Motion perception deficits in glaucomatous optic neuropathy

AbstractThe mechanisms mediating impaired motion perception in glaucoma were investigated. Direction discrimination thresholds for low (4.2 deg/sec) and high (12.5 deg/sec) velocity random-dot kinematograms were measured in controls and patients with glaucoma or ocular hypertension. Thresholds were elevated significantly in glaucoma patients and individual ocular hypertensives. Threshold elevations were not due to blur or pupil size. After compensating for motion reversals, high but not low velocity thresholds remained elevated. Only high velocity thresholds correlated with differential luminance sensitivity. A hypothesis that different mechanisms mediate glaucoma-induced deficits at high and low velocities is presented

Variation in the carotid bifurcation geometry of young versus older adults: Implications for geometric risk of atherosclerosis

Background and Purpose - Retrospective analysis of clinical data has demonstrated major variations in carotid bifurcation geometry, in support of the notion that an individual\u27s vascular anatomy or local hemodynamics may influence the development of atherosclerosis. On the other hand, anecdotal evidence suggests that vessel geometry is more homogenous in youth, which would tend to undermine this geometric risk hypothesis. The purpose of our study was to test whether the latter is indeed the case. Methods - Cross-sectional images of the carotid bifurcations of 25 young adults (24±4 years) and a control group of 25 older subjects (63±10 years) were acquired via MRI. Robust and objective techniques were developed to automatically characterize the 3D geometry of the bifurcation and the relative dimensions of the internal, external, and common carotid arteries (ICA, ECA, and CCA, respectively). Results - Young vessels exhibited significantly less interindividual variation in the following geometric parameters: bifurcation angle (48.5±6.3° versus 63.6±15.4°); ICA angle (21.6±6.7° versus 29.2±11.3°); CCA tortuosity (0.010±0.003 versus 0.014±0.011); ICA tortuosity (0.025±0.013 versus 0.086±0.105); ECA/CCA diameter ratio (0.81±0.06 versus 0.75±0.13), ICA/CCA (0.81 ±0.06 versus 0.77±0.12) diameter ratio, and bifurcation area ratio (1.32±0.15 versus 1.19±0.35). Conclusions - The finding of more modest interindividual variations in young adults suggests that, if there is a geometric risk for atherosclerosis, its early detection may prove challenging. Taken together with the major interindividual variations seen in older vessels, it suggests a more complex interrelationship between vascular geometry, local hemodynamics, vascular aging, and atherosclerosis, the elucidation of which now calls for prospective studies. © 2005 American Heart Association, Inc

Pain patterns in patients with polycystic kidney disease

Pain patterns in patients with polycystic kidney disease.BackgroundPain is a common problem in patients with polycystic kidney disease (PKD), but patterns have not been characterized as to frequency and severity. Physicians should be aware of pain problems so an approach to chronic pain management can be pursued.MethodsOne hundred seventy-one completed questionnaires out of 300 distributed to PKD patients whose renal function ranged from normal to end-stage renal disease (ESRD) were analyzed. Age at diagnosis of PKD was documented, and patients noted how the diagnosis was made. Location, severity, and frequency of pain were characterized. The Visual Analogue Scale (VAS) was used to measure pain intensity.ResultsThere were 94 females and 77 male respondents, with a mean age of 47.4 years. Initial diagnosis of PKD occurred at a mean age of 31.6 years. Caucasians comprised 92.2% of the respondents. Patients' symptoms, a family history of PKD, and discovery of PKD during evaluation for hypertension or hematuria were the most frequent factors that led to the diagnosis. Order of frequency of pain was: low back pain, abdominal pain, headache, chest pain, and leg pain. Severity of pain, documented by the VAS intensity, was 4 to 5/10 in the majority of patients.ConclusionPain, which can be diffuse, is the most frequent symptom that led to the diagnosis of PKD in patients who responded to this questionnaire, and occurs with greater frequency than generally appreciated. Physicians need to obtain a detailed history about pain in their PKD population so as to allow an approach to pain management

Gauge Dependence of Four-Fermion QED Green Function and a Breakdown of Gauge Invariance in Atom-Like Bound State Calculations

We derive a relation between four-fermion QED Green functions of different covariant gauges which defines the gauge dependence completely. We use the derived gauge dependence to check the gauge invariance of atom-like bound state calculations. We find that the existing QED procedure does not provide gauge invariant binding energies. A way to a corrected gauge invariant procedure is pointed out.Comment: 11 pages, LaTex, no figures, to appear in Nucl. Phys.

Mouse spleen lymphoblasts generated in vitro. Their replication and differentiation in vitro

Mouse spleen lymphoblasts induced with lipopolysaccharide and fetal calf serum were obtained in high yield and purity in their first proliferative cell cycle by floatation in dense bovine plasma albumin columns (3). The blasts were maintained in vitro for 3 more days. The cultures were examined in bulk on each day, and in addition, those cells in S phase initially were tagged with [(3)H]thymidine and followed continuously in vitro. Grain count dilution data indicated that most blasts divided but twice over a 2- to 3-day interval in vitro. [(3)H]Thymidine pulse radiolabeling and flow microfluorometry suggested that at least 50-70 percent of the proliferating blasts withdrew from proliferative activity after 2-3 days of culture. Morphologic studies demonstrated that lymphoblasts persisted as such for 1-2 days in vitro and then matured into typical plasma cells. Many of the blastprogeny had small nuclei and considerable basophilic cytoplasm on Giemsa-stained cell smears; abundant rough endoplasmic reticulum by electron microscopy; and readily detectable cytoplasmic Ig by immunocytochemistry. Reversion of blasts to small lymphocytes could not be detected; however, some blasts persisted even after 3 days of culture. The viability of the cultured lymphoblast was followed by initially tagging the cells with [(3)H]thymidine as well as several other techniques. Little cell death was documented during the first day of culture. The number of labeled progeny increased twofold whereas the grain count halved. But 40- 50 percent of the cell-associated label was lost during each of the second and third days, and fewer labeled progeny than predicted by grain count dilution were identified. The culture medium could not be implicated in this loss of lymphoblast progeny, and we suggest that the maturation of the lymphoblast to a short-lived plasma cell was responsible. Therefore mitogen-stimulated B blasts seem to mature into typical plasma cells after just two cycles of cell division. The plasma cells resemble those produced in situ during an immune response in their cytologic features, withdrawal from active proliferative activity, and short life-span

Nanosensor Detection of an Immunoregulatory Tryptophan Influx/Kynurenine Efflux Cycle

Mammalian cells rely on cellular uptake of the essential amino acid tryptophan. Tryptophan sequestration by up-regulation of the key enzyme for tryptophan degradation, indoleamine 2,3-dioxygenase (IDO), e.g., in cancer and inflammation, is thought to suppress the immune response via T cell starvation. Additionally, the excreted tryptophan catabolites (kynurenines) induce apoptosis of lymphocytes. Whereas tryptophan transport systems have been identified, the molecular nature of kynurenine export remains unknown. To measure cytosolic tryptophan steady-state levels and flux in real time, we developed genetically encoded fluorescence resonance energy transfer nanosensors (FLIPW). The transport properties detected by FLIPW in KB cells, a human oral cancer cell line, and COS-7 cells implicate LAT1, a transporter that is present in proliferative tissues like cancer, in tryptophan uptake. Importantly, we found that this transport system mediates tryptophan/kynurenine exchange. The tryptophan influx/kynurenine efflux cycle couples tryptophan starvation to elevation of kynurenine serum levels, providing a two-pronged induction of apoptosis in neighboring cells. The strict coupling protects cells that overproduce IDO from kynurenine accumulation. Consequently, this mechanism may contribute to immunosuppression involved in autoimmunity and tumor immune escape

Roughening of the (1+1) interfaces in two-component surface growth with an admixture of random deposition

We simulate competitive two-component growth on a one dimensional substrate of $L$ sites. One component is a Poisson-type deposition that generates Kardar-Parisi-Zhang (KPZ) correlations. The other is random deposition (RD). We derive the universal scaling function of the interface width for this model and show that the RD admixture acts as a dilatation mechanism to the fundamental time and height scales, but leaves the KPZ correlations intact. This observation is generalized to other growth models. It is shown that the flat-substrate initial condition is responsible for the existence of an early non-scaling phase in the interface evolution. The length of this initial phase is a non-universal parameter, but its presence is universal. In application to parallel and distributed computations, the important consequence of the derived scaling is the existence of the upper bound for the desynchronization in a conservative update algorithm for parallel discrete-event simulations. It is shown that such algorithms are generally scalable in a ring communication topology.Comment: 16 pages, 16 figures, 77 reference

Joint analysis of stressors and ecosystem services to enhance restoration effectiveness

With increasing pressure placed on natural systems by growing human populations, both scientists and resource managers need a better understanding of the relationships between cumulative stress from human activities and valued ecosystem services. Societies often seek to mitigate threats to these services through large-scale, costly restoration projects, such as the over one billion dollar Great Lakes Restoration Initiative currently underway. To help inform these efforts, we merged high-resolution spatial analyses of environmental stressors with mapping of ecosystem services for all five Great Lakes. Cumulative ecosystem stress is highest in near-shore habitats, but also extends offshore in Lakes Erie, Ontario, and Michigan. Variation in cumulative stress is driven largely by spatial concordance among multiple stressors, indicating the importance of considering all stressors when planning restoration activities. In addition, highly stressed areas reflect numerous different combinations of stressors rather than a single suite of problems, suggesting that a detailed understanding of the stressors needing alleviation could improve restoration planning. We also find that many important areas for fisheries and recreation are subject to high stress, indicating that ecosystem degradation could be threatening key services. Current restoration efforts have targeted high-stress sites almost exclusively, but generally without knowledge of the full range of stressors affecting these locations or differences among sites in service provisioning. Our results demonstrate that joint spatial analysis of stressors and ecosystem services can provide a critical foundation for maximizing social and ecological benefits from restoration investments. www.pnas.org/lookup/suppl/doi:10.1073/pnas.1213841110/-/DCSupplementa