Knowledge that Transforms

The pathogenesis of Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is still controversial. Our hypothesis is that primary infection of oligodendrocytes (OLGs) is not a crucial event in the pathogenesis of demyelination in this model. In fact, it has been proposed that myelin may be destroyed, as an innocent bystander, following an antiviral delayed-type hypersensitivity (DTH) response. This hypothesis would not need widespread oligodendroglial infection, because virus present in other cells would be sufficient to trigger a DTH response. The present study demonstrates that cultured OLGs and astrocytes from susceptible strains of mice (SJL and DBA) and immortalized OLGs can be infected with TMEV in vitro. Infection of OLGs, however, is at very low levels and does not result in overt cytolytic effect. In contrast, infection of immortalized OLGs is very efficient and results in clear cytolysis. Because an important characteristic of DTH responses is the liberation of potentially injurious cytokines into adjacent tissues, we also examined the effects of mouse recombinant tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and interferon-gamma (IFN-gamma) on cultured OLGs and immortalized OLGs. We found that TNF-alpha caused immortalized OLG cytotoxicity in a time- and dose-dependent manner. In contrast, no cytotoxicity was observed on primary OLGs with any of the above cytokines. To determine whether functional effects could be demonstrated on primary OLGs by either virus or cytokines, we measured mRNA expression of different myelin proteins in primary and immortalized OLGs exposed to virus or TNF-alpha. Neither the BeAn strain or the GDVII strain of TMEV interfered with myelin protein mRNA expression in primary OLGs, whereas GDVII virus dramatically reduced myelin OLG glycoprotein (MOG) mRNA in immortalized OLGs. Interestingly, although even high concentrations of TNF-alpha (10,000 U/ml) did not produce primary OLG cytotoxicity, they resulted in a significant reduction in mRNA for both myelin basic protein (MBP) and MOG in these cells. TNF-alpha (at 500 U/ml) also specifically reduced MOG mRNA in immortalized OLGs. Because immortalized OLGs are considered to be arrested at an early stage of maturation, our results suggest that immature OLGs are susceptible to both virus- and cytokine-dependent cytotoxicity, whereas mature OLGs are resistant to cytolysis by either TMEV or cytokines. TNF-alpha, however, is capable of reducing mRNA expression of myelin proteins in primary OLGs; therefore, it may participate in the induction of demyelination, as suggested by the DTH-mediated hypothesis.

This paper examines how closely the minimum wage has been set to the most popularly stated goals of minimun‐wage policy. I first estimate these goals: the minimum‐wage rate at which the relevant labor demand is unitary elastic‐maximizing the total earnings of minimum‐wage workers (about $5.35)‐and the level that would lift a typical minimum‐wage worker's family out of poverty (about $5.17). I can reject that the actual minimum‐wage policy has been driven by desire to achieve these goals and find that a simple interest group model best explains the historical path of the minimum‐wage rate.

The paper's main contribution is to provide a rational for advocacy. After observing that many organizations (corporations, judiciary, and the executive and legislative branches of government) use competition among enfranchised advocates of special interests to improve policy making, it argues that advocacy has two major benefits. First, the advocates' rewards closely track their pursuing several conflicting causes at one time. Second, advocacy enhances the integrity of decision making by creating strong incentives to appeal in case of an abusive decision. The paper also analyzes the costs of advocacy in terms of manipulation and garbling of information. It further shows that it may be costly for both the organization and interested parties themselves to let these parties plead their own causes instead of being represented. The paper concludes with two applications to comparative legal systems and to the organization of Congress and with suggestions for future research.

The hypothesis that increases in the schooling of women enhance the human capital of the next generation and thus make a unique contribution to economic growth is assessed on the basis of data describing green revolution India. Estimates are obtained that indicate that a component of the significant and positive relationship between maternal literacy and child schooling in the Indian setting reflects the productivity effect of home teaching and that the existence of this effect, combined with the increase in returns to schooling for men, importantly underlies the expansion of female literary following the onset of the green revolution.