Inhibited interferon production after space flight.

Several studies have been performed in our laboratories indicating that interferon production may be impaired in rodents after space flight. Using an antiorthostatic suspension model that simulates some of the effects of microgravity seen during space flight, we have shown that interferon-alpha/beta production was inhibited. The inhibition was not due solely to the stress of suspension. The inhibited interferon production was transient, as suspended animals returned to normal caging recovered the ability to produce interferon. Antiorthostatic suspension of mice also resulted in a loss of resistance to infection with the diabetogenic strain of encephalomyocarditis virus, which correlated with the drop in interferon production. In rats flown in US Space Shuttle mission SL-3, interferon-gamma production was inhibited severely when spleen cells were challenged with concanavalin-A upon return to earth. In contrast, interleukin-3 production by these cells was normal. These results suggest that immune responses may be altered after antiorthostatic modeling or space flight, and the resistance to viral infections may be especially affected.

Inhibited interferon-gamma but normal interleukin-3 production from rats flown on the space shuttle.

Rats were flown on Space Shuttle SL-3 for 1 week. When spleen cells were removed from these rats and challenged with concanavalin-A, interferon-gamma production was severely inhibited, while interleukin-3 production was unaffected compared to ground-based control rats. These data indicate that there is a defect in interferon-gamma production in rats that have been exposed to spaceflight. This defect could contribute to, and be one reason for, immunosuppression observed after spaceflight.

Effect of treatment with interferon-gamma and concanavalin A on the course of infection of mice with Salmonella typhimurium strain LT-2.

Lymphokines have been shown to affect the resistance of mice to bacterial infections. To explore this effect further, mice were pretreated with 34 units per day for 5 days of a hybridoma supernatant containing primarily interferon-gamma activity. Then, the mice were infected with one LD50 of Salmonella typhimurium strain LT-2. The hybridoma supernatant fluid-treated mice were not protected; in fact, they died faster than did mice only infected with S. typhimurium. When mice were pretreated under the same regimen with pure murine IFN-gamma produced by recombinant DNA technology prior to infection, the mice were protected and 95% survived the infection. The hybridomas had been treated with concanavalin A (ConA) to induce IFN-gamma. When mice were directly treated with ConA prior to infection with S. typhimurium, they also died more quickly than untreated controls. These data suggest that IFN-gamma pretreatment can protect mice against infection with S. typhimurium, but that ConA pretreatment can counteract that effect.

Enhancement of viral pathogenesis in mice maintained in an antiorthostatic suspension model: coordination with effects on interferon production.

Both rodents and men returning from spaceflight and the attendent microgravity or weightlessness conditions have exhibited alterations in immune responses and, in particular, interferon production. We have utilized a model for antiorthostatic (20 degrees head-down tilt). hypokinetic, hypodynamic suspension of mice that simulates some aspects of weightlessness. Female Swiss/Webster mice that are normally resistant to infection with the D variant of encephalomyocarditis virus showed a marked increase in susceptibility to infection when suspended. This correlated with a drop in interferon production. Control, orthostatically suspended mice (no head-down tilt) showed no increase in susceptibility to the virus. These data suggest that maintenance of mice in the antiorthostatic suspension model for simulating some aspects of weightlessness yielded increased susceptibility to virus infection that was coincident with inhibited interferon production.

Trypanosoma brucei rhodesiense infection in mice prevents virus-induced diabetes: possible role of interferon and immunological mechanisms.

B10.BR, DBA/2, and BALB/c by J mice were infected with Trypanosoma brucei rhodesiense (Lou Tat clone 1). Subsequent infection with the D variant of encephalomyocarditis virus (EMC-D) resulted in no diabetes or encephalitis, even in the susceptible DBA/2 and BALB/c by J strains. Low levels of circulating interferon (IFN) were detected in trypanosome-infected mice at the time of EMC-D infection. All strains were severely immunosuppressed as a result of trypanosome infection, as evidenced by decreased virus-specific neutralizing antibody titers, compared to virus-infected controls. We attempted to simulate some aspects of T.b. rhodesiense infection in B10.BR mice by pretreating mice with cyclophosphamide and IFN prior to EMC-D infection. Immunosuppression by cyclophosphamide greatly enhanced the pathogenesis of EMC-D, while IFN protected against the diabetogenic effect of this virus. Our results indicate that: (i) T.b. rhodesiense infection inhibited EMC-D-induced diabetes, (ii) this inhibition was not due solely to the immunosuppression generated by the trypanosome infection, and (iii) IFN generated by the trypanosome infection could play some protective role in the inhibition of EMC-D-induced diabetes by trypanosome infection.

Virus-induced murine diabetes. Enhancement by immunosuppression.

Adult, male ICR Swiss mice are susceptible to the diabetogenic effects of the D-variant of encephalomyocarditis virus (EMC-D) in contrast to adult C3H/HeJ male mice, which are relatively resistant. To date, experimental evidence suggests that the immune system plays a role in the pathogenesis of this infection. We have investigated the potential involvement of the immune system in the pathogenesis of EMC-D-induced diabetes using cyclosporin-A (CyA), a potent immunosuppressive drug. The data show that treatment with CyA results in increased severity and incidence of diabetes in susceptible ICR Swiss mice and induction of diabetes in resistant C3H/HeJ mice. It is concluded that immune mediation probably is not involved in the early pathogenesis of EMC-D-induced diabetes in mice.

Foster care for child maltreatment. II. Impact on school performance.

At least 150,000 children currently reside in foster care in the United States because of child maltreatment. Nearly 15% of all confirmed maltreatment reports record foster care as one of the acute interventions. Yet, the impact of foster care has been largely unexamined. We conducted a historical cohort study of the impact of foster care on subsequent school performances for 114 children placed in foster care because of maltreatment. A comparison cohort was constituted of 106 maltreated children who were similar in age, race, sex, and year of diagnosis but who were left in their homes after report. School records were reviewed for 96 of the foster care children and 69 of the home care children. School attendance had improved for both groups at the time of follow-up nearly 8 years later. Children in school at the time of report who were then placed in foster care missed an average of 15.6% of the school year prior to the report compared with missing only 3.48% of the most recent school year. The children from the comparison group missed an average of 8.5% of the school year prior to their index maltreatment report and 7.2% of their most recent year in school. Forty-four percent of the foster care group achieved average or above average grades on follow-up compared with the passing rate for the home care group of 32% (P = .17). The foster care children were more likely to receive special education services. Overall, both groups were doing poor work in school an average of 8 years after maltreatment report. There appears to be no evidence for a significant rehabilitative effect of foster care as measured by subsequent school performance.

Foster care for child maltreatment: impact on delinquent behavior.

Previous reports of child maltreatment sequelae have not systematically examined the effects of societal intervention. A historical cohort study has been undertaken to examine the impact of one intervention, foster care, on the subsequent development of juvenile delinquency among child victims. One hundred fourteen foster children, aged 11 to 18 years, in foster care for three or more years, and who were in foster care as a result of maltreatment were studied. A comparison cohort was composed of 106 victims of maltreatment who were left in their family home; these children were similar to the children in foster care with regard to age, race, sex, and year of diagnosis. Cohort differences in maternal education, type of abuse, history of prior maltreatment, sex, and race were controlled in the analysis. Foster children committed 0.050 crimes per person-year after age 11 years; home care children committed 0.059 crimes per person-year after age 11 years (P greater than .2). Foster children were more likely to have committed criminal assault. Among foster children, increased number of foster home placements correlated with increased number of delinquency convictions. Overall, there appears to be no support for the idea that foster care is responsible for a significant portion of later problems encountered by victims of maltreatment.

Exacerbation of the pathogenesis of the diabetogenic variant of encephalomyocarditis virus in mice by interferon.

Adult male ICR Swiss mice develop insulin-dependent diabetes when infected with the D variant of encephalomyocarditis virus (EMC-D). In contrast, adult C57Bl/6 males are relatively resistant to the diabetogenic effects of this virus. We have been studying the role of interferon (IFN) in the pathogenesis of infection by EMC-D and development of virus-induced murine diabetes mellitus. The data show that when IFN beta or IFN gamma were administered four days after virus infection, the frequency and severity of diabetes were exacerbated in ICR Swiss mice, and the diabetic state was induced in the resistant C57Bl/6 strain. In addition, animals treated with either of the IFNs or the IFN-inducer poly I:C, developed symptoms of severe encephalomyocarditis. Analysis of ICR Swiss mouse tissues revealed that IFN-treatment resulted in virus replication in the heart and brain and the reappearance of the virus in the pancreas. It is concluded that under certain conditions, the diabetic state is exacerbated and the normal course of (EMC-D)-infection in mice is altered by IFN.

Replication of diabetogenic and nondiabetogenic variants of encephalomyocarditis (EMC) virus in ICR Swiss mice.

The replication of the diabetogenic D (EMC-D) and nondiabetogenic B (EMC-B) variants of encephalomyocarditis virus in various tissues of the murine host was determined. Pancreatic insulin levels were also measured. EMC-D replicated in the spleen, pancreas, heart, lung, and intestines, while EMC-B was limited to the spleen and pancreas. EMC-B interfered with the replication of EMC-D in each of the tissues examined. Insulin levels were initially increased by both viruses. By 4 days postinfection, insulin levels were either normal or undetectable in (EMC-D)-infected animals, but were dramatically elevated in those infected with EMC-B.

Virus-induced diabetes mellitus in ICR Swiss mice is age dependent.

Adult male ICR Swiss mice develop diabetes mellitus when infected with the D variant of encephalomyocarditis virus. It was determined that the disease syndrome caused by the virus in this mouse strain is dependent upon the age of the animals. Mice younger than 7 weeks developed lethal encephalitis, whereas those past this age developed diabetes. The susceptibility of young mice to the diabetogenic effects of encephalomyocarditis virus was enhanced by testosterone.

Determinants of foster care placement for the maltreated child.

This study examined the records of the North Carolina Central Registry of Child Abuse and Neglect to determine which social, family, and child characteristics were most influential in the decision to place a child in foster care. These records contained all theoretically relevant factors as well as demographic data. Analysis included the computation of odds ratios for foster care for each of 250 variables. A maximum likelihood logistic regression model was constructed to obtain the independent and cumulative contribution of each factor. Some expected variables such as parental stress factors (substance abuse) and types of abuse (burns and scalds) placed a child at a significant risk for placement in foster care (p less than 0.01). However, less obvious factors such as referral source (law enforcement agencies) or geographic area also placed children at risk. Overall, the model explained little of the variance of these decisions (R2 = 0.168) and poorly predicted placement (sensitivity 66.3 per cent, specificity 74.6 per cent). Using existing data, we were unable to adequately describe the decision process in selecting foster care.

Determinants of foster care placement for the maltreated child.

This study examined the records of the North Carolina Central Registry of Child Abuse and Neglect to determine which social, family, and child characteristics were most influential in the decision to place a child in foster care. These records contained all theoretically relevant factors as well as demographic data. Analysis included the computation of odds ratios for foster care for each of 250 variables. A maximum likelihood logistic regression model was constructed to obtain the independent and cumulative contribution of each factor. Some expected variables such as parental stress factors (substance abuse) and types of abuse (burns and scalds) placed a child at a significant risk for placement in foster care (p less than 0.01). However, less obvious factors such as referral source (law enforcement agencies) or geographic area also placed children at risk. Overall, the model explained little of the variance of these decisions (R2 = 0.168) and poorly predicted placement (sensitivity 66.3 per cent, specificity 74.6 per cent). Using existing data, we were unable to adequately describe the decision process in selecting foster care.