Search PubMed⌕ Search

Biomedical subjects

J L Emery

Publications and source records attributed to J L Emery.

At least 19 recordsLinked to original sources

Phosphoinositide 3-kinase in T cell activation and survival.

PI3Ks (phosphoinositide 3-kinases) regulate diverse signalling pathways involved in growth, proliferation, survival, differentiation and metabolism. In T cells, PI3Ks can be activated by a number of different receptors, including the TcR (T cell receptor), co-stimulatory receptors, cytokine receptors and chemokine receptors. However, the specific roles of PI3Ks downstream of these receptors vary. An inactivating mutation in the leucocyte-specific PI3K isoform p110delta results in impaired TcR-dependent proliferation under circumstances where CD28 co-stimulation is blocked or not required. Recruitment and activation of PI3K by CD28 promotes survival by inducing increased expression of Bcl-X(L). However, CD28 engages additional signals that regulate proliferation and interleukin-2 production independently of PI3K. Thus a model emerges whereby PI3K is involved in both TcR and CD28 signalling, but each receptor may only exploit a subset of the signalling pathways potentially controlled by PI3K activation.

Animals↗

Myocardial mechanics and collagen structure in the osteogenesis imperfecta murine (oim).

Because the amount and structure of type I collagen are thought to affect the mechanics of ventricular myocardium, we investigated myocardial collagen structure and passive mechanical function in the osteogenesis imperfecta murine (oim) model of pro-alpha2(I) collagen deficiency, previously shown to have less collagen and impaired biomechanics in tendon and bone. Compared with wild-type littermates, homozygous oim hearts exhibited 35% lower collagen area fraction (P:<0.05), 38% lower collagen fiber number density (P:<0.05), and 42% smaller collagen fiber diameter (P:<0.05). Compared with wild-type, oim left ventricular (LV) collagen concentration was 45% lower (P:<0.0001) and nonreducible pyridinoline cross-link concentration was 22% higher (P:<0.03). Mean LV volume during passive inflation from 0 to 30 mm Hg in isolated hearts was 1.4-fold larger for oim than wild-type (P:=NS). Uniaxial stress-strain relations in resting right ventricular papillary muscles exhibited 60% greater strains (P:<0.01), 90% higher compliance (P:=0.05), and 64% higher nonlinearity (P:<0.05) in oim. Mean opening angle, after relief of residual stresses in resting LV myocardium, was 121+/-9 degrees in oim compared with 45+/-4 degrees in wild-type (P:<0.0001). Mean myofiber angle in oim was 23+/-8 degrees greater than wild-type (P:<0.02). Decreased myocardial collagen diameter and amount in oim is associated with significantly decreased fiber and chamber stiffness despite modestly increased collagen cross-linking. Altered myofiber angles and residual stress may be beneficial adaptations to these mechanical alterations to maintain uniformity of transmural fiber strain. In addition to supporting and organizing myocytes, myocardial collagen contributes directly to ventricular stiffness at high and low loads and can influence stress-free state and myofiber architecture.

Animals↗

The estimation of body mass index and physical attractiveness is dependent on the observer's own body mass index.

A disturbance in the evaluation of personal body mass and shape is a key feature of both anorexia and bulimia nervosa. However, it is uncertain whether overestimation is a causal factor in the development of these eating disorders or is merely a secondary effect of having a low body mass. Moreover, does this overestimation extend to the perception of other people's bodies? Since body mass is an important factor in the perception of physical attractiveness, we wanted to determine whether this putative overestimation of self body mass extended to include the perceived attractiveness of others. We asked 204 female observers (31 anorexic, 30 bulimic and 143 control) to estimate the body mass and rate the attractiveness of a set of 25 photographic images showing people of varying body mass index (BMI). BMI is a measure of weight scaled for height (kg m(- 2)). The observers also estimated their own BMI. Anorexic and bulimic observers systematically overestimated the body mass of both their own and other people's bodies, relative to controls, and they rated a significantly lower body mass to be optimally attractive. When the degree of overestimation is plotted against the BMI of the observer there is a strong correlation. Taken across all our observers, as the BMI of the observer declines, the overestimation of body mass increases. One possible explanation for this result is that the overestimation is a secondary effect caused by weight loss. Moreover, if the degree of body mass overestimation is taken into account, then there are no significant differences in the perceptions of attractiveness between anorexic and bulimic observers and control observers. Our results suggest a significant perceptual overestimation of BMI that is based on the observer's own BMI and not correlated with cognitive factors, and suggests that this overestimation in eating-disordered patients must be addressed directly in treatment regimes.

Anorexia Nervosa↗

Visual cues to female physical attractiveness.

Evolutionary psychology suggests that a woman's sexual attractiveness is based on cues of health and reproductive potential. In recent years, research has focused on the ratio of the width of the waist to the width of the hips (the waist-to-hip ratio (WHR). A low WHR (i.e. a curvaceous body) is believed to correspond to the optimal fat distribution for high fertility, and so this shape should be highly attractive. In this paper we present evidence that weight scaled for height (the body mass index (BMI)) is the primary determinant of sexual attractiveness rather than WHR. BMI is also strongly linked to health and reproductive potential. Furthermore, we show how covariation of apparent BMI and WHR in previous studies led to the overestimation of the importance of WHR in the perception of female attractiveness. Finally, we show how visual cues, such as the perimeter-area ratio (PAR), can provide an accurate and reliable index of an individual's BMI and could be used by an observer to differentiate between potential partners.

Adult↗

A computer-graphic technique for the study of body size perception and body types.

We present a novel approach for measuring body size estimation in normal and eating-disordered women and men. Clinical categories of body types were used as prototypes. By comparing the subjective appearance of a person's body with prototypes, we can understand how different attributes of his or her body shape contribute to perception of body size. After lifelike random distortions have been applied to parts of their body image, individuals adjust their body shapes until they converge on their perceived veridical appearance. Exaggeration and minimization of particular body areas measured with respect to their true shape and with different prototypes can be expressed as numerical deviations. In this way, perceived body size and body attractiveness can be appraised during the course of diagnosis and treatment of eating disorders.

Body Constitution↗

Residual strain in ischemic ventricular myocardium.

Structural remodeling during acute myocardial infarction affects ventricular wall stress and strain. To see whether acute myocardial infarction alters residual stress and strain in the left ventricle (LV), we measured opening angles in rat hearts after 30 minutes of left coronary artery occlusion. The mean opening angle in 18 ischemic hearts (51 +/- 20 deg) was significantly greater than in five sham-operated controls (29 +/- 11 deg, P < 0.05). To determine whether these alterations in residual strain may be associated with strain softening caused by systolic overstretch of the noncontracting ischemic tissue, we also measured opening angles in isolated hearts that had been passively inflated to high LV pressures (120 mmHg). The mean opening angle of the strain-softened hearts was not significantly different from the sham-operated hearts (34 +/- 27 deg, P = 0.74). Mean collagen area fractions in the myocardium were not significantly different between ischemic hearts (0.027 +/- 0.014) and the nonischemic group (0.022 +/- 0.011). Although there were significant differences in opening angles measured with ischemia, they do not appear to be a result of altered extracellular collagen content or softening associated with overstretch. Thus, there is a significant change in residual strain associated with acute ischemia that may be related to changes in collagen fiber structure, myocyte structure, or metabolic state.

Animals↗

Strain softening in rat left ventricular myocardium.

We investigated whether strain softening (or the Mullins effect) may explain the reduced left ventricular stiffness previously associated with the strain-history-dependent preconditioning phenomenon. Passive pressure-volume relations were measured in the isolated, arrested rat heart during LV balloon inflation and deflation cycles. With inflation to a new higher maximum pressure, the pressure-volume relation became less stiff, particularly in the low (diastolic) pressure range, without a significant change in unloaded ventricular volume. In five different loading protocols in which the maximum passive cycle pressure ranged from 10 to 120 mmHg, we measured increases at 10 mmHg in LV volume up to 350 percent of unloaded volume that depended significantly on the history (p < 0.05) and magnitude (p < 0.01) of maximum previous pressure. Although a quasi-linear viscoelastic model based on the pressure-relaxation response could produce a nonlinear pressure-volume relation with hysteresis, it was unable to show any significant change in ventricular stiffness with new maximum pressure. We incorporated a strain softening theory proposed by Johnson and Beatty (1992) into the model by modifying the elastic response with a volume-amplification factor that depended on the maximum previous pressure. This model more accurately reproduced the experimentally observed behavior. Thus, the preconditioning behavior of the myocardium is better explained by strain softening rather than viscoelasticity and may be due to damage to elastic components, rather than the effect of viscous tissue components.

Animals↗

Biaxial mechanics of the passively overstretched left ventricle.

Overstretching the intact ventricle increases global compliance as a function of maximum previously experienced load and may have an important role in the diseased heart, but the corresponding changes in local myocardial mechanics and structure are unknown. Therefore, we measured two-dimensional strain on the left ventricular (LV) epicardium in isolated arrested rat hearts sequentially inflated to increasing cavity pressures of 10, 30, and 120 mmHg. Strains at matched LV pressures increased significantly (P < 0.002) as the maximum pressure previously experienced by the LV (Pmax) increased. Compared with Pmax = 10 mmHg, relative increases in fiber strain for Pmax = 30 and 120 mmHg (100 and 149%, respectively) were significantly greater (P < 0.001) than the corresponding increases in cross-fiber (51 and 78%, respectively) and fiber shear (57 and 86%, respectively) strains. Using an optimized prolate spheroidal finite-element model of the rat LV that reliably reproduced experimental strains, we estimated progressive decreases in epicardial biaxial wall stiffness up to 87% with increasing Pmax that were not different in the fiber and cross-fiber directions. Thus, although passive ventricular overloading causes direction-dependent increases in epicardial strain, these changes are the consequence of local myocardial softening that is actually independent of direction.

Animals↗

Mechanical regulation of myocardial growth during volume-overload hypertrophy in the rat.

Alteration of hemodynamic preload leads to ventricular growth and remodeling, but the specific diastolic mechanical factors, such as myocardial stress or strain, that regulate the hypertrophic response remain unclear. To assess the relative importance of these factors in a model of volume-overload hypertrophy, we measured passive pressure-strain relationships by using ultrasonic crystals in the left ventricle (LV) midwall of rats at 1, 2, 4, and 6 wk after an arteriovenous fistula (AVF). Compared with baseline, mean strain in the muscle fiber direction (Eff) at an end-diastolic (ED) pressure corresponding to the acute elevation in hemodynamic load with AVF increased by 96% from 0.056 +/- 0.028 to 0.110 +/- 0.044 (P < 0.05). Eff returned to normal levels after 6 wk of remodeling (0.045 +/- 0.029). Fiber stress at ED pressure, computed from an optimized prolate spheroidal finite-element model for each group, increased by 82% in the acute response, rose to 5.8 times normal level at 1 wk, and remained substantially elevated (5.2 times) at 6 wk. Concurrently, stiffness in both fiber and cross-fiber directions was increased in all groups and reached a maximum of 10 times normal values by 6 wk. Collagen area fraction, as measured in picrosirius-stained sections of the LV free wall, was not different between 6 wk and control. Thus we conclude that ED strain, rather than stress, is normalized during volume hypertrophy through changes in ventricular geometry and wall stiffness that appear unrelated to changes in collagen content.

Aging↗

Deaths of infants on polystyrene-filled beanbags.

We have reviewed 35 deaths of infants who were found face down on polystyrene-filled beanbags or their equivalents. Most of the deaths were recorded as sudden infant death syndrome. One-half of the children died before the age of 2 months. It is suggested that the bags played a major factor in the babies' deaths and are dangerous for young children. Mechanisms involved in the deaths of infants on beanbags may also be applicable to deaths of infants on other types of bedding.

Accidents, Home↗

An assessment of sources of information in post-perinatal infant death reviews.

The objective of this study was to identify adverse social and medical factors contributory to post-perinatal deaths and at which stage of the case study each factor was found. The sources of information assessed were: (i) recorded data from case notes, laboratory and postmortem findings, and (ii) created information from (a) home interview and (b) case discussion held in the family doctor's office. The deaths were categorized into seven clinicopathological groups and adverse factors into general demographic and personal psychosocial. Among the 87 sequential post-perinatal infant deaths, 325 adverse factors were identified; of these, 125 (38%) were judged to be actionable by the carers. Of 183 (56%) adverse factors found in the case notes, only 36 were actionable. Forty-five more adverse factors were found at home interview; 26 (58%) of these were actionable. At case discussion another 97 adverse factors were revealed; 63 (65%) were actionable, thus proving the most important source of actionable information.

Humans↗

Child abuse, sudden infant death syndrome, and unexpected infant death.

There is now evidence, from a variety of approaches, that indicate that between one tenth and one fifth of children currently diagnosed as cases of sudden infant death syndrome are not natural deaths. There is also equally strong evidence, where the possibility of filicide has been explored, that the majority of children diagnosed as cases of sudden infant death syndrome do die of natural causes.

Child Abuse↗

Recurrence of unexpected infant death.

Families which had experienced two or more unexpected infant deaths were the subject of detailed confidential enquiries, including necropsy examination. Cases were derived from two main sources: first, deaths occurring during a nationwide programme of support for families with a subsequent baby (8 families) plus 2 families from a series of confidential enquiries in Sheffield, and second, direct referrals from paediatricians (17 families). Fifty-seven deaths were studied. Twenty-four families had experienced 2 and three had experienced 3 deaths; 11 deaths (19%) were found to be adequately explained by history or post-mortem findings; 7 (12%) were probably accidental; 31 (55%) were most probably due to an action by one of the parents (filicide); only 5 (9%) were considered to be true or idiopathic sudden infant death syndrome; in 3 (5%) cases there was insufficient information to draw a conclusion. Five (18%) of the families lived in circumstances of serious social deprivation. A history of psychiatric illness was present in one or both parents in 18 (67%) of the families.

Age Distribution↗