Variations in human corneal endothelial cell morphology and permeability to fluorescein with age

Fluorophotometry with topically applied fluorescein and endothelial cell photography were performed on 80 normal subjects (age 5-79 yr). Variations in endothelial cell morphology and function, flow of aqueous humor, and intraocular pressure were recorded. The mean endothelial cell size was 332.3 +/- 46.3 micron 2. A 28% increase in endothelial cell size was measured over the eight decades (r = 0.53, P less than 0.001). The coefficient of variation of cell size also increased with age (r = 0.41, P less than 0.001). The percentage of hexagonal endothelial cells decreased by 14% (r = -0.48, P less than 0.001), while the percentage of pentagonal and heptagonal cells increased by 50% (r = 0.44, P less than 0.001) and 40% (r = 0.33, P less than 0.002), respectively, with age. The mean endothelial permeability to fluorescein was 4.03 +/- 0.63 x 10(-4) cm min-1. A 23% increase in endothelial permeability with age was observed (r = 0.44, P less than 0.001). No change in central corneal thickness or endothelial pump rate was found. Flow of aqueous humor remained stable with age, despite a 25% increase in intraocular pressure (r = 0.50, P less than 0.001). Polarization of fluorescence of fluorescein in the corneal stroma decreased with age (r = -0.46, P less than 0.001). We conclude that with age the human corneal endothelium becomes morphologically less regular and may become more permeable to fluorescein.     

Melatonin receptors and signal transduction during development in Siberian hamsters (Phodopus sungorus).

Maternal melatonin communicates daylength information to the fetus in Siberian hamsters. Fetal sensitivity to melatonin declines near birth. In this report, we describe melatonin receptor distribution and a second messenger response to melatonin in Siberian hamsters during the perinatal period. The sites of high-affinity 2-[125I]iodomelatonin ([125I]MEL) binding were generally similar throughout the perinatal period. The non-hydrolyzable GTP analog, guanosine-5'-O-(3-thiotriphosphate) (100 microM) inhibited [125I]MEL binding at each age, suggesting the melatonin receptors are associated with guanine nucleotide binding proteins (G proteins). Furthermore, melatonin (10 nM) inhibited forskolin-stimulated cAMP accumulation in median eminence/pars tuberalis (ME/PT) explants as early as 4 days before birth, when sensitivity to melatonin in vivo is high. The cAMP regulatory system appeared disrupted on the day of birth, in that forskolin (10 microM) stimulation of cAMP accumulation was reduced, and melatonin did not inhibit cAMP accumulation stimulated by forskolin. A higher forskolin dose (100 microM) elevated cAMP levels more clearly on the day of birth, and melatonin inhibited forskolin-stimulated cAMP accumulation. These results suggest that the decreased physiological responsiveness to melatonin at the end of gestation may be due to alterations in the cAMP regulatory system.     

Isolation and characterization of an olfactory mutant in Drosophila with a chemically specific defect.

A Drosophila mutant was isolated and shown to exhibit defective response to the chemical odorant benzaldehyde in two distinctly different behavioral assays. The defect exhibited chemical specificity: response to three other chemicals was normal. The mutant also showed abnormalities in pigmentation and fertility. Genetic mapping and complementation analysis provide evidence that the olfactory, pigmentation, and fertility defects arise as a result of a lesion at the pentagon locus. The specificity of the olfactory defect suggests the possibility that the mutation may define a molecule required in reception, transduction, or processing of a specific subset of chemical information in the olfactory system.     

Human balance and posture control during standing and walking

The common denominator in the assessment of human balance and posture is the inverted pendulum model. If we focus on appropriate versions of the model we can use it to identify the gravitational and acceleration perturbations and pinpoint the motor mechanisms that can defend against any perturbation.

We saw that in quiet standing an ankle strategy applies only in the A/P direction and that a separate hip load/unload strategy by the hip abd/adductors is the totally dominant defence in the M/L direction when standing with feet side by side. In other standing positions (tandem, or intermediate) the two mechanisms still work separately, but their roles reverse. In the tandem position M/L balance is an ankle mechanism (invertors/evertors) while in the A/P direction a hip load/unloading mechanism dominates.

During initiation and termination of gait these two separate mechanisms control the trajectory of the COP to ensure the desired acceleration and deceleration of the COM. During initiation the initial acceleration of the COM forward towards the stance limb is achieved by a posterior and lateral movement of the COP towards the swing limb. After this release phase there is a sudden loading of the stance limb which shifts the COP to the stance limb. The COM is now accelerated forward and laterally towards the future position of the swinging foot. Also M/L shifts of the COP were controlled by the hip abductors/adductors and all A/P shifts were under the control of the ankle plantar/dorsiflexors. During termination the trajectory of both COM and COP reverse. As the final weight-bearing on the stance foot takes place the COM is passing forward along the medial border of that foot. Hyperactivity of that foot's plantarflexors takes the COP forward and when the final foot begins to bear weight the COP moves rapidly across and suddenly stops at a position ahead of the future position of the COM. Then the plantarflexors of both feet release and allow the COP to move posteriorly and approach the COM and meet it as quiet stance is achieved. The inverted pendulum model permitted us to understand the separate roles of the two mechanisms during these critical unbalancing and rebalancing periods.

During walking the inverted pendulum model explained the dynamics of the balance of HAT in both the A/P and M/L directions. Here the model includes the couple due to the acceleration of the weight-bearing hip as well as gravitational perturbations. The exclusive control of A/P balance and posture are the hip extensors and flexors, while in the M/L direction the dominant control is with the hip abductors with very minor adductor involvement. At the ankle the inverted pendulum model sees the COM passing forward along the medial border to the weight-bearing foot. The model predicts that during single support the body is falling forward and being accelerated medially towards the future position of the swing foot. The model predicts an insignificant role of the ankle invertors/evertors in the M/L control. Rather, the future position of the swing foot is the critical variable or more specifically the lateral displacement from the COM at the start of single support. The position is actually under the control of the hip abd/adductors during the previous early swing phase.

The critical importance of the hip abductors/adductors in balance during all phases of standing and walking is now evident. This separate mechanism is important from a neural control perspective and clinically it focuses major attention on therapy and potential problems with some surgical procedures. On the other hand the minuscule role of the ankle invertors/evertors is important to note. Except for the tandem standing position these muscles have negligible involvement in balance control.     

Shared care: a review of the literature

This review examines broad issues of concern regarding the primary/secondarycare interface. The main purpose was to identify areas of goodpractice which could be adapted for more general use. One ofthe most fundamental aspects identified was communication, whichis discussed in some detail. Also covered are shared prescribingand disease management. The data suggest that the most effectivesystem(s) of shared care has yet to be established. Furtherqualitative and economic evaluations are required, taking intoaccount patient preferences. Although the literature does describecertain practice exemplars, it is clear that inter- and intra-professionalcommunication continues to be a problem. Whilst informationtechnology may provide some of the solutions, it is concludedthat a culture change, which compels health professionals tomake sharing of patient information a much higher priority,is reauired. Keywords. Shared care, seamless care, hospital, general practice, family practice.     

Asbestos-related focal lung masses: manifestations on conventional and high-resolution CT scans

In 260 asbestos-exposed individuals evaluated by means of computed tomography (CT), 43 unsuspected pulmonary masses were found in 27 individuals. The masses included fissural pleural plaques (n = 10), dense fibrotic bands (n = 3), round atelectasis (n = 11), carcinomas (n = 3), and other presumed benign masses (n = 16). The most helpful features in the diagnosis of rounded atelectasis with CT were (a) contiguity to areas of diffuse pleural thickening, (b) a lentiform or wedge-shaped outline, (c) evidence of volume loss in the adjacent lung, and (d) a characteristic "comet tail" of vessels and bronchi sweeping into the margins of the mass. Less advanced areas of focal atelectasis had fewer classic features. Intrafissural pleural plaques were readily identified with high-resolution CT. In asbestos-related masses, the demonstration of stability over time is necessary. Careful interpretation of CT and high-resolution CT features and close surveillance can obviate the need for biopsy in the majority of instances.     

Health locus of control and participation in physical activity

Abstract The purpose of this study was to determine the physical activity participation patterns of college students when defined by their Health Locus of Control orientation. One thousand thirty-three college-aged students completed the Wellness Activity Profile, a questionnaire that yielded data on Health Locus of Control and self-reported frequency of participation in physical activities. Discriminant analyses indicated that the combination of physical activities associated with internally and externally oriented students were different for both males and females. Participation in high caloric expenditure activities was more frequent among internal subjects (Male: bicycling, volleyball, other individual sports, and snorkel/scuba diving; Female: basketball, weight training, tennis, fast walking/jogging/running, and judo/karate), while low caloric expenditure activities were associated with an external orientation (Male: baseball/softball, sailing, fishing, golf, and other recreational sports; Female: track and field jumping and fishing).     

The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas

The majority of pediatric anaplastic large cell lymphomas (ALCLs) carry the t(2;5)(p23;q35) chromosomal translocation that juxtaposes the dimerization domain of nucleophosmin with anaplastic lymphoma kinase (ALK). The nucleophosmin-ALK fusion induces constitutive, ligand-independent activation of the ALK tyrosine kinase leading to aberrant activation of cellular signaling pathways. To study the early consequences of ectopic ALK activation, a GyrB-ALK fusion was constructed that allowed regulated dimerization with the addition of coumermycin. Expression of the fusion protein caused a coumermycin-dependent increase in cellular tyrosine phosphorylation and c-Myc immunoreactivity, which was paralleled by a rise in c-myc RNA. To assess the clinical relevance of this observation, c-Myc expression was determined in pediatric ALK-positive and -negative lymphomas. Co-expression of c-Myc and ALK was seen in tumor cells in 15 of 15 (100%) ALK-positive ALCL samples, whereas no expression of either ALK or c-Myc was seen in six of six cases of ALK-negative T-cell lymphoma. C-Myc may be a downstream target of ALK signaling and its expression a defining characteristic of ALK-positive ALCLs.