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Biomedical subjects

M H Johnson

Publications and source records attributed to M H Johnson.

At least 109 records · Page 6Linked to original sources

Experimental manipulations of compaction and their effects on the phosphorylation of uvomorulin.

Compaction of the eight-cell stage mouse embryo is a critical event in the generation of different cell types within the preimplantation embryo. Uvomorulin, a member of the cadherin family of cell adhesion molecules, is important during compaction and its phosphorylation increases early in the eight-cell stage, suggesting that this posttranslational modification may be important for compaction to proceed. We have assessed the importance of the phosphorylation of uvomorulin during compaction by preventing, reversing, or inducing adhesion prematurely. The only condition that affected the overall level of uvomorulin phosphorylation was the prevention of compaction through prolonged exposure of four-cell embryos to low Ca2+. This treatment reduced the level of uvomorulin phosphorylation in eight-cell embryos, and perturbed its localization to regions of cell-cell contact. Thus, whilst the phosphorylation of uvomorulin does not appear to regulate directly uvomorulin's adhesive function, it may be associated with the redistribution of uvomorulin during compaction.

Actins↗

The development and temporal dynamics of spatial orienting in infants.

Shifts of visual attention can be studied in adults by cueing a particular spatial location and assessing the speed of detection of targets presented in the cued location as compared to other locations. A number of studies have used spatial cueing paradigms in an attempt to study attention shifts in infants. However, these studies have employed different procedures, time courses, measures, and age groups, making comparison between them difficult. The present experiments were designed to investigate the effects of varying the cue-target time interval on the speed and direction of orienting in 2-, 4-, and 6-month-old infants. The results of Experiment 1 indicated that, while 2-month-old infants showed only weak effects of the cue, 4-month-old infants show facilitation to a cued location when a target appears 200 ms after cue onset, and inhibition of responses to the same location when the target appears 700 ms after the cue onset. Six-month-old infants showed evidence of inhibition, but not facilitation. One account of this pattern of data is that 6-month-olds shift attention faster than do 4-month-olds. This hypothesis was tested in Experiment 2 in which four different cue-target intervals were used with a group of 7-month-old infants. The results obtained were consistent with the hypothesis that infants get faster to shift attention to a spatial location with age.

Age Factors↗

The emergence of hierarchical clustered representations in a Hebbian neural network model that simulates aspects of development in the neocortex.

In this paper we show how clustered representations emerge within a simple neural network which simulates some aspects of the development of the mammalian neocortex. Synapse death and stabilization, postulated to occur in the real neocortex are modelled. The representations that emerge under certain conditions show a spatially hierarchical coarse- and fine-grain cluster structure. In two sets of simulations where the relative lengths of excitory and inhibitory links are different we show that the emergence of clustered representations depends upon changes to this parameter.

Journal Article↗

The distribution of alpha- and gamma-tubulin in fresh and aged human and mouse oocytes exposed to cryoprotectant.

The distribution of alpha- and gamma-tubulin in human and mouse oocytes has been investigated immunocytochemically. Comparisons have been made between freshly recovered and aged oocytes (both human and mouse), and also between human oocytes before and after exposure to cryoprotectant. Control fresh human oocytes had compact anastral spindles oriented orthogonal to the oolemma, with the pole adjacent to the oolemma being smaller than that directed towards the centre of the oocyte. Each pole was associated with a ring of particulate gamma-tubulin staining that extended a short distance into the body of the spindle. No alpha- and gamma-tubulin staining was found elsewhere in the ooplasm. Human oocytes which had failed to fertilize after an 18 h incubation with spermatozoa and had spent a further 6-8 h in culture showed an increased incidence of spindle abnormalities and of the proliferation of ooplasmic microtubules, which became more pronounced with age post-ovulation. The gamma-tubulin staining pattern of these aged human oocytes revealed greater staining over the whole of the spindle than in fresh oocytes. Examination of mouse oocytes aged in vitro or in vivo showed similar evidence of microtubule proliferation and disorganization, and the gamma-tubulin staining pattern was a sensitive indicator of ageing. The spindles of most fresh human oocytes exposed to 1.5 M dimethyl sulphoxide (DMSO) at 4 degrees C differed from controls in being slightly reduced in size or in having more pointed spindle poles with smaller diameters, both indications that some dismantling of the microtubules had occurred. The distribution of gamma-tubulin in these oocytes extended over more of the spindle. Restoration of DMSO-exposed oocytes to control medium at 37 degrees C for an extended period restored spindle structure to a state closely resembling that in controls. However, recovery of an exclusively polar gamma-tubulin staining did not occur. In both controls and DMSO-exposed human oocytes, chromosomes were arranged on the metaphase equatorial plate. In contrast, exposure of oocytes to 4 degrees C in the absence of DMSO caused dismantling of the spindle. It is concluded that (i) changes in microtubule organization with ageing of oocytes makes them unsuitable for use therapeutically after re-insemination or intracytoplasmic sperm injection, (ii) conditions of cryoprotectant addition previously found optimal for the stabilization of the spindle in the mouse oocyte also appear to be effective in stabilizing the spindle of the human oocyte, and (iii) the distribution of gamma-tubulin in relation to the spindle of the human oocyte appears to be sensitive to age and conditions.

Animals↗

2-Hydroxydesipramine and desipramine plasma levels: how are they related to antidepressant response?

Thirty-six outpatients aged 20 to 51 with RDC primary major depressive disorder (MDD) completed a 5-week trial of desipramine following a week of single-blind placebo. Five had a past history of hypomanic disorder. For all but one patient, daily dosage at bedtime was constant for the final 4 weeks, with a mean (S.D.) of 168.1 (46.5) mg. Plasma samples drawn at the three final weekly visits were assayed by high-performance liquid chromatography for 2-hydroxydesipramine (2-OH-DMI) and desipramine. Mean (S.D.) plasma levels were 59.8 (30.0) ng/ml for 2-OH-DMI and 142.9 (138.6) ng/ml for desipramine. Thirteen patients (36%) had a final 17-item Hamilton depression rating < and = 6 and were classified as responders. According to receiver operating characteristics analysis, patients with plasma 2-OH-DMI levels > and = 58 and < 92 ng/ml had a greater likelihood of responding than those with lower or higher levels (p = 0.005, Fisher's exact test), while patients with plasma desipramine levels > and = 64 ng/ml were more likely to respond than those with lower levels (p = 0.032, Fisher's exact test). Results using an alternate response criterion were similar. These findings suggest that in desipramine-treated outpatients with primary MDD the relationship between therapeutic response and plasma levels is curvilinear for 2-OH-DMI and linear for desipramine.

Adult↗

Regional strengths of bonding agents to cervical sclerotic root dentin.

The regional bond strengths of three current-generation bonding systems (All Bond 2, Scotchbond Multi-Purpose, and Clearfil Liner Bond 2) were measured in natural wedge-shaped defects in the cervical area of extracted human teeth. A microtensile testing method was used to compare the strengths of resin bonds made to occlusal margins with those made to gingival margins. Controls consisted of normal teeth which had artificial wedge-shaped defects, of the same depth and dimension, created with a high-speed bur. The results indicated that there were no regional differences in bond strength, although bonds made to natural lesions were from 20 to 45% lower than those made to normal dentin in artificially created wedge-shaped defects, depending on the bonding agent. Scanning electron microscopy revealed that Clearfil Liner Bond 2 created the thinnest hybrid layers, which were difficult to measure in the natural lesions. The natural lesions contained sclerotic dentin, whereas the artificial lesions were composed of normal dentin. Although the bond strengths to sclerotic dentin were lower than those to normal dentin, the absolute values (ca. 16 to 17 MPa) were high relative to previous-generation bonding agents.

Acid Etching, Dental↗

A direct measurement of increased divalent cation influx in fertilised mouse oocytes.

On fertilisation of mouse oocytes, the fusing spermatozoon triggers a series of repetitive calcium (Ca2+) spikes. The Ca2+ spikes seem to be necessary for successful progression through the cell cycle and are regulated in a cell-cycle-dependent manner. The spikes appear to require the linkage of continuous Ca2+ influx to the periodic release of Ca2+ from intracellular stores by a process of Ca(2+)-induced Ca2+ release. The precise role of Ca2+ influx was explored using the manganese (Mn2+)-quench technique to monitor unidirectional cation influx into single mouse oocytes. There was a marked stimulation of cation influx associated closely with the upsweep of the first and subsequent fertilisation Ca2+ spikes. A smaller but significant increase in the rate of cation influx persisted in the interspike period in fertilised oocytes. Spike-associated entry was not as apparent in oocytes stimulated to spike repetitively by thimerosal or acetylcholine application. Instead, there was a continuous increase in cation influx underlying Ca2+ spiking which commenced with the onset of the first spike. Using the specific microsomal inhibitor thapsigargin and the Ca2+ ionophore ionomycin, we found evidence for a capacitative entry mechanism in mouse oocytes. We propose that the persistent influx of Ca2+ observed in response to all stimuli examined is controlled by a capacitative mechanism and sets the frequency of spiking by determining the time taken to refill the internal stores to a point where they are again sensitive enough to initiate the next spike.

Acetylcholine↗

Assessing the effects of 10 percent carbamide peroxide on oral soft tissues.

To examine the effects of a 10 percent carbamide peroxide bleaching gel on the oral soft tissues, the authors conducted a prospective, double-blind, placebo-controlled clinical investigation. Fifty-two patients completed a two-week treatment regimen, applying either a placebo or a 10 percent carbamide peroxide gel in a soft tray for eight hours a day. Clinicians examined the participants' oral soft tissues at baseline and one week, two weeks and six weeks after the first treatment. The examiners recorded the Silness and Löe plaque and gingival indexes, nonmarginal gingival index and nongingival oral mucosal index at each examination. The data collected at these intervals did not indicate that any soft tissue damage had occurred as a result of the bleaching regimen.

Adult↗

An investigation of the gate control theory of pain using the experimental pain stimulus of potassium iontophoresis.

This study investigated a prediction derived from gate control theory-that there would be a pulse of pain as a pain stimulus was being ramped off due to the rapidly transmitting, inhibitory large fiber activity falling away sooner at the spinal level than the excitatory activity of the slow-transmitting, small nociceptive afferents. A further prediction was that the more distant the peripheral stimulus was from the spine, the greater the pain pulse would be. Fourteen subjects had the pain stimulus of iontophoretically applied potassium ions (K+) applied to an upper and a lower site on the dominant arm. In a threshold detection task using the double random staircase method, subjects were asked to indicate whether they could detect a pulse of additional pain during this ramp-off phase. The average rate of stimulus ramp-off in order to detect a pain pulse was statistically greater for the upper-arm site (14.3 micrograms K+/sec) than for the lower-arm site (9.4 micrograms K+/sec). These results were consistent with gate control theory. Alternative explanations, including intrinsic differences in nociceptive responding for different dermatomes and anode break, were considered. It was concluded that the detection of a pain pulse during the ramping off of a peripheral pain stimulus potentially provides a quantitative measure of the spinal modulation of pain.

Adult↗

The inhibition of automatic saccades in early infancy.

Adult patients with damage centered around the frontal eye fields are severely impaired in the ability to suppress unwanted automatic saccades and in the ability to make volitional eye movements. Over the first few weeks of life most saccades generated by infants appear to be automatic, and are triggered in response to exogenous factors. In the first experiment, the ability of 4-month-old infants to inhibit automatic saccades was studied by exposing them to a series of trials in which a peripheral cue stimulus predicted the location (opposite) in which a colorful, dynamic target stimulus appeared. The results indicate that 4-month-old infants are able to learn to inhibit automatic saccades to a peripheral stimulus, implying maturation of the frontal eye fields by this age. The results of Experiment 2, in which there was no contingent relationship between the cue and target, indicated that the decline in orienting to the cue observed in the first experiment was not due to differential habituation to the less-complex stimulus.

Attention↗

Cytoskeletal organization in the oocyte, zygote, and early cleaving embryo of the stripe-faced dunnart (Sminthopsis macroura).

Ovulation occurs in Sminthopsis macroura approximately 160 hr after administration of 1.3 IU PMSG, and yields significantly more oocytes than does spontaneous ovulation (P = 0.001). Germinal vesicle (GV)-stage oocytes have a thin cortical rim of microfilaments, which is disrupted by exposure to cytochalasin D. After GV breakdown, the first meiotic spindle forms subcortically and parallel to the oolemma. It rotates during anaphase and telophase to extrude the first polar body. This rotation is associated with a local cortical concentration of microfilaments, which is extruded in the first polar body. The second meiotic spindle is orthogonal to the surface, and extrusion of the second polar body is not associated with obvious local changes in cortical actin, resulting in a polar body containing little polymerized actin. The sites of second polar body emission and sperm entry are always in the half of the oocyte opposite the concentrating yolk mass, and are within 60 degrees of each other in most oocytes. During the concentration and eccentric movement of the yolk, microfilaments condense around it. During yolk expulsion, these microfilaments become continuous with those located subcortically. During early cleavage, the cytocortex of the zygote, but not of the extruded yolk mass, stains heavily for polymerised actin. Multiple sites of pericentriolar material are detectable in the cytoplasm of some secondary unfertilized oocytes which, in the presence of taxol, generate large cytasters and pseudospindle structures. After fertilization, a large aster is formed in association with the sperm entry point and serves as the center of an extensive cytoplasmic network of microtubules which surrounds but does not enter the yolk mass. Taxol treatment generates small cytasters within this meshwork and promotes selective stabilization of some periyolk microtubules opposite to the sperm aster.

Actin Cytoskeleton↗

Working memory in infancy: six-month-olds' performance on two versions of the oculomotor delayed response task.

The capacity of 6-month-old infants to maintain information in working memory for several seconds was studied using two versions of an oculomotor delayed response task. Infants were presented with either a cue stimulus in a target location (Experiment 1), or an abstract, central stimulus (Experiment 2) which could be used to predict the peripheral location in which an attractive target stimulus subsequently appeared. Eye movements during delay periods from 600 to 5000 ms were recorded. The results indicated that infants maintained information about stimulus locations in working memory for 3-5 s. These results imply maturity of regions of the prefrontal cortex closely associated with a similar task used in neurophysiological and neuroimaging studies.

Association Learning↗

Posterior circulation infarction: anatomy, pathophysiology, and clinical correlation.

Posterior circulation cerebrovascular disease may be responsible for clinical syndromes that are determined by the vascular territory affected. An anatomic/topographic approach to the brain stem and cerebellum, relating the cross-sectional and functional anatomy to the vascular supply territories, is useful in the analysis of imaging studies of patients with posterior circulation cerebrovascular disease. Knowledge of the typical vascular distributions may be particularly useful for cases that do not show the classical clinical brain stem and cerebellar infarction syndromes. This approach may serve to improve our understanding of cerebrovascular disease in the posterior fossa.

Brain Stem↗

Nausea, vomiting, and retching: the management of the symptom experience.

OBJECTIVES: To examine the physiology of nausea, vomiting, and retching (NVR); the impact of NVR on the patient: current measures to control NVR; and selfcare interventions. DATA SOURCES: Research studies, abstracts, and review articles relating to NVR associated with cancer treatment as well as pharmacological and nonpharmacological interventions. CONCLUSIONS: Management of the individual symptoms of NVR require expert, ongoing assessment of the patient's symptom experience that extends beyond the clinic or hospital visit. Although a number of pharmacological antiemetic agents are currently available and additional antiemetic drugs are in phase II or II trials, nonpharmacological interventions are essential to achieve effective management. IMPLICATIONS FOR NURSING PRACTICE: Continual assessment of the individual's symptom experience is imperative. Effective management of the symptom experience depends on the oncology nurses's ability to implement current knowledge of antiemetic, and other drugs; non-pharmacological interventions; and cost-effective and clinically useful patient outcomes.

Antiemetics↗