Molecular cloning of schistosome genes.
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Animals↗
Biomedical subjects
D W Taylor
Publications and source records attributed to D W Taylor.
Secretion of a malarial histidine-rich protein (Pf HRP II) from Plasmodium falciparum-infected erythrocytes.
Plasmodium falciparum-infected erythrocytes (IRBCs) synthesize several histidine-rich proteins (HRPs) that accumulate high levels of [3H]histidine but very low levels of amino acids such as [3H]isoleucine or [35S]methionine. We prepared a monoclonal antibody which reacts specifically with one of these HRPs (Pf HRP II) and studied the location and synthesis of this protein during the parasite's intracellular growth. With the knob-positive Malayan Camp strain of P. falciparum, the monoclonal antibody identified a multiplet of protein bands with major species at Mr 72,000 and 69,000. Pf HRP II synthesis began with immature parasites (rings) and continued through the trophozoite stage. The Mr 72,000 band of Pf HRP II, but not the faster moving bands of the multiplet, was recovered as a water-soluble protein from the culture supernatant of intact IRBCs. Approximately 50% of the total [3H]histidine radioactivity incorporated into the Mr 72,000 band was extracellular between 2 and 24 h of culture. Immunofluorescence and cryothin-section immunoelectron microscopy localized Pf HRP II to several cell compartments including the parasite cytoplasm, as concentrated "packets" in the host erythrocyte cytoplasm and at the IRBC membrane. Our results provide evidence for an intracellular route of transport for a secreted malarial protein from the parasite through several membranes and the host cell cytoplasm.
Animals↗
Definition of a virulence-related antigen of Neisseria gonorrhoeae with monoclonal antibodies and lectins.
Variants of one strain of Neisseria gonorrhoeae, grown in vivo or in vitro, that have been previously shown to differ in infectivity, serum resistance, and capsule production were compared with use of monoclonal antibodies and lectins. Monoclonal antibodies to virulent gonococci recognized an antigenic site of the lipopolysaccharide (LPS) produced in large amounts by gonococci grown in vivo but present only in a small proportion of in vitro-grown gonococci. This antigen (C-LPS) was found in all 85 different gonococcal isolates studied but not among nonpathogenic neisseriae. It was shared by group B and C meningococci but not by groups A and D. Enzyme-linked immunosorbent assay and Western blot analysis showed that N-acetylglucosamine and N-acetylgalactosamine form part of the epitope. The C-LPS antigen was shown by immunofluorescence to be present on the surface of the gonococci and also free as slime. This antigen appears to confer resistance to killing by normal sera.
Animals↗
Hypertension control in two Canadian communities: evidence for better treatment and overlabelling.
We evaluated the prevalence and control of hypertension in two Canadian cities without university medical centre facilities. A stratified multistage probability sample was selected, and we interviewed 6258 adults between the ages of 30 and 69 inclusive. Blood pressure measurements were obtained during home interviews. Up to two further visits were made to people with untreated blood pressure elevation. By a diagnostic criterion of 90 mmHg, the hypertension prevalence was 114/1000. Six per cent of the hypertensives were undetected, 6% detected but untreated, 17% treated but uncontrolled and 70% were being treated and controlled. Control was better in females and older subjects. These findings show no disadvantages to hypertensives living away from university medical centres. We found a hypertension prevalence of 143/1000 among people who reported being diagnosed as hypertensive but who had normal blood pressure while not on medication. These results suggest a problem with over-labelling of hypertensives.
Adult↗
Genetic influence on the antibody response to antigens of Schistosoma mansoni in chronically infected mice.
Immunoprecipitations of in vitro translation products of mRNA from adult Schistosoma mansoni worms with sera from chronically infected mice of 12 inbred strains reveal a strain-dependent heterogeneity in the antibody responses to schistosome antigens. Of the strains tested the response to the 86K antigen was restricted to mice of haplotypes H-2d H-2k, and H-2a while the 14K antigen was only recognized by H-2k mice. Responses to other antigens revealed the influence of non-H-2 genes on the antibody response although no clear correlation was apparent between the antigens recognized and the non-H-2 genes of the strains. Both dominant and recessive responses towards individual antigens were seen in F1 animals. Some of these results support the cross tolerance model of Ir gene function.
Animals↗
Use of a two-sited monoclonal antibody assay to detect a heat-stable malarial antigen in the sera of mice infected with Plasmodium yoelii.
Antigens, circulating in the blood during malarial infections, have been implicated in immune protection, immunosuppression, and immune-complex formation. We used a monoclonal antibody (MAb 7H8) to identify an antigen (Ag-7H8) in the sera of mice infected with Plasmodium yoelii. The major form of the antigen has a molecular weight of approximately 120,000 in P. yoelii, with minor components of 220,000; 65,000 to 75,000; and 45,000. Ag-7H8 remains antigenic after boiling for 5 min. A two-sited assay was developed with MAb 7H8 that demonstrated that the Ag-7H8 has at least two similar epitopes per molecule. The two-sited assay was used to follow Ag-7H8 in the blood of mice during lethal (strain 17XL) and nonlethal (strain 17XNL) P. yoelii infections. Ag-7H8 appeared on days 6 and 7 after infection with 10(6) and 10(4) 17XL P. yoelii parasites, respectively, and remained until the animals died. It was in plasma samples between days 6 and 14 after 17XNL P. yoelii injections in several inbred strains of mice, regardless of the course of parasitemia. Thus, the kinetics of antigenemia correspond with early stages of infection and not with the number of circulating parasites. Indirect immunofluorescence assays demonstrated that MAb 7H8 detects a cross-reactive antigen in other malarial parasites, including Plasmodium berghei and Plasmodium falciparum. Thus, this two-sited assay may have general application for the serodiagnosis of malaria and may be beneficial in determining the relationship of circulating antigens to malarial immunity.
Animals↗
Clinical trial of common treatments for low back pain in family practice.
The results of a multicentered randomised clinical trial are reported of bed rest and of a physiotherapy and education programme for patients who presented in family practice with an acute episode of low back pain. No beneficial effect of either treatment was observed on several clinical outcome measures, including straight leg raising, lumbar flexion, activities of daily living, and pain. In fact the results favoured early mobilisation over bed rest and suggested that the physiotherapy and education programme was doing more harm than good. Moreover, additional analyses, which focused on clinically interesting patient subgroups, discovered no subset of patients who benefited from either of the treatments under study. Having failed to identify any clinically important benefits, or other explanations for these negative results, we can only conclude that family doctors have little reason to prescribe either bed rest or isometric exercises to patients who suffer from low back pain.
Back Pain↗
The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure.
Cycle and treadmill exercise tests are unsuitable for elderly, frail and severely limited patients with heart failure and may not reflect capacity to undertake day-to-day activities. Walking tests have proved useful as measures of outcome for patients with chronic lung disease. To investigate the potential value of the 6-minute walk as an objective measure of exercise capacity in patients with chronic heart failure, the test was administered six times over 12 weeks to 18 patients with chronic heart failure and 25 with chronic lung disease. The subjects also underwent cycle ergometer testing, and their functional status was evaluated by means of conventional measures. The walking test proved highly acceptable to the patients, and stable, reproducible results were achieved after the first two walks. The results correlated with the conventional measures of functional status and exercise capacity. The authors conclude that the 6-minute walk is a useful measure of functional exercise capacity and a suitable measure of outcome for clinical trials in patients with chronic heart failure.
Aged↗
Should study subjects see their previous responses?
To test the relative merits of administering questionnaires with previous responses available (the informed condition) or unavailable (the blind condition), we administered blind and informed versions of a quality of life questionnaire to two groups of patients. One, a group of 43 stable subjects with chronic cardiorespiratory disease, were seen three times at fortnightly intervals; a separate series of 13 patients with chronic lung disease were evaluated before and after optimization of therapy. In the stable patients the informed strategy resulted in substantial decrease in the variance in the measurement of dyspnea, fatigue, and of emotional function. Large improvements in dyspnea, fatigue, and emotional function seen in patients undergoing treatment optimization were comparable using blind and informed methods. These results suggest that by letting patients see their previous responses we can decrease the sample size needed to detect changes in quality of life in clinical trials.
Aged↗
Thiazides for patients with recurrent calcium stones: still an open question.
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Benzothiadiazines↗
Parasitologic and immunologic studies of experimental Plasmodium falciparum infection in nonsplenectomized chimpanzees (Pan troglodytes).
Parasitologic, hematologic, and immunologic parameters were monitored in intact (nonsplenectomized), adult chimpanzees infected with a "chimp-adapted" strain of Plasmodium falciparum. Following primary and secondary injections of 10(9) P. falciparum-infected erythrocytes, each chimpanzee developed a low grade parasitemia (up to 1,000/mm3) and maintained the infection without evidence of eliminating the parasites. Hematologic and serum biochemical values, as well as the majority of immunologic parameters tested, remained unaltered in infected chimpanzees. However, 2 weeks after infection T cells from infected chimpanzees demonstrated an enhanced response in vitro to stimulation with the mitogen PHA, and monocyte phagocytic activity for antibody-coated erythrocytes (Fc-mediated phagocytosis) increased significantly. During malarial infection, apes developed a strong T cell proliferative response to P. falciparum antigens and monocytes showed enhanced phagocytic activity for P. falciparum-infected erythrocytes in the absence of immune serum. These results suggest that cellular immune mechanisms, especially macrophage activation, may help control, but not eliminate, P. falciparum malaria in chimpanzees.
Animals↗
Identification of surface proteins of juvenile stages of Fasciola hepatica.
Maturation of newly excysted Fasciola hepatica juvenile flukes in mice is accompanied by distinct changes in the pattern of radiolabelling of surface proteins. The major proteins identified on the surface of newly excysted juvenile flukes have apparent molecular weights of 78,000, 45,500, 30,000, 26,000, 13,500, 13,000 and 10,500 as measured by sodium dodecylsulphate polyacrylamide gel electrophoresis. By day 7 after infection the 13,000 molecular weight protein is no longer expressed on the surface of the parasite. By day 14 after infection there is an additional loss of the 78,000, 30,000 and 26,000 molecular weight proteins. It is suggested that these changes may be associated with the temporal variation in distribution of the T0, T1 and T2 granules in the tegument syncytium.
Animals↗
Educational package on hypertension for primary care physicians.
The usefulness of an educational package on hypertension that provides clinically important, up-to-date medical information and office "aids" to primary care physicians was tested in a randomized controlled trial. Fifty-six physicians completed a pretest multiple-choice questionnaire and were allocated at random either to a group that received the educational package (the "study group") or to a control group. There was a highly significant correlation between the pretest scores and the number of years since graduation (r = -0.55, p less than 0.0001), which indicated that younger physicians are more likely than older physicians to have an up-to-date knowledge of the management of hypertension. The increase in knowledge in the study group (17.5%) was significantly greater than that in the control group (2.7%). Furthermore, although the post-test scores in the control group were still significantly correlated with the number of years since graduation, those in the study group were not. It was concluded that although the older physicians knew less than their younger colleagues about hypertension, the use of the educational package significantly increased knowledge, and the increase was not limited by the physician's age.
Age Factors↗
Immunoglobulin isotype distribution of malaria-specific antibodies produced during infection with Plasmodium chabaudi adami and Plasmodium yoelii.
The antibody response of mice to Plasmodium chabaudi adami and Plasmodium yoelii has been compared using a solid phase isotype-specific radioimmunoassay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Serological cross-reactivity between these parasites was substantial. Studies using a radioimmunoassay detecting all classes of malaria-specific antibody demonstrated that during the early part of infection it was not possible to distinguish between homologous and heterologous reactions. Immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that 50% or more of the protein antigens detected were apparently shared by both parasites although the intensity of bands was always greater with homologous reactions. However, the distribution of isotypes in the antibody (Ab) response differed in the two infections. P. chabaudi infections were characterized by a predominant and persistent IgM response, moderate IgG2 and IgG3 and little significant IgG1 response during a primary infection. By contrast, IgM antibodies were transient in P. yoelii infection, IgG2 was the predominant isotype, and both IgG1 and IgG3 antibodies were present during a primary infection. These differences in isotypes were also detected when sera were tested on the heterologous antigen extracts suggesting that antigens shared by P. chabaudi and P. yoelii do not necessarily induce similar antibody responses in the two infections.
Animals↗
Effects of labelling on income, work and social function among hypertensive employees.
Two hundred and thirty hypertensive Canadian steelworkers were followed for 5 years after screening and referral. Data on income, absenteeism and measures of work and social function were collected on these men and on a matched group of 230 normotensive employees. In the fifth year after screening, hypertensive employees earned an average of Can. $1093 less than normotensive employees despite similar incomes in the year before screening. This adverse effect on income was observed regardless of awareness of hypertension at the time of screening or compliance with treatment. Illness-related absenteeism among hypertensives rose in the year following screening and remained elevated for 4 years after screening. Normotensive and hypertensive employees reported similar levels of physical ability and psychological well-being. These findings need verification in other settings before inclusion in cost-effectiveness analyses of the management of hypertension.
Absenteeism↗
Labelling in hypertension: a review of the behavioural and psychological consequences.
Recent evidence has suggested that the detection and treatment of hypertension can result in adverse psychological and behavioural consequences. Furthermore, there is evidence to suggest that these consequences may outweigh the gains in the case of mild hypertension where the benefit of treatment has not yet been established. This paper reviews the literature to date regarding the behavioural and psychological changes which have occurred upon the detection and labelling of hypertension. In addition, an explanation is posed which may resolve some of the contradictory findings with regard to the phenomenon. Finally, a strategy to alleviate, or at least minimize, the deleterious labelling of individuals as "hypertensive" is proposed for testing in future experiments.
Absenteeism↗
Isolation and purification of microfilariae from nodules of Onchocerca volvulus.
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Animals↗
Immunoprecipitation of surface antigen precursors from Schistosoma mansoni messenger RNA in vitro translation products.
Messenger RNA has been isolated from adults and eggs of Schistosoma mansoni and translated in vitro in mRNA dependent rabbit reticulocyte lysate. The in vitro translation products have been immunoprecipitated using a wide variety of hyperimmune and infection sera from rabbits, mice and humans. A large number of in vitro translation products are precipitated by these sera, and we have identified a subset of the immunoprecipitated polypeptides which are expressed on the surface of the young schistosomulum. Messenger RNA from both adults and eggs directs the synthesis of these polypeptides suggesting that at least some of the surface proteins of the young schistosomulum are being synthesised throughout the life cycle. cDNA clone banks prepared from adult mRNA will therefore contain the genes for these schistosomulum surface antigens greatly facilitating their isolation.
Animals↗