Angiogenesis is coordinated with follicular cell growth in goitrogenesis. The angiopoietins, Ang-1 and Ang-2, are angiogenic growth factors acting through Tie-2, a tyrosine kinase receptor. We have ...examined the expression and regulation of the angiopoietins and Tie-2 in human and rat thyroids. In human goiters there was increased Tie-2 immunostaining, compared with that in normal thyroids, on both follicular and endothelial cells. In an induced goiter in rats, in situ hybridization showed increased expression of messenger ribonucleic acids (mRNAs) for Tie-2 and Ang-1 in follicular cells. As Tie-2 has previously been believed to be restricted to cells of endothelial lineage in adults, we examined its expression further in isolated follicular cells. Tie-2 and Ang-1 mRNA expression in human thyrocytes was confirmed by ribonuclease protection assay. Ang-2 mRNA was not detected in human cultures or rat thyroids. In both human follicular cell cultures and FRTL-5 cells, immunoblotting showed that Tie-2 expression was increased by TSH and agents that increased intracellular cAMP. In conclusion, we have demonstrated the expression of Tie-2 and Ang-1 in thyroid epithelial and endothelial cells, and have shown the regulation of Tie-2 by TSH and cAMP in follicular cells. Tie-2 expression is increased in goiter in both humans and rats, consistent with a role in goitrogenesis.
Anderson-Fabry Disease (AFD) is a storage disease that mimics hypertrophic cardiomyopathy. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance occurs in approximately 50% of ...patients in the basal inferolateral LV wall, but how an intracellular storage disease causes focal LGE is unknown. We present a whole-heart histological validation that LGE is caused by focal myocardial collagen scarring. This scarring may be the substrate for electrical re-entry and sudden arrhythmic death. The reasons for this distribution of fibrosis are unclear, but may reflect inhomogeneous left ventricular wall stress.
A system is described for calculating volume from a sequence of multiplanar 2D ultrasound images. Ultrasound images are captured using a video digitising card (Hauppauge Win/TV card) installed in a ...personal computer, and regions of interest transformed into 3D space using position and orientation data obtained from an electromagnetic device (Polhemus, Fastrak). The accuracy of the system was assessed by scanning 10 water filled balloons (13–141 mL), 10 kidneys (147–200 mL) and 16 fetal livers (8–37 mL) in water using an Acuson
128XP
10
(5 MHz curvilinear probe). Volume was calculated using the ellipsoid, planimetry, tetrahedral and ray tracing methods and compared with the actual volume measured by weighing (balloons) and water displacement (kidneys and livers). The mean percentage error for the ray tracing method was 0.9 ± 2.4%, 2.7 ± 2.3%, 6.6 ± 5.4% for balloons, kidneys and livers, respectively. So far the system has been used clinically to scan fetal livers and lungs, neonate brain ventricles and adult prostate glands.
A set of nomograms based on the Dubbo Osteoporosis Epidemiology Study predicts the five- and ten-year absolute risk of fracture using age, bone mineral density and history of falls and low-trauma ...fracture. We assessed the discrimination and calibration of these nomograms among participants in the Canadian Multicentre Osteoporosis Study.
We included participants aged 55-95 years for whom bone mineral density measurement data and at least one year of follow-up data were available. Self-reported incident fractures were identified by yearly postal questionnaire or interview (years 3, 5 and 10). We included low-trauma fractures before year 10, except those of the skull, face, hands, ankles and feet. We used a Cox proportional hazards model.
Among 4152 women, there were 583 fractures, with a mean follow-up time of 8.6 years. Among 1606 men, there were 116 fractures, with a mean follow-up time of 8.3 years. Increasing age, lower bone mineral density, prior fracture and prior falls were associated with increased risk of fracture. For low-trauma fractures, the concordance between predicted risk and fracture events (Harrell C) was 0.69 among women and 0.70 among men. For hip fractures, the concordance was 0.80 among women and 0.85 among men. The observed fracture risk was similar to the predicted risk in all quintiles of risk except the highest quintile of women, where it was lower. The net reclassification index (19.2%, 95% confidence interval CI 6.3% to 32.2%), favours the Dubbo nomogram over the current Canadian guidelines for men.
The published nomograms provide good fracture-risk discrimination in a representative sample of the Canadian population.
The Electric and Magnetic Field Instrument and Integrated Science (EMFISIS) investigation on the NASA Radiation Belt Storm Probes (now named the Van Allen Probes) mission provides key wave and very ...low frequency magnetic field measurements to understand radiation belt acceleration, loss, and transport. The key science objectives and the contribution that EMFISIS makes to providing measurements as well as theory and modeling are described. The key components of the instruments suite, both electronics and sensors, including key functional parameters, calibration, and performance, demonstrate that EMFISIS provides the needed measurements for the science of the RBSP mission. The EMFISIS operational modes and data products, along with online availability and data tools provide the radiation belt science community with one the most complete sets of data ever collected.
A model for predicting the response of a conductimetric urea biosensor was developed and validated experimentally. The biosensor under consideration is formed by immobilizing the enzyme urease onto ...the surface of a planar interdigitated electrode array. The enzymatic hydrolysis of urea produces ionic products, such as ammonium and bicarbonate ions, which increase the electrical conductivity of the solution proximal to the electrode array. The model combines an analysis of the diffusive transport and enzymatic hydrolysis of urea in the vicinity of the biosensor surface with an electric fields model for calculating interelectrode impedance. To validate the model, urea biosensors were constructed by immobilizing urease to the interdigit space of microfabricated interdigitated electrodes. The responses of these sensors were investigated in urea solutions prepared in deionized water, at concentrations ranging from 10 μM to 5 mM. Using reasonable estimates for the parameters, the predictions of the model were in good agreement with the experimental data over the entire range of concentrations.
We sought to identify factors associated with mortality in persons recently diagnosed with probable Alzheimer's disease (AD).
Predicting mortality in AD in needed both in patient care and public ...health planning. Previous studies have identified several factors which contribute to mortality in AD, but few longitudinal studies of population-based cohorts exist.
In a longitudinal follow-up study 327 patients with newly diagnosed probable AD (mean Mini-Mental State Examination MMSE score of 20) from a large, stable health maintenance organization were identified. Demographic characteristics, dementia severity, and comorbid conditions were identified at enrollment. Patients were followed longitudinally (median 3.3 years, total 898 person-years). Baseline characteristics were used to predict survival in univariate and multivariate models.
Increased mortality was seen in patients with probable AD (9.0 deaths per 100 person-years) compared with the community population adjusted for age and gender (4.3 deaths per 100 person-years). On univariate analysis we found increased age, male gender, impairment on MMSE or Blessed dementia rating scale (DRS), rate of MMSE decline, wandering or agitation, vascular disease, and sensory impairment affecting the ability to read or hear to be moderately associated with decreased survival. After adjusting for age and gender in a multivariate model, Blessed DRS score and sensory impairment affecting the ability to read were independently associated with decreased survival.
Short-term mortality is increased in patients newly diagnosed with probable AD. Measures of dementia severity, measures of general debility, and vascular disease are associated with increased mortality. Of these, general debility and sensory impairment were more strongly associated with shortened survival.
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