Amos E. Palmer

Betamethasone and the rhesus fetus: Multisystemic effects

In this controlled study of betamethasone administration to pregnant rhesus monkeys, using dosages per gram of fetal body weight similar to those reported in several human clinical studies, the most significant fetal pulmonary changes observed were increases in maximum lung volumes. The fact that comparable increases in peak volumes were demonstrated on saline filling supports our contention that these changes are related primarily to lung structural alterations rather than surfactant effects. Additional findings in the treated animals included reduced fetal head circumference, thymus weight, adrenal weight, placental weight, and maternal postoperative weight and increased fetal hepatic weight. Any of these glucocorticoid-induced changes could portend serious side effects. Further studies are needed to delineate the risk:benefit ratio of such treatment.

Glucocorticoids and the rhesus fetal lung

The effects of glucocorticoids on primate fetal lung function have not been clearly delineated. In this prospective study of preterm rhesus fetuses exposed in utero to betamethasone for 72 hours, the most significant alteration was a striking increase in maximum lung volumes. Functionally less significant increases in residual lung volumes were also noted. The lungs of the treated fetuses did not exhibit lower extract surface tensions or increased phospholipid concentrations. These findings suggest that the major effect of betamethasone is on lung connective tissue elements, with minimal effects on alveolar surfactant. Additional evidence of the multisystemic effects of glucocorticoids was obtained in that significant differences in fetal, adrenal, hepatic, and placental weights also were observed.

Differences among Isolates of Simian Hemorrhagic Fever (SHF) Virus

Abstract Simian hemorrhagic fever (SHF) virus is a member of the Togaviridae family which currently is unclassified to genus. We have studied the relatedness of four different SHF virus isolates obtained from infected macaque or patas monkeys. Differences were found among isolates in type and severity of disease produced in patas monkeys, cell sensitivity to infection, viral antigens, and levels of specific antibody induced in patas monkeys. Based on these criteria, the four isolates have been grouped in two categories: those producing acute infections in patas monkeys (LVR, P-180) and those producing persistent infections (P-248, P-741). The P-180 isolate induced the most severe disease in experimentally infected patas monkeys, but only occasionally were their infections fatal. Persistently infected patas monkeys were viremic over a period of years, but showed no signs or symptoms of infection. All four isolates were found to be antigenically related by use of enzyme-linked immunosorbent assay (ELISA); the P-248 isolate showing the weakest antigenic relationship. However, none of the four isolates induced cross-neutralizing antibodies in infected patas monkeys. High titers of specific IgG antibody (up to 31,250 as determined by ELISA) were induced in acutely infected patas monkeys (LVR, P-180), but antibody was barely detectable (≤50) in persistently infected patas monkeys (P-248, P-741). LVR lyrically infected USU-104 cells, patas monkey peritoneal macrophages (PMAC), and rhesus monkey PMAC. The P-180 isolate lytically infected both patas monkey PMAC and rhesus monkey PMAC, but not USU-104 cells. The isolates producing persistent infections (P-248, P-741) lytically infected only-rhesus monkey PMAC. These results show that marked differences exist among isolates of SHF virus from naturally infected animals. These differences should be useful in categorizing new isolates.

Epizootic of Simian Haemorrhagic Fever

Two epizootics of simian haemorrhagic fever (SHF) have been reported among quarantined Indian rhesus monkeys (Macaca mulatta). The first outbreak occurred in July 1964 at the Sukhumi Institute of Experimental Pathology and Therapy, USSR1,2; the second occurred in October 1964 at the US National Institutes of Health (NIH) quarantine colony3,4. The virus causing the NIH epizootic was isolated in cell culture and characterized5. Although the Soviet workers showed that the disease could be transmitted from monkey to monkey, they have not yet isolated the causative agent in either cell culture or small laboratory animals. This report describes the isolation in cell culture of the virus causing the Sukhumi epizootic and the serological relationship between the viruses causing the Sukhumi and NIH outbreaks.

Elimination of Persistent Simian Hemorrhagic Fever (SHF) Virus Infection in Patas Monkeys

Abstract Devastating epizootics of simian hemorrhagic fever (SHF) have been iatrogenically initiated in captive colonies of macaque monkeys by strains of SHF virus emanating from asymptomatic persistently infected patas monkeys. We have found that persistently infected patas monkeys can be cleared of their infection by superinfection with strains of SHF virus which cause acute infections in this species. All 20 persistently infected animals subjected to this procedure have been cleared of their infection within 3 months. These animals were shown to be virus free by the most sensitive in vitro and in vivo tests currently available and periodic tests of serum from these animals over several years have shown them to remain virus free. Superinfection has in some cases caused some adverse clinical symptoms (anorexia, lethargy, facial edema, dehydration, and mild subcutaneous hemorrhages), but with supportive care, no fatal infections have occurred. Thus, superinfection with acute strains of SHF virus is a highly effective method of eliminating persistent infection in patas monkeys.

Simian Haemorrhagic Fever (SHF): New Virus Isolate from a Chronically Infected Patas Monkey

A new strain of simian haemorrhagic fever (SHF) virus was isolated from chronically infected patas monkey no. 248 (P-248) in USU-104 cells. The P-248 isolate had the same size, morphology and cytoplasmic site of replication as the prototype LVR strain. However, the P-248 isolate caused a persistent infection without noticeable cytopathology in USU-104 cells rather than the strongly lytic infection produced by prototype LVR virus. The capacity of P-248 virus to produce a persistent, non-lytic infection of USU-104 cells was a very stable characteristic of the isolate. Extensive serial passage of this isolate through USU-104 cells (over 50 passages) and rhesus monkeys (six passages) failed to unmask virus with lytic properties for USU-104 cells. Culture medium from persistently infected cultures assayed in rhesus monkey peritoneal mononuclear phagocytes, where measurable cytopathology occurs, was found to contain about 10(5) to 10(6) TCID50/ml of cell-free P-248 virus. Immunolabelling techniques showed only a low percentage of infected cells in persistently infected cultures. The mechanism of persistence of the P-248 isolate in USU-104 cells has not been determined but evidence suggests it does not involve interferon or defective interfering particles.

Growth and hematologic development of the patas monkey (Erythrocebus patas) to one year of age.

Data from 338 blood samples of 31 patas monkeys is presented to show the normal hematolgoic development from birth to one year of age, and is compared to 120 samples from normal adults. Marked changes in hematocrit, hemoglobin, red cell numbers, and leukocyte distribution which occurred during the first month were followed by a slow progression to adult values. Body weight data is also presented which shows a linear growth rate during the first year of life.

Disodium Phosphonoacetate in Cream Base as a Possible Topical Treatment for Skin Lesions of Herpes Simplex Virus in Cebus Monkeys

Disodium phosphonoacetate (PAA) in a cream-ointment base was applied to herpesvirus skin lesions on the genitalia of cebus monkeys. The lesions had been produced by the intradermal injection of herpes simplex virus type 2. Concentrations of 0.2, 2, and 5% PAA were used. Liberal application of PAA at concentrations of 2 and 5% proved extremely irritating and produced extensive, severe lesions over the treated area. The 2% PAA, when applied carefully to the lesion area, proved less irritating, but did not reduce healing time when compared with the placebo-treated animals. The 0.2% PAA caused slight reduction in lesion size and duration, but these differences were not statistically significant when compared with placebo-treated animals.

Isolation of viruses from primary dog cell cultures and the occurrence of viral antibody in donor animals.

Summary Fifty-five different lots of primary dog kidney cell cultures and 30 lots of primary liver cell cultures (derived from stray dogs) were incubated for 4-5 weeks and examined for viruses. Ten ICHVs, ten CDVs, and one herpesvirus were isolated from kidney cultures; three ICHVs were isolated from liver cultures. Thirty-eight % of kidney cultures and 10% of liver cultures contained viruses. CDV was isolated only from dogs studied in early fall; no CDV was isolated from dogs studied in late winter and early spring. No characteristic antibody pattern was found in dogs yielding or not yielding viruses, since ICHV and CDV were isolated from dogs with and without antibody. Cell-free homogenates of CDV-infected kidneys were inadequate for demonstrating the virus, whereas primary cell cultures from these kidneys readily yielded virus. There was evidence from direct isolations and from antibody reactions that no adenovirus other than ICHV infected the dogs studied. ICHV antibody detection was about 60 times more sensitive by neutralization tests than by CF.

Attempts to infect rhesus monkeys with human type 4 adenovirus

Summary In searching for an animal model for human adenovirus studies we have attempted to infect rhesus monkeys with a human type 4 adenovirus. The results were inconclusive but we have some evidence to suggest that infection and replication might have occurred in several animals. Communicability among cagemates was not demonstrated. The difficulty encountered in infecting rhesus monkeys despite the large virus dose employed indicates that this animal would not serve as a useful model for vaccine testing.