Immunization of pigs against influenza virus infection by DNA vaccine priming followed by killed-virus vaccine boosting.

In a previous study of particle-mediated DNA vaccination of pigs, it was found that administration of an influenza virus hemagglutinin (HA) gene elicited low levels of virus-specific antibody, but did not provide significant protection from challenge infection (as evidenced by virus shedding in nasal secretions). However, the vaccinated pigs developed high antibody titers after exposure to the challenge virus, suggesting strong priming of humoral immune responses by DNA vaccination. In the present study, pigs given a conventional, inactivated influenza virus vaccine 4 weeks after a priming dose of HA DNA developed higher levels of virus-specific serum antibodies and were protected from challenge virus infection to a significantly greater degree than pigs that received two doses of DNA vaccine.

Systemic and mucosal immune responses to H1N1 influenza virus infection in pigs.

Influenza is a common respiratory disease in pigs, and since swine influenza viruses are zoonotic pathogens, they also pose human health risks. Pigs infected with influenza virus mount an effective immune response and are protected from subsequent challenge, whereas the currently available, inactivated-virus vaccine does not consistently confer complete protection to challenge. To develop and evaluate new vaccination strategies, it is imperative to fully understand the immune responses that are associated with protection following natural infection. Therefore, we have evaluated the phenotype and kinetics of immune responses to primary and re-challenge infection with H1N1 swine influenza virus in the pig. Through the use of isotype-specific antibody secreting cell ELISPOT assays, interferon-gamma ELISPOT assays and isotype-specific ELISAs on serum, nasal wash and bronchoalveolar lavage samples, we defined the humoral and cellular immune responses, both locally in the respiratory tract and systemically, to this viral infection. Virus-specific serum IgG, IgA, and HI titers all peaked 2-3 weeks after primary infection and did not substantially increase after re-challenge. The predominant virus-specific isotype in serum was IgG. Pigs responded with virus-specific IgG and IgA in both the upper (nasal washes) and lower (bronchoalveolar lavages) airways; IgA was the predominant isotype in both sites. Despite the fact that the pigs were completely protected from re-challenge, the antibody titers in the nasal washes increased. Results of the antibody-secreting cell ELISPOT assays demonstrated that the numbers of both IgG and IgA secreting cells in the nasal mucosa were dramatically higher than in any other tissue examined. In contrast, IFN-gamma secreting cells were predominantly localized to the spleen and tracheobronchial lymph nodes. These data will be helpful in the future development and evaluation of novel vaccines.

Coadministration of DNA encoding interleukin-6 and hemagglutinin confers protection from influenza virus challenge in mice.

This study was conducted to investigate whether Accell gene gun coadministration of DNA encoding human interleukin-6 (IL-6) would enhance protective immune responses in mice to an equine influenza A virus hemagglutinin (HA) DNA vaccine. Mice that received HA DNA alone exhibited accelerated clearance of homologous challenge virus but were not protected from infection. In contrast, mice that received both HA and IL-6 DNA had no detectable virus in their lungs after challenge. These results strongly support the use of IL-6 as a cytokine adjuvant in DNA vaccination.

The development of health protective behaviors among college students.

This study uses structural equation modeling and a panel design to explain participation in health protective behavior (HPB) among college students. The direct, indirect, and total effects of gender, social influences (parental and peer behavior), social attachments (activity involvement, social support, and romantic involvement), social triggers (personal health, acute illnesses, and personal or family health crisis), health value, and effort to improve health behavior on HPB are examined. A path model with a high goodness of fit and an R2 of .418 shows that gender; health value, and effort to change health behaviors are the most powerful predictors of HPB participation, while parents and peers influence HPB indirectly through influence on health value and effort to change. Neither the social attachment nor social trigger items influenced HPB in this sample. Implications of these findings are discussed.

Identification of urinary metabolites of 8-methyl-8-azabicyclo-[3,2,1] octan-3-yl 3,5-dichlorobenzoate (MDL 72,222) in the dog and monkey.

The metabolism of 8-methyl-8-azabicyclo- 3,2,1]octan-3-yl 3,5-dichlorobenzoate (MDL 72,222) was studied in the dog and monkey. Four urinary metabolites were detected by HPLC, HPLC/MS, and GC/MS, and were identified by comparison to authentic standards. The major metabolite in the dog, approximately 41% of the administered dose excreted between 0 and 120 hr, was the MDL 72,222-N-oxide. On the other hand, the major metabolite in the monkey was the glycine conjugate of 3,5-dichlorobenzoic acid (greater than 56% of the dose). Seven percent of the dose in the monkey urine was free 3,5-dichlorobenzoic acid. N-Desmethyl MDL 72,222 was present at 2.5 and 1% in the dog and monkey, respectively. Very little (less than 1%) of the parent compound was found in urine. The major pathways of metabolism of MDL 72,222 are N-oxidation, N-demethylation, ester hydrolysis, and amino acid conjugation.

Disposition of 8-methyl-8-azabicyclo[3,2,1]octan-3-yl 3,5-dichlorobenzoate, a potent 5-hydroxytryptamine antagonist, and two metabolites in dogs and monkeys.

The disposition of 8-methyl-8-azabicyclo[3,2,1]octan-3-yl 3,5-dichlorobenzoate (MDL 72,222; 1), a potent 5-hydroxytryptamine antagonist, and its N-demethylated and N-oxide metabolites was studied in dogs and monkeys. After single, intravenous doses of 1 at 5 mg/kg, the mean terminal half-lives of 1 in plasma were 2.6 h in the dog and 3.8 h in the monkey. The mean half-life of the N-demethylated metabolite in dogs (approximately 20 h) was very similar to that in monkeys. However, the mean half-life of the N-oxide metabolite in dogs (10.8 h) was different from that in monkeys (3.9 h). The steady-state volume of distribution of 1 was 16 L/kg in dogs and 8.9 L/kg in monkeys. Examination of the mean residence times revealed that 1, in both species, and the N-oxide metabolite, in dogs, distributed to the peripheral tissue, whereas the distribution of the N-demethylated metabolite in both species and the N-oxide metabolite in monkeys was limited mainly to the systemic circulation. Compound 1 was metabolized extensively in both species. In dogs, 0.7, 2.5 and 40.6% of the administered dose were excreted in 0-120-h urine samples as 1 and its N-demethylated and N-oxide metabolites, respectively. In monkeys, however, the corresponding percentages were 0.8, 0.7, and 1.8%. Most of the administered dose in monkeys was excreted in urine as 3,5-dichlorobenzoic acid and its glycine conjugate.

Health value and gender in predicting health protective behavior.

This research analyzes the influence of selected social psychological factors (health locus of control and health value), social support factors (influence of parents and peers, organizational involvement, and reliance on others during stressful times), and health-specific factors (recent health crisis and self-assessment of health status) on participation in health protective behaviors by males and females. While much research has focused on identifying determinative factors (often with inconsistent findings), little research has been directed to understanding if and how predictive factors vary by gender. Data for the research were obtained from personal interviews with 167 undergraduate college students collected during the fall semester of their freshman year and again during their sophomore year. Female students averaged statistically significant more health protective behaviors than did male students, and increased involvement in HPBs from their freshman to sophomore years (while male students' participation declined). Among the factors studied, peer practices (collected in time 2) is a statistically significant predictor for both males and females. Value placed on health predicts for females but not males, while grade point average predicts for males but not females. Overall, females and high GPA males are most likely to engage in HPBs.

Enhancing the utilization of outpatient mental health services.

This article describes two sets of field studies undertaken by the program evaluation unit of a community mental health center. These studies analyzed clients' utilization of service and assessed service impact in the process of testing procedural variations in service delivery. In the first set of studies, a procedure for ensuring verbal client-therapist contact prior to the first appointment was developed and tested. This procedure reduced the no-show rate for initial appointments from 22 to 12%. In the second set of studies, a brief pretherapy orientation nearly eliminated dropout during the first month of therapy. Orientation had both short- and long-range impact on the amount of services used by clients as well as on their outcomes. Therapist's global ratings of client functioning reflected more change for oriented clients, who reported greater short-term symptom reduction as well. Non-oriented clients were more likely to drop out early and to impress their therapists less favorably. The results of these studies suggest that a combination of pretherapy orientation and verbal client-therapist contact prior to the initial appointment might greatly reduce the failure to complete treatment.

Empirical Explorations of SYNCHEM.

During the past several years, a substantial body of experience has accumulated in the use of SYNCHEM, a large-scale program which is able to discover synthesis routes for relatively complex organic structures without on-line guidance on the part of its chemist user. These results indicate that the approach to computer-directed organic synthesis route discovery embodied in the program has been valid and reasonable, and that SYNCHEM is likely to be fruitful from the point of view of its intended users as well as for our research objectives in artificial intelligence. The experiments have revealed a number of insufficiencies in the program as well. Most of these are rectified in SYNCHEM2, a revised version of the program which includes, among other improvements, a more highly developed synthesis search algorithm and the routine consideration of stereochemistry.

Acceptance of general personality interpretations prior to and after receipt of diagnostic feedback supposedly based on psychological, graphological, and astrological assessment procedures.

There was no difference in the acceptance of a general personality interpretation supposedly based on psychological, graphological, or astrological assessment procedures. Ss told that their general personality interpretation was based on one of the three assessment procedures, however, accepted the interpretation to a greater degree than did Ss told the interpretation was "generally true of people." S faith in all assessment procedures and perceived diagnostician skill increased significantly from before to after receipt of the diagnostic feedback. Ss elicited a halo response after they had received the interpretation, such that they generated a highly consistent positive (or negative) view of the assessment procedures and diagnostician skills. Implications of results from this acceptance paradigm were discussed for diagnosticians and therapists.