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Biomedical subjects

A Lees

Publications and source records attributed to A Lees.

At least 73 records · Page 4Linked to original sources
PubMed1998

Cognitive performance in recreational users of MDMA of 'ecstasy': evidence for memory deficits.

Cognitive task performance was assessed in three groups of young people: 10 regular users of 3,4-methylenedioxymethamphetamine (MDMA) who had taken 'ecstasy' 10 times or more; 10 novice MDMA users who had taken 'ecstasy' one to nine times; and 10 control subjects who had never taken MDMA. A computerized battery of cognitive tasks (Cognitive Drug Research system) was undertaken on a day when subjects were drug free. Performance on the response speed and vigilance measures (simple reaction time, choice reaction time, number vigilance), was similar across the three subgroups. However on immediate word recall and delayed word recall, both groups of MDMA users recalled significantly less words than controls. Animal research has shown that MDMA can lead to serotonergic neurodegeneration, particularly in the hippocampus and frontal cortex. Although the design of this study was far from ideal, these data are consistent with other findings of memory decrements in recreational MDMA users, possibly caused by serotonergic neurotoxicity.

Adolescent↗
PubMed1998

Characterization of early activation events in cord blood B cells after stimulation with T cell-independent activators.

Human neonates are immunologically immature, particularly in their humoral antibody responses to T cell-independent antigens, as exemplified by their increased susceptibility to infections with polysaccharide-encapsulated bacteria. To clarify the mechanism(s) underlying the unresponsiveness of neonates to polysaccharide antigens, we used an in vitro model with neonatal cord blood cells that has been shown to mimic surface Ig-dependent signaling in the adult by T cell-independent antigens. We studied the ability of cord blood human B cells to become activated after ligation of their surface Ig by unconjugated anti-Ig, dextran-conjugated anti-Ig, and Staphylococcus aureus Cowan A1, and compared their response with that of adult B cells. After the addition of nanogram concentrations of anti-Ig-dextran, neonatal cord blood B cells proliferated at levels comparable to that observed with adult B cells. The majority of cord blood B cells showed a marked rise in intracellular calcium, increased surface expression of human leukocyte antigen DR, and an increase in cell size. Direct activation of protein kinase C by phorbol esters in neonatal B cells led to cellular proliferation, and when combined with anti-Ig, a synergistic effect on proliferation was observed. These data suggest that the unresponsiveness of human neonates to polysaccharide antigens does not represent an inability of these antigens to induce early activation events in circulating B cells.

Adult↗
PubMed1997

Linear epitopes of colonization factor antigen I and peptide vaccine approach to enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) cause diarrhea in infants and in travelers to developing countries. The bacteria utilize colonization factors (CF) for adherence to intestinal epithelia, then release toxins causing diarrhea. CF are strong immunogens as well as protective antigens. While 20 ETEC CF have been described in the literature, 11 CF are prominent enough to be considered for vaccine targeting. Of this group, six of the members fall into the CFA/I family of CF. Geysen pin (peptide) linear epitope analysis demonstrated that three regions containing linear epitopes exist in CFA/I, and that both B- and T-cell linear epitopes of CFA/I were concentrated at the N-terminus of the protein. We have determined N-terminal sequence of the CFA/I family members not previously sequenced. Comparison of the protein sequence of the six members of the family showed a strong homology up to residue 36. A peptide of 36 amino acids representing a consensus of the six sequences was synthesized and used to immunize animals. The antibody induced to the peptide was reactive to the peptide as well as cross-reactive to each member of the CFA/I family in Western blots. In addition, this antibody agglutinated three of the six members of the CFA/I family when added to whole cells expressing the native CF. We are currently evaluating different carriers and conjugation methods to maximize production of high titer, agglutinating antibody. It is hoped that this and related research will result in an effective and inexpensive cross-reactive and cross-protective ETEC vaccine.

Amino Acid Sequence↗
PubMed1997

Changes in stature following plyometric drop-jump and pendulum exercises.

The aim of this study was to compare the changes in stature following the performance of plyometric exercises using drop-jumps and a pendulum swing. Eight male participants aged 21.7 +/- 1.8 years with experience of plyometric training gave their informed consent to act as participants. Participants undertook two exercise regimens and a 15-min standing test in a random order. The exercises entailed the performance of 50 drop-jumps from a height of 0.28 m or 50 pendulum rebounds. Participants were instructed to perform maximal jumps or rebounds using a 'bounce' style. Measurements of stature were performed after a 20-min period of standing (pre-exercise), 2-min after exercise (post-exercise) and after a 20-min standing recovery (recovery). Back pain and muscle soreness were assessed using an analogue-visual scale, at each of the above times and also 24 and 36 h after the test. Peak torque during isokinetic knee extension at 1.04 rads-1 was measured immediately before and after the exercise bouts, to assess the degree of muscular fatigue. Ground/wall reaction force data were recorded using a Kistler force platform mounted in the floor for drop-jumps and vertically on the rebound wall for pendulum exercises. Drop-jumps resulted in the greatest (p < 0.05) change in stature (-2.71 +/- 0.8 mm), compared to pendulum exercises (-1.77 +/- 0.7 mm) and standing (-0.39 +/- 0.2 mm). Both exercise regimens resulted in a significant (p < 0.01) decrease in stature when compared to the standing condition. Drop-jumps resulted in significantly greater peak impact forces (p < 0.05) than pendulum exercises (drop-jumps = 3.2 +/- 0.5 x body weight, pendulum = 2.6 +/- 0.5 x body weight). The two exercise conditions both invoked a small degree of muscle soreness but there were no significant differences between conditions. Both exercise regimens resulted in a non-significant decrease in peak torque indicating a similar degree of muscular fatigue. Based on the lower shrinkage resulted and lower peak forces, it can be concluded that pendulum exercises pose a lower injury potential to the lower back than drop-jumps performed from a height of 28 cm.

Adult↗
PubMed1997

Induction of B cell apoptosis by co-cross-linking CD23 and sIg involves aberrant regulation of c-myc and is inhibited by bcl-2.

A novel system to study the effects of co-cross-linking CD23/FceRII and sIg on murine B lymphocytes utilizes a highly multivalent form of anti-Ig prepared by covalently linking anti-Ig antibodies to a DNP-dextran backbone. CD23-sIg co-cross-linking is accomplished by the addition of DNP-specific monoclonal IgE. Previous studies demonstrated that co-cross-linking CD23 and sIg significantly inhibited mouse B cell proliferation, especially at high doses of the multivalent anti-Ig. Interestingly, examination of early activation signals reveals no difference in B cells subjected to co-cross-linking conditions as compared to B cells activated with anti-Ig alone. Total cellular protein tyrosine phosphorylation levels are unchanged by co-cross-linking. Analysis of B cell mRNA reveals that co-cross-linking the receptors does not alter the expression levels of ornithine decarboxylase 8 h after stimulation as compared to the controls. In contrast, levels of the proto-oncogene c-myc were significantly elevated 1 h after inducing B cell activation under co-cross-linking conditions. However, it remains unclear whether this aberrant c-myc regulation plays any role in inducing apoptosis. In addition, on day 3 after stimulation, the co-cross-linking of CD23 and sIg resulted in the formation of apoptotic B cells, determined by both photomicroscopy of the B cell cultures and FACS analysis of B cell nuclei. B cells obtained from bcl-2 transgenic mice proliferated as well as controls, and failed to undergo apoptosis when CD23 and sIg were co-cross-linked on their surface. These studies indicate that co-cross-linking of CD23 with B cell sIg inhibits B cell proliferation by a mechanism that is distinct from that seen by co-cross-linking of the Fc gamma RII and sIg. In addition, these results suggest a means by which antigen-specific IgE can down-regulate additional B cell activation and IgE synthesis.

Animals↗
PubMed1997

The neonatal consequences and neonatal cost of reducing the number of embryos transferred following IVF.

This clinical audit project examined the effects of change of policy between 1990 and 1993 transferring an average two (maximum three for particular cases) embryos to women undergoing IVF in the West of Scotland programme. All women who achieved clinical pregnancy in 1990 (92 women) and 1993 (93 women) as a result of the IVF programme were included in the study. The hospital records of women via the programme were analysed. The results of the study showed that there was a significant reduction in the rate of multiple pregnancy, preterm birth and low birth weight babies in the 1993 group (new policy). The cost of neonatal intensive care in 1993 for babies born following IVF was about nine times lower than that in 1990 (old policy). This study concluded that a policy of transferring two embryos (or three for particular cases) to women in an IVF programme, had improved the perinatal outcome and reduced the cost of the neonatal service for those babies.

Chi-Square Distribution↗
PubMed1996

Dendritic cells can present antigen in vivo in a tolerogenic or immunogenic fashion.

Dendritic cells (DC) are unmatched among APCs in their ability to bind, process, and present Ag. Presentation by such potent APCs, if always immunogenic and never tolerogenic, might stimulate pathogenic autoimmune responses. To determine whether Ag presentation by DC can induce tolerance, mice were injected with a rat IgG2b anti-splenic DC mAb, 33D1, and challenged 13 to 28 days later with a stimulatory rat IgG2b mAb. Injection of mice with 1 ng/100 micrograms of 33D1 rarely induced an anti-rat IgG2b Ab response and, in most mice, induced rat IgG2b-specific T cell and B cell tolerance. Tolerant mice had decreased ability to secrete Ab and make both type 1 and type 2 cytokine mRNA and protein in response to immunization with rat IgG2b. 33D1 was 100- to 1000-fold more potent as a tolerogen than an isotype-matched control rat IgG2b mAb. Injecting mice with aggregated 33D1, 33D1 plus anti-IgD mAb, or 33D1 plus IL-1 induced an IgG1 anti-rat IgG2b Ab response rather than tolerance. IL-1 injected 3 days after 33D1 still induced an Ab response rather than tolerance. Not all anti-DC mAbs are tolerogenic. Injection of a DC-specific hamster anti-CD11c mAb (N418) stimulates an IgG anti-hamster response, and injection of 33D1 plus N418 stimulates both anti-hamster and anti-rat IgG2b responses. These observations indicate that DCs can present Ag in either a tolerogenic or stimulatory manner and suggest that inflammatory stimuli can convert an otherwise tolerogenic signal to a stimulatory signal.

Animals↗
PubMed1996

Comparison of shoe insole materials by neural network analysis.

The effects of two insole materials within the shoe are compared using neural network analysis. Seven male subjects without locomotor disorders walk on a treadmill at a controlled speed and cadence wearing a common shoe and no socks, under three conditions; these are two types of insole of the same thickness, and a no insole condition. Pressure-related data from under the foot, within the shoe, are obtained by the MICRO-EMED system during walking. A back-propagation neural network is trained to associate sets of pressure-related data with the insole conditions. Subsequently neural network analysis is performed to reveal the abstract rules that govern the decision-making processes within the neural network, based on the synergistic interactions between the measured variables. Data are also analysed using ANOVA. The neural network analysis finds trends in the way in which the trained neural network responds. The interpretation of those trends gives a delicate description of the dynamic behaviour of the insoles despite the fact that no significant differences are found using ANOVA. It is concluded that neural network analysis can distinguish between insole behaviour during use, even though these differences are not significantly different based on statistical tests.

Adult↗
PubMed1996

Activation of soluble polysaccharides with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate for use in protein-polysaccharide conjugate vaccines and immunological reagents.

Neonates have poor immune responses to type 2 T-cell independent antigens (TI-2), such as polysaccharides and immunization of human infants with these antigens does not induce protective levels of serum antibodies. Conjugating proteins to TI-2 antigens converts the immune response to one which is T-cell dependent. We used an organic cyanylating reagent, 1-cyano-4-dimethylaminopyridinium tetrafluroborate (CDAP), to activate polysaccharides, in water, and subsequently react them with hexanediamine, in preparation for coupling proteins to the polysaccharide. CDAP activation of polysaccharide is rapid (< 2 min) and efficient. CDAP can be used to activate polysaccharides of diverse chemical natures, including dextrans and pneumococcal types 6, 14, 19 and 23. The critical parameters in CDAP activation of polysaccharides were the reagent concentrations and the pH. Activation can be performed over a broad alkaline pH range, with an optimum of pH 9-10. Furthermore, proteins can be coupled to CDAP-activated polysaccharides without the use of a spacer. Direct conjugation of protein to CDAP-activated polysaccharides can be performed under mildly alkaline conditions (pH 7-9). These conditions allow CDAP to be used with alkaline-sensitive polysaccharides and proteins. Mice immunized with BSA-pneumococcal type 14 polysaccharides (Pn14) conjugates, prepared either by direct conjugation or via a spacer, had high anti-Pn14 and anti-BSA serum antibody IgG1 titers, whereas no IgG1 antibody was induced to the unconjugated components. The ease of use and mild activating conditions should prove of value in using CDAP to prepare conjugate vaccines, as well as other immunologically useful reagents.

Animals↗
PubMed1996

The interpretation of relative momentum data to assess the contribution of the free limbs to the generation of vertical velocity in sports activities.

The contribution that the free limbs (the arms and lead leg) make to vertical velocity at take-off during jumping activities was determined by using a relative momentum approach. This requires the momentum of each free limb to be quantified relative to the joint at which the limb is attached to the body between the touchdown (or start of movement) and the take-off. The contribution that each makes to the vertical velocity at take-off requires interpretation of the momentum data. It has been shown that two interpretations cited in the literature pose difficulties, and a third is offered. This interpretation is that: (1) the contribution of a single limb to vertical velocity at take-off is determined by the increase in the positive relative momentum value between the beginning (touchdown) and end (take-off) of the action; (2) when considering a single limb, the negative relative momentum can be ignored as it makes no direct contribution to upward movement; and (3) the contribution of relative momentum for a number of limbs together is the increase in the positive value of the sum of the relative momentum for all limbs between the start and end of the action. This interpretation was applied to a counter-movement vertical jump and a running stride. In the counter-movement jump, the arms were found to produce a relative momentum of 30.9 N s, which was 12.7% of the peak total body vertical momentum. In running, the arms produced a relative momentum of 3.75 N s, which corresponded to 6.4% of the peak total body vertical momentum, while the arms and lead leg combined produced a peak value of 2.45 N s, which corresponds to a contribution of 4.2%. We conclude that the proposed interpretation enabled sensible estimations to be made of the contribution of the arms to jumping performance.

Arm↗
PubMed1995

Purification of a variant-specific surface protein of Giardia lamblia and characterization of its metal-binding properties.

Giardia lamblia, an intestinal parasite of humans and other vertebrates, undergoes surface antigenic variation by modulating the expression of different variant-specific surface proteins (VSP). VSPs are cysteine-rich surface proteins that bind zinc and other heavy metals in vitro. We developed an immunoaffinity chromatographic method to purify a VSP in order to determine its biochemical properties. The sequences of two different proteolytic fragments agreed with the sequence deduced from the cloned gene, and amino-terminal sequence indicated the removal of a 14-residue signal peptide, consistent with the transport of VSP to the cell surface. The protein is not glycosylated and has an isoelectric point of 5.3. X-ray microanalyses indicated that the major metals in Giardia trophozoites, as well as purified VSP, are zinc and iron. The zinc concentration in Giardia cells was found to be 0.43 mM and the iron concentration 0.80 mM when compared with standard samples (zinc) or calculated from a known physical constants (iron). We propose that metal coordination stabilizes VSPs, rendering them resistant to proteolytic attack in the upper small intestine. Moreover, the ability to bind ions by Giardia may play a role in nutritional deficiency and/or malabsorption in heavily infected persons.

Amino Acid Sequence↗
PubMed1995

Development of a connectionist expert system to identify foot problems based on under-foot pressure patterns.

The first phase of developing a connectionist expert system is described in this study. Dynamic pressure patterns below the foot obtained by the emed f system of 18 subjects were classified into one of the three categories: normals, pes cavus and hallux valgus. As opposed to the traditional approach for the analysis of the pressure patterns by quantifying isolated segments, a neural network based expert system was trained to perform objective classification of the patterns while keeping their integrity. The results of the backpropagation paradigm were unexpectedly good considering the limiting factors which hindered the performance of the neural networks. The successes indicate the potential of artificial intelligence in automated analysis of foot pathologies based on theemed f system. RELEVANCE:--This paper describes the first steps towards a novel automated screening system, which classifies the patient with foot abnormalities into the pathological category he or she belongs to, based on the pressure pattern below the foot. The decision making is objective, and shows a practical example of the use of artificial intelligence.

Journal Article↗
PubMed1995

T cell independent antigens.

T cell independent antigens type 2 (TI-2), which are represented predominantly by polysaccharide antigens, stimulate humoral antibody responses in the absence of T-cell help. We and others have recently reported that natural killer cells and/or natural killer cell derived lymphokines may provide a form of 'help' that is necessary for the induction and maintenance of TI-2 responses. Two natural killer cell derived lymphokines, interferon-gamma and granulocyte-macrophage colony-stimulating factor, show synergistic stimulatory activity in inducing Ig secretion in B cells stimulated by a multivalent ligand that mimics TI-2 antigens. The recent finding that natural killer cells have receptors for various classes of polysaccharides supports a role for these cells in regulating responses to TI-2 antigens.

Antigens, Differentiation↗
PubMed1995

The effectiveness of a pendulum swing for the development of leg strength and counter-movement jump performance.

Various training devices have been developed to facilitate 'plyometric' training, one such device being the 'pendulum swing'. To assess the effectiveness of the pendulum swing, the results of a 3 week training programme using a combination of pendulum swing and weight-training exercises were compared to those of a weight-training programme. Subjects were assigned to one of two groups (n = 9) for weight-training only or for combined pendulum and weight-training. Both groups performed the same number of exercise repetitions. Measurements of isometric knee and hip extension-flexion, 1-RM squat weight, maximum jump height and power for a counter-movement jump were taken pre-training, 2 days after the end of the programme and 2 weeks after the end of the programme. The data were analysed using two-way MANOVA and MANCOVA techniques. Both methods showed significant (P < 0.05) increases in knee and hip extension strength. Hip and knee flexion strength increased only for the weight-trained group. Counter-movement jump height increased for both groups (weight-trained, P < 0.05; combined, P < 0.01). Maximum power increased only for the combined group (P < 0.05). When the pre-training scores were used as a covariate, the weight-trained group showed a greater increase in hip flexion and extension strength and knee flexion strength than the combined training group (P < 0.05). The combined group showed the greatest increase in knee extensor strength. It is concluded that the pendulum system induces a training effect which could be used to supplement weight-training for improving vertical jump performance.

Adult↗
PubMed1995

Cutaneous infection with Mycobacterium abscessus.

Cutaneous infection with rapidly growing mycobacteria is uncommon and diagnosis may be difficult. However, the histopathological features are distinctive and may aid diagnosis. The three pathogenic species, Mycobacterium fortuitum, M. chelonae and M. abscessus, show major differences in their antimicrobial sensitivities, and species identification is therefore important. We describe a case of infection with M. abscessus, and discuss the clinical and pathological features of such infections, and approaches to their treatment.

Aged↗