Phosphodiesterase-4 Inhibition Alters Gene Expression and Improves Isoniazid – Mediated Clearance of Mycobacterium tuberculosis in Rabbit Lungs

Tuberculosis (TB) treatment is hampered by the long duration of antibiotic therapy required to achieve cure. This indolent response has been partly attributed to the ability of subpopulations of less metabolically active Mycobacterium tuberculosis (Mtb) to withstand killing by current anti-TB drugs. We have used immune modulation with a phosphodiesterase-4 (PDE4) inhibitor, CC-3052, that reduces tumor necrosis factor alpha (TNF-α) production by increasing intracellular cAMP in macrophages, to examine the crosstalk between host and pathogen in rabbits with pulmonary TB during treatment with isoniazid (INH). Based on DNA microarray, changes in host gene expression during CC-3052 treatment of Mtb infected rabbits support a link between PDE4 inhibition and specific down-regulation of the innate immune response. The overall pattern of host gene expression in the lungs of infected rabbits treated with CC-3052, compared to untreated rabbits, was similar to that described in vitro in resting Mtb infected macrophages, suggesting suboptimal macrophage activation. These alterations in host immunity were associated with corresponding down-regulation of a number of Mtb genes that have been associated with a metabolic shift towards dormancy. Moreover, treatment with CC-3052 and INH resulted in reduced expression of those genes associated with the bacterial response to INH. Importantly, CC-3052 treatment of infected rabbits was associated with reduced ability of Mtb to withstand INH killing, shown by improved bacillary clearance, from the lungs of co-treated animals compared to rabbits treated with INH alone. The results of our study suggest that changes in Mtb gene expression, in response to changes in the host immune response, can alter the responsiveness of the bacteria to antimicrobial agents. These findings provide a basis for exploring the potential use of adjunctive immune modulation with PDE4 inhibitors to enhance the efficacy of existing anti-TB treatment

College is not Optional

A mixed collection of fictional short stories and poems concerned with the dynamics of interpersonal relationships. The stories are steeped in the absurdist tradition while striving to maintain realist character interactions. The poems attempt to show that, even in absurd situations, we long for a connection with another

The Role of Race in Football Card Prices

Objective. Several studies have examined the impact of race and the value of baseball cards, but few have investigated the role of race on football card values. Methods. Data were derived from 1,279 black and white football players who were selected to participate in at least one Pro Bowl and who started their careers between 1946, the year professional football in the United States became racially integrated when Kenny Washington played in a game for the Los Angeles Rams, and 1988, the last year of Topps' monopoly in the football card market. Data for each player's race, value of their rookie card, card availability, card vintage, performance, Hall of Fame status, and position were obtained. Results. When controlling for other factors, race has no effect on the value of players' rookie cards, whereas card vintage exerted the most influence on the value of players' cards. Conclusions. Football card values are largely driven by objective markers, supporting the conclusion that the market performs pretty much as expected for a collector market. Speculations on the absence of race effect, limitations related to the study, and suggestions for future research are offered.No Full Tex

Racial bias in baseball card collecting revisited

Although research examining the role of racial bias in the secondary sports card market has been an emerging area of inquiry, empirical knowledge on the question: “Does the race of the player on a sports card affect the value of the card?” remains inconclusive. This paper revisits one of the first studies on this topic. Data were derived for 66 Black, White, and Latino members of the National Baseball Hall of Fame who were elected by a vote of the Baseball Writers’ Association of America. Data for each player's race, career performance statistics, rookie card price, and card availability were obtained from secondary sources. Findings indicate that card availability and, to a lesser extent, player performance is the most important factor affecting the value of a player's card, while importantly, a player's race is not a significant contributor to card value. Suggestions for future research are outlined

Investigating Customer Racial Discrimination in the Secondary Baseball Card Market

A growing body of literature in a variety of disciplines has appeared over the last 20 years examining customer racial bias in the secondary sports card market; however, consensus on the matter has yet to emerge. In this article, we explore the more subtle ways that a player's race / ethnicity may affect the value of his sports card including a player's skin tone (light- to dark-skinned). Data were obtained for 383 black, Latino, and white baseball players who had received at least one vote for induction into Major League Baseball's Hall of Fame including their career performance statistics, rookie card price, card availability, Hall of Fame status, and skin tone. Findings indicate that card availability is the primary determinant of card value while a player's skin tone has no direct effect. Subsequent analysis demonstrates that a player's race (white / non-white) rather than skin tone did have an effect as it interacts with Hall of Fame status to influence his rookie card price.No Full Tex

The Role of Race in Football Card Prices

Several studies have examined the impact of race and the value of baseball cards, but few have investigated the role of race on football card values. Copyright (c) 2010 by the Southwestern Social Science Association.

Does race matter? Assessing consumer discrimination in the secondary basketball card market

► Using data obtained for 215 retired basketball players, we explore whether a players’ race influences the value collectors place on his rookie card. ► Our results reveal no direct effect of race on rookie card prices. ► We find an interaction effect between race and Hall of Fame status. ► Controlling for other factors, the cards of Black Hall of Fame members are worth significantly more than those of White Hall of Fame members and non-Hall of Fame members of both races. Sociologists continue to observe the ways race permeates America's social institutions, the institution of sport being no exception. Although researchers have explored customer racial discrimination via examinations of the secondary sports card market, only three studies have explored the phenomenon in the context of basketball, a sporting context with a higher proportion of non-White players than the baseball and football leagues that have been the primary focus to date. We explore the unique way race matters on the hardwood by employing a methodological approach that previously has been used to study card collecting in other contexts. Data were obtained for 215 retired players and their rookie cards. Controlling for other factors, to include career performance, position, and card scarcity, the results reveal no direct effect of race on card values, but there is an interaction effect between race and Hall of Fame status that impacts card prices. The potential source and implications of this interaction are discussed as well as suggestions for future research

T Cell Immunity in Connective Tissue Disease Patients Targets the RNA Binding Domain of the U1-70kDa Small Nuclear Ribonucleoprotein

Although the T cell dependence of autoimmune responses in connective tissue diseases has been well established, limited information exists regarding the T cell targeting of self Ags in humans. To characterize the T cell response to a connective tissue disease-associated autoantigen, this study generated T cell clones from patients using a set of peptides encompassing the entire linear sequence of the 70-kDa subunit of U1 snRNP (U1-70kDa) small nuclear ribonucleoprotein. Despite the ability of U1-70kDa to undergo multiple forms of Ag modification that have been correlated with distinct clinical disease phenotypes, a remarkably limited and consistent pattern of T cell targeting of U1-70kDa was observed. All tested T cell clones generated against U1-70kDa were specific for epitopes within the RNA binding domain (RBD) of the protein. High avidity binding of the RBD with U1-RNA was preserved with the disease-associated modified forms of U1-70kDa tested. The high avidity interaction between the U1-RBD on the polypeptide and U1-RNA may be critical in immune targeting of this region in autoimmunity. The T cell autoimmune response to U1-70kDa appears to have less diversity than is seen in the humoral response; and therefore, may be a favorable target for therapeutic intervention