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Biomedical subjects

M G Taylor

Publications and source records attributed to M G Taylor.

At least 55 records · Page 3Linked to original sources
PubMed1995

Field evaluation of an improved Kato-Katz thick smear technique for quantitative determination of helminth eggs in faeces.

A new method for the quantification of helminth eggs in faeces was developed, in which 7.5% nigrosin in 10% formaldehyde mixed with 5% eosin yellow in 10% formaldehyde was substituted for the malachite green solution used in the standard Kato-Katz method. This modification revealed the eggs of parasites like Schistosoma mansoni, Ascaris lumbricoides, Trichuris trichiura and hookworms distinctly. The slides made with this new technique could be accurately read within one hour. Faecal smears from 100 pupils in Kigungu, Entebbe, Uganda, were studied with both methods. The egg counts of S. mansoni, A. lumbricoides and T. trichiura by both methods were equal. The modified method, however, showed significantly higher hookworm egg counts (p < 0.001). Hookworm eggs were equal one hour after preparation of the slides as 16 hours after preparation. The intensity of infection detected was higher with the modified method for both S. mansoni and hookworms.

Ancylostomatoidea↗
PubMed1994

The effect of multiple transfers of immune serum on maturing Schistosoma bovis infections in calves.

To investigate the role of humoral factors in immunity, serum from cattle with naturally acquired immunity to Schistosoma bovis was injected intraperitoneally into calves that had been infected 4 weeks earlier with 10,000 S. bovis cercariae. Serum was injected weekly until 12 weeks post-infection to a total of 4,500 ml per calf and controls received normal serum or saline. No significant difference in worm or in faecal or tissue egg counts were seen in the three groups of recipients in spite of the observation that the serum donors had proved highly resistant to experimental challenge. In a second experiment, pre-infection or 4-, 8- or 12-week post-infection serum from donors given a single experimental infection with 10,000 S. bovis cercariae was injected intraperitoneally into groups of calves that had been infected 4 weeks earlier with 20,000 S. bovis cercariae. Injections were given weekly up to week 10 post-infection to a total of 2000-3500 ml serum per calf. In calves injected with immune serum there was a reduction in faecal and tissue egg counts and in the numbers of worms recovered as compared with the controls. In recipients of 8- and 12-week serum the reductions in faecal and tissue egg counts were higher than those in worm recovery, suggesting that 8- and 12-week post-infection sera contained factors capable of causing, in addition to worm death, suppression of worm fecundity. This provides further evidence of the importance of fecundity suppression in immunity to schistosomiasis.

Animals↗
PubMed1994

Aortic compliance measured by non-invasive Doppler ultrasound: application of a personal computer based MkII system and its repeatability.

A non-invasive pulse-wave-velocity Doppler ultrasound technique for the assessment of aortic compliance is described. A computational approach for correcting for the effect of non-chronic changes in blood pressure is considered and applied to compliance measurements performed on an age-select cohort of 70 normotensive, normal healthy volunteers. In order to permit the wider availability of the pulse-wave-velocity Doppler ultrasound technique, the authors have developed a MkII system based on a standard 80486/33 MHz IBM compatible WINDOWS based personal computer; real-time spectral analysis being achieved using a relatively inexpensive but fast analogue to digital signal processing card. An overview of the new apparatus is provided and verification work to compare the repeatability of the MkI and MkII systems is described. Medical disorders such as atherosclerosis, diabetes mellitus, familial hypercholesterolaemia, growth hormone deficiency, and Ehlers-Danlos and Marfan's syndromes have all been shown to affect arterial wall compliance. We suggest that the in vivo clinical measurement of blood pressure corrected aortic distensibility using the MkII system may be a useful, reproducible, non-invasive tool for assessing such patients' susceptibility to atheromatous arterial disease as well as for monitoring their response to therapeutic interventions. Measurements in the aorta may be especially pertinent since the natural history of fatty streaks there tends to parallel that in the coronary vasculature thereby potentially affording a convenient surrogate estimate of coronary heart disease.

Aorta↗
PubMed1994

Calcium magnesium phosphate granules: atomistic simulations explaining cell death.

1. A large number of invertebrates have cells that produce intracellular granules of amorphous calcium magnesium phosphates that are thought to act as ion stores or sites of metal detoxification. 2. The interatomic potentials and force constants have been calculated for these ions, and computer simulations of the crystal lattices have been used to determine the effects of ion substitutions on these lattice energies. 3. The results provide insights into the mechanisms of granule formation and the effects of ion substitutions on cell physiology.

Animals↗
PubMed1994

Schistosomiasis vaccines: Farewell to the God of Plague?

Control and even eradication of schistosomiasis have been achieved in some countries using integrated measures but this disease remains endemic in 74 countries with 600 million at risk of whom 200 million are currently infected. The application of control measures, particularly population-based chemotherapy, has in many countries greatly reduced the incidence of serious disease manifestations, but vaccines are urgently needed to supplement existing control measures. Great advances are being made in vaccine development and the first clinical trials are expected to begin shortly.

Animals↗
PubMed1993

High-resolution mapping of the HyHEL-10 epitope of chicken lysozyme by site-directed mutagenesis.

The complex formed between hen egg white lysozyme (HEL) and the monoclonal antibody HyHEL-10 Fab fragment has an interface composed of van der Waals interactions, hydrogen bonds, and a single ion pair. The antibody overlaps part of the active site cleft. Putative critical residues within the epitope region of HEL, identified from the x-ray crystallographic structure of the complex, were replaced by site-directed mutagenesis to probe their relative importance in determining affinity of the antibody for HEL. Twenty single mutations of HEL at three contact residues (Arg-21HEL, Asp-101HEL, and Gly-102HEL) and at a partially buried residue (Asn-19HEL) in the epitope were made, and the effects on the free energies of dissociation were measured. A correlation between increased amino acid side-chain volume and reduced affinity for HELs with mutations at position 101 was observed. The D101GHEL mutant is bound to HyHEL-10 as tightly as wild-type enzyme, but the delta delta Gdissoc is increased by about 2.2 kcal (9.2 kJ)/mol for the larger residues in this position. HEL variants with lysine or histidine replacements for arginine at position 21 are bound 1.4-2.7 times more tightly than those with neutral or negatively charged amino acids in this position. These exhibit 1/40 the affinity for HyHEL-10 Fab compared with wild type. There is no side-chain volume correlation with delta delta Gdissoc at position 21. Although Gly-102HEL and Asn-19HEL are in the epitope, replacements at these positions have no effect on the affinity of HEL for the antibody.

Amino Acid Sequence↗
PubMed1993

Validation and reproducibility of pressure-corrected aortic distensibility measurements using pulse-wave-velocity Doppler ultrasound.

A non-invasive Doppler ultrasound technique is described for the assessment of aortic compliance based on the in vivo measurement of pulse wave velocity along the thoraco-abdominal aortic pathway. A structured protocol, which has been developed to improve the reproducibility of the technique, is validated. A method of correcting for the effect of non-chronic changes in blood pressure on arterial elasticity is considered and applied to compliance measurements performed on 66 normal, healthy volunteers. The results of a study to ascertain the overall reproducibility of the method are provided and problems associated with the technique are discussed. Medical disorders such as atherosclerosis, diabetes mellitus, familial hypercholesterolaemia and growth hormone deficiency have all been shown to affect arterial wall compliance. It is suggested that the in vivo measurement of pressure-corrected aortic distensibility may be a useful, non-invasive tool for assessing such patients' susceptibility to atheromatous arterial disease and for monitoring their response to therapy. Measurements in the aorta may be especially pertinent since the natural history of fatty streaks there tends to parallel that in coronary arteries thereby potentially affording a convenient surrogate estimate of coronary heart disease.

Adolescent↗
PubMed1993

Mechanisms involved in the loss of antibody-mediated adherence of macrophages to lung-stage schistosomula of Schistosoma mansoni in vitro.

Sera from rabbits vaccinated with irradiated cercariae mediated cell (P388D1 or mouse peritoneal macrophage) adherence to lung-stage schistosomula (LS) but such antibody-mediated cell adherence was short-lived in contrast to cell adherence to mechanically transformed schistosomula (MS). Thus LS lost 50% of their adherent cells within 3-6 h in culture and up to 90% by 24 h, whereas adherence to MS was undiminished during this time. Rapid loss of adherent cells was unique to schistosomula that had developed to the lung stage because schistosomula recovered from the skin up to 3 days post-infection did not exhibit the rapid cell loss shown by 3-day LS. To determine whether cell loss was caused by loss of surface antigenicity during culture LS were cultured on their own for up to 24 h and at various intervals samples of schistosomula were tested for antigenicity by addition of immune serum and cells. Levels of adherence to both MS and LS were maintained throughout the incubation period. When antibody-opsonized schistosomula were washed and indicator cells added at progressive intervals, persistence of adherence was again demonstrated, showing that antibody binding to LS had not promoted surface antigen loss or degradation of bound antibody. It was then shown, by adding fresh macrophages to cultures up to 24 h old that LS which had lost their adherent cells nevertheless retained bound antibody, and comparison of adherence of 'used' and 'fresh' cells to MS and LS showed that the cytoadherence properties of macrophages were not significantly reduced during their culture with LS from which cells had been lost.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Suppression of Schistosoma bovis egg production in cattle by vaccination with either glutathione S-transferase or keyhole limpet haemocyanin.

Two of the antigens which have shown vaccine potential in animal experiments against Schistosoma mansoni are glutathione-S-transferase (GST) and GP38, protective epitopes of which are shared with keyhole limpet haemocyanin (KLH). We therefore tested S. bovis GST and KLH for vaccine efficacy against S. bovis in the natural Zebu cattle host. In a preliminary experiment three vaccinations with a total of 1.39 mg of native GSTs of S. bovis induced specific antibody at the time of challenge as detected by Western blotting and ELISA and mean faecal egg counts between weeks 6-10 post-challenge were reduced by 56.4 to 82.5% compared to non-vaccinated controls. Mean adult worm recoveries and tissue egg densities in large intestine and liver samples were also reduced in the vaccinated group, but these differences were not statistically significant. In a subsequent experiment one group of calves was vaccinated with a similar schedule to that used above; a second group of calves was given only two injections of GST (total 0.48 mg protein); a third group of calves was vaccinated twice with a total of 2.0 mg KLH in PBS. All three vaccination schedules induced specific antibody. Both GST vaccination schedules induced significant reductions in faecal egg counts compared to non-vaccinated controls and in this experiment tissue egg densities were also significantly reduced. A striking finding, however, was that adult worm counts were not reduced by vaccination. An essentially similar outcome resulted from KLH vaccination, since there were significant reductions in faecal and tissue egg counts in the absence of a reduction in adult worm numbers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1993

A blood pressure independent index of aortic distensibility.

A non-invasive Doppler ultrasound technique for the assessment of aortic compliance based on the in vivo measurement of pulse wave velocity along the thoraco-abdominal aortic pathway is described. An approach for correcting for the effect of blood pressure on aortic compliance is considered. The derivation of an index of distensibility, Cp, which is independent of blood pressure is provided and applied to data collected from 58 normal, healthy volunteers. Medical disorders such as atherosclerosis, diabetes mellitus and familial hypercholesterolaemia have all been shown to affect arterial distensibility. We suggest that the clinical measurement of Cp may be a useful, non-invasive tool for assessing such patients' susceptibility to atheromatous arterial disease as well as for monitoring their response to therapy.

Adolescent↗
PubMed1993

An alternative approach to the semi-quantitative assessment of the transplanted renal artery velocity sonogram.

There are theoretical problems with the use of resistance based indices, i.e. pulsatility index (PI) or resistive index (RI) as stand alone measures in the renal allograft. PI and RI are heart rate dependent and input pressure dependent for autoregulating organs. A new non-invasive index, termed Pz, has been proposed. Pz may be thought of as the arterial back pressure generated by the kidney representing the pressure which needs to be overcome in perfusing the glomeruli. On a theoretical basis Pz can be shown to be independent of heart rate and resistance and to allow for variations in mean systemic blood pressure. In an initial study, a group of 53 well functioning renal allografts demonstrated a significant reduction in the coefficient of variance for Pz (12.8%) when compared to PI (25.4%). A second study on recently transplanted allografts indicated that acute tubular necrosis could not be separated from rejection on the basis of Pz. Pz did however consistently perform better than PI in terms of reduced variability within pathological groups. We conclude that Pz is more useful than PI in this application.

Blood Flow Velocity↗
PubMed1992

Non-invasive Doppler ultrasound technique for the in vivo assessment of aortic compliance.

A non-invasive Doppler ultrasound technique for the assessment of aortic compliance is described. This is based on the in vivo measurement of pulse wave velocity along the thoraco-abdominal aortic pathway. A structured protocol has been developed to improve the reproducibility of the technique as well as for the purposes of operator training. Preliminary results of a study of both the intra- and inter-observer variability of the method are provided and problems associated with the technique are discussed. Medical disorders such as atherosclerosis, diabetes mellitus and familial hypercholesterolaemia have all been shown to affect arterial wall compliance. We suggest that the measurement of aortic compliance in vivo may be a useful, non-invasive tool for assessing these patients' susceptibility to atheromatous arterial disease and for monitoring their response to therapy.

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

Evaluation of an enzyme linked immunosorbent assay (ELISA) using Schistosoma mansoni soluble egg antigen as a diagnostic tool for Schistosoma mansoni infection in Ethiopian schoolchildren.

Evaluation of the performance of an ELISA test using S. mansoni soluble egg antigens (SEA) in relation to the standard parasitological diagnostic procedure (Kato) was conducted in a specially set up study on 400 Ethiopian schoolchildren. Faecal samples were collected on 3 successive days for preparation of Kato thick smears and two finger prick blood samples were collected onto filter paper from all the children on day 1. All helminth ova present in the triplicate Kato slides were counted and the ELISA test was carried out on both eluted serum samples. Prevalence of infection by Kato was 83.5% in the endemic area and the sensitivity and specificity of the ELISA test were 97.6% and 30.3% respectively, whereas the specificity of the ELISA in the non-endemic area was 95.5%. The main cause of 'false positivity' in the endemic area appeared to be inapparent S. mansoni infection. Because of its high sensitivity, this ELISA test will clearly be of value for seroepidemiological surveys.

Adolescent↗
PubMed1991

6-Mercapto-FAD and 6-thiocyanato-FAD as active site probes of phenol hydroxylase.

Recently, the synthesis and properties of several 6-substituted flavins as active site probes for flavoproteins have been reported (Ghisla, S., Massey, V., and Yagi, K. (1986) Biochemistry 25, 3282-3289). Here, we report results of experiments in which 6-thiocyanato-FAD and 6-mercapto-FAD have been substituted for the native flavin of phenol hydroxylase. The 6-SCN-FAD enzyme was converted spontaneously to the 6-mercaptoflavin form probably due to dissociation of flavin, followed by attack of external protein thiols. The pK alpha values of uncomplexed and phenol-bound 6-mercapto-FAD enzyme were determined. Both the spontaneously formed 6-mercapto-FAD enzyme and the enzyme reconstituted with preformed 6-mercapto-FAD were treated with a variety of thiol-specific reagents, and reaction rates were followed by spectroscopic means. Comparison with the corresponding rates found with free flavin suggested a high degree of accessibility to the flavin 6-position. Accessibility was somewhat decreased in the presence of phenol. Upon treatment with low concentrations of methyl methanethiosulfonate or N-ethylmaleimide (NEM), extremely rapid spectral changes were apparent. The former reaction, however, was reversed spontaneously within 2 h. Reaction with NEM was biphasic, with spectral changes consistent with the mechanism previously proposed (Steenkamp, D. J., McIntire, W., and Kenney, W. C. (1978) J. Biol. Chem. 253, 2818-2824), followed by a small absorbance decrease due to protein conformational changes. The NEM reaction is unusual, being easily reversed by addition of excess dithiothreitol.

Binding Sites↗
PubMed1991

Kinetic and isotopic studies of the oxidative half-reaction of phenol hydroxylase.

Phenol hydroxylase, an FAD-containing monooxygenase, catalyzes the conversion of substituted phenols to the corresponding catechol. Use of metapyrocatechase, capable of dioxygenation of several catechols to give highly absorbing products, permitted determination of the time course of product release from phenol hydroxylase. Product dissociated prior to complete reoxidation of the enzyme, most likely concomitant with formation of the 4a-hydroxyflavin species (intermediate III). Deuterated phenol and thiophenol exhibited no kinetic isotope effect during the oxidative half-reaction. Isotope effects of 1.7 to 3.7 were found with resorcinol for the conversion of the second intermediate to intermediate III. These effects limited the possible models for phenol hydroxylation. An attempt was made to distinguish whether the spectrum of intermediate II is due entirely to that of the flavin moiety of phenol hydroxylase or whether some radical intermediate form involved in the formation of catechol makes a significant visible contribution. Reduced native and 6-hydroxy-FAD phenol hydroxylase were reacted with oxygen and resorcinol in order to provide evidence for the identity of intermediate II.

Isotopes↗
PubMed1991

Interpretation of pulsatility index in feeder arteries to low-impedance vascular beds.

A simple electrical circuit is proposed as a model for peripheral vascular beds of low impedance. The model consists of a flow and pressure source, i.e. the 'feeder' artery, with the vascular bed represented by a Zener diode Z giving rise to a 'back pressure' P(z) and a pure resistance R. By applying Ohm's law to the definition of pulsatility index PI(flow) of flow in the feeder artery, it is shown that PI(flow) is dependent only on the mean blood pressure (input), the pulse pressure and P(z), and is independent of R. For those vascular beds where the impedance is largely resistive, e.g. the brain, the kidney and the uterine-placental complex, it is suggested that P(z) may be a more useful characterizing parameter than the value of PI(flow) as at present used by some workers.

Journal Article↗