Pertussis toxin (PTX) is the primary component responsible for eliciting the majority ofbiological activities associated with Bordetella pertussis, including the induction of several tissue-adjuvant models of organ-specific autoimmune disease. PTX, when administered in vivo, enhances vascular permeability, which is made manifest by a concomitant increase in sensitivity to a variety of agents and treatments affecting the vascular bed. One such agent is histamine, and the response to PTX, as measured by hypersensitivity following vasoactive amine challenge, is genetically controlled by the Bphs locus. Susceptibility to the induction of both experimental allergic encephalomyelitis (EAE) and experimental allergic orchitis (EAO) in mice is associated with, and in the latter case linked to, a susceptible allele at this locus. We report here the mapping of the Bphs locus to mouse chromosome 6, telomeric of Tcrb and centromeric of Prp (D6Nds8). This region also contains a number of loci of immunologic relevance including Igk, Ly-2, Ly-3, ll-5r, Ly-35, Ly-4, and Tnfr-2.
Mice thymectomized at three days of age (D3Tx) develop during adulthood a variety of organ-specific autoimmune diseases, including autoimmune ovarian dysgenesis (AOD). The phenotypic spectrum ofAOD is characterized by the development ofanti-ovarian autoantibodies, oophoritis, and atrophy. The D3Tx model ofAOD is unique in that disease induction depends exclusively on perturbation of the normal developing immune system, is T-cell-mediated, and is strain specific. For example, D3Tx A/J mice are highly susceptible to AOD, whereas C57BL/6J mice are resistant. After D3Tx, self ovarian antigens, expressed at physiological levels, trigger an autoimmune response capable of eliciting disease. The D3Tx model provides, therefore, the opportunity to focus on
The existence of immunoregulatory genes conferring dominant resistance to autoimmunity is well documented. In an effort to better understand the nature and mechanisms of action of these genes, we utilized the murine model of autoimmune orchitis as a prototype. When the orchitis-resistant strain DBA/2J is crossed with the orchitissusceptible strain BALB/cByJ, the F1 hybrid is completely resistant to the disease. By using reciprocal radiation bone marrow chimeras, the functional component mediating this resistance was mapped to the bone marrow-derived compartment.
The application of network perspectives and methods to study complex problem and policy domains has proliferated in the public management literature. Network metrics are highly sensitive to boundary decisions as findings are a direct reflection of who and what was considered to be part of the network. The more complex the problem domain, the messier the network and the more challenging it is for researchers to determine network boundaries. Laumann, Marsden, and Prensky's seminal (1989) article on network bounding highlighted the theoretical and methodological significance associated with determinations of network boundaries in social network research. However, despite an expansion of network scholarship, the advancement of frameworks aimed at assisting scholars in thinking through the relative advantages and disadvantages of different boundary determinations has received limited attention. This article addresses this gap. Drawing insights from three network studies, we argue that problem domain characteristics and concerns such as formal structures, isolates, disconnected subgroups and/or the duration of the ties will be differentially emphasized with different boundary approaches. We leverage these insights to advance a framework for aiding network scholars working in complex problem domains to consider the strengths and limitations of varied bounding approaches in relation to the question at hand.
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