Compromised late-stage motion processing in schizophrenia.

BACKGROUND: Visual motion processing is compromised in schizophrenia, as shown in deficient velocity discrimination. Processing of motion signals comprises progressive stages along the geniculate-striate-extrastriate-cortex pathway. Based on neurophysiologic and brain lesion studies, a velocity discrimination deficit can implicate early-stage motion processing if it is contrast-dependent or late-stage motion processing if it is contrast-independent. METHODS: To determine which stage underlies the deficient velocity discrimination in schizophrenia, we examined the effects of visual contrast on velocity discrimination. We measured velocity discrimination thresholds in schizophrenia patients (n = 34) and normal control subjects (n = 17) at both low and high contrasts, using each subject's contrast detection threshold to equate contrast levels. RESULTS: Schizophrenia patients showed poor velocity discrimination that improved little with high contrast, whereas normal control subjects showed enhanced velocity discrimination with increased contrast. CONCLUSIONS: The finding that the velocity discrimination deficit in schizophrenia is independent of contrast modulation implicates the later, rather than the earlier, stages of motion processing, which is mediated in the extrastriate cortex.     

Glucocorticoid receptor enhancement of pregnane X receptor-mediated CYP2B6 regulation in primary human hepatocytes.

Although the glucocorticoid receptor (GR) facilitates the xenobiotic-induced expression of CYP2B in rodents, its role in the regulation of human CYP2B6 is unclear. In this report, the role of human GR in the regulation of CYP2B6 was evaluated using primary human hepatocytes and transfection assays with Huh7 cells. CYP2B6 expression was not induced in primary hepatocytes treated with dexamethasone (DEX) concentrations (0.01-1 microM) known to activate GR. In contrast, treatment with 0.1 microM DEX enhanced CYP2B6 induction by different pregnane X receptor (PXR) activators, including rifampin, phenytoin, clotrimazole, and phenobarbital. In Huh7 cells, cotransfection of human (h)GR and hPXR with CYP2B6-phenobarbital-responsive enhancer module (PBREM) reporter constructs revealed that all hPXR ligands induce CYP2B6 reporter gene activity, and this ligand-dependent activation is greatly enhanced by activated hGR. CYP2B6 reporter gene expression was not induced in the presence of hPXR ligands when hGR alone was cotransfected with CYP2B6 reporter construct. In hGR and human constitutive androstane receptor (hCAR) cotransfection assays, activated hGR increased the constitutive activation of PBREM reporter constructs by hCAR in the absence of inducers. In the presence of activated hGR and known inducers of CYP2B6, only PB treatment caused a further 2-fold activation of hCAR compared with control. These studies show that hGR is involved synergistically in the xenobiotic-responsive regulation of human CYP2B6 by hPXR and hCAR. Moreover, the results suggest that the GR-enhanced expression of CYP2B6 is mediated through an indirect mechanism that does not require increased expression of nuclear receptor.     

The National Occupational Research Agenda: a model of broad stakeholder input into priority setting.

OBJECTIVES: No single organization has the resources necessary to conduct occupational safety and health research to adequately serve the needs of workers in the United States. The National Institute for Occupational Safety and Health (NIOSH) undertook the task of setting research priorities in response to a broadly perceived need to systematically address those topics most pressing and most likely to yield gains to workers and to the nation. METHODS: NIOSH and its public and private partners used a consensus-building process to set priorities for the next decade for occupational safety and health research--the National Occupational Research Agenda. RESULTS: The process resulted in the identification of 21 research priorities grouped into 3 categories: disease and injury, work environment and workforce, and research tools and approaches. CONCLUSIONS: Although the field of occupational safety and health is often contentious and adversarial, these research priorities reflect a remarkable degree of concurrence among a broad range of stakeholders who provided input into a clearly defined and open process.     

Responses of mitochondrial superoxide dismutase, catalase and glutathione peroxidase activities to aging

The previous observation (Eur. J. Biochem., 82 (1978) 563--567) that age-dependent accumulation of lipid peroxides follows as a consequence of increased radical formation in mitochondria has prompted an examination of the response of a set of protective enzymes to the above situation. Levels of mitochondrial catalase activity as well as selenium-dependent glutathione peroxidase activity were found to be increased with age, while superoxide dismutase activity remained unchanged. No selenium-independent glutathione peroxidase activity could be detected either in preparations from young 3-month-old controls or in preparations from 2-year-old rats. Both the relatively high and unchanged levels of reduced glutathione and kinetic considerations suggest that glutathione peroxidase is preferentially involved in lipid peroxide metabolism, while catalase predominantly metabolizes mitochondrial H2O2.     

Developmental reprogramming of rat GLUT5 requires glucocorticoid receptor translocation to the nucleus

Fructose consumption has increased dramatically but little is known about mechanisms regulating the intestinal fructose transporter GLUT5 in vivo . In neonatal rats, GLUT5 can be induced only by luminal fructose and only after 14 days of age, unless the gut is primed with dexamethasone prior to fructose perfusion. To elucidate the mechanisms underlying dexamethasone modulation of GLUT5 development, we first identified the receptor mediating its effects then determined whether those effects were genomic. The glucocorticoid receptor (GR) antagonist RU486 dose-dependently prevented the dexamethasone-mediated effects on body weight, intestinal arginase2 (a known GR-regulated gene) and GLUT5. In contrast, an antagonist of the mineralocorticoid receptor as well as agonists of progesterone (PR) and pregnane-X (PXR) receptors did not block the effects of dexamethasone. These receptor antagonists and agonists had no effect on the intestinal glucose transporter SGLT1. Translocation of the GR into the enterocyte nucleus occurred only in dexamethasone-injected pups perfused with fructose, was accompanied by marked increases in brush border GLUT5 abundance, and was blocked by RU486. A priming duration of ∼24 h is optimal for induction but actinomycin D injection before dexamethasone priming prevented dexamethasone from allowing luminal fructose to induce GLUT5. Actinomycin D had no effect on dexamethasone-independent fructose-induced increases in glucose-6-phosphatase mRNA abundance, suggesting that it did not prevent fructose-induction of GLUT5, but instead prevented dexamethasone-induced synthesis of an intermediate required by fructose for GLUT5 regulation. In suckling rats < 14 days old, developmental regulation of transporters may involve cross-talk between hormonal signals modulating intestinal maturation and nutrient signals regulating specific transporters.     

Culicoides mohave (Diptera: Ceratopogonidae): new occurrence records and potential role in transmission of hemorrhagic disease

Biting midges of the genus Culicoides are important in the transmission of viral diseases affecting wild and domestic ungulates, including bluetongue (BLU) and epizootic hemorrhagic disease (EHD). The primary known vector for these viruses is C. sonorensis Wirth & Jones, however, it has been speculated that other species of Culicoides may also be involved. One potential candidate is C. mohave, a poorly studied species found in inland desert areas of the southwestern United States. In 2000 and 2001, we collected C. mohave and C. sonorensis at six sites in a previously unsurveyed area in the Sonoran Desert of southwestern Arizona and used PCR to detect nucleic acids associated with BLU and EHD viruses. C. mohave was abundant at two low-elevation sites on the study area, but uncommon or absent elsewhere. C. sonorensis commonly occurred along with C. mohave at one site, but was much less abundant. All C. mohave pools were negative for BLU viral RNA, however, 35% yielded positive results for EHD. All C. sonorensis were negative for both BLU and EHD. Our results suggest that C. mohave is a potential vector of EHD virus in this area, however additional studies are needed to determine its ability to transmit EHD.     

Determination of neutron spectra in a MOX plant for the qualification of the BD-PND bubble detector

As a result of the introduction of the ICRP 60 recommendations and the increasing contribution of the neutron dose to the total dose of the personnel at the Belgonucleaire Mox fuel fabrication plant, the BD-PND bubble detector manufactured by Bubble Technology industries was introduced as a new, reliable personal neutron dosimeter. In the framework of the evaluation program of the bubble detector, measurements and calculations of the neutron spectra in the installations of the fuel fabrication plant were performed. The measurements were carried out with a ROSPEC neutron spectrometer, and the calculations were performed by means of the Monte Carlo code MCNP 4A. Comparison between measurements and calculations revealed good agreement. On the basis of the obtained neutron spectra, a correction factor was determined to take into account the new ICRP 60 recommendations and the difference between the calibration spectrum of the bubble detectors and the observed neutron spectra at the plant. This correction factor was applied to the calibration factor provided by Bubble Technology Industries.