used, mouse and rat. The mouse totally permissive host like human, show prominent-T cell control in the acquisition of resistance. But other mechanisms like antibody mediated cytotoxicity (ADCC) involving eosinophils and IgG antibodies described in humans, are observed in rats. Also in this animal, it is observed specific IgE antibody high production and blood and tissue eosinophilia. Using the rat model and schistosomula as target, some ADCC features have emerged: the cellular population involved are bone marrow derived inflammatory cell (mononuclear phagocytes, eosinophils and platelets), interacting with IgE through IgE Fc receptors. Immunization has been attempted using the recombinant protein Sm28/GST. Protection has been observed in rodents with significant decrease of parasite fecundity and egg viability affecting the number, size and volume of liver egg granulomas. The association of praziquantel and immunization with Sm28/GST increases the resistance to infection and decreases egg viability. The authors suggest the possibility of the establishment of a future vaccine against Schistosoma mansoni.

Animals↗
PubMed1992

Vaccine strategies against schistosomiasis.

Schistosomiasis, the second major parasitic disease in the world after malaria affects at least 200 million people, 500 million being exposed to the risk of infection. It is widely agreed that a vaccine strategy which could lead to the induction of effector mechanisms reducing the level of reinfection and ideally parasite fecundity would deeply affect the incidence of pathological manifestations as well as the parasite transmission potentialities. Extensive studies performed in the rat model have allowed the identification of novel effector mechanisms involving IgE antibodies and various inflammatory cell populations (eosinophils, macrophages and platelets) whereas regulation of immune response by blocking antibodies has been evidenced. Recent epidemiological studies have now entirely confirmed in human populations the role of IgE antibodies in the acquisition of resistance and the association of IgG4 blocking antibodies with increased susceptibility. On the basis of these concepts, several schistosome target proteins have been identified and their encoding genes cloned. One of them, a schistosome glutathione S-transferase (Sm 28 GST) appears as a promising vaccine candidate. Immunization experiments have shown that two complementary goals can be achieved: (a) a partial but significant reduction of the worm population (up to 60% in rats); (b) a significant reduction of parasite fecundity (up to 70% in mice and 85% in cattle) and egg viability (up to 80%). At least two distinct immunological mechanisms account for these two effects. IgE antibodies appear as a major humoral component of acquired resistance whereas IgA antibodies appear as a major humoral factor affecting parasite fecundity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Angiotensin-converting enzyme in bronchoalveolar lavage fluid in sarcoidosis.

This is the first Australian study of angiotensin converting enzyme (ACE) in bronchoalveolar lavage fluid in 51 patients with sarcoidosis. The aim was: 1) to establish the range of lavage ACE in healthy smokers and non-smoking patients with sarcoidosis. 2) to evaluate the clinical usefulness of lavage ACE. Seventeen control subjects and 51 sarcoid patients all underwent bronchoalveolar lavage, the latter also having 67Gallium scan, spirometry and carbon monoxide uptake. Eighteen patients had all tests repeated six months later. Lavage ACE was significantly higher in sarcoid non-smokers than control non-smokers (p < 0.05). In the 51 sarcoid patients, lavage ACE/albumin ratios were 10-fold higher than serum ACE/albumin ratios (p < 0.0001). In sarcoid patients with raised intrathoracic 67Gallium uptake, lavage ACE was significantly higher than those patients with normal uptake (p < 0.05). Expressing lavage ACE as ACE/albumin ratios reduced the statistical significance of correlations with other parameters, eg, lavage % lymphocytes, and lavage IgG. Lavage ACE levels changed concordantly with lung function 67Gallium scan and lavage lymphocytes, albumin and IgG. However, the wide distribution of lavage ACE in control and sarcoid subjects and the influence of smoking history severely limits its clinical application.

Adult↗
PubMed1991

Inhaled respiratory medications and the use of chlorofluorocarbons (CFCs). Thoracic Society of Australia and New Zealand.

OBJECTIVE: To assess the use of chlorofluorocarbons (CFCs) in metered-dose aerosols against the background of community concerns regarding the adverse environmental effects of CFCs. DATA SOURCES: Data on the constituents of currently available metered-dose aerosols were supplied by the manufacturers, and details of chemistry and safety were obtained from monographs and papers published in the medical literature. STUDY SELECTION: Five papers, published in the early 1970s when metered-dose aerosols first became popular, were reviewed for safety data on CFCs. Several chapters in monographs were searched for data on the nature and function of CFCs in metered-dose aerosols, and five papers were the source of information on alternatives to CFCs as vehicles for the delivery of inhaled respiratory drugs. DATA SYNTHESIS: The medical use of CFCs accounts for only 1.5% of the total production in Australia, the majority being used for refrigeration, air-conditioning and other commercial or industrial purposes. The physicochemical properties of CFCs are such that they function as a suitable storage medium for active drugs within the canister and as an ideal vehicle for drug delivery. Approximately 20 s after inhalation of a clinically recommended dose of a bronchodilator metered-dose aerosol, CFCs are detectable in the blood, but the concentrations decline rapidly (half-life less than 40 s). Although CFCs have been shown to sensitise the myocardium to the arrhythmogenic effects of catecholamines in experimental animals, the requisite concentrations can only be achieved by patients if they inhale from a canister on every breath for approximately 20 successive breaths. CONCLUSIONS: CFCs used in metered-dose aerosols are an effective storage medium and a convenient vehicle for drug delivery. They are non-toxic--unless amounts far in excess of the clinically recommended doses are used, when arrhythmogenic effects may occur. The medical use of CFCs has minimal environmental impact compared with their industrial and commercial use. Dry powder delivery systems offer an alternative approach, and future research will yield nonozone-depleting CFCs suitable for replacing those in current metered-dose aerosols.

Administration, Inhalation↗
PubMed1991

Antigenicity and immunogenicity of a multiple peptidic construction of the Schistosoma mansoni Sm-28 GST antigen in rat, mouse, and monkey. 1. Partial protection of Fischer rat after active immunization.

Among the schistosome proteins characterized as vaccine candidates, an Ag of 28 kDa (Sm-28-GST) has received considerable attention. It was shown to be antigenic in humans and protective in mice, rats, hamsters, and baboons. Synthetic peptides derived from its sequence have been used to characterize the immune response to the molecule and one of these, comprising aminoacids 115-131 has been shown to incorporate both T and B cell recognition sites in a variety of experimental models. An octameric ("octopus") construction of the 115-131 peptide has been synthesized and its antigenicity and immunogenicity have been examined. The octopus construct is immunogenic in rats, mice and baboons in the presence of CFA (for rodents) and Bacille-Calmette-Guérin vaccine (for primates) as adjuvants. This clearly indicates that the construction allowed the conservation of the immune sites of the cognate protein. Moreover, anti-octopus sera from immunized Fischer rats were able to mediate platelet-, macrophage-, and eosinophil-dependent cytotoxicity toward schistosomula. Rats immunized with the 115-131 octopus were partially protected against a challenge infection with Schistosoma mansoni cercariae and this was paralleled by an increased level of IgG and more importantly, of IgE Sm-28-GST-specific antibodies.

Amino Acid Sequence↗