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Biomedical subjects

Ken Kono

Publications and source records attributed to Ken Kono.

5 recordsLinked to original sources

Group B coxsackievirus diabetogenic phenotype correlates with replication efficiency.

Group B coxsackieviruses can initiate rapid onset type 1 diabetes (T1D) in old nonobese diabetic (NOD) mice. Inoculating high doses of poorly pathogenic CVB3/GA per mouse initiated rapid onset T1D. Viral protein was detectable in islets shortly after inoculation in association with beta cells as well as other primary islet cell types. The virulent strain CVB3/28 replicated to higher titers more rapidly than CVB3/GA in the pancreas and in established beta cell cultures. Exchange of 5'-nontranslated regions between the two CVB3 strains demonstrated a variable impact on replication in beta cell cultures and suppression of in vivo replication for both strains. While any CVB strain may be able to induce T1D in prediabetic NOD mice, T1D onset is linked both to the viral replication rate and infectious dose.

Animals↗

Coxsackievirus B3 infection and type 1 diabetes development in NOD mice: insulitis determines susceptibility of pancreatic islets to virus infection.

Group B coxsackieviruses (CVB) are believed to trigger some cases of human type 1 diabetes (T1D), although the mechanism by which this may occur has not been shown. We demonstrated previously that inoculation of young nonobese diabetic (NOD) mice with any of several different CVB strains reduced T1D incidence. We also observed no evidence of CVB replication within islets of young NOD mice, suggesting no role for CVB in T1D induction in the NOD mouse model. The failure to observe CVB replication within islets of young NOD mice has been proposed to be due to interferon expression by insulin-producing beta cells or lack of expression of the CVB receptor CAR. We found that CAR protein is detectable within islets of young and older NOD mice and that a CVB3 strain, which expresses murine IL-4, can replicate in islets. Mice inoculated with the IL-4 expressing CVB3 chimeric strain were better protected from T1D onset than were mock-infected control mice despite intraislet viral replication. Having demonstrated that CVB can replicate in healthy islets of young NOD mice when the intraislet environment is suitably altered, we asked whether islets in old prediabetic mice were resistant to CVB infection. Unlike young mice in which insulitis is not yet apparent, older NOD mice demonstrate severe insulitis in all islets. Inoculating older prediabetic mice with different pathogenic CVB strains caused accelerated T1D onset relative to control mice, a phenomenon that was preceded by detection of virus within islets. Together, the results suggest a model for resolving conflicting data regarding the role of CVB in human T1D etiology.

Age Factors↗

Sustainability of cross-functional teams for marketing strategy development and implementation.

This article presents a case study on a cross-functional team used for marketing strategy development and execution at a health insurance company. The study found a set of success factors that contributed to the initial success of the team, but the factors were not enough to maintain the team's high level of productivity over time. The study later identified a set of 8 factors that helped sustain the team's high-productivity level. The 2 sets (ie, success and its subsequent sustainability factors) are analyzed against a normative model of team effectiveness. All the factors are explained by the normative model except for 1 sustainability factor, "challenge motivator." In fact, the study found the "challenge motivator" to be the most critical factor to keep up the team's productivity over time. Apart from a performance crisis, the authors developed 3 "challenge motivators"--first, more granular market information that could unearth hidden performance issues; second, constant value creation to shareholders as the firm being publicly traded; and third, the firm's strategic mandate to meet and exceed customer expectations that puts ultimate performance pressure on the marketing strategy team.

Efficiency, Organizational↗