Relative stability of alloys

A mathematical function, the relative stability, is defined which combines advantages of Darken's stability and excess stability function. The relative stability is finite over the entire composition range and approaches the value of one in terminal regions. A simple classification is given whether a solution phase is more stable than an ideal solution, less stable or even unstable in terms of values of the relative stability > 1, <1 or <0, respectively. The zero's of this function represent spinodal points. This concept is explained for binary regular solutions and applied to non-simple phases with strong deviations from regular solution behavior, specifically the liquid Cu-O and Cu-S alloys. An extension to ternary systems is given and the direction-dependency of the stabilities is discussed. A quantitative analysis in terms of the relative stability is given for the example of Fe-Cu-Ni alloys.     

Defects in enteric innervation and kidney development in mice lacking GDNF

Glial-lial-cell-line-derived neurotrophic factor (GDNF) has been isolated as neurotrophic factor for midbrain dopaminergic neurons. Because of its neurotrophic activity on a wide range of neuronal populations in vitro and in vivo, GDNF is being considered as a potential therapeutic agent for neuronal disorders. During mammalian development, it is expressed not only in the nervous system, but also very prominently in the metanephric kidney and the gastrointestinal tract, suggesting possible functions during organogenesis. We have investigated the role of GDNF during development by generating a null mutation in the murine GDNF locus, and found that mutant mice show kidney agenesis or dysgenesis and defective enteric innervation. We demonstrate that GDNF induces ureter bud formation and branching during metanephros development, and is essential for proper innervation of the gastrointestinal tract.     

Effects of cytoskeletal inhibitors on the accumulation of vincristine in a resistant human lung cancer cell line with high level of polymerized tubulin

We have previously established a vincristine resistant human lung cancer cell line (PC-9/VCR) by a stepwise exposure of parental line PC-9 to vincristine. In this study the resistant cells showed enhanced vincristine cytotoxicity in the presence of cytochalasin B and D. The increase in cytotoxicity was associated with an enhanced accumulation and a reduced efflux of vincristine. Colchicine and taxol had no effects on vincristine accumulation. Several cytoplasmic proteins were overexpressed in the resistant cells. The two major ones, with molecular weights of 58.8 kDa and 83.2 kDa, were shown by western blotting to be beta-tubulin and actin, respectively. The polymerized tubulin level in the resistant cells was significantly (p < 0.05) higher than that in the parental cells. These results suggest that the cellular cytoskeletons might play an important role in VCR resistance in the PC-9/VCR human lung cancer cell line.     

Chronic morphine induces visible changes in the morphology of mesolimbic dopamine neurons

The mesolimbic dopamine system, which arises in the ventral tegmental area (VTA), is an important neural substrate for opiate reinforcement and addiction. Chronic exposure to opiates is known to produce biochemical adaptations in this brain region. We now show that these adaptations are associated with structural changes in VTA dopamine neurons. Individual VTA neurons in paraformaldehyde-fixed brain sections from control or morphine-treated rats were injected with the fluorescent dye Lucifer yellow. The identity of the injected cells as dopaminergic or nondopaminergic was determined by immunohistochemical labeling of the sections for tyrosine hydroxylase. Chronic morphine treatment resulted in a mean approximately 25% reduction in the area and perimeter of VTA dopamine neurons. This reduction in cell size was prevented by concomitant treatment of rats with naltrexone, an opioid receptor antagonist, as well as by intra-VTA infusion of brain-derived neurotrophic factor. In contrast, chronic morphine treatment did not alter the size of nondopaminergic neurons in the VTA, nor did it affect the total number of dopaminergic neurons in this brain region. The results of these studies provide direct evidence for structural alterations in VTA dopamine neurons as a consequence of chronic opiate exposure, which could contribute to changes in mesolimbic dopamine function associated with addiction.     

Competitive and non-competitive NMDA antagonists block the development of antinociceptive tolerance to morphine, but not to selective mu or delta opioid agonists in mice

N-Methyl-D-aspartate (NMDA) receptor antagonists have been shown to block the development of antinociceptive tolerance to morphine. Assessment of the effects of NMDA antagonists on development of antinociceptive tolerance to selective opioid mu (mu) and delta (delta) agonists, however, has not been reported. In these experiments, selective mu and delta receptor agonists, and morphine, were repeatedly administered to mice either supraspinally (i.c.v.) or systemically (s.c.), alone or after pretreatment with systemic NMDA antagonists. Antinociception was evaluated using a warm-water tail-flick test. Repeated i.c.v. injections of mu agonists including morphine, fentanyl, [D-Ala2, NMePhe4, Gly-ol]enkephalin (DAMGO) and Tyr-Pro-NMePhe-D-Pro-NH2 (PL017) or [D-Ala2, Glu4]deltorphin, a delta agonist, or s.c. injections of morphine or fentanyl, produced antinociceptive tolerance as shown by a significant rightward displacement of the agonist dose-response curves compared to controls. Single injections or repeated administration of MK801 (a non-competitive NMDA antagonist) or LY235959 (a competitive NMDA antagonist) at the doses employed in this study did not produce behavioral toxicity, antinociception or alter the acute antinociceptive effects of the tested opioid agonists. Consistent with previous reports, pretreatment with MK801 or LY235959 (30 min prior to agonist administration throughout the tolerance regimen) prevented the development of antinociceptive tolerance to i.c.v. or s.c. morphine. Neither NMDA antagonist, however, affected the development of antinociceptive tolerance to i.c.v. fentanyl, DAMGO, or [D-Ala2, Glu4]deltorphin. Additionally, MK801 pretreatment did not affect the development of antinociceptive tolerance to i.c.v. PL017 or to s.c. fentanyl. Further, MK801 pretreatment also did not affect the development of tolerance to the antinociception resulting from a cold-water swim-stress episode, previously shown to be a delta-opioid mediated effect. These data lead to the suggestion that the mechanisms of tolerance to receptor selective mu and delta opioids may be regulated differently from those associated with morphine. Additionally, these findings emphasize that conclusions reached with studies employing morphine cannot always be extended to 'opiates' in general.     

Rat intestinal brush border membrane peptidases. I. Solubilization, purification, and physicochemical properties of two different forms of the enzyme

Two brush border peptidases have been isolated from the particulate fraction of the rat intestinal mucosa and purified to homogeneity as judged by polyacrylamide gel electrophoresis, starch gel electrophoresis, isoelectric focusing, and double immunodiffusion. For convenience, the peptidases have been designated peptidase F (fast) and S (slow) on the basis of their anodic mobilities. The isoelectric point of peptidase F was 4.76 and of peptidase S, 5.10. Both enzymes are glycoproteins. The amino acid compositions of the two peptidases are similar. The same carbohydrates are found in both enzymes, but there are differences in the molar concentrations of individual sugars. Peptidase S has greater concentrations of mannose and galactose and of hexosamines than peptidase F, while sialic acid is slightly greater in peptidase F. Carbohydrate accounted for approximately 19% and 23% of the weight of peptidases F and S, respectively. Estimates of the molecular weights of both enzymes by gel filtration gave values of 280,000. Electrophoresis of the enzymes under denaturing conditions on sodium dodecyl sulfate polyacrylamide gels indicated that each enzyme is a dimer consisting of two subunits of equal molecular weight, 140,000.     

Multiple sclerosis and measles: a study of cellular sensitization

Lymphocyte sensitization to measles has been studied in comparable groups of multiple sclerosis, other neurologic disease and normal subjects. The macrophage electrophoretic mobility test has been used. No difference between the three groups has been found, though there is a small group of children with obscure neurological disease which might well be multiple sclerosis and which fails to mount an adequate response to measles. The role of measles (and other banal infections) in aetiopathogenesis of multiple sclerosis is briefly discussed.