Notes: Abstract: Nitric oxide has been proposed to mediate cytotoxic effects in inflammatory diseases. To investigate the possibility that overproduction of nitric oxide might play a role in the neuropathology of inflammatory and noninflammatory neurological diseases, we compared levels of the markers of nitric oxide, nitrite plus nitrate, in the CSF of controls with those in patients with various neurologic diseases, including Huntington's and Alzheimer's disease, amyotrophic lateral sclerosis, and HIV infection. We found that there were no significant increases in the CSF levels of these nitric oxide metabolites, even in patients infected with HIV or in monkeys infected with poliovirus, both of which have significantly elevated levels of the neurotoxin quinolinic acid and the marker of macrophage activation, neopterin. However, CSF quinolinic acid, neopterin, and nitrite/nitrate levels were significantly increased in a small group of patients with bacterial and viral meningitis.

Notes: Abstract: We have characterized a high-affinity [35S]-glutathione ([35S]GSH) binding site in mouse and human spinal cord. [35S]GSH binding sites in mouse and human spinal cord were observed largely within the gray matter in both the dorsal and ventral horns of spinal cord at cervical, thoracic, and lumbosacral segments. High-affinity [35S]GSH binding was saturable, showing a Bmax of 72 fmol/mg of protein and a KD of 3.0 nM for mouse spinal cord and a Bmax of 52 fmol/mg of protein and a KD of 1.6 nM for human spinal cord. [35S]GSH binding was displaceable by GSH, l-cysteine, and S-hexyl-GSH, but not by glutamate, glycine, or NMDA. These [35S]GSH binding sites exhibited kinetic and saturation characteristics similar to GSH binding sites in rat brain astrocytes. To determine whether [35S]GSH binding sites could be regulated by protein kinase C, we exposed human spinal cord sections to phorbol 12,13-diacetate for 1 h before ligand binding. Phorbol ester treatment increased [35S]GSH binding by ∼60%, an effect that could be blocked by exposure of spinal cord sections to 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, a general protein kinase inhibitor. [35S]GSH binding sites in the spinal cord of both species exhibited many of the characteristics of a receptor including saturable binding, high affinity, ligand specificity, and modulation by kinase activity. These data suggest that GSH is a neurotransmitter in the CNS.

Notes: The expressions of 78 protein kinases, 24 protein phosphatases and 31 phosphoproteins were investigated by Kinetworks™ analysis in brain and spinal cord tissue of transgenic mice over-expressing G93A mutant superoxide dismutase (mSOD), a murine model of amyotrophic lateral sclerosis (ALS). In the brains of affected mSOD mice, we observed increased expression of cAMP-dependent protein kinase (PKA, 111% increase compared with control), and protein phosphatase 2B Aα-catalytic subunit (calcineurin, 109% increase), and reductions in the levels of PAK3 (76% decrease) and protein phosphatase 2C Cβ-subunit (32% decrease). Increased Ser259 phosphorylation of Raf1 (126% increase) in mSOD mice correlated with higher expression of p73 Raf1 (147% increase). There was also increased p73 Raf1 (69% increase) and Ser259 phosphorylation (45% increase) in the spinal cords of mSOD mice. While adducin underwent enhanced phosphorylation (αS724, 90% increase; γS662, 290% increase) in mSOD brain, its phosphorylation was lower in the mSOD spinal cord (αS724, 53% decrease; γS662, 46% decrease). In spinal cords of affected mSOD mice, we also observed elevated expression of casein kinase 1δ (CK1δ, 157% increase), JAK2 (84% increase), PKA (183% increase), protein kinase C (PKC) δ (123% increase), p124 PKCµ (142% increase), and RhoA kinase (221% increase), and enhanced phosphorylation of extracellular regulated kinases 1 (ERK1, T202/Y204, 90% increase), and 2 (ERK2, T185/Y187, 73% increase), p38 MAP kinase (T180/Y182, 1570% increase), and PKBα (T308, 154% increase; S473, 61% increase). There was also reduced phosphorylation of RB (S780, 45% decrease; S807/S811, 65% decrease), Src (Y418, 63% decrease) and p40 SAPK/JNKβ (T183/Y185, 43% decrease). Variability in the expression of kinases, phosphatases and phosphorylation of their substrates was observed even in mutant animals having a similar phenotype. The expression and phosphorylation differences between mSOD and control mice were dissimilar to those between ALS patients and controls. This finding indicates that the activation of protein kinases and phosphoproteins is different with neuron loss in the mSOD mouse compared with that seen in patients with the sporadic form of ALS.

Notes: Abstract Two cosmological models represent the observed magnitudes and redshifts of 150 quasars well with 〈Mv〉=−22.75 and −22.67, respectively. The luminosity function is derived.

Notes: Abstract Observed redshifts and magnitudes of seven classes of extragalactic objects, and number counts of QSRS are compared with predictions made by cosmological models. The uniform model U 1 and the proposed non-expanding model RHL 5 represent the observations very well. The latter offers numerous advantages. Absolute magnitudes and colors are determined.

Notes: Abstract A method for the determination of distances of quasars and sites of absorbing media is presented. It is illustrated by application to 3C 191 and PKS 0237-23. The results are compared with those obtained from the traditional Hubble Law.