Tandem affinity purification of protein complexes from mammalian cells.
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Animals↗
Biomedical subjects
D M Cox
Publications and source records attributed to D M Cox.
Influence of mouse strain, infective dose and larval burden in the brain on activity in Toxocara-infected mice.
Outbred LACA mice and inbred NIH mice were administered low (100 ova), medium (1000 ova), high (3000 ova) and trickle (4x250 ova) doses of Toxocara canis ova and the effect of infection on activity was examined with respect to: (i) the dose of ova administered and (ii) the number of larvae recovered from the brain. Larval recovery from the brain was significantly reduced in NIH mice compared to LACA mice for the 1000, 3000 and trickle doses. Mice from each strain were divided into larval intensity groupings based upon the number of larvae recovered from their brain. Activity for each mouse was measured pre- and post-infection by observing its behaviour in the home cage. Activity was assessed by monitoring six different independent categories of murine behaviour - ambulation, grooming, rearing, digging, climbing and immobility. Within each behavioural category, the duration of time spent at each behaviour per mouse within one thousandth of a second, the number of short bouts performed and the number of long bouts of behaviour performed were recorded over a 20 min period. Activity of LACA and NIH mice differed prior to infection. LACA mice spent more time immobile compared to NIH mice, which ambulated and climbed more. Variations in activity were also observed between groups of mice prior to infection. The effect of infection differed by strain, by dose and by larval intensity. Post-infection LACA mice became more immobile and ambulated less. NIH mice showed reduced immobility, but while ambulation decreased digging and climbing increased post-infection. Short bouts of activity remained unchanged among LACA mice post-infection but showed an increase for some behaviours in NIH mice.
Animals↗
Relationship between three intensity levels of Toxocara canis larvae in the brain and effects on exploration, anxiety, learning and memory in the murine host.
Outbred LACA mice were administered low (100 ova), medium (1000 ova), high (3000 ova) and trickle (4x250 ova) doses of Toxocara canis ova and the effect of infection was examined with respect to the number of larvae recovered from the brain and their behaviour. Recovery of larvae from the brain was generally low with the % recovery expressed in terms of the total dose administered being highest for the 3000 dose (6.1%) and 1000 dose (6%), followed by the 100 (4.4%) and trickle (3.5%) doses. The variation in larval recoveries was large between individual mice receiving similar doses. The level of infection in the brain was lower in mice receiving a multiple as opposed to an equivalent single dose of ova. Mice were then divided into three larval intensity groupings based upon the number of larvae recovered from their brain. The ranges for the groups were as follows: low intensity group, 0-15 larvae; moderate intensity group, 27-55 larvae; high intensity group, 66-557 larvae. Three behavioural tests were carried out on control and infected mice. Exploration and response to novelty was examined using a 'T' maze and learning was investigated by means of a water-finding task. Anxiety was measured using an elevated plus maze apparatus. Infected mice were less explorative and less responsive to novelty in the 'T' maze and this was particularly pronounced for the heavily infected mice. In the elevated plus maze, infected mice displayed reduced levels of anxiety to aversive and exposed areas of the maze, particularly in the case of the moderate and high intensity mice. There was evidence for impaired learning ability in the water task apparatus for moderate and high intensity mice. In general, the effects of infection on behaviour were more pronounced in the moderate and high intensity groups compared to the low intensity group.
Animals↗
Toxocara in the mouse: a model for parasite-altered host behaviour?
The objective of this paper is to critically evaluate the significance of parasite-altered host behaviour in the Toxocara mouse model particularly in the light of the Manipulation Hypothesis. Murine behaviours were examined in both outbred and inbred strains of mice infected with different doses of Toxocara canis ova. Behaviours investigated included activity, exploration, response to novelty, anxiety, learning, memory and social behaviour. Subsequent modifications to the behaviour of infected mice were investigated with respect to dose administered and larval accumulation in the brain. There was substantial variation in the number of larvae recovered from brains of individual mice, which received similar doses of Toxocara ova. Furthermore, the numbers of larvae recovered at different doses differed significantly between an outbred and inbred strain of mouse. Alterations in infected host behaviour occurred and were related to the number of larvae recovered from the brain. For social behaviour in outbred mice, a high infection in the brain reduced levels of aggressive behaviour and increased levels of flight and defensive behaviours. In contrast, outbred mice with a low infection in the brain displayed a greater level of risk behaviour in respect of predator odour and the light/dark box compared to control or high infection mice. Post-infection, outbred mice were more immobile whereas inbred mice showed reduced immobility and increased digging and climbing. Impaired learning ability was observed in outbred mice with moderate and high levels of infection in the brain compared to control and low infection mice. Toxocara infection has an impact upon a diverse range of murine behaviours with little evidence for a specific and hence an adaptive alteration. Many of the effects on murine host behaviour by Toxocara are likely to be pathological side effects of infection rather than as a consequence of adaptive host-manipulation. Observed changes in murine behaviour may be relevant to human toxocariasis.
Animals↗
Cell signaling and the regulation of muscle-specific gene expression by myocyte enhancer-binding factor 2.
Skeletal muscle is an extremely adaptable tissue. Underlying the biochemical adaptation invoked by changes in activity or during development are dramatic alterations in gene expression. Recent advances in our understanding of the molecular machinery that regulates gene expression in muscle is allowing insight into the pathways that control muscle growth and differentiation. We review developments concerning how cellular signaling pathways induce genetic reprogramming in skeletal muscle.
DNA-Binding Proteins↗
Post-translational control of the MEF2A transcriptional regulatory protein.
Myocyte enhancer factor 2 (MEF2) transcriptional regulatory proteins are key regulators of muscle-specific gene expression and also play a general role in the cellular response to growth factors, cytokines and environmental stressors. To identify signaling pathway components that might mediate these events, the potential role of MAP kinase and PKC signaling in the modulation of MEF2A phosphorylation and transcriptional activity were therefore studied. In transient transfection reporter assays, activated p38 MAP kinase potently increased MEF2A trans -activating potential, PKC[delta] and [epsiv] isotypes enhanced MEF2A transactivation to a lesser extent, while the ERK1/2 and JNK/SAPK pathways were without effect. A GAL4-based assay system showed that p38 MAP kinase and PKC[delta] target the MEF2A transactivation domain. We also observed an increase in p38 MAP kinase activity in congruence with the increase in MEF2A expression in differentiating primary muscle cells. COS cells overexpressing MEF2A alone or with one of the kinases were metabolically labeled with [32P]orthophosphate and MEF2A was immunoprecipitated using specific anti-MEF2A antibodies. MEF2A from cells co-transfected with activated p38 MAP kinase showed a decreased electrophoretic mobility due to phosphorylation. Subsequent phosphopeptide mapping and phosphoamino acid analysis indicated the appearance of several phoshopeptides due to p38 MAP kinase activation of MEF2A which were due to phosphorylation on serine and threonine residues. These studies position MEF2A as a nuclear target for the p38 MAP kinase signaling pathway.
Animals↗
The mixed nerve silent period is prolonged during a submaximal contraction sustained to failure.
The purpose of this study was to determine the effect of a sustained contraction of vastus lateralis on the silent period (SP) in the surface electromyogram (EMG) following direct neural stimulation. Five men and 5 women performed isometric knee extension at 30% maximal voluntary contraction (MVC) to the limit of endurance. During the contraction, EMG increased, and superimposed twitch amplitude and time to peak tension decreased, but the SP duration did not change. After 10 min of recovery, MVC had returned to its initial value, and the potentiated twitch amplitude was 70% of initial value, but the SP was now 11% shorter. Based on these results, we hypothesize that during a sustained contraction of 30% MVC, the increase in central drive may have been offset by inhibitory input from the periphery, but after 10 min of recovery the SP was shortened because of increased central drive. This aspect of the SP's behavior should be taken into account whenever it is employed as a diagnostic tool.
Adult↗
The relationship between numbers of larvae recovered from the brain of Toxocara canis-infected mice and social behaviour and anxiety in the host.
The effect of the nematode Toxocara canis on social behaviour and anxiety levels of adult male outbred (LACA) mice was examined following infection with a single dose of 2000 ova. The actual number of larvae recovered from the brain of each individual mouse was determined after behavioural testing. The effect of the parasite on mouse behaviour was analysed by both the initial dose administered (i.e. infected versus control) and the degree of infection in the brain. There was substantial variation in the number of larvae recovered from the brains of the individual mice and the magnitude of behavioural change was associated with the level of infection. Examination of social behaviour for both analyses revealed that the infection reduced levels of aggressive behaviour and increased levels of flight and defensive behaviours. High infection in the brain induced the greatest degree of behavioural change which decreased in mice with lower infections. In contrast the analysis of anxiety levels in mice by initial dose administered revealed no difference between infected and control mice. Mice with low infection in the brain, however, displayed a greater level of risk behaviour by spending more time in the vicinity of a predator odour and in the light area of a light/dark paradigm than control or high infection mice. The results suggest that the behaviour of mice infected with T. canis is influenced by the number of larvae accumulated in the brain. This may have important consequences for the conclusions drawn on the effect of this parasite on murine behaviour.
Animals↗
Generalization from single sentence to multisentence production in severely aphasic patients.
Multisentence production was examined in three nonfluent aphasic patients who had undergone a single sentence production training program using a computerized visual communication system (C-VIC). Patients were required to describe videotaped vignettes in English and using C-VIC. C-VIC allowed for an investigation of production abilities previously impossible to measure in severely aphasic patients, since C-VIC does not require internal generation of appropriate lexical items or phonological and articulatory realization. Results are discussed in the context of language production models in an attempt to determine the breakdown(s) in the production system that result in difficulty in trying to produce multiple sentences.
Adult↗
Remediating production of tense morphology improves verb retrieval in chronic aphasia.
Production of tense markers in C-VIC, a computerized visual communication system, was utilized as a treatment for three patients with severe expressive aphasia. Patients practiced constructing C-VIC tense marked sentences and then producing English equivalents. After training, all patients demonstrated significant improvements in English verb retrieval and production of correct tense morphology. Generalization of morphological rules for past tense production was seen for regular, but not irregular verbs. These results support the LaPointe and Dell (1989) extension of the Garrett (1975, 1992) model specifying a search through so-called verb phrase notion stores as a process mediating transition from functional to positional levels, but also suggest an additional constraint on the output of the verb notion store search.
Adult↗
Survey of sexual concerns among organ transplant recipients.
This study identified frequency of sexual dysfunction, degree of satisfaction with sexual relationship, differences in sexual function, overall satisfaction and life quality, and desire for and receipt of instruction regarding sexual dysfunction in kidney, pancreas/kidney, and liver transplant recipients. Of the 768 adult recipients surveyed by mailed questionnaire, 39% responded. Intimate relationships were reported by 69.9%; 66.7% indicated satisfaction with their relationship. Twenty-six percent were not sexually active. Transplant groups did not differ significantly regarding satisfaction, sexual function, or quality of life. Satisfaction groups differed significantly regarding intimacy and expected future life and health quality. Frequency of intercourse, desire, orgasm, erection dysfunctions, and the acceptance of partners' advances related to relationship satisfaction. Sixty-seven percent received no instruction concerning sexuality or fertility. Education efforts could validate and support sexual identity among this patient population.
Adult↗
Category and attribute knowledge deterioration in Alzheimer's disease.
A prevalent theory regarding the deterioration of semantic memory in Alzheimer's disease is that it is a bottom-up process. If this is true, performance on tests of attribute knowledge should decline more rapidly than performance on tests of categorical knowledge as dementia severity increases. In the present study, a convincing pattern of findings to either support or reject the theory failed to emerge. This raised questions regarding the ability to separate attribute and categorical knowledge, and whether one can be tested without influence of the other. Questions also were raised regarding the additional cognitive processes needed to complete tasks of semantic memory.
Aged↗
Chromosomal analysis of sperm from men with idiopathic infertility using sperm karyotyping and fluorescence in situ hybridization.
OBJECTIVE: To determine if idiopathic infertile men having oligozoospermia, asthenozoospermia, or teratozoospermia have an elevated risk of transmitting chromosomal abnormalities to their offspring. DESIGN: Sperm chromosomal complements from five somatically normal infertile men were assayed using the human sperm-hamster oocyte fusion system and the disomy frequencies for chromosomes 1, 12, and the sex chromosomes were determined using fluorescence in situ hybridization. SETTING: Infertile men and normal donors were volunteers in an academic research environment. PATIENTS: Five men with the appropriate semen characteristics were recruited among patients concerned about their infertility. INTERVENTIONS: Sperm fused with hamster oocytes resulting in sperm chromosomes or the sperm nuclei were prepared for fluorescence in situ hybridization. MAIN OUTCOME MEASURE: Structural and numerical abnormalities assessed by sperm karyotypes and the disomy frequency determined by fluorescence in situ hybridization analysis. RESULTS: The infertile men showed increased frequencies of numerical abnormalities and total abnormalities as determined by sperm karyotyping. Analysis of sperm nuclei by fluorescence in situ hybridization indicated a significant increase in the frequency of disomy for chromosome 1 and XY disomy. CONCLUSIONS: Sperm from infertile men may contain an increased frequency of chromosomal abnormalities.
Adult↗
Ethical aspects of dementia research: informed consent and proxy consent.
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Aged↗
Advance directives and the patient self-determination act.
Advance directives cover a wide variety of situations concerning the advance planning for medical care. Advance directives have existed for approximately 20 years; however, their forms and uses are presently expanding and evolving. This article presents advance directives, their various forms and uses, and reviews the current data on how well they achieve their desired goal. The Patient Self Determination Act, which was designed to promote the acknowledgment and completion of advance directives, is also discussed, as well as practical suggestions for the current and future uses for advance directives.
Advance Directives↗
Familial complex chromosomal rearrangement resulting in duplication/deletion of 6q14 to 6q16.
A familial complex chromosomal rearrangement (CCR) was ascertained through a mentally retarded, dysmorphic individual. Carriers of the CCR have the karyotype 46,XX or XY, t(6;15)(q16;q21), ins(3;6)(q12;q14q16), and malsegregation of the CCR resulted in loss of the segment 6q14 to 6q16 in the proband, and in an additional copy of the same segment in three members of the extended family. The proband has features similar to other reported cases with deletion of 6q1. The individuals with duplication of 6q14 to 6q16 have moderate mental retardation, short stature, obesity, microcephaly, brachycephaly, a short smooth philtrum, central hair whorl, simian creases, 5th finger brachydactyly and skeletal disproportion. In the 4-generation family, CCR carriers have a 20% empiric risk of phenotypically abnormal livebirths.
Adult↗
9qh+ variant band in two families.
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Chromosome Banding↗