Action spectrum of antiviral factor from chicken sera.

Rous sarcoma virus infections of regressor line chickens stimulate the transient production of antiviral factors in the serum. Earlier the present authors reported that a viral neutralization factor (VNF) inactivated Rous sarcoma virus during a 3-h incubation. The VNF is likely to have a broad antiviral and antimicrobial spectrum because it is active against several unrelated pathogenic poultry viruses. The present study measured the activity of VNF against Newcastle disease virus, infectious bursal disease virus, and infectious bronchitis virus. The VNF is active in immunologically incompetent systems and must be preincubated with the virus in order to inhibit it. Based upon the current experiments, it is proposed that VNF is not an immunomodulator but directly inactivates the virus. The VNF agent appears to be one of a newly identified class of nonspecific antiviral agents produced in vivo in chickens in response to a viral infection.

Complications following blunt and penetrating injuries in 216 victims of chest trauma requiring tube thoracostomy.

Tube thoracostomy (TT) is required in the treatment of many blunt and penetrating injuries of the chest. In addition to complications from the injuries, TT may contribute to morbidity by introducing microorganisms into the pleural space or by incomplete lung expansion and evacuation of pleural blood. We have attempted to assess the impact of TT following penetrating and blunt thoracic trauma by examining a consecutive series of 216 patients seen at two urban trauma centers with such injuries who required TT over a 30-month period. Ninety-four patients suffered blunt chest trauma; 122 patients were victims of penetrating wounds. Patients with blunt injuries had longer ventilator requirements (12.6 +/- 14 days vs. 3.7 +/- 7.1 days, p = 0.003), longer intensive care stays (12.2 +/- 12.5 days vs. 4.1 +/- 7.5 days, p = 0.001), and longer periods of TT, (6.5 +/- 4.9 days vs. 5.2 +/- 4.5 days, p = 0.018). Empyema occurred in six patients (3%). Residual hemothorax was found in 39 patients (18%), seven of whom required decortication. Recurrent pneumothorax developed in 51 patients (24%) and ten required repeat TT. Complications occurred in 78 patients (36%). Patients with blunt trauma experienced more complications (44%) than those with penetrating wounds (30%) (p = 0.04). However, only seven of 13 patients developing empyema or requiring decortication had blunt trauma. Despite longer requirements for mechanical ventilation, intensive care, and intubation, victims of blunt trauma seemed to have effective drainage of their pleural space by TT without increased risk of infectious complications.

Responses of regressor and progressor lines of chickens to intracerebral inoculations of Rous sarcoma virus.

Two-day-old chickens of the Arkansas B1 progressor (Pr) line and the B1 regressor (R) line were inoculated intracerebrally with three dilutions of Rous sarcoma virus. Chickens that died between 7 and 42 days postinoculation were examined for lesions attributable to Rous sarcomas. Mortality was 93% for the progressor chickens as compared with 65% for the regressor chicken. Macroscopic lesions were found on the head in 64 chickens, as hemorrhage in the brain in 38, on the heart in 15, on the liver in 9, and in the parenchyma of the brain in one chicken, from a total of 117 chickens inoculated. Surviving chickens were inoculated in the wingweb with Rous sarcoma virus. Of the progressor line chickens three of four developed tumors and two died. The third chicken exhibited abnormal neurological behavior. Of the regressor line, 15 of 20 were immune and of the five that developed tumors, four had complete regressions. The fifth chicken also showed neurological abnormality. The two chickens with neurological dysfunction were sacrificed, and their histopathology examinations revealed lesions in the brain with features belonging to Rous sarcomas, paralleling those reported for other types of sarcomas.

Transfer of blood lymphocytes and macrophages between histocompatible progressor and regressor chickens infected with Rous sarcoma virus.

The development of histocompatible White Leghorn (progressor) and Arkansas Regression (regressor) chicken lines was described. When challenged with Rous sarcoma virus, progressor chickens developed fatal tumors while the regressor chickens eliminated the sarcoma. When sensitized histocompatible peritoneal macrophages and blood lymphocytes were transferred from regressor donors to progressor recipients, they both eradicated growing tumors. Histoincompatible cells were ineffective in inducing tumor remission. Within the two age groups tested, the sensitized blood lymphocytes and macrophages were only effective when transferred between age-matched donor and recipient chickens.

Genetic aspects of antibody responses in chickens to different classes of antigens.

Six breeding groups of chickens, each characterized by a different haplotype of the B blood group system, were challenged with different classes of antigens, namely Newcastle disease vaccine (ND), infectious bronchitis vaccine (IB), infectious bursal disease viral agent (IBD), Salmonella pullorum antigen (P), and sheep red blood cells (SRBC). Parents were challenged at 20 weeks of age, and their offspring were challenged at 3 weeks of age. Blood samples were taken from the parents at 1 week after challenge, and from the offspring at 1, 2, 3, and 4 weeks after challenge for determination of antibody titers to each antigen. The offspring were also challenged at 8 weeks of age in the wing-web with Rous sarcoma virus (RSV). Tumor scores were taken weekly on individual chickens for the next 10 weeks. There were significant differences (P less than .01) between breeding groups of parents for antibody titer responses to ND, IB, P, and SRBC. There were significant differences (P less than .05) between the breeding groups of offspring for antibody titer responses to ND, IB, IBD, P, and SRBC. There were significant (P less than .01) differences between the breeding groups in the accumulative tumor scores over the 10-week period. The lines that cause regression of Rous sarcomas (R-lines) were significantly (P less than .01) superior in resisting tumor growth to those lines that allow progressive growth of tumors (Pr-lines). The only antigen to which the R-lines gave significantly (P less than .01) higher titers of antibody responses than the Pr-lines was SRBC.

Parabiosis between avian embryos resistant and susceptible to Rous sarcoma virus.

Parabiosis of chicken embryos was used to determine if resistance or susceptibility to Rous sarcoma virus (RSV) tumors could be transferred between RSV-resistant (R) and RSV-susceptible (S) embryos. Eggs from RSV-R and RSV-S lines were parabiosed at 12 days of incubation. One week after hatching the chicks were inoculated in the wing web with RSV. Birds were examined for tumor lesions through 9 weeks of age. Lesion scores of the nonparabiosed RSV-S line were significantly higher than nonparabiosed RSV-R lines. Lesion scores of RSV-R chicks that had been parabiosed to RSV-S chicks were higher than nonparabiosed RSV-R chicks. Lesion scores of RSV-S chicks parabiosed to RSV-R chicks were not different from nonparabiosed RSV-S chicks. These results suggest that the resistance to RSV was not transferred between parabionts but that there was significant transfer of susceptibility from the RSV-S embryos to the RSV-R embryos.

Stimulation of progressor and regressor chicken leukocytes with Con A, PHA-P, and Rous sarcoma tumor antigens.

Progressor (Pr) and regressor (R) chickens from the University of Arkansas lines were used as leukocyte donors. Peripheral blood leukocytes were stimulated with two mitogens, concanavalin A (Con A) and phytohemagglutinin-P (PHA-P). Both Pr and R leukocytes displayed the same Con A-stimulated dose dependency on blastogenesis. The regressor leukocytes were stimulated more than the progressor leukocytes at high concentrations of PHA-P. There did not appear to be any correlation between the response of individual chickens to mitogens and their ability to regress a Rous sarcoma. We concluded that the R-Rs-1 gene, which controls the animal's response to Rous sarcoma, and the Con A and PHA-P response genes are probably located at different loci in the chicken genome. Mitogen-induced blastogenesis does not appear to be a useful index to predict regression response in the chicken. Under our experimental conditions, regressor leukocytes showed a sensitization to sarcoma antigens, but the progressor leukocytes did not. The data suggest that the R-Rs-1 gene does not confer a generally enhanced immune status to the chicken but acts as an Ir response gene to augment the immune response to specific antigens.

Evaluation of Arkansas Rous sarcoma regressor and progressor lines and giant jungle fowl for genetic resistance to the northern fowl mite.

Arkansas B1B1R, B2B2R, and B3B3R regressor lines, Arkansas B1B1Pr, B2B2Pr, and B3B3Pr progressor lines, and Giant Jungle Fowl were infested simultaneously at 28 weeks of age with northern fowl mites. The chickens were maintained in similar environments and mite ratings were recorded weekly for 5 months. No strains were completely resistant to mites, but there were significant (P less than or equal to .05) differences among strains in degree of infestation. The regressor lines generally showed significantly (P less than or equal to .05) less infestation than the progressor lines for both female and male chickens. The regressor lines appear to have genetic factors from the Giant Jungle Fowl in the development of the regressor lines that imparted increased resistance to the northern fowl mite.

Isolation of high and low molecular weight components from chicken sera that have Rous sarcoma virus neutralizing activity.

Blood sera components from Arkansas regressor line (R-line) and progressor line (Pr-line) chickens are compared for the first time for Rous sarcoma virus neutralizing activity. Sera was fractionated by Sephadex G-100 filtration into a high molecular weight fraction I (HMW-I) and a low molecular weight fraction II (LMW-II) component (HMW-I greater than 14,000 daltons, LMW-II less than 5,000 daltons). Both fractions from each line of chickens exhibit activity against Rous sarcoma virus (RSV) judged by a wing web assay. Both HMW-I (principally antibodies) and LMW-II neutralized RSV when obtained from hyperimmune R-chickens and Pr-chickens with large progressing tumors. However, HMW-I and LMW-II obtained from R- or Pr-chickens before challenge contain so RSV neutralizing activity. The novel low molecular weight fraction II disappeared from the sera of R-line chickens 2 weeks after tumor regression, whereas the HMW-I persisted after tumor regression.

Heritabilities for regression and progression of rous sarcomas in the chicken.

Variance components for hatch, line, and sire expressed as percentages of the total variance for each parameter of regression and progression of Rous sarcomas in chickens were obtained. Some parameters measured specific stages of regression or progression, and other parameters measured the entire process of regression or progression of Rous sarcomas. Heritabilities of each parameter were estimated. Additive genetic variation is strongly implicated in the defense of the chicken against early tumor growth and during the entire process of regression. Environmental variation is important in influencing the point in time of tumor growth when the first reduction in size of tumor occurs. There is evidence of genetic variation exclusive of the R-Rs-1 gene locus that assists the chicken to resist tumor growth. The coefficient of variation for each of the parameters is very large as compared with the coefficient of variation for economic traits such as body weight at broiler age.

Immunologic response in chickens from different genetic lines to Rous sarcoma virus.

Twelve young chickens of the Tumor Progressor and Tumor Regressor Lines were studied in respect to their humoral immunologic response to challenge with Rous sarcoma virus via inoculation into the wing web. On day 1, prior to virus inoculation and on days 10, 15, and 20 after injection of virus, the birds were bled and their serums tested for the presence of anti-RSV factors by standard procedures of serum-neutralization tests. From the conducting of statistical analyses of the data, it was determined that a strong association occurs between an early, increasing, and sustained presence of biologically active anti-RSV factors in the blood of the chicken and its ability to effect complete regression of the Rous sarcoma.

Effect of Mycoplasma gallisepticum on genetically defined chickens.

Three parameters were used to measure differences between Arkansas progressor and regressor lines of chickens in response to Mycoplasma gallisepticum inoculations. The responses of regressor and progressor lines to M. gallisepticum did not differ as judged by antibody response, severity of airsacculitis, and resistance of tracheal ring tissue cultures from 20-day-old progressor and regressor chick embryos to M. gallisepticum.

The infectivity of fluid from regressing Rous sarcomas.

Fluid was withdrawn from the site of regressing Rous sarcomas in chickens and inoculated into the wing-webs of untreated chickens from three strains of chickens with divergent degrees of resistance to Rous sarcomas. The transfer of fluid initiated progressive tumors in all three strains of chickens. The infectivity of the fluid was apparently due to tumor cells and not to virus.

Immune response in progressor and regressor strains of chickens at specific intervals after a primary challenge with Rous sarcoma virus.

A progressor line and a regressor line of chickens were compared for development of immune response, after an initial inoculation of Rous sarcoma virus in the wing-web. Quantitative measures of immunity were determined for the two contrasting lines of chickens at specific intervals after the initial challenge. It was found that subsequent challenges, with either Rous sarcoma virus or tumor homogenate, in the opposite wing-web were met by an early immune response from the regressor line. This early response was absent in the progressor line. However, both lines showed a similar immune response after a time interval of 15 days from the initial challenge. The genes for regression exert this early immune response which is the key to spontaneous regression of Rous sarcomas.

The interaction between Mycobacterium bovis (BCG) and genotype of chicken in increasing the percentage of regression of Rous sarcomas.

Four breeding groups of chickens were inoculated in the wing-web with Rous sarcoma virus at 8 weeks of age. Treated birds were given a single dose of live organisms of a mile strain of Mycobacterium bovis of variety Calmette Guerin (BCG) as a subcutaneous inoculation adjacent to the emerging tumor. Control birds received no BCG. The breeding groups of chickens included a line selected for ability to cause a high percentage of spontaneous regression of tumors, a susceptible line with a very low level of regression of tumors, and the two reciprocal crosses between these lines. Treatment with BCG greatly enhanced the percentage of regression in the line selected for regression and in the two reciprocal crosses, but was ineffective in the low regression line. Bursectomy of chicks from the low regression line did not permit BCG treatment to increase regression of Rous sarcomas.