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Biomedical subjects

M H Johnson

Publications and source records attributed to M H Johnson.

At least 19 recordsLinked to original sources

Is high-spatial frequency information used in the early stages of face detection?

The present study examined the role of high-spatial frequency information in early face processing, as indexed by the N170 face-sensitive ERP component. Participants detected 4 versions of famous faces, including full spectrum faces, and bandpass filtered faces containing predominantly high-spatial frequencies, low-spatial frequencies or both. The power spectra of all stimuli were balanced by superimposing the faces onto a visual noise background that included the spatial frequency information that was missing in filtered faces, e.g., high-spatial frequency faces were presented on a high- and low-spatial frequency background. An additional condition comprising of filtered visual noise only was also created to ensure that any observed effects were related to the processing of faces and not simply due to variations between spatial frequency information. Both behavioral and electrophysiological results replicated previous findings of a low-spatial frequency advantage for face processing. However, our results also show that faces containing both high and low-spatial frequency information are detected faster and more accurately than faces containing predominantly low-spatial frequencies. Furthermore, this advantage occurred with an enhanced amplitude of the N170. Together, these findings refute the suggestion that high-spatial frequencies are redundant in face perception.

Adult↗

Developmental and reproductive performance in circadian mutant mice.

BACKGROUND: Genes underlying circadian rhythm generation are expressed in many tissues. We explore a role for circadian rhythms in the timing and efficacy of mouse reproduction and development using a genetic approach. METHODS: We compare fecundity in Clock(Delta19) mutant mice (a dominant-negative protein essential for circadian rhythm activity) and in Vipr2-/- null mutant mice (affecting the generation and output of the circadian rhythm of the hypothalamic suprachiasmatic nucleus) with wild type (WT) litter mates under both a 12 h:12 h light:dark cycle and continuous darkness. RESULTS: Uteri from Clock(Delta19) mice show no circadian rhythm and Vipr2-/- mice show a phase-advanced rhythm compared to WT uteri. In neither mutant line were homozygous or heterozygous fetuses lethal. Sexually mature adults of both mutant lines showed mildly reduced male in vivo (but not in vitro) fertility and irregular estrous cycles exacerbated by continuous darkness. However, pregnancy rates and neonatal litter sizes were not affected. The Clock(Delta19) mutant line was distinguishable from the Vipr2-/- null mutant line in showing more peri-natal delivery problems and very poor survival of offspring to weaning. CONCLUSIONS: A fully functional central and peripheral circadian clock is not essential for reproduction and development to term, but has critical roles peri-natally and post-partum.

Animals↗

The Medical College of Georgia Fitkid project: the relations between program attendance and changes in outcomes in year 1.

OBJECTIVE: To investigate the relations of attendance of children in an after-school physical activity (PA) program to changes in body composition and cardiovascular fitness (CVF). DESIGN: Eight-month after-school PA-based intervention. SUBJECTS: In all, 278 third-grade boys and girls from nine elementary schools (age, 8.7 y (s.d. = 0.6 y), body mass index (BMI) 19.1 kg/m2 (s.d. = 4.4) and percent body fat (%BF) 26.0 (s.d. = 9.0)). MEASUREMENTS: Body composition (from dual-energy X-ray absorptiometry), BMI (from height and weight), waist circumference (WC) and CVF (from the YMCA submaximal bench-stepping test). RESULTS: There was a significant negative linear trend between level of attendance in the after-school program and change in %BF and fat mass; there was also a significant positive linear trend between program attendance and change in CVF. There was a marginally significant linear trend between program attendance and fat-free mass. Greater increases in bone mineral density were observed with higher program attendance. Changes in BMI and WC were not influenced by program attendance. CONCLUSION: Understanding the dose-response effect of PA on health outcomes, particularly body composition, in children is crucial in our effort to prevent overweight and its health consequences. Since there is limited data available to base PA dose recommendations for youths, findings from this study are relevant, and suggest that greater health benefits can be obtained in young children with more frequent participation in PA.

Body Composition↗

Radiotherapy for recurrent choroidal neovascularisation complicating age related macular degeneration.

AIMS: To report the safety and visual outcome data of external beam irradiation for recurrent choroidal neovascularisation complicating age related macular degeneration. METHODS: Eighteen consecutive eyes received external beam irradiation with seven fractions of 2 Gy (total dose 14 Gy). The next 16 consecutive eyes received external beam irradiation with five fractions of 3 Gy (total dose 15 Gy). Main outcome measure was change in visual acuity. Secondary outcome variables were contrast sensitivity and fundus photographic/fluorescein angiographic progression. RESULTS: The 3 Gy fraction group lost fewer lines of distance visual acuity at the three and six month follow up. At one year follow up, this difference was not maintained with 2 Gy fraction and 3 Gy fraction eyes. At one year follow up a decrease in visual acuity of three or more lines (moderate visual loss) occurred in 58% of 2 Gy and 42% of 3 Gy fraction eyes (p<0.36). At one year follow up a decrease in visual acuity of six or more lines (severe visual loss) occurred in 41% of 2 Gy eyes and 17% of 3 Gy eyes (p<0.23). At three months follow up, 3 Gy eyes were less likely (0%) than 2 Gy eyes (47%) to show moderate visual loss (p<0.003). However, Kaplan Meier curves estimate a significantly lower rate of severe visual loss in the 3 Gy group (p = 0.02). There were no significant differences in contrast sensitivity loss or fluorescein angiographic stabilisation rates. No evidence of radiation toxicity was observed. CONCLUSION: Our results are consistent with trends for a palliative benefit with higher fraction sizes and doses. The radiobiologic differences between low and high fraction size groups in this study are modest and correlate with the modest and short term difference in visual outcomes. These trends support further investigation of radiotherapy using fraction sizes of 4 Gy or higher.

Aged↗

A feedback model of visual attention.

Feedback connections are a prominent feature of cortical anatomy and are likely to have a significant functional role in neural information processing. We present a neural network model of cortical feedback that successfully simulates neurophysiological data associated with attention. In this domain, our model can be considered a more detailed, and biologically plausible, implementation of the biased competition model of attention. However, our model is more general as it can also explain a variety of other top-down processes in vision, such as figure/ground segmentation and contextual cueing. This model thus suggests that a common mechanism, involving cortical feedback pathways, is responsible for a range of phenomena and provides a unified account of currently disparate areas of research.

Algorithms↗

Expression and role of the ether-à-go-go-related (MERG1A) potassium-channel protein during preimplantation mouse development.

Potassium channels play important roles in many cellular processes, including cell-cycle progression and cell differentiation. In the present study, we investigated the pattern of expression of the mouse ether-à-go-go-related (KCNH2; MERG1A) potassium channel during mouse embryogenic development. Analysis by reverse transcription-polymerase chain reaction revealed maternal MERG1A transcripts until the late 2-cell stage of development, after which MERG1A expression from the zygotic genome was low until the 8-cell stage, then rose in the morula, but was low in trophoblast compared to inner cell mass cells. A trophoblast stem cell line also was shown to express MERG1A mRNA. Immunoblotting of oocytes, blastocysts, and the trophoblast stem cell line revealed different posttranslationally processed forms of MERG1A. Immunofluorescence analysis showed that the subcellular localization of MERG1A varied at different stages of the embryogenic cell cycle. In addition, MERG1A protein levels increased following compaction at the 8-cell stage, and its distribution became polarized. This relocalization of MERG1A was affected by treatment with specific inhibitors of ether-à-go-go-related gene (ERG)-channel function and of actin polymerization. Puromycin treatment of morulae indicated that membrane-associated MERG1A had a half-life of greater than 24 h. The ERG-specific inhibitor E-4031 reduced the incidence of blastocyst formation and the number of cells per blastocyst. These results show that MERG1A is developmentally regulated and suggest that it might play a role in early mouse embryogenic development.

Animals↗

Cortical specialisation for face processing: face-sensitive event-related potential components in 3- and 12-month-old infants.

The adult N170 is considered to be an electrophysiological marker of specialised mechanisms for face processing, but little is known about its developmental origin. Previous work has identified two face-sensitive infant ERP components (N290 and P400) (J. Cog. Neurosci. 14 (2002), 199). In the present study, we assessed the specificity (to upright human faces) of these infant components at 3 and 12 months. At 12 months the degree of specificity observed in both components was similar to that seen in the adult N170. In contrast, at 3 months of age the N290 and P400 did not show the same level of specificity for human faces as that observed at 12 months. Our findings suggest that (1) both face-sensitive components increase in their specificity for upright human faces during development, and (2) the adult N170 is not preceded by a single developmental precursor, but rather emerges as a consequence of the integration of two functionally and morphologically distinct components (N290 and P400).

Animals↗

Time and development.

The role that biological timers play in gametogenesis and development is reviewed through use of selected examples. Some general features of biological timers are also reviewed, and two types of timing mechanism are discussed in more detail: circadian rhythms and cell-cycle-based timers. In particular, the recent evidence that oscillatory ion channel activity may play an important role in timing mechanisms is summarized. The activity and properties of an oscillatory K(+) channel present during preimplantation mouse development are described, and preliminary results from its neutralization are discussed.

Animals↗

Developmental changes in the management of acid loads during preimplantation mouse development.

Intracellular pH recovery in Quackenbush Swiss mouse preimplantation embryos following acid loading was investigated under conditions of H+-monocarboxylate cotransporter inactivity. Isoform-sensitive inhibitors of Na+-H+ exchange (NHE) were used to block the Na+-dependent component of the response. A biphasic dose-response curve for HOE-694 and N-methylisopropylamiloride (MIA) suggested that two isoforms (putatively NHE1 and NHE3) are active in the oocyte, 1-cell, and 2-cell stages. By the blastocyst stage, loss of one of the MIA-sensitive NHE activities (putatively NHE3) was observed in isolated inner cell masses, and an MIA-resistant component of the recovery was identified. The MIA-resistant component was inhibited by 2 mM amiloride and enhanced by external K+ and by 4,4'-diisothiocyanostilbene-2,2'-disulfonate, suggesting NHE4 activity. However, unlike NHE4 in other tissues, the MIA-resistant component did not transport Li+ in exchange for H+, and reverse transcription-polymerase chain reaction detected NHE4 mRNA in the oocyte but not in later stages. Trophoblast, whether in intact or collapsed blastocysts, did not show measurable NHE activity or MIA-sensitive activity during recovery from acid load. Both trophoblast and pluriblast manifested an H+ conductance in response to acid load. This H+ conductance was first detected at the 8-cell stage and was blocked by zinc in the isolated inner cell mass but not in trophoblast. No other effective inhibitors of its activity were found.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Assisting medical students to conduct empathic conversations with patients from a sexual medicine clinic.

OBJECTIVE: To describe an exercise, the structure and content of which assists medical students to conduct potentially embarrassing conversations concerning sexual health which require expression of empathy, to integrate previous learning, to identify their further learning needs, and to develop and test strategies to meet these needs. METHOD: Students' role play, sequentially, speakers (patients) and listeners (clinical students) in a "carousel," in which all students are engaged at all times in a sequence of pairings which change at rapid intervals. Half way through the exercise, students reflect on the experience, identify difficulties and successes, and develop and share strategies for experimental use in the second half of the exercise. RESULTS: Qualitative comments from the written student evaluations are reported. CONCLUSIONS: The exercise provides a formative student centred approach to the integration and further development of previously learnt knowledge and skills of value for promoting sexual health education. It is useful for educators interested in promoting more open and informed learning about sexual health.

Attitude to Health↗

Preintegration lateral inhibition enhances unsupervised learning.

A large and influential class of neural network architectures uses postintegration lateral inhibition as a mechanism for competition. We argue that these algorithms are computationally deficient in that they fail to generate, or learn, appropriate perceptual representations under certain circumstances. An alternative neural network architecture is presented here in which nodes compete for the right to receive inputs rather than for the right to generate outputs. This form of competition, implemented through preintegration lateral inhibition, does provide appropriate coding properties and can be used to learn such representations efficiently. Furthermore, this architecture is consistent with both neuroanatomical and neurophysiological data. We thus argue that preintegration lateral inhibition has computational advantages over conventional neural network architectures while remaining equally biologically plausible.

Algorithms↗

Disordered visual processing and oscillatory brain activity in autism and Williams syndrome.

Two developmental disorders, autism and Williams syndrome, are both commonly described as having difficulties in integrating perceptual features, i.e. binding spatially separate elements into a whole. It is already known that healthy adults and infants display electroencephalographic (EEG) gamma-band bursts (around 40 Hz) when the brain is required to achieve such binding. Here we explore gamma-band EEG in autism and Williams Syndrome and demonstrate differential abnormalities in the two phenotypes. We show that despite putative processing similarities at the cognitive level, binding in Williams syndrome and autism can be dissociated at the neurophysiological level by different abnormalities in underlying brain oscillatory activity. Our study is the first to identify that binding-related gamma EEG can be disordered in humans.

Adult↗

Health status and quality of life of people with multiple sclerosis.

PURPOSE: The aim of this study was to ascertain the health status and quality of life of a community based cohort of people with multiple sclerosis. METHOD: A postal questionnaire with self-completed measures of impairment, disability, physical dependency and quality of life was sent to a random sample of 203 people with multiple sclerosis from a population register. The sample was stratified according to five disease courses. The population register is of the prevalent population of 760 people with multiple sclerosis resident in the Leeds Health Authority. The register used multiple sources of ascertainment and is prospectively maintained with new incident cases. RESULTS: The estimated mean age of people with multiple sclerosis is 46 years (SE: 0.85), and mean duration of disease is 14.4 years (SE: 0.69). Almost four in five (78 %) are female, and one in six (17%) live alone. Impairments of balance, vision and memory are common and in all cases there is little difference in the frequency between disease course groups. In contrast, impairments of bladder and bowel are more common in those with a progressive disease course. Disability is more common in those with a progressive disease course but all scores on the SF36 Physical Function scale are low and demonstrate the disabling consequences of the disease, irrespective of disease course. These consequences must contribute to the fact that over two-thirds (68 %) were not employed at the time of the survey. Quality of life does not differ across disease course groups, but rather varies by age and duration. CONCLUSIONS: People with multiple sclerosis experience a range of impairments and disabilities. Those with progressive disease courses experience greater levels of impairment and disability than other groups. There is not a straightforward exchange between health status and quality of life. A measure of subjective quality of life may reflect adjustment to disease, such that, for example, the longer the duration, the older the individual, the more likely the person will report a relatively good quality of life.

Female↗

Mammalian development: axes in the egg?

An enduring but erroneous belief is that the post-fertilisation period is irrelevant for axis development in mammals. Two recent studies further undermine this belief. Is information for axial developmental encoded in the egg cortex?

Animals↗

Human infertility, reproductive cloning and nuclear transfer: a confusion of meanings.

The Chief Medical Officer of Health of the United Kingdom has recommended that the 1990 Human Fertilisation and Embryology Act should be amended to allow cloning in humans for research purposes only. He also recommended that: "The transfer of an embryo created by cell nuclear replacement into the uterus of a woman (so called 'reproductive cloning') should remain a criminal offence" (recommendation 7, Ref. 1). This recommendation implies that nuclear replacement and cloning are the same. They are not. Nuclear transfer constitutes reproductive cloning only when the individual created is genetically identical to the nuclear donor. In this paper, we describe a possible future use of nuclear transfer for the treatment of infertile individuals. The treatment yields an individual that receives approximately equal genetic contributions from each parent. We use this example to illustrate how semantic confusion might lead to plausibly moral and justifiable treatments being legally banned. In doing so, we hope to encourage a more accurate and informed use of language in science, law and politics, so that legislation is properly informed by science and achieves what it intends. BioEssays 23:359-364, 2001.

Animals↗

Cognitive and perceptual development during infancy.

Over the past seven years, the main advances in our understanding of infant development have involved the application of cognitive neuroscience methods such as neuroimaging and computer modelling. Results obtained using these methods have illuminated further the complex interactions between nature and nurture that underlie early postnatal development.

Child Development↗

Reproduction in the Noughties: will the scientists have all the fun?

The past 20-30 years have seen major advances in our understanding of human reproduction and in our ability to manipulate it, as well as major social changes in human reproductive and sexual attitudes. Many of these advances and changes developed out of the first successful in vitro fertilisation (IVF) of the human oocyte. It is also the case that 30 years ago few foresaw what was to come, and many were at best doubtful and often were very critical of the scientific work which led to human IVF and to many of the subsequent developments. This lack of foresight provides us with a lesson about the dangers that we face in looking forward and attempting to predict the future. This review will try to convey, not comprehensively but through examples, the flavour of current activities in Assisted Reproduction clinics and research laboratories around the world and what is being talked about for the future in respect of emergent patient demands and anticipated clinical needs. This clinically driven approach will form the basis for consideration of some underlying scientific aspects of reproductive research, some of the ethicolegal issues that may arise, and the implications of this anticipated future for our current approaches to medical education. The future will be considered not simply in terms of the New Reproduction itself but also in its interaction with the opportunities and challenges presented by the New Genetics. It is perhaps in the interaction between these two fields of endeavour that some of the most difficult challenges ahead lie.

Adult↗