Background and purpose:
Trabecular meshwork (TM) is an ocular tissue involved in the regulation of aqueous humour outflow and intraocular pressure (IOP). CB1 receptors (CB1) are present in TM and ...cannabinoid administration decreases IOP. CB1 signalling was investigated in a cell line derived from human TM (hTM).
Experimental approach:
CB1 signalling was investigated using ratiometric Ca2+ imaging, western blotting and infrared In‐Cell Western analysis.
Key results:
WIN55212‐2, a synthetic aminoalkylindole cannabinoid receptor agonist (10–100 μM) increased intracellular Ca2+ in hTM cells. WIN55,212‐2‐mediated Ca2+ increases were blocked by AM251, a CB1 antagonist, but were unaffected by the CB2 antagonist, AM630. The WIN55,212‐2‐mediated increase in Ca2+i was pertussis toxin (PTX)‐insensitive, therefore, independent of Gi/o coupling, but was attenuated by a dominant negative Gαq/11 subunit, implicating a Gq/11 signalling pathway. The increase in Ca2+i was dependent upon PLC activation and mobilization of intracellular Ca2+ stores. A PTX‐sensitive increase in extracellular signal‐regulated kinase (ERK1/2) phosphorylation was also observed in response to WIN55,212‐2, indicative of a Gi/o signalling pathway. CB1‐Gq/11 coupling to activate PLC‐dependent increases in Ca2+ appeared to be specific to WIN55,212‐2 and were not observed with other CB1 agonists, including CP55,940 and methanandamide. CP55940 produced PTX‐sensitive increases in Ca2+i at concentrations ≥15 μM, and PTX‐sensitive increases in ERK1/2 phosphorylation.
Conclusions and implications:
This study demonstrates that endogenous CB1 couples to both Gq/11 and Gi/o in hTM cells in an agonist‐dependent manner. Cannabinoid activation of multiple CB1 signalling pathways in TM tissue could lead to differential changes in aqueous humour outflow and IOP.
British Journal of Pharmacology (2007) 152, 1111–1120; doi:10.1038/sj.bjp.0707495; published online 8 October 2007
Aging has been associated with a decline in memory abilities dependent on hippocampal processing. We investigated whether the functional interactions between the hippocampus and related cortical ...areas were modified by age. Young and old subjects' brain activity was measured using positron emission tomography (PET) while they performed a short-term memory task (delayed visual discrimination) in which they determined which of two successively presented sine-wave gratings had the highest spatial frequency. Behavioral performance was equal for the two groups. Partial least squares (PLS) analysis of PET images identified a hippocampal voxel whose activity was similarly correlated with performance across groups. Using this voxel as a seed, a second PLS analysis identified cortical regions functionally connected to the hippocampus. Quantification of the neural interactions with structural equation modeling suggested that a different hippocampal network supported performance in the elderly. Unlike the neural network engaged by the young, which included prefrontal cortex Brodmann's area (BA) 10, fusiform gyrus, and posterior cingulate gyrus, the network recruited by the old included more anterior areas, i.e., dorsolateral prefrontal cortex (BA 9/46), middle cingulate gyrus, and caudate nucleus. Recruitment of a distinct corticolimbic network for visual memory in the elderly suggests that age-related neurobiological deterioration not only results in focal changes but also in the modification of large-scale network operations.
Purpose
To identify the optimal size threshold and to assess the prognostic significance of supradiaphragmatic lymph nodes at initial presentation of patients with high-grade serous ovarian cancer ...(HGSC).
Methods
This IRB-approved, HIPAA-compliant retrospective study included baseline pretreatment staging abdominal CTs of 88 women (mean age 62 years, SD 10.4, range 29–85) with FIGO stage III HGSC. Patients with stage IV disease were excluded due to worse prognosis and management guided by distant metastases. Two fellowship-trained radiologists independently reviewed abdominal CTs to record the presence of supradiaphragmatic nodes, abdominal lymphadenopathy, peritoneal carcinomatosis, and ovarian mass. Progression-free survival (PFS) and overall survival (OS) were recorded after median 79 months follow-up (IQR 58–115, range 13–144). The optimal short-axis size threshold for supradiaphragmatic lymphadenopathy was determined by correlating 3, 4, 5, 6, 7, and 10 mm thresholds with PFS and OS using Log-rank test. Prognostic significance of supradiaphragmatic lymphadenopathy was assessed using Cox proportional hazards models.
Results
There was good interobserver agreement for presence (
κ
= 0.65, 95%CI 0.51–0.79) and size (ICC = 0.77, 95%CI 0.66–0.86) of supradiaphragmatic nodes. 5 mm short-axis size threshold was associated with significantly shorter PFS (median 14 months, IQR 11–17 vs. 23 months, IQR 12–59;
p
= 0.02) and OS (median 44 months, IQR 27–69 vs. 65 months, IQR 45–96;
p
= 0.03). Total 38/88 (43%) patients had supradiaphragmatic lymphadenopathy. On Cox proportion hazards analysis, supradiaphragmatic lymphadenopathy was significantly associated with shorter PFS (
p
= 0.02; HR 1.81, 95%CI 1.11–2.96) and OS (
p
= 0.008; HR 2.11, 95%CI 1.21–3.65).
Conclusion
In patients with stage III HGSC, supradiaphragmatic lymphadenopathy is associated with shorter PFS and OS. Further studies would help determine its implications on staging, decision regarding neoadjuvant therapy, and surgical technique.
Isoscaling parameters α and β have been explored as a function of breakup angle in binary excited projectile-like fragment decays produced in collisions of 70Zn+ 70Zn and 64Zn+ 64Zn at 35 MeV per ...nucleon. In this analysis, focus was placed on isoscaling the second heaviest fragment with 4 ≤ ZL ≤ 8 emitted from the excited projectile-like fragment in events that contained a heavy fragment with ZH ≥ 12. The breakup orientation θprox was defined as the angle between the heavy and light fragments’ center-of-mass velocity and the fragment pairs’ relative velocity. Breakups between 0° < θprox ≤ 80° have been shown to be dominated by dynamical contributions, while break-up angles of θprox > 100° are predominantly statistical. Historically, isoscaling has often been understood and applied in a statistical context, assuming that the fragments are produced after statistical equilibrium is achieved. Finally, studying isoscaling parameters as a function of θprox reveals the sensitivity of α and β to the mechanism of fragment production.
The dual-axis duo-lateral position-sensitive silicon detector was developed to detect charged particles with high quality position and energy resolution. When these detectors were used with ...conventional signal processing electronics, an empirically determined correction was used to improve energy resolution. In this work, the waveforms from the detector after preamplification are studied in detail to investigate position information contained in the waveforms. A 7.22 MeV/nucleon alpha particle beam was impinged directly on a masked dual-axis duo-lateral detector. Data obtained using a 228Th alpha particle source was also used. By studying the waveform characteristics that give rise to the position-dependent distortions, a new summed trigger analysis method has been developed to significantly improve linearity in position reconstruction without sacrificing energy resolution.
Aligned fragment emission associated with peripheral and midperipheral dissipative collisions of {sup 124}Xe+{sup 124}Sn at E/A=50 MeV is examined. Binary decay of the excited projectile-like ...fragment (PLF*) is correlated with significant velocity damping from the projectile velocity. Both a forward emission component, attributed to standard statistical emission, and a backward component are observed. The backward component arises from both statistical and dynamical decay processes. This backward component manifests a strong alignment with the direction of the PLF* velocity and is found to depend sensitively on the atomic number of the light fragment, Z{sub L}, and the velocity of the PLF{sup *}. The yield of the backward component is significantly enhanced relative to the forward component. The composition of fragments emitted in the backward direction reveals that a correlation between alignment and neutron excess exists for fragments with Z<8. From the measured asymmetry of the angular distributions, the angular distribution for dynamical fragment emission is deduced. Comparison with a schematic one-dimensional Langevin model allows extraction of both the magnitude and the dependence on Z{sub L} of the transient initial deformation of the PLF*. Fragment emission times of the order of 0.25-1.5x10{sup -21} s are extracted.
This study assessed the interobserver and intraobserver grading reliability of the Keith-Wagener-Barker (KWB) system to the proposed Mitchell-Wong 'simplified' three-grade classification for ...hypertensive retinopathy.
Digital retinal images of normal and hypertensive human fundii (n = 50 per group) were randomly graded by an optometrist and an ophthalmologist using the two systems. Interobserver agreement was compared to a 'gold standard' research grader. Intraobserver agreement was assessed through a repeat grading after 6 months. Cohen's kappa coefficients were used to assess the degree of agreement.
Both clinicians demonstrated a good level of agreement with the KWB and simplified classification compared with a 'gold standard' grader; there was no significant difference in the level of agreement for either of the two classification methods for either observer. The simplified classification was found to be equally as efficacious as the KWB system with respect to interobserver and intraobserver agreement for both practitioners.
These findings indicate that the simplified classification of hypertensive retinopathy is both reliable and repeatable. The advantage of the simplified method over the KWB system in correlating retinal microvascular signs to incident cardiovascular risk supports its adoption in clinical practice.
SπRIT: A time-projection chamber for symmetry-energy studies Shane, R.; McIntosh, A.B.; Isobe, T. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
06/2015, Letnik:
784, Številka:
C
Journal Article
Recenzirano
Odprti dostop
A time-projection chamber (TPC) called the SAMURAI Pion-Reconstruction and Ion-Tracker (SπRIT) has recently been constructed at Michigan State University as part of an international effort to ...constrain the symmetry-energy term in the nuclear Equation of State (EoS). The SπRIT TPC will be used in conjunction with the SAMURAI spectrometer at the Radioactive Isotope Beam Factory (RIBF) at RIKEN to measure yield ratios for pions and other light isospin multiplets produced in central collisions of neutron-rich heavy ions, such as 132Sn+124Sn. The SπRIT TPC can function both as a TPC detector and as an active target. It has a vertical drift length of 50cm, parallel to the magnetic field. Gas multiplication is achieved through the use of a multi-wire anode plane. Image charges, produced in the 12096 pads, are read out with the recently developed Generic Electronics for TPCs.
The investigation of the isospin dependence of multifragmentation reactions relies on precise reconstruction of the fragmenting source. The criteria used to assign free emitted neutrons, detected ...with the TAMU Neutron Ball, to the quasi-projectile source are investigated in the framework of two different simulation codes. Overall and source-specific detection efficiencies for multifragmentation events are found to be model independent. The equivalence of the two different methods used to assign experimentally detected charged particles and neutrons to the emitting source is shown. The method used experimentally to determine quasi-projectile emitted free neutron multiplicity is found to be reasonably accurate and sufficiently precise as to allow for the study of well-defined quasi-projectile sources. Experimental QP neutron multiplicity distributions for three similar reactions with different isospin content are also presented. An increase in neutron emission is found for more n-rich systems.
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