Genistein, a selective protein tyrosine kinase inhibitor, inhibits interleukin-2 and leukotriene B4 production from human mononuclear cells,

In this study, genistein, a selective protein tyrosine kinase (PTK) inhibitor, inhibited peripheral blood mononuclear cell (PBMC) proliferation and interleukin-2 production from cultures that were stimulated with phytohemagglutinin (PHA), phorbol 12-myristate 13-acetate (PMA) plus A23187, or PHA plus PMA, and genistein effectively blocked the PHA plus IL-2-induced PBMC proliferation. Further, we also found that genistein inhibited LTB4 production from A23187-stimulated cultures whereas H-7, a PKC inhibitor, had no effect on LTB4 production. Our results suggest that PTK may be necessary for the synthesis of LTB4.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29309/1/0000372.pd

Induction of lymphokine-activated killer activity in rat splenocyte cultures: The importance of 2-mercaptoethanol and indomethacin

The role of 2-mercaptoethanol and indomethacin in the induction of lymphokine-activated killer (LAK) activity by interleukin-2 (IL-2) in rat splenocyte cultures was investigated. Spleens from 4-month-old male rats of five different strains were tested. Splenocytes were cultured for 3-5 days in the presence of IL-2 (1000 U/ml) and LAK activity was assessed by 4-h51Cr release assays with P815 and YAC-1 cells as targets. LAK activity could be induced by IL-2 in splenocytes from all rat strains, but only when 2-mercaptoethanol was present in the culture medium. Optimal LAK activity was induced when the 2-mercaptoethanol concentration in splenocyte cultures was at least 5 μM. Different rat strains showed differences in levels of in vitro induction of LAK activity. In the presence of 2-mercaptoethanol the level of LAK activity induced by IL-2 was high in BN and Lewis rats, intermediate in Wistar and Wag rats, and low in DZB rats. In the absence of 2-mercaptoethanol no or minimal LAK activity was induced. Furthermore we observed that addition of 50 μm indomethacin to the culture medium in the presence of 2-mercaptoethanol augmented the induction of LAK activity to some extent. In the absence of 2-mercaptoethanol, addition of indomethacin resulted only in low levels or no induction of LAK activity. We conclude that for optimal induction of LAK activity by IL-2 in rat splenocyte cultures 2-mercaptoethanol is essential, while indomethacin can only marginally further improve this induction

Statistical Process Monitoring With MTConnect

Statistical Process Control (SPC) techniques are used widely in the manufacturing industry. However, it is sometimes observed that a deviation that is within the acceptable range of inherent process variation does not necessarily conform to specifications. This is especially true in the case of low volume; high precision manufacturing that is customary in aerospace and defense industries. In order to study the limitations posed by conventional SPC techniques in such manufacturing environments, a study was undertaken at TechSolve Inc., Cincinnati to develop a standalone SPC tool. The SPC tool so developed effectively communicates with an on-machine probe and analyzes the collected data to carry out a statistical analysis. MTConnect, a new-generation machine tool communications protocol, was used in developing the communication interfaces with the on-machine probe on a Computer Numerical Control (CNC) machine. The XML (eXtensible Markup Language) code used to extend the MTConnect schema to include the data obtained from the probing routines is also presented. The statistical analysis was developed as a Graphical User Interface (GUI) in LabVIEW. The statistical analysis was carried out as a case study by producing a widget. Real machining was carried out to produce 48 of these widgets using a combination of end mills and face mills. The data obtained during the subsequent quality testing was used to carry out the statistical analysis. The limitations of conventional SPC techniques during the developmental and analytical phases of the study are discussed. The presence of a chip during an on machine probing routine, the variations due to disparities in tool macro geometry, and the demand for conformance to requirements are studied in the view of a statistical process monitoring standpoint. Various alternatives are also discussed that aim to correct and improve the quality of machined parts in these scenarios.</jats:p

Mechanism of action of glucocorticoid-induced immunoglobulin production: role of lipoxygenase metabolites of arachidonic acid.

Abstract Glucocorticoids stimulate polyclonal immunoglobulin (Ig) production in cultures of human peripheral blood lymphocytes. The mechanism of action of glucocorticoids in this system, and indeed in any physiologic system, is unknown. Because glucocorticoids stimulate the production of phospholipase A2-inhibitory glycoproteins, we investigated whether glucocorticoids stimulate polyclonal Ig production by inhibition of arachidonic acid metabolism. Nonspecific lipoxygenase/cyclooxygenase inhibitors stimulate polyclonal Ig production in a manner similar to the effect of glucocorticoids, whereas specific cyclooxygenase inhibitors actually inhibit Ig production. Two specific 5-lipoxygenase inhibitors, with little or no activity against cyclooxygenase or other lipoxygenases, also stimulate Ig production. The dose-response effect of all of these drugs on Ig production was similar to the dose response of inhibition of 5-lipoxygenase. Leukotriene B4 (LTB4) added in low concentrations (10(-10)M) on days 1, 2, and 3 of a culture eliminated the stimulatory effect of glucocorticoids or 5-lipoxygenase inhibitors, whereas LTC4, LTD4, prostaglandin E, or 5-hydroxyeicosatetraenoic acid had no effect. These results suggest that the relevant action of glucocorticoids in stimulating Ig production might be in preventing endogenous arachidonic acid metabolism, perhaps the endogenous production of LTB4.</jats:p