Localization of metallothionein-I and -III expression in the CNS of transgenic mice with astrocyte-targeted expression of interleukin 6

The effect of interleukin-6 (IL-6) on metallothionein-I (MT-I) and MT-III expression in the brain has been studied in transgenic mice expressing IL-6 under the regulatory control of the glial fibrillary acidic protein gene promoter (GFAP-IL6 mice), which develop chronic progressive neurodegenerative disease. In situ hybridization analysis revealed that GFAP-IL6 (G16-low expressor line, and G36-high expressor line) mice had strongly increased MT-I mRNA levels in the cerebellum (Purkinje and granular layers of the cerebellar cortex and basal nuclei) and, to a lesser degree, in thalamus (only G36 line) and hypothalamus, whereas no significant alterations were observed in other brain areas studied. Microautoradiography and immunocytochemistry studies suggest that the MT-I expression is predominantly localized to astrocytes throughout the cerebrum and especially in Bergman glia in the cerebellum. However, a significant expression was also observed in microglia of the GFAP-IL6 mice. MT-III expression was significantly increased in the Purkinje cell layer and basal nuclei of the cerebellum, which was confirmed by Northern blot analysis of poly(A)+ mRNA and by ELISA of the MT-III protein. In contrast, in the G36 but not G16 mice, transgene expression of IL-6 was associated with significantly decreased MT-III RNA levels in the dentate gyrus and CA3 pyramidal neuron layer of the hippocampus and, in both G36 and G16 mice, in the occipital but not frontal cortex and in ependymal cells. Thus, both the widely expressed MT-I isoform and the CNS specific MT-III isoform are significantly affected in a MT isoform- and CNS area-specific manner in the GFAP-IL6 mice, a chronic model of brain damage.     

Plasma and platelet concentration and platelet uptake of serotonin in normal and pre-eclamptic pregnancies

Pharmacologic and methodologic advances over the last decade have resulted in a body of information implicating serotonin as a mediator in the genesis of pre-eclamptic hypertension. Platelets contain the largest storage of serotonin in peripheral blood and have the ability to take up this amine from surroundings, store and release it by several mechanisms. Plasma and platelet serotonin concentrations and platelet serotonin uptake have been measured in 8 non-pregnant women, 12 normal pregnant women and 8 women with severe pre-eclampsia. Plasma serotonin concentration was significantly higher in severely preeclamptic women, compared with age and gestation matched normal pregnant women. In addition, plasma serotonin concentration was directly related to systolic and diastolic blood pressure with severity of the syndrome. Furthermore, platelet serotonin concentration in women with pre-eclampsia was significantly higher than in non-pregnant controls, but it was not significantly different from the normal pregnant women. Moreover, serotonin is effectively taken up by platelets through a saturable transport process. The calculated apparent Km for serotonin uptake process did not differ significantly among non-pregnant women, normal pregnant women and women with pre-eclampsia. However, Vmax values were significantly higher in women with pre-eclampsia than in the normotensive pregnant women. As the actions of serotonin in the periphery could be terminated primarily by active uptake system by platelets and placenta, significant alterations in the rate of transport could result in physiologically significant changes in serotonin levels. These data raise the possibility that abnormal regulation of transporter function is involved in the etiology of pre-eclampsia.     

Solutions to Industrial Engineering problems using integrated software environments

The development of word processing systems and the spreadsheet environment marked the beginning of the professional computing movement. For the first time, programs were available that were both highly functional and highly usable, even by non-computer people. The next group of “hot” programs in the business market were “integrated” packages providing a combination of word processing, spreadsheet, database, graphics, and telecommunications. Unfortunately, these integrated packages have not displaced such single purpose programs as Lotus 1-2-3, dBase and WordPerfect as the dominant forces in desktop computing. Integrated packages are generally perceived as complex, cumbersome, and difficult to master. An important point to note, however, is that high proficiency is not necessary; successful users of commercial software seldom know or use more that 40% of a programs functionality.

This paper addresses the use of integrated software packages to solve Industrial Engineering problems. More specifically, examples are presented demonstrating the use of Ashton Tate's Framework II to solve production and operations management problems. Sample applications include forecasting, after tax economic analysis, and data storage and retrieval, demonstrating the advantages of linking word processing, spreadsheets, and databases.     

Computational Technique to Assess Warhead Lethality against Ballistic Missile

This paper addresses a computational procedure to assess the lethality of kinetic energy projectile warheads against tactical ballistic missile payloads with an innovative and rational damage metric. The individual lethality of different projectile geometries impacting at hypervelocity at different configurations is estimated via a numerical damage index computed from hydrocode simulations. The highest count of possible impacts to the payload is achieved by optimizing the warhead’s configuration and time of detonation, a priori knowledge of the target’s location and speed. The total damage to the payload characterizes the warhead’s lethality for the particular engagement conditions. An example shows the application of the process and potential advantages.