Search PubMed⌕ Search

Biomedical subjects

M J Taylor

Publications and source records attributed to M J Taylor.

At least 37 records · Page 2Linked to original sources

Magnetoencephalographic evidence of early processing of direction of gaze in humans.

Despite the crucial importance of direction of gaze in social interactions, it is only recently that there has been interest in human brain responses to gaze direction. Using full-head magnetoencephalography, we investigated the correlates of direction of gaze in full faces and in eyes-only stimuli, measuring the early face-responsive component between 145 and 225 ms. Faces with eyes forward or averted had larger responses than faces with eyes up or closed. For eyes-only stimuli the shortest latencies were seen for eyes averted and the smallest amplitudes were seen for eyes closed. The data were explained by two dipoles in inferior-temporal regions, which showed greater activation for upright faces than face parts or inverted faces, as well as some sensitivity to direction of gaze in this very early stage of processing.

Adult↗

Severe reactions to filarial chemotherapy and release of Wolbachia endosymbionts into blood.

Wolbachia bacteria seem to have evolved as essential endosymbionts of their filarial nematode hosts. Studies in mice have suggested that these bacteria are associated with systemic inflammatory reactions to filarial chemotherapy. We took blood samples from 15 Indonesian patients before and after treatment with diethylcarbamazine for Brugia malayi infection, and recorded the severity of any post-treatment inflammatory reactions. Blood from all three patients with severe adverse reactions and from one of six with moderate reactions was positive for Wolbachia DNA 4-48 h after diethylcarbamazine treatment. We suggest that these severe inflammatory reactions are associated with the release of endosymbionts into the blood after treatment for filariasis.

Animals↗

Binding occurs at early stages of processing in children and adults.

Conjoining features in a high-rate serial presentation was studied in children and adults using event-related potentials. Three blocks of trials were run in which targets were defined by colour, by orientation or by a conjunction of colour and orientation. Only adults had faster RTs when detecting targets defined by a single feature than by a combination of features. Compared with adults, children had longer RTs, longer N1 and P2 latencies, and larger P1 and P2 amplitudes. Amplitudes asymmetries were consistent with differing cortical regions being implicated in the processing of colour and form. There were, however, no ERP latency effects as a function of task, suggesting that the binding of features proceeds in parallel with the processing of single features.

Adult↗

Eyes first! Eye processing develops before face processing in children.

Faces and eyes are critical social stimuli which adults process with ease, but how this expertise develops is not yet understood. Neural changes associated with face and eye processing were investigated developmentally using ERPs (N170), in 128 subjects (4-15 year olds and adults). Stimuli included upright faces to assess configural processing, eyes and inverted faces to assess feature-based processing. N170 was present in the youngest children with similar patterns of face sensitivity seen in adults. Development of N170 to upright faces continued until adulthood, suggesting slow maturation of configural processing. In contrast, N170 was shorter latency and much larger to eyes than faces in children and was mature by 11 years, suggesting the early presence of an eye detector, with a rapid maturational course.

Adolescent↗

Intrauterine rescue transfusion in monochorionic multiple pregnancies with recent single intrauterine death.

To assess the role of fetal blood sampling and intrauterine transfusion in monochorionic (MC) multiple pregnancy complicated by single intrauterine death (IUD), we reviewed ten cases over a 4-year period in a tertiary referral centre which underwent fetal blood sampling within 24 h of death of its MC co-twin. Intrauterine rescue transfusion was performed in all seven anaemic fetuses (hematocrit; Hct < 30%) to raise the fetal Hct to > or = 40%. The rationale was to prevent death and/or brain injury. Two fetuses, which were severely acidaemic at blood sampling, died in utero within 24 h of the procedure. In two cases, the surviving twins manifested abnormal sonographic findings of the fetal brain 2-5 weeks later and underwent late termination. In two cases, the pregnancies continued uneventfully until delivery at 35 and 40 weeks' gestation with good neonatal outcome. In one case the co-twin delivered 1 week later at 29 weeks but died within 12 h. Fetuses without anaemia were not transfused and had normal clinical outcomes. We suggest that intrauterine rescue transfusion before the development of severe acidaemia in anaemic surviving MC co-twins may prevent fetal death, but does not necessarily prevent brain injury. Until its role becomes clearer, we recommend that its use be restricted to situations in which the parents and the local jurisdiction allow late termination as an option if brain injury subsequently manifests on ultrasound.

Acidosis↗

The effect of jararhagin, a metalloproteinase from Bothrops jararaca venom, on pro-inflammatory cytokines released by murine peritoneal adherent cells.

The release of pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) from murine peritoneal adherent cells (MPAC) was studied after exposure to jararhagin, a metalloproteinase/disintegrin isolated from Bothrops jararaca venom. MPACs were treated with LPS (lipopolysaccharide), jararhagin, or EDTA-inactivated jararhagin for up to 24h. Following incubation, the culture supernatant was assayed by ELISA for the presence of cytokines, while the cells were analysed for viability and cytokine mRNA expression. The cells exposed to native jararhagin released TNF-alpha and IL-1beta after 4 and 24h respectively. When MPACs were exposed to Jararhagin treated with EDTA, TNF-alpha and IL-1beta production was sustained throughout the culture period and IL-6 production was observed. TNF-alpha, IL-6 and IL-1beta mRNA were detected 4h after stimulation with either native or EDTA-treated jararhagin. Addition of jararhagin to LPS stimulated cells resulted in a dramatic decrease in the release of IL-6 and TNF-alpha. RT-PCR showed that this inhibition does not occur at the transcriptional level and further experiments showed that jararhagin degraded soluble cytokines by proteolytic activity. This study suggests that jararhagin induces TNF-alpha, IL-1beta and IL-6 expression, which may be rapidly degraded by its proteolytic activity.

Animals↗

Development of three-dimensional power Doppler ultrasound imaging of fetoplacental vasculature.

To develop an off-line system for three-dimensional (3-D) ultrasound (US) reconstruction of fetoplacental vasculature using colour segmentation and reconstruction software and to determine sources of error in fully freehand ultrasound image acquisition. US images were acquired freehand with the Acuson Sequoia (5C 2-MHz transducer) using power Doppler. After digital transfer to a personal computer, CQ Analysis software (Kinetic Imaging Ltd, Liverpool, UK) was used to segment the colour information from these images, and the resulting 8-bit grey-scale images were used for 3-D rendering using commercial software (VoxBlast, Vaytek Inc., Fairfield, IA, USA). 2-D scanning, software and freehand acquisition accuracy were assessed using a linear test rig and distance and volume phantoms (Dansk Phantom Service Ltd); 2-D scanning accuracy was within 1.3%, and software reconstruction accuracy within 1% for x and y planes and up to 3% for the z plane. Fully freehand acquisition was associated with a 12% to 18% mean percentage error in distance measurement in the plane of acquisition. Volumetric reconstruction inaccuracy was between 1.5% and 19.7% for precisely separated images and between 16.2% and 39.2% for fully freehand image acquisition. Rendered 3-D US vascular images clearly delineated vascular anatomy within the placenta and cord. Fully freehand 3-D US does have a role in off-line reconstruction of vascular anatomy, although variability in the z plane precludes its use for volumetric measurement. (E-mail: a.welsh@ic.ac.uk)

Female↗

Compound gravity receptor polarization vectors evidenced by linear vestibular evoked potentials.

The utricle and saccule are gravity receptor organs of the vestibular system. These receptors rely on a high-density otoconial membrane to detect linear acceleration and the position of the cranium relative to Earth's gravitational vector. The linear vestibular evoked potential (VsEP) has been shown to be an effective non-invasive functional test specifically for otoconial gravity receptors (Jones et al., 1999). Moreover, there is some evidence that the VsEP can be used to independently test utricular and saccular function (Taylor et al., 1997; Jones et al., 1998). Here we characterize compound macular polarization vectors for the utricle and saccule in hatchling chickens. Pulsed linear acceleration stimuli were presented in two axes, the dorsoventral (DV, +/- Z axis) to isolate the saccule, and the interaural (IA, +/- Y axis) to isolate the utricle. Traditional signal averaging was used to resolve responses recorded from the surface of the skull. Latency and amplitude of eighth nerve components of the linear VsEP were measured. Gravity receptor responses exhibited clear preferences for one stimulus direction in each axis. With respect to each utricular macula, lateral translation in the IA axis produced maximum ipsilateral response amplitudes with substantially greater amplitude intensity (AI) slopes than medially directed movement. Downward caudal motions in the DV axis produced substantially larger response amplitudes and AI slopes. The results show that the macula lagena does not contribute to the VsEP compound polarization vectors of the sacculus and utricle. The findings suggest further that preferred compound vectors for the utricle depend on the pars externa (i.e. lateral hair cell field) whereas for the saccule they depend on pars interna (i.e. superior hair cell fields). These data provide evidence that maculae saccule and utricle can be selectively evaluated using the linear VsEP.

Afferent Pathways↗

Direction of gaze effects on early face processing: eyes-only versus full faces.

The N170 event-related potential (ERP) reflects an early stage of face processing. We wished to determine if it would also index the intuitively important information provided by direction of gaze. Two studies were run. In one, stimuli included full faces with the eyes looking forward, to the left or closed; in the other study the stimuli included eyes-only, looking forward, left or closed. Gaze direction had no effects on amplitude, but longer latencies were found for faces with eyes closed. With eyes-only stimuli, more marked effects on latencies and borderline effects on amplitudes were seen. We suggest that there can only be limited evidence of gaze-specific sensitivity in ERP studies in humans, without eye movement.

Adult↗

Neurophysiological correlates of verbal and nonverbal short-term memory in children: repetition of words and faces.

The neurophysiological correlates of verbal and nonverbal memory have been extensively studied in adults, but comparable investigations of children are limited. A memory paradigm that is well established with adults is the repetition task, which finds a positive shift in the ERP waveform in response to repeated items, called the "repetition effect." This is thought to represent the brain's memory trace for previously seen information and is reported predominantly at midline frontal and parietal electrodes. We recorded ERPs in thirteen 11- to 14-year old children during repetition tasks of words and faces. Performance was better and ERP latencies shorter for the word than the face task. Although a repetition effect similar to adults was seen at parietal electrodes with increased positivity to repeated items, increased negativity was observed at frontal electrodes; this suggests that the neural substrates of recognition memory continue to develop beyond 11 to 14 years of age. The demonstration of a repetition effect in children provides a basis for studying the neural correlates of specific childhood memory deficits.

Child↗

Regional cerebral blood flow in cocaine- versus methamphetamine-dependent patients with a history of alcoholism.

Although abuse of cocaine or methamphetamine usually takes place in the context of heavy drinking, there is little information on the effects of such substance use comorbidity on brain perfusion. We explored similarities and differences in the effects of these two drugs in combination with alcohol on brain function using SPECT. Global and regional cerebral blood flow (CBF) were examined in 7 abstinent cocaine-dependent alcoholics (CDA; mean age = 39.2 yr, S.D. = 9.2 yr), 7 abstinent methamphetamine-dependent alcoholics (MDA; mean age = 36.8 yr, S.D. = 5.0 yr), and 7 non-alcoholic/non-stimulant abusing controls (NAC; mean age = 37.3 yr, S.D. = 9.6 yr). MDA had significantly lower global CBF than CDA who, in turn, were significantly lower than NAC. In addition, CDA had abnormal perfusion in the superior posterior frontal region compared to NAC; while MDA did not display specific regional deficits. Therefore, it appears that cocaine alters the relationship between global and regional CBF in alcoholics, while methamphetamine does not.

Adult↗

Freehand three-dimensional Doppler demonstration of monochorionic vascular anastomoses in vivo: a preliminary report.

OBJECTIVES: To demonstrate the three-dimensional vascular anatomy of monochorionic placental anastomoses in vivo, both arterioarterial and arteriovenous. DESIGN: Two-dimensional placental mapping techniques were used to locate arterioarterial and arteriovenous anastomoses. A freehand sweep was performed across the anastomotic site, and multiple images were stored to disk, at 17 Hz. These were then segmented to show only color information (vascular flow) using purpose-designed software (CQ analysis) and the files reconstructed into a three-dimensional volume, for multidirectional viewing and movie generation. RESULTS: Both arterioarterial and arteriovenous anastomoses could be visualized in detail. Reconstruction of a dual volume of gray-scale and segmented color images allowed recreation of the vascular anatomy within the placental substance, as well as retention of the original directional flow information. CONCLUSIONS: Detailed anastomotic anatomy can be demonstrated three dimensionally in vivo. Given the increasing evidence implicating various anastomotic configurations in pathological intertwin transfusion, this technique may prove useful in the antenatal assessment and treatment of monochorionic twin pregnancies.

Arterio-Arterial Fistula↗

Wolbachia bacteria in filarial immunity and disease.

Lymphatic filarial nematodes are infected with endosymbiotic Wolbachia bacteria. Lipopolysaccharide from these bacteria is the major activator of innate inflammatory responses induced directly by the parasite. Here, we propose a mechanism by which Wolbachia initiates acute inflammatory responses associated with death of parasites, leading to acute filarial lymphangitis and adverse reactions to antifilarial chemotherapy. We also speculate that repeated exposure to acute inflammatory responses and the chronic release of bacteria, results in damage to infected lymphatics and desensitization of the innate immune system. These events will result in an increased susceptibility to opportunistic infections, which cause acute dermatolymphangitis associated with lymphoedema and elephantiasis. The recognition of the contribution of endosymbiotic bacteria to filarial disease could be exploited for clinical intervention by the targeting of bacteria with antibiotics in an attempt to reduce the development of filarial pathology.

Animals↗

Current status and future prospects of the Global Lymphatic Filariasis Programme.

Lymphatic filariasis is recognized as one of the world's most disabling diseases. Adult lymphatic filarial nematodes live for several years; they infest the lymphatic and blood systems, and are transmitted via mosquito vectors. Acute and chronic disease can develop, manifesting as acute inflammation, hydrocoele, lymphoedema and elephantiasis. The development of a global programme for the elimination of lymphatic filariasis (focusing on disease caused by Wuchereria bancrofti) followed a resolution by the World Health Assembly in 1997 that endemic countries should develop programmes to eliminate lymphatic filariasis as a public health problem. This developed from an earlier recommendation by the International Task Force for Disease Eradication in 1993 that lymphatic filariasis was one of six diseases that could, in theory, be eradicated. Herein we review the current status and future prospects of the Global Lymphatic Filariasis Programme, which was launched in 2000.

Animals↗

A new approach to the treatment of filariasis.

The symbiosis of filarial nematodes and intracellular Wolbachia bacteria has recently been exploited as a target for antibiotic therapy of filariasis. Antibiotic treatment of filarial nematodes results in sterility and inhibits larval development and adult worm viability. In the first trial on human onchocerciasis depletion of bacteria following treatment with doxycycline resulted in a complete and long-term block of embryogenesis. Bacteria are unable to repopulate nematode tissues up to 18 months after depletion, suggesting these effects may be permanent. Following ivermectin treatment, individuals given antibiotic therapy showed sustained reductions in skin microfilariae, with the majority of people remaining microfilarial negative 12-18 months after treatment. Since Wolbachia also contribute to the inflammatory pathogenesis of filarial disease, antibiotic therapy could, in addition to effects on worm fertility or viability, prevent the onset or development of filarial pathology.

Animals↗

Down-regulated lymphoproliferation coincides with parasite maturation and with the collapse of both gamma interferon and interleukin-4 responses in a bovine model of onchocerciasis.

Onchocerciasis is a debilitating parasitic infection caused by the filarial nematode Onchocerca volvulus. Infections are chronic, and persistence of the parasites for several years argues for highly adapted mechanisms of immune evasion. Due to the restricted host repertoire of O. volvulus, we have used the cattle parasite Onchocerca ochengi to investigate the nature of immunomodulation underpinning these long-term infections. Cattle were infected with a single inoculation of 350 infective-stage larvae under laboratory conditions (n = 6). Intradermal nodules containing immature adult worms were detected from 110 days postinfection, and microfilariae in skin were detected from day 280 postinfection. Parasite-specific responses during early infection were nonpolarized with respect to the major Th cytokines (interleukin-4 [IL-4], IL-2, and gamma interferon [IFN-gamma]) produced by antigen-stimulated peripheral blood mononuclear cells (PBMC) or serum antibody isotypes. Antigen-induced proliferation of PBMC peaked shortly after exposure and remained high during the prepatent infection. As the parasites matured and animals developed patent infections, there was a profound down-regulation of lymphoproliferation, accompanied by sharp falls in the expression of both IL-4 and IFN-gamma and a gradual decline in IL-2. Levels of immunoglobulin G2 (IgG2) fell, while those of IgG1 remained high. We conclude that neither a classical Th2 response nor a simple Th1-to-Th2 switch is sufficient to explain the immunomodulation associated with patent Onchocerca infections. Instead, there is an initial Th0 response, which matures into a response with some, but not all of the features of a Th2 response. The natural host-parasite relationship of O. ochengi in cattle may be useful as both a descriptive and predictive tool to test more refined models of immunomodulation in onchocerciasis.

Animals↗