Down-modulation of CD4+ T helper type 2 and type 0 cells by T helper type 1 cells via Fas/Fasligand interaction

Fas was recently demonstrated to be the major target molecule engaged by CD4⁺ cytolytic T lymphocytes (CTL). We examined Fas expression on various cloned T cell subpopulations and their susceptibility to lysis by CD4⁺ or CD8⁺ CTL. A reciprocal relationship in Fas and Fas-ligand expression was observed in CD4⁺ T helper (Th)1- and Th2-type clones, and Fas mRNA was predominantly detected in Th2 clones, whereas Fas-ligand mRNA was principally found in Th1 clones. The two Th0 clones tested expressed both Fas and Fas-ligand, but only one exhibited cytolytic activity, whereas both were sensitive to CD4-mediated lysis. A functional consequence of the inverse Fas-Fas-ligand expression pattern was that Th2 and Th0 cells were sensitive to lysis by both Th1 CD4⁺ CTL and a CD8⁺ CTL clone in a Fas-dependent manner. These results suggest that cytolytic CD4⁺ Th1 cells may play an immunomodulatory role, regulating a Th2/Th0 response by Fas-mediated lysis.     

Civic responsibility among Australian adolescents: Testing two competing models

The development of civic responsibility is considered to be an important component of healthy adolescent development. However, the study of its development has been relatively neglected and few studies have attempted to ground understanding of its development in a theoretical framework. The present study operationalized civic responsibility as attitudes and behaviors relating to political and community issues that are beneficial to society and compared two theoretical causal models, the social development model (SDM) and a coping‐competency model for their predictive value. Gender differences were also assessed. A total of 500 subjects, drawn from a longitudinal study (the Australian Temperament Project), participated in the study, using questionnaire and interview data. Approximately 1 in 5 adolescents actively engaged in behaviors reflecting community civic responsibility and less than 1 in 10 actively participated in the political arena. However, positive levels of social awareness were evident. Hierarchical multiple regression analyses indicated that the SDM had the most predictive value for political and community civic responsibility. Peer encouragement and peer participation were the most significant predictors. Variables from the coping‐competency model played some role in the prediction of community, but not political, civic responsibility. Gender differences in community civic responsibility, but not political civic responsibility, were found. One in two adolescents indicated that they would participate in volunteer work or political activities if more opportunities existed. This suggests the need for greater availability of appropriate community‐oriented activities for adolescents. © 2004 Wiley Periodicals, Inc. J Comm Psychol 32: 229–255, 2004.     

The effects of indoramin on histamine and antigen-induced changes in respiration in guinea-pigs

Indoramin, a drug which blocks alpha-adrenergie, histamine and serotonin receptors, was tested as a protective agent during challenge with bronchoconstrictor agents in guinea-pigs. In conscious guinea-pigs, the time of onset of respiratory distress during continuous administration of aerosolized solutions of histamine, serotonin or ovalbumin (with animals pre-sensitized to this antigen) was measured using a force-displacement transducer applied to the animal's back. This time interval for each guinea-pig was compared with and without indoramin pre-treatment. Indoramin was administered by intraperitoneal injection or by aerosol treatment. In anaesthetized animals under artificial respiration, respiratory distress was induced by intravenous injection of histamine and measured by the Konzett-Rössler technique. Indoramin treatment significantly protected guinea-pigs in both types of experiment from the effects of each challenging agent.     

CXCR2 blockade influences Anaplasma phagocytophilum propagation but not histopathology in the mouse model of human granulocytic anaplasmosis

Anaplasma phagocytophilum is an obligate intracellular bacterium that infects neutrophils and causes human granulocytic anaplasmosis. Infection induces neutrophil secretion of interleukin-8 or murine homologs and perpetuates infection by recruiting susceptible neutrophils. We hypothesized that antibody blockade of CXCR2 would decrease A. phagocytophilum tissue load by interrupting neutrophil recruitment but would not influence murine hepatic pathology. C3H-scid mice were treated with CXCR2 antiserum or control prior to or on day 14 after infection. Quantitative PCR and immunohistochemistry for A. phagocytophilum were performed and severity of liver histopathology was ranked. Control mice had more infected cells in tissues than the anti-CXCR2-treated group. The histopathological rank was not different between treated and control animals. Infected cells of control mice clustered in tissue more than in treated mice. The results support the hypothesis of bacterial propagation through chemokine induction and confirm that tissue injury is unrelated to A. phagocytophilum tissue load.     

The determinants of attitudinal change among medical students participating in home care training: a multi-center study.

PURPOSE: To report attitudinal changes of medical students from five medical schools rotating through a home care program, and to determine which of the program characteristics influenced attitudes the most. METHOD: A survey instrument covering four home care domains (general attitudes, home-based therapies, home care training, and time and reimbursement) was designed and validated by the five schools involved. Using pre- and post-rotation scores, analyses were done to evaluate for attitudinal changes within and among schools. The programs had similar basic characteristics (home visits, attending physicians' involvement, didactics), but had differing degrees of these components. RESULTS: Significant improvements in attitude scores were found in three domains: general attitudes, homebased therapies, and home care training. For time and reimbursement, only three schools improved significantly between pre- and post-rotation scores. Among the five schools, there were significant differences in the homebased therapies and home care training domains (p <.05), and in the time and reimbursement domain the difference approached significance (p =.06). None of the students' characteristics but all of the programs' characteristics significantly correlated with changes in total scores. In the first multiple regression model, educational level (third year instead of fourth) was the only independent predictor of change in score, (adjusted r(2) =.14). In Model 2, the strongest predictor was "contact with physician-program director," followed by "number of visits" and "physician-precepted visits" (r(2) =.23). CONCLUSION: Educational home care programs of varying intensities can positively affect medical students' attitudes towards home care. At least three program characteristics, (the physician-program director, number of visits, and physician-precepted home visits), are important parts of a successful program.     

Emphysematous lung destruction by cigarette smoke. The effects of latent adenoviral infection on the lung inflammatory response.

This study was designed to test the hypothesis that cigarette smoke-induced inflammation and emphysema are amplified by the presence of latent adenoviral (Ad) infection, and to determine whether this emphysematous process can be reversed by all-trans-retinoic acid (RA) treatment. The results confirm that in guinea pigs, chronic cigarette-smoke exposure caused lesions similar to human centrilobular emphysema. They also show that latent Ad infection combined with cigarette-smoke exposure caused an excess increase in lung volume (P < 0.001), air-space volume (P < 0.001), and lung weight (P < 0.01), and further decrease in surface-to-volume ratio (P < 0.001) compared with smoke exposure alone. RA treatment failed to reverse these emphysematous changes. Analysis of inflammatory response in parenchymal and airway tissue showed that smoking caused an increase of polymorphonuclear leukocytes (PMNs) (P < 0.0002), macrophages (P < 0.001), and CD4 cells (P < 0.0009), and that latent Ad infection independently increased PMNs (P < 0.001), macrophages (P = 0.003), and CD8 cells (P < 0.001). We conclude that latent Ad infection amplifies the emphysematous lung destruction and increases the inflammatory response produced by cigarette-smoke exposure. In this study, the increase in CD4 was associated with cigarette smoke and the increase in CD8 cells with latent Ad infection.