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Biomedical subjects

A W Thomas

Publications and source records attributed to A W Thomas.

At least 37 records · Page 2Linked to original sources
PubMed2001

A comparison of rheumatoid arthritis and fibromyalgia patients and healthy controls exposed to a pulsed (200 microT) magnetic field: effects on normal standing balance.

Specific weak time varying pulsed magnetic fields (MF) have been shown to alter animal and human behaviors, including pain perception and postural sway. Here we demonstrate an objective assessment of exposure to pulsed MF's on Rheumatoid Arthritis (RA) and Fibromyalgia (FM) patients and healthy controls using standing balance. 15 RA and 15 FM patients were recruited from a university hospital outpatient Rheumatology Clinic and 15 healthy controls from university students and personnel. Each subject stood on the center of a 3-D forceplate to record postural sway within three square orthogonal coil pairs (2 m, 1.75 m, 1.5 m) which generated a spatially uniform MF centered at head level. Four 2-min exposure conditions (eyes open/eyes closed, sham/MF) were applied in a random order. With eyes open and during sham exposure, FM patients and controls appeared to have similar standing balance, with RA patients worse. With eyes closed, postural sway worsened for all three groups, but more for RA and FM patients than controls. The Romberg Quotient (eyes closed/eyes open) was highest among FM patients. Mixed design analysis of variance on the center of pressure (COP) movements showed a significant interaction of eyes open/closed and sham/MF conditions [F=8.78(1,42), P<0.006]. Romberg Quotients of COP movements improved significantly with MF exposure [F=9.5(1,42), P<0.005] and COP path length showed an interaction approaching significance with clinical diagnosis [F=3.2(1,28), P<0.09]. Therefore RA and FM patients, and healthy controls, have significantly different postural sway in response to a specific pulsed MF.

Adaptation, Physiological↗
PubMed2001

Proteolytic processing and primary structure of Plasmodium falciparum apical membrane antigen-1.

Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is a malaria merozoite integral membrane protein that plays an essential but poorly understood role in invasion of host erythrocytes. The PfAMA-1 ectodomain comprises three disulfide-constrained domains, the first of which (domain I) is preceded by an N-terminal prosequence. PfAMA-1 is initially routed to secretory organelles at the apical end of the merozoite, where the 83-kDa precursor (PfAMA-1(83)) is converted to a 66-kDa form (PfAMA-1(66)). At about the time of erythrocyte invasion, PfAMA-1(66) selectively translocates onto the merozoite surface. Here we use direct microsequencing and mass spectrometric peptide mass fingerprinting to characterize in detail the primary structure and proteolytic processing of PfAMA-1. We have determined the site at which processing takes place to convert PfAMA-1(83) to PfAMA-1(66) and have shown that both species possess a completely intact and unmodified transmembrane and cytoplasmic domain. Following relocation to the merozoite surface, PfAMA-1(66) is further proteolytically cleaved at one of two alternative sites, either between domains II and III, or at a membrane-proximal site following domain III. As a result, the bulk of the ectodomain is shed from the parasite surface in the form of two soluble fragments of 44 and 48 kDa. PfAMA-1 is not detectably modified by the addition of N-linked oligosaccharides.

Amino Acid Sequence↗
PubMed2001

Chiral symmetry and the intrinsic structure of the nucleon.

Understanding hadron structure within the framework of QCD is an extremely challenging problem. In order to solve it, it is vital that our thinking should be guided by the best available insight. Our purpose here is to explain the model-independent consequences of the approximate chiral symmetry of QCD for two famous results concerning the structure of the nucleon. We show that both the apparent success of the constituent quark model in reproducing the ratio of the proton to neutron magnetic moments and the apparent success of the Foldy term in reproducing the observed charge radius of the neutron are coincidental. That is, a relatively small change of the current quark mass would spoil both results.

Journal Article↗
PubMed2001

Human standing balance is affected by exposure to pulsed ELF magnetic fields: light intensity-dependent effects.

There is evidence in animals that behavioral and physiological responses to static and extremely low frequency magnetic fields (ELFMF) is affected by the presence of light during magnetic field exposures. Here we report that the effect of a specific pulsed ELFMF (PEMF) on human standing balance is modulated by light intensity during exposure. Under a low light condition (0.12 W/m2), nine healthy human volunteers stood on a 3D forceplate, throughout four 2 min exposures (eyes open/eyes close, sham/PEMF of 200 +/- 1 microTpk, order randomized). There was a significant increase in standing movement during PEMF exposure during eyes closed. In a second experiment on 26 normal subjects exposed to the identical protocol, but at greater light intensities (0.51 W/m2), a significant but opposite effect was observed.

Adult↗
PubMed2001

Antibodies to glycans dominate the host response to schistosome larvae and eggs: is their role protective or subversive?

Multiple exposures of chimpanzees to the radiation-attenuated schistosome vaccine provoked a strong parasite-specific cellular and humoral immune response. Specific IgM and IgG were directed mainly against glycans on antigens released by cercariae; these were also cross-reactive with soluble antigens from larvae, adult worms, and eggs. Egg deposition was the major antigenic stimulus after challenge of vaccinated and control chimpanzees with normal parasites, eliciting strong antiglycan responses to egg secretions. Glycan epitopes recognized included LacdiNAc, fucosylated LacdiNAc, Lewis(X) (weakly), and those on keyhole limpet hemocyanin. Antibodies to peptide epitopes became prominent only during the chronic phase of infection, as glycan-specific IgM and IgG decreased. Because of their intensity and cross-reactivity, the antiglycan responses resulting from infection could be a smoke screen to subvert the immune system away from more vulnerable larval peptide epitopes. Their occurrence in humans might explain the long time required for antischistosome immunity to build up after infection.

Animals↗
PubMed2001

Human subjects exposed to a specific pulsed (200 microT) magnetic field: effects on normal standing balance.

Static and time-varying magnetic fields have been shown to alter animal and human behaviors, such as directional orientation, learning, pain perception (nociception or analgesia) and anxiety-related behaviors. Human volunteers (12 male, 12 female, 18-34 years old) stood on a force plate while within three square magnetic field coil pairs (2, 1.75 and 1.5 m) arranged orthogonal with the uniform magnetic field volume centered at head level. Analysis of the data shows a significant improvement of normal standing balance or center of pressure, with eyes open or eyes closed, by a specific pulsed 200 microT(pk) magnetic field (PEMF). There was no significance found in control condition testing, such as sham-sham exposure of subjects or sham/PEMF exposure of a 60 kg saline phantom. There were no significant effects of gender or age.

Adolescent↗
PubMed2001

Magnetic field exposure and behavioral monitoring system.

To maximize the availability and usefulness of a small magnetic field exposure laboratory, we designed a magnetic field exposure system that has been used to test human subjects, caged or confined animals, and cell cultures. The magnetic field exposure system consists of three orthogonal pairs of coils 2 m square x 1 m separation, 1.751 m x 0.875 m separation, and 1.5 m x 0.75 m separation. Each coil consisted of ten turns of insulated 8 gauge stranded copper conductor. Each of the pairs were driven by a constant-current amplifier via digital to analog (D/A) converter. A 9 pole zero-gain active Bessel low-pass filter (1 kHz corner frequency) before the amplifier input attenuated the expected high frequencies generated by the D/A conversion. The magnetic field was monitored with a 3D fluxgate magnetometer (0-3 kHz, +/- 1 mT) through an analog to digital converter. Behavioral monitoring utilized two monochrome video cameras (viewing the coil center vertically and horizontally), both of which could be video recorded and real-time digitally Moving Picture Experts Group (MPEG) encoded to CD-ROM. Human postural sway (standing balance) was monitored with a 3D forceplate mounted on the floor, connected to an analog to digital converter. Lighting was provided by 12 offset overhead dimmable fluorescent track lights and monitored using a digitally connected spectroradiometer. The dc resistance, inductance of each coil pair connected in series were 1.5 m coil (0.27 Omega, 1.2 mH), 1.75 m coil (0.32 Omega, 1.4 mH), and 2 m coil (0.38 Omega, 1.6 mH). The frequency response of the 1.5 m coil set was 500 Hz at +/- 463 microT, 1 kHz at +/- 232 microT, 150 micros rise time from -200 microT(pk) to + 200 microT(pk) (square wave) and is limited by the maximum voltage ( +/- 146 V) of the amplifier (Bessel filter bypassed).

Animals↗
PubMed2001

A detailed ethological analysis of the mouse open field test: effects of diazepam, chlordiazepoxide and an extremely low frequency pulsed magnetic field.

The open field test (OFT) is a widely used procedure for examining the behavioral effects of drugs and anxiety. Detailed ethological assessments of animal behavior are lacking. Here we present a detailed ethological assessment of the effects of acute treatment with the benzodiazepines, diazepam (DZ, 1.5mg/kg) and chlordiazepoxide (CDP, 5.0 and 10.0mg/kg), as well as exposure to a non-pharmacological agent, a specific pulsed extremely low frequency magnetic field (MAG) on open field behavior. We examined the duration, frequency and time course of various behaviors (i.e. exploration, walk, rear, stretch attend, return, groom, sit, spin turn, jump and sleep) exhibited by male mice in different regions of a novel open field. Both DZ and CDP consistently reduced the typical anxiety-like behaviors of stretch attend and wall-following (thigmotaxis), along with that of an additional new measure: 'returns', without producing any overall effects on total locomotion. The drugs also differed in their effects. CDP elicited a shift in the locomotor pattern from a 'high explore' to a 'high walk', while DZ mainly elicited alterations in sit and groom. The MAG treatment was repeated twice with both exposures reducing horizontal and vertical (rearing) activity and increasing grooming and spin turns. However, the anxiety-like behaviors of stretch attend and return were marginally reduced by only the first exposure. We conclude that a detailed ethological analysis of the OFT allows not only the detection of specific effects of drugs and non-pharmacological agents (i.e. pulsed magnetic field) on anxiety-like behaviors, but also permits the examination of non-specific effects, in particular those on general activity.

Animals↗
PubMed2001

Dipalmitoylphosphatidylcholine modulates inflammatory functions of monocytic cells independently of mitogen activated protein kinases.

Phosphatidylcholine (PC) is the major phospholipid of pulmonary surfactant and it is hypothesized that PC and its subspecies modulate the functions of alveolar macrophages. The most abundant of these subspecies is dipalmitoylphosphatidylcholine (DPPC). This study was undertaken to determine the effect of PC on monocyte function using a human monocytic cell line, MonoMac-6 (MM6). This study showed that preincubation of MM6 cells with DPPC at 125 microg/ml for 2 h inhibited the oxidative response to either zymosan or phorbol-12-myristate-13-acetate (PMA) by 30% (P < 0.001). This inhibition with DPPC was independent of LPS priming. When DPPC was replaced with 1-palmitoyl-2-arachidonoyl phosphatidylcholine (PAPC) there was no inhibition and in contrast a significant increase in oxidant production was observed. We also demonstrated that total PC (tPC; a heterogeneous species of PC from egg) and DPPC but not PAPC significantly inhibited the release of TNF-alpha from MM6 cells (P < 0.05). DPPC did not inhibit phosphorylation of the mitogen activated protein kinases (MAPKs) p44/p42 or p38 in stimulated cells. Measurements of membrane fluidity with spin label EPR spectroscopy indicate that DPPC incorporation significantly alters the membrane fluidity of MM6 cells. These results suggest that DPPC, the major component of pulmonary surfactant, may play a role in modulating leucocyte inflammatory responses in the lung. This may in part be related to membrane effects but does not include alterations in p44/p42 or p38 MAPK signalling.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2001

Analysis of a polycytosine tract and heteroplasmic length variation in the mitochondrial DNA D-loop of patients with diabetes, MELAS syndrome and race-matched controls.

AIM: The T to C substitution at position 16189 nt of the human mitochondrial genome has been associated with the development of heteroplasmic length variation in the control region of mtDNA. Previous reports have suggested that this defect may be associated with the development of other pathogenic mtDNA mutations, including the diabetogenic A to G mutation in the tRNALEU(UUR). Recently the 16189 nt variant has also been associated with insulin resistance in British adult men. In order to investigate these associations further we studied 23 patients with the 3243 nt mutation, 150 patients with Type 2 diabetes and 149 non-diabetic controls. METHODS: The region around 16189 nt was investigated by polymerase chain reaction-restriction fragment length polymorphism analysis and automated sequencing. RESULTS: We find that the T to C substitution at 16189 nt is associated with heteroplasmic length variation only when the resultant polycytosine tract is not interrupted by a second mutation. There are no significant differences in the prevalence of the 16189 nt variant or heteroplasmic length variation between patients with the 3243 nt mutation, patients with Type 2 diabetes or race-matched normal controls. CONCLUSIONS: We conclude that these variants are likely to represent normal polymorphisms and that previously reported associations should be treated with caution unless they can be replicated in other populations.

Adult↗
PubMed2001

Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees.

The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection.

Animals↗
PubMed2000

Dynamical symmetry breaking in the sea of the nucleon.

We derive the nonanalytic chiral behavior of the flavor asymmetry d - u. Such behavior is a unique characteristic of Goldstone boson loops in chiral theories, including QCD, and establishes the unambiguous role played by the Goldstone boson cloud in the sea of the proton. Generalizing the results to the SU(3) sector, we show that strange chiral loops require that the s - s distribution be nonzero.

Journal Article↗
PubMed2000

Extremely low frequency magnetic fields can either increase or decrease analgaesia in the land snail depending on field and light conditions.

Results of prior investigations with opioid peptide mediated antinociception or analgaesia have suggested that these extremely low frequency (ELF) magnetic field effects are described by a resonance mechanism rather than mechanisms based on either induced currents or magnetite. Here we show that ELF magnetic fields (141-414 microT peak) can, in a manner consistent with the predictions of Lednev's parametric resonance model (PRM) for the calcium ion, either (i) reduce, (ii) have no effect on, or (iii) increase endogenous opioid mediated analgaesia in the land snail, Cepaea nemoralis. When the magnetic fields were set to parameters for the predictions of the PRM for the potassium ion, opioid-peptide mediated analgaesia increased and there was evidence of antagonism by the K(+) channel blocker, glibenclamide. Furthermore, these effects were dependent on the presence of light; the effects were absent in the absence of light. These observed increases and decreases in opioid analgaesia are largely consistent with the predictions of Lednev's PRM.

Analgesia↗
PubMed2000

Molecular characterisation of Plasmodium reichenowi apical membrane antigen-1 (AMA-1), comparison with P. falciparum AMA-1, and antibody-mediated inhibition of red cell invasion.

Apical membrane antigen 1 is a candidate vaccine component for malaria. It is encoded by a single copy gene and has been characterised in a number of malaria species as either an 83-kDa de novo product (Plasmodium falciparum; Pf AMA-1) or a 66-kDa product (all other species). All members of the AMA-1 family are expressed during merozoite formation in maturing schizonts and are initially routed to the rhoptries. Processed forms may subsequently be associated with the merozoite surface. Because of the unique occurrence of the 83-kDa form in P. falciparum we were interested to determine whether the phylogenetically closely related chimpanzee malaria Plasmodium reichenowi shared characteristics with Pf AMA-1. Here we show that the molecular structure, the localisation and processing are similar to that of Pf AMA-1 and that in vitro growth inhibitory mAbs reactive with Pf AMA-1 also inhibit P. reichenowi growth in an in vitro assay. Polymorphism in the 83-kDa AMA-1 family was analysed through comparison of Pr ama-1 with Pf ama-1 alleles, which showed the most significant evidence for selection maintaining polymorphism in Domains I-III of AMA-1 in P. falciparum. The most substantial divergence between Pr AMA-1 and Pf AMA-1 sequences was in the N-terminal region unique to the 83-kDa form of AMA-1. It was confirmed that the specific Pr ama-1-type allele was not present among P. falciparum parasites in an African population, and an allele coding for lysine at amino acid 187 was uniquely associated with field isolates in this population.

Adolescent↗
PubMed2000

Origin of Plasmodium falciparum malaria is traced by mitochondrial DNA.

The origin and geographical spread of Plasmodium falciparum is here determined by analysis of mitochondrial DNA sequence polymorphism and divergence from its most closely related species P. reichenowi (a rare parasite of chimpanzees). The complete 6 kb mitochondrial genome was sequenced from the single known isolate of P. reichenowi and from four different cultured isolates of P. falciparum, and aligned with the two previously derived P. falciparum sequences. The extremely low synonymous nucleotide polymorphism in P. falciparum (pi=0.0004) contrasts with the divergence at such sites between the two species (kappa=0.1201), and supports a hypothesis that P. falciparum has recently emerged from a single ancestral population. To survey the geographical distribution of mitochondrial haplotypes in P. falciparum, 104 isolates from several endemic areas were typed for each of the identified single nucleotide polymorphisms. The haplotypes show a radiation out of Africa, with unique types in Southeast Asia and South America being related to African types by single nucleotide changes. This indicates that P. falciparum originated in Africa and colonised Southeast Asia and South America separately.

Africa↗