Measurement of time-averaged flow in the middle cerebral artery by magnetic resonance imaging.
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Blood Flow Velocity↗
Biomedical subjects
M G Taylor
Publications and source records attributed to M G Taylor.
Biotransformation of intracellular minerals by zinc ions in vivo and in vitro.
Inorganic granules of the general type CaMgP2O7 are found within cells of a wide range of species. The granules are amorphous to X-rays and occur in membrane-bound compartments. They accumulate a variety of cations from the body fluids of these animals. The interaction of zinc ions with pyrophosphate granules from cells of the snail Helix aspersa have been studied in vivo and in vitro by X-ray absorption spectroscopy and X-ray diffraction. The in vivo deposits incorporate zinc and remain amorphous although the pyrophosphate is hydrolysed to orthophosphate. In this in vitro reaction the mineral becomes crystalline but there is little change in the form of the The results clearly indicate a role for the cellular system in maintaining the amorphous state and in the hydrolysis of pyrophosphate to orthophosphate. As such they provide a model system for some of the changes observed in precursors of bone mineral and in pathological changes in the calcification of cartilage.
Animals↗
Decay of the 4a-hydroxy-FAD intermediate of phenol hydroxylase.
The oxidative half-reaction of phenol hydroxylase involves the formation of three spectrally distinct intermediates (Detmer, K.M., and Massey, V. (1985) J. Biol. Chem. 260, 5998-6005). Addition of an aerobic NADPH-regenerating system, phenol, and azide quantitatively converted oxidized enzyme to the third intermediate, a 4a-hydroxy-FAD species (Detmer, K.M., and Massey, V. (1984) J. Biol. Chem. 259, 11265-11272). This intermediate was isolated in the presence of azide and a wide variety of phenolic ligands. Decay rates were followed for the dehydration of 4a-hydroxy-FAD enzyme resulting in the original oxidized form. Deviation from the rate observed in the absence of phenolic ligands was presumed to be indicative of a binding interaction. Several phenols displayed further stabilization of the 4a-hydroxyflavin species. These ligands exhibited saturation kinetics with respect to the decay half-lives, consistent with a mechanistic model in which both free and bound 4a-hydroxy-FAD enzyme may be directly dehydrated to produce the oxidized species. The lack of stabilization by catechol, the natural product, suggests that product is released from the enzyme during turnover by the time that this intermediate is formed. A pH profile, generated for the decay rates in the absence and presence of phenolic ligand, suggests both acid and base catalysis by hydronium ion and hydroxide, respectively.
Chromatography, Gel↗
Antibody-dependent killing of Schistosoma mansoni schistosomula in vitro by starch-elicited murine macrophages. Critical role of the cell surface integrin Mac-1 in killing mediated by the anti-Mr 16,000 mAb B3A.
Starch-elicited murine peritoneal macrophages were able to kill schistosomula in vitro in the presence of a variety of immune sera. Dose response experiments revealed the superior "quality" of serum from mice vaccinated four times with highly irradiated cercariae (4xVMS) in mediating killing at titers comparable to the other sera tested. B3A, a partially protective mAb (IgG3) that recognizes a Mr 16,000 schistosomular surface Ag, mediated higher levels of killing than any of the sera at comparable titers. In contrast, H12, a partially protective mAb (IgG2a; anti-Mr 32,000), and C1C9, a nonprotective McAb (IgG3; anti-Mr 38,000) failed to mediate killing. Two anti-Mac-1 alpha-chain mAb (5C6 and M1/70) mediated substantial dose-dependent blocking of 4xVMS and B3A-mediated macrophage killing. In contrast, a mAb to the Mac-1-associated beta-chain was less effective, whereas the mAb F4/80 did not significantly block killing despite being present on this macrophage population. Although whole 5C6 Ig was the most efficient at inhibiting B3A-mediated killing, 5C6 Fab fragments were still effective at concentrations as low as 0.5 microgram/ml (10 nM). On a molar basis 5C6 appeared to be more effective at blocking 4xVMS-mediated killing than M1/70, while only M1/70 was capable of inhibiting macrophage adherence to schistosomula. These findings, together with the observation that anti-alpha chain mAb were far more effective at blocking killing than the anti-beta-chain mAb, rules out the possibility that 5C6 is nonspecifically inhibiting B3A-FcR interaction. The data also imply a functional relationship between Mac-1 and FcRIII, the receptor for B3A, in macrophage killing.
Animals↗
An online technique for estimating cerebral carbon dioxide reactivity.
A technique for measuring cerebral reactivity using transcranial pulsed Doppler ultrasound is described; the system includes a spectrum analyser and capnometer. Data acquisition and manipulation is under software control. Main stem middle cerebral artery blood velocity is monitored continuously using the transcranial Doppler technique, whilst the operator initiates data collection and controls the inspired gas composition. The calculation of cerebral CO2 reactivity is based upon linear regression analysis of normalized, time-averaged middle cerebral velocity on end-tidal pCO2 and is displayed graphically. Measurement of middle cerebral CO2 reactivities can be completed within 15 min. Results from two subjects, a healthy volunteer and a patient with occlusive disease, are shown to illustrate the technique.
Blood Flow Velocity↗
The measurement of time-averaged flow by magnetic resonance imaging using continuous acquisition in the carotid arteries and its comparison with Doppler ultrasound.
A continuous acquisition method was used to measure the time-averaged flow in the carotid arteries of 10 normal volunteers, using an interleaved flow-sensitive and flow-compensated field echo sequence on a 1.5 T magnetic resonance (MR) system. Validation of the sequence and technique was performed using a pulsatile rotating phantom. The measured flow rates for the common carotid arteries were compared with Doppler ultrasound values obtained immediately after the MR measurement using a Duplex scanner. The correlation (r = 0.52, P less than 0.01) was significant with data spread accounted for by the inherent errors of both techniques. The difference between time-averaged flow measured by MR and Doppler ultrasound was 1.9%. Short-term reproducibility of each technique was assessed by consecutive measurements with values of 6.8% and 6.6% respectively for MR and Doppler; measurements after a 2 - 4 week interval gave a long-term reproducibility of 11.8% and 9.8% respectively. The advantages of continuous acquisition make the method suitable for non-invasive flow measurements, particularly for vessels that are not accessible to ultrasound.
Blood Flow Velocity↗
The role of antibody affinity and titre in immunity to Schistosoma mansoni following vaccination with highly irradiated cercariae.
Sera from rabbits and rats vaccinated with highly irradiated cercariae of Schistosoma mansoni (VRabS, VRatS) were found to be of substantially higher affinity than sera from CBA mice vaccinated four times (4 X CVMS), single sex sera (SSS) or chronic infection sera (CIS). In contrast, VRabS and SSS appeared to possess the highest titres of antibody, followed by CIS and VRatS, with 4 X CVMS displaying the lowest titre. Two mouse strains selectively bred for high-affinity (HA) or low-affinity (LA) antibody following vaccination were tested for their ability to resist a challenge infection. LA mice, which produce high titres of low-affinity antibody, manifested significantly more resistance than HA mice, which produce low titres of high-affinity antibody. Immunoprecipitation studies demonstrated that sera from vaccinated LA mice (LVMS) recognized 125I-labelled schistosomular surface antigens more intensely than sera from vaccinated HA mice (HVMS). However, peritoneal macrophages from HA and LA mice in the presence of HVMS, LVMS or 4 X CVMS, and naive macrophages activated in vitro with interferon-gamma (IFN-gamma)/lipopolysaccharide (LPS) mediated comparable levels of schistosomula killing in vitro. The experiments described here provide evidence that the titre of antibody rather than its affinity may be a more critical factor in the development of optimal immunity to S. mansoni.
Animals↗
Immunity to Schistosoma mansoni in vivo: contradiction or clarification?
In recent years controversy and contradiction have hindered the elucidation of the immune effector mechanisms that are most effective against Schistosoma mansoni - an essential goal for the development of an effective vaccine. However, recent in-vivo studies have clarified the relative contributions of such mechanisms to protection. Here, Dario Vignali and colleagues summarize current evidence that suggests that both antibody and CD4+ T cells, in cooperation with macrophages, are crucial for the development of an effective response. In addition, a model is presented that may account for some of the discrepancies observed and which could be used as a basis for future research.
Animals↗
Histological examination of the cellular reactions around schistosomula of Schistosoma mansoni in the lungs of sublethally irradiated and unirradiated, immune and control rats.
Histopathological data on the cellular reactions (foci) around Schistosoma mansoni schistosomula in the lungs of both irradiated (750 rad) and unirradiated, passively immunized and normal rats were consistent with the idea that a significant proportion of immune-mediated attrition in passively immunized rats occurs in the lungs. In unirradiated rats, immune serum elicited an enhanced (i.e. larger) and accelerated (i.e. more rapidly developing) inflammatory cellular infiltration around lung-stage parasites when administered 5 days post-infection, when the parasites were already in the lungs. This demonstrated the antigenicity of lung-stage schistosomula and their potential as targets for immune attack. In irradiated rats, innate immunity was decreased as judged by an increase in the number of worms recovered by portal perfusion, and was accompanied by an overall decreased percentage of trapped parasites compared with unirradiated controls, suggesting that trapping in the lungs is involved in innate, as well as acquired immunity. In contrast to the results in unirradiated rats, passive transfer of immune serum into irradiated recipients did not result in larger lung foci than in the NRS-recipients. However, there was evidence of an accelerated response resulting in an essentially similar ratio of trapped parasites (VRS- compared with NRS-recipients) in irradiated rats, as compared with unirradiated rats, reflecting the similar levels of resistance manifested in both groups of rats. This also lent credence to the notion that it was the speed of immune recognition of the migrating schistosomula and the establishment of trapping foci that were of greater importance rather than the size of the enveloping granulomata.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
A role for CD4+ but not CD8+ T cells in immunity to Schistosoma mansoni induced by 20 krad-irradiated and Ro 11-3128-terminated infections.
The role of CD4+ (L3/T4+) and CD8+ (Lyt-2+) T cells in immunity to Schistosoma mansoni induced by 20 krad-irradiated and Ro 11-terminated infections in mice was investigated directly by in vivo depletion of these subsets with cytotoxic rat monoclonal antibodies (mAb). Effective physical depletion was demonstrated by flow cytometric analysis and immunohistochemical staining. Functional depletion of helper activity following anti-CD4 treatment was indicated by an abrogation of concanavalin A(Con A)-induced colony-stimulating factor (CSF) release, while anti-CD8 treatment had no effect in these assays. Pre-existing S. mansoni-specific antibody levels were unaffected by anti-CD4 and anti-CD8 treatment. In vivo depletion of CD4+ T cells resulted in a dramatic reduction in immunity induced by one (up to 100%) and two (up to 70%) vaccinations with 20 krad-irradiated cercariae and also of resistance induced by Ro 11-attenuated infections (up to 100%). Depletion of CD8+ T cells had no effect on resistance induced by any of the vaccination protocols investigated. A correlation was observed between resistance and T cell-induced, macrophage-mediated killing of schistosomula in vitro, both of which were abrogated following anti-CD4 treatment but were unaffected by CD8+ T-cell depletion. The possible role of CD4+ T cells in vivo and the implications for vaccine development are discussed.
Animals↗
Studies on immunity to Schistosoma mansoni in vivo: whole-body irradiation has no effect on vaccine-induced resistance in mice.
Actively immunized mice, whole-body irradiated with 650 or 525 rad., manifested comparable levels of resistance to Schistosoma mansoni compared with unirradiated, immunized mice in spite of a marked reduction in circulating leucocytes (greater than 90%) and platelets (greater than 85%), and despite an abrogation of delayed-type hypersensitivity (DTH) (Type IV) response to schistosomular antigens (as determined by footpad swelling, 24 h after injection of antigen). However, limited histopathological comparison of lung sections from irradiated and unirradiated mice 7 days post-challenge showed that cellular reactions ('foci') around parasites were essentially similar in size and cellular composition except that in irradiated mice, eosinophils were poorly represented both in the foci and in lung tissue in general. Neither presumed immune complex-mediated (Type III, Arthus reaction) hypersensitivity (as determined by footpad swelling, 5 h after injection of antigen) nor serum anti-schistosomulum extract antibody levels (as determined by ELISA) were affected. In addition, the pattern of 125I-labelled schistosomular surface antigens immunoprecipitated with serum from irradiated and unirradiated mice was essentially similar. These results are consistent with antibody playing an important role in vaccine-induced immunity in mice but suggest that radiosensitive T cell function and radiosensitive cells, such as platelets and polymorphonuclear cells, including eosinophils, may not be essential.
Animals↗
Comparison of the role of complement in immunity to Schistosoma mansoni in rats and mice.
In vivo depletion of C3 with cobra venom factor (CoF) was used to demonstrate the participation of complement in the innate immunity to S. mansoni and in the acquired immunity of both actively and passively immunized rats. Complement was shown to play an important role in innate immunity, being more involved later in larval migration (Days 8-13 post-infection) than at earlier times (Days--1-3 and Days 3-8 post-infection). Furthermore, the specific component of immunity conferred by immune serum transferred at the lung-migration stage also required complement for optimal expression. This supports the notion that both innate and acquired immunity act not against the much studied early post-penetration stages, but primarily against the lung stages. Although decomplementation at earlier stages of parasite migration (up to 3 days post-infection) did cause some reduction of innate immunity, there was no evidence of any effect on the levels of resistance actively induced by exposure to irradiated cercariae. This suggests that, while complement may play a role in innate immunity during the skin-migration phase, specific complement-mediated attrition does not play a crucial role at this time. The situation was very different in the mouse model, since no involvement of complement in either innate or irradiated vaccine-induced immunity could be demonstrated within the first 15 days of infection. Thus, there appear to be phases in the parasite migration in rats, but not in mice, during which complement becomes a critical factor in both innate and acquired immunity to S. mansoni.
Animals↗
Serum enzyme changes in calves experimentally infected with Schistosoma bovis.
The activities of the enzymes SD, GD, AAT, 5'NT, GGT, LDH and CPK were determined weekly in sera of two calves each infected with 10,000 S. bovis cercariae and in two controls. In infected animals, LDH activity increased from the first week of exposure and remained high throughout the experiment (22 weeks). GGT activity increased nine weeks after exposure and remained high. CPK activity was elevated during weeks 8-15 of infection. No change was detected in the activity of the other enzymes, nor in any enzymes of the controls.
Animals↗
Studies on heterologous resistance between Schistosoma mansoni and Fasciola hepatica in inbred rats.
Fischer rats infected with Fasciola hepatica showed significant resistance to Schistosoma mansoni challenge, and vice versa, whereas immunization with 20 Krad-irradiated S. mansoni cercariae failed to protect against F. hepatica challenge, but did protect against homologous challenge. When groups of rats received intraperitoneal implants of newly excysted juvenile flukes, 20- to 22-day-old juveniles, or 8- to 10-week-old flukes, none was significantly protected against S. mansoni challenge, whereas juvenile implants did protect against homologous F. hepatica challenge. In passive transfer experiments in rats, serum from F. hepatica-infected rats or rabbits protected recipients against homologous, but not heterologous challenge, and serum from rats vaccinated with 20 Krad-irradiated S. mansoni cercariae protected recipients against homologous, but not heterologous challenge. These experiments provide evidence that the mechanisms involved in homologous and heterologous resistance are different, the latter lacking immunological specificity. Microsphere injections in F. hepatica-infected rats demonstrated 'shunting' from the portal system to the systemic circulation. If migrating schistosomula are also 'shunted' in Fasciola-infected rats, this, rather than immunologically specific effector mechanisms, might explain their failure to establish in the portal system.
Animals↗
Immunity to Schistosoma mansoni in congenitally athymic, irradiated and mast cell-depleted rats.
Immunity to Schistosoma mansoni was investigated in congenitally athymic (Nu/Nu) rats, irradiated rats and in mast cell-depleted rats. Nu/Nu rats failed to develop significant resistance following vaccination with irradiated cercariae, although Nu/Nu recipients of serum from vaccinated Fischer rats (VRS) manifested resistance comparable to heterozygous controls, suggesting that T-cells were required in the induction of resistance but were not involved in the efferent arm of antibody-dependent elimination. Radiosensitive cells (including eosinophils, basophils, neutrophils, lymphocytes and mast cells) were apparently not essential for the antibody-dependent elimination of lung or post-lung stages since irradiated (700-750 rad.) recipients of VRS manifested comparable degrees of resistance to unirradiated controls in spite of a greater than 85% reduction in total blood leucocyte counts after irradiation. Depletion of 99% of tissue mast cells by treatment of rats with Compound 48/80 had no significant effect on the attrition of a challenge infection in rats rendered immune by vaccination with irradiated cercariae or by transfer of VRS. However, there was a significant increase in worm recovery in unimmunized and mast cell-depleted or irradiated rats, indicating that mast cells and perhaps other radio-isotope sensitive cells may be involved in innate resistance.
Animals↗
Reevaluation of the potential of Fasciola hepatica antigens for immunization against Schistosoma mansoni infection.
Previous workers have reported that significant resistance to Schistosoma mansoni cercarial challenge can be induced in mice by immunization with various Fasciola hepatica antigen preparations. We have attempted to reproduce these observations and have also carried out similar experiments in rats. In our hands, however, CBA mice did not develop either antibodies against the schistosomular surface, or significant resistance to challenge after immunization with heterologous antigens. Similar results were obtained in Fischer rats, but rats did develop significant resistance after immunization with homologous (schistosomular) antigens, even without adjuvant, and the homologous 'protective' antigens could be separated by antibody-affinity chromatography using serum from rats vaccinated with irradiated cercariae. Thus, we found no evidence for the existence of shared 'protective' antigens between S. mansoni and F. hepatica, and suggest that this is further evidence that where heterologous resistance can be demonstrated between these two parasites, it is probably due to immunologically non-specific mechanisms.
Adjuvants, Immunologic↗
The isotypes of antibody responsible for the 'late' passive transfer of immunity in rats vaccinated with highly irradiated cercariae.
The role of different antibody isotypes in the transfer of protection with serum from rats vaccinated with irradiated cercariae were investigated by immunoadsorption of IgG, IgG2a and IgG2c, and by heating at 56 degrees C to remove IgE. Only depletion of IgG2a reduced the levels of vaccine-induced immunity transferred, whereas immunity transferred by infection serum was reduced by both IgG2a and IgE depletion. It was also shown that exposure to irradiated parasites did not lead to either specific or non-specific induction of an IgE response. The successful passive-transfer experiments using serum from non-resistant 25 week-infected rats into recipient animals demonstrated that the waning of resistance observed in 25 week-infected rats was not due to a failure of the humoral response to protective antigens.
Animals↗
Solid-state 13C NMR and X-ray diffraction of dermatan sulfate.
Dermatan sulfate in the solid state has been studied by 13C CP/MAS nmr and X-ray diffraction in order to establish the ring conformation of the L-iduronate moiety. The solid state nmr spectrum is similar to the solution spectrum obtained previously, indicating that a ring conformation at least approximating to 1C4 predominates in the solid state. X-ray powder diffraction data from the same sample indicate the presence of the 8-fold helix form previously observed by fiber diffraction, and interpreted in terms of a 4C1 ring form. A likely explanation of the results is that a distorted 1C4 L-iduronate ring conformation, not considered in the initial X-ray analysis, may emerge to provide a satisfactory interpretation of all available physical-chemical data.
Animals↗