A female chimpanzee developed premature sex skin swelling, breast budding, advanced bone age, and moderate estrogen effect of the vaginal cytology. Extensive radiographic and hormonal studies excluded all the known causes of precocious puberty and pseudo‐puberty, yielding a diagnosis of idiopathic true precocious puberty. To our knowledge this is the first observation of idiopathic true precocious puberty in a chimpanzee.

An influenza A virus isolated from seals [A/Seal/Mass/1/80 (H7N7)] and an isolate of this virus obtained from a human conjunctiva were evaluated for replication and virulence in squirrel monkeys. When the seal virus was administered intratracheally, it replicated in lungs and nasopharynges and induced illness almost to the same extent that a human influenza A virus [A/Udorn/72 (H3N2)] did. In one monkey that died of pneumonia, the seal virus was recovered from spleen, liver, and muscle as well as lung. After conjunctival administration in monkeys, the seal virus replicated to a peak titer in the conjunctivae 30-fold greater than that attained by the human virus, but this difference was not statistically significant. In contrast, the seal virus replicated less well than the human virus in the tracheae and nasopharynges when administered by the conjunctival route. These results indicate that the seal virus can replicate efficiently in primates, that it can spread systemically, and that it might differ from human virus in being able to replicate slightly better in primate conjunctival tissue.

Reproductive statistics were gathered over a 5½-year period on a colony of Erythrocebus patas. Pregnancies occurred throughout the year under laboratory conditions with a suggestion of a mating peak in the late fall and early winter. Menstrual cycles were monitored and found to average 30.6 days in length. Maximal vaginal cornification occured on day 15 of the cycle suggesting a midcycle ovulation. However, production of timed-mated pregnancies indicated ovulation occurred earlier and that breeding on days 10, 11, and 12 after menstruation was more likely to result in pregnancy. The gestation length was found to average 167.2 days in 142 harem-bred females and 167.5 days in 11 timed-mated pregnancies. Sixty-two percent of all pregnancies resulted in live births; 28% of the conceptions terminated with in-utero death of the fetus. Stillborn infants were delivered in 9% of the pregnancies. Infant mortality during the first 6 months of life was 10.2%. Females raised in the colony conceived their first offspring at approximately 3 years of age and males were able to sire infants at 3 years and 8 months.

Two marmosets imported from Iquitos, Peru, were found to be infected with Angiostrongylus costaricensis. Both animals had large solitary granulomas involving the wall and adjacent mesentery of the small intestine. Histopathologic examination showed the adult nematodes in the lumina of the mesenteric arteries that coursed through these granulomas. The inflammatory reaction was associated with numerous degenerating eggs and larvae. This is the first report of this parasite in nonhuman primates and extends its geographic range to Peru. In addition, in one animal, Dipetalonema sp were seen free in the abdominal cavity, and pleroceroid larvae (spargana) were in the loose connective tissue of the left axilla. This animal also had microgranulomas associated with eggs and larvae of Angiostrongylus in the kidney, liver, lung, and heart.

Ten serologically distinct avian influenza A viruses were administered to squirrel monkeys and hamsters to compare their replication and virulence with those of human influenza A virus, A/Udorn/307/72 (H3N2). In squirrel monkeys, the 10 avian influenza A viruses exhibited a spectrum of replication and virulence. The levels of virus replication and clinical response were closely correlated. Two viruses, A/Mallard/NY/6874/78 (H3N2) and A/Pintail/Alb/121/79 (H7N8), resembled the human virus in their level and duration of replication and in their virulence. At the other end of the spectrum, five avian viruses were restricted by 100- to 10,000-fold in replication in the upper and lower respiratory tract and were clearly attenuated compared with the human influenza virus. In hamsters, the 10 viruses exhibited a spectrum of replication in the nasal turbinates, ranging from viruses that replicated as efficiently as the human virus to those that were 8,000- fold restricted. Since several avian viruses were closely related serologically to human influenza viruses, studies were done to confirm the avian nature of these isolates. Each of the avian viruses plaqued efficiently at 42°C, a restrictive temperature for replication of human influenza A viruses. Avian strains that had replicated either very efficiently or very poorly in squirrel monkeys still grew to high titer in the intestinal tracts of ducks, a tropism characteristic of avian, but not mammalian, influenza viruses. These observations indicate that some avian influenza A viruses grow well and cause disease in a primate host, whereas other avian viruses are very restricted in this host. These findings also provide a basis for determining the gene or genes involved in the restriction of replication that is observed with the attenuated avian viruses. Application of such information may allow the preparation of reassortant viruses derived from a virulent human influenza virus and an attenuated avian virus for possible use in a live attenuated vaccine for prevention of influenza in humans.

Five fatal cases of disseminated strongyloidiasis were identified in Erythrocebus patas caged singly or in groups of two to four in an indoor research facility. This is the first report of fatal hyperinfective strongyloides infection in a species other than great apes and man. Severe pulmonary hemorrhage, duodenitis, and proximal colitis with microscopically demonstrable larvae in affected tissues were the key necropsy findings. E. patas is an available, suitable model for the study of disseminated strongyloidiasis.

An esophageal stricture was noted in a 10-yr-old chimpanzee who presented with dysphagia, vomiting, and weight loss. After radiographic, esophagoscopic, and histopathologic evaluation of the stricture, antegrade bougienage was performed. The animal began eating solid food again without regurgitating after the third dilation and since that time has been asymptomatic. Additional dilations were performed at 3 and 6 months post-stricture.

An influenza A reassortant virus that contained the hemagglutinin and neuraminidase genes of a virulent human virus, A/Udorn/72 (H3N2), and the six other influenza A virus genome segments from an avirulent avian virus, A/Mallard/New York/6750/78 (H2N2), was evaluated for its level of replication in squirrel monkeys and hamsters. In monkeys, the reassortant virus was as attenuated and as restricted in its level of replication in the upper and lower respiratory tract as its avian influenza virus parent. Nonetheless, infection with the reassortant induced significant resistance to challenge with virulent human influenza virus. In hamsters, the reassortant virus replicated to a level intermediate between that of its parents. These findings suggest that the nonsurface antigen genes of the avian parental virus are the primary determinants of restriction of replication of the reassortant virus in monkeys. Attenuation of the reassortant virus for primates is achieved by the inefficient functioning of the avian influenza genes in primate cells, while antigenic specificity of the human influenza virus is provided by the neuraminidase and hemagglutinin genes derived from the human virus. This approach could lead to the development of a live influenza A virus vaccine that is attenuated for man if the avian influenza genes are similarly restricted in human cells.

Previous investigations of the effect of glucocorticoids on fetal lung development have suggested that changes in lung structural properties may be of greater functional significance than changes in lung surfactant. In this study we examined the mechanism of the glucocorticoid-induced change in lung structure and compared it with the changes that occur during normal development. Rhesus monkeys (Macaca Mulatta) were treated with betamethasone prior to 133 days gestational age and then delivered by cesarian section either at 133 days or near term at 160 days. Our results show that normal fetal lung development over the last month of gestation occurs with a 45% increase in lung dry weight and a 56% increase in the maximal air volume per gram lung (Vmax/g). The immediate effect of the steroid was to cause a similar percentage increase in Vmax/g but no increase in lung weight. In fact, there were significant decreases in lung weight at both 133 and 160 days in the treated animals. In addition, we found no significant changes in the mean alveolar size either with normal development or with the steroid treatment. We thus conclude that in the rhesus monkey, the lung maturation process involves both an increase in lung mass and an increase in the number of alveoli per gram of that mass. The betamethasone treatment results in accelerated recruitment of alveoli coupled with impaired growth of lung tissue.

The livers of 33 captive woodchucks were examined histologically in 30 biopsy and 10 autopsy specimens and the findings were correlated with serum determinations for woodchuck hepatitis virus (WHV), surface antigen (WHsAg) and antibody (anti-WHs), and WHV DNA and DNA polymerase. The liver appeared normal in all 3 serum-negative animals, 7 of 16 with indeterminate WHV status, and 1 of 4 with anti-WHs, but not in 10 animals with WHsAg, WHV DNA, and DNA polymerase. Mild hepatic inflammation was found in 7 woodchucks with indeterminate status, 4 with anti-WHs, and 2 with each marker of WHV infection. Significant inflammation was found in 2 of indeterminate status and 4 with every marker, whereas more severe lesions (2 of chronic active type) occurred, almost always in autopsy specimens, in 8 animals with every marker. Eight of 10 animals with all markers had orcein-positive inclusions (Shikata's technique) and 6 had hepatocellular carcinoma associated with acute and chronic hepatic inflammation and, usually, neoplastic nodules in the noncarcinomatous parenchyma. Features distinguishing the woodchuck lesion from human hepatitis B disease were: association of carcinoma with acute hepatic inflammation (but not with cirrhosis) and DNA polymerase in the serum; transition to carcinoma from neoplastic nodules; conspicuous plasma-cellular reaction of hepatic inflammation, and hematopoietic cells in the tumor. Significant hepatic lesions in the woodchucks were regularly associated with serum WHsAg, WHV DNA, and DNA polymerase. In contrast to man, hepatocellular carcinoma in woodchucks was regularly associated with these markers of active viral replication. The nature of the orcein-positive inclusions requires elucidation, although they may assist in screening for similar viruses in other species. The woodchuck may help in the study of the relation between hepatocellular carcinoma and hepatitis B, including the possibility of cocarcinogenic factors.

The occurrence and pathogenetic role of intrahepatic deposits of immunoglobulins in experimental viral infection have been evaluated by determining with immunofluorescence their capacity to fix complement in vitro [in vitro complement fixation (VCF)]. Liver biopsies from chimpanzees chronically or acutely infected with hepatitis B virus or the hepatitis B surface antigen (HBsAg)-associated delta agent were used in the study. VCF was observed in each animal expressing hepatitis B core antigen (HBcAg) or delta antigen in the liver and concurrently circulating the homologous antibody in the blood. In acutely infected animals, VCF appeared at the same time that the homologous serum antibody appeared, and the intensity of VCF staining was proportional to the antibody titer in the serum. In animals expressing sequentially the HBcAg/antibody system and then delta antigen and antibody to delta, VCF was first observed in HBcAg-containing nuclei and then in nuclei expressing delta antigen. There was no relationship between VCF and intrahepatic expression of HBsAg or serologic expression of hepatitis B e antigen (HBeAg). A positive VCF reaction appears related to the formation of intrahepatic immune complexes between HBcAg or delta antigen and the homologous antibody. Although acute hepatitis developed in parallel with the occurrence of VCF in two animals, strong VCF fluorescence was also observed in each of the asymptomatic carriers of HBsAg, and, in one of them, preexisting VCF staining of HBcAg disappeared in parallel with development of acute hepatitis. In experimentally infected chimpanzees, the finding in liver biopsies of immune complexes detectable by VCF appears to be a common epiphenomenon without pathogenic significance.

Glucocorticoids are reported to accelerate fetal lung development, whereas insulin is alleged to interfere with this effect of glucocorticoids. A paradox exists, however, in that glucocorticoids also induce hyperinsulinemia. The purpose of this study was to explore the interrelationships of betamethasone, hyperinsulinemia, and hyperglycemia to fetal lung maturation. In this rhesus preparation, maternal betamethasone administration produced an alarming increase in maternal and fetal plasma insulin values. A significant increase in total lung volumes also occurred, but lung surfactant properties (as measured by amniotic fluid lecithin/sphingomyelin concentrations, lung alveolar deflation stability, and lung phosphatidylcholine concentrations) remained unchanged. These findings are consistent with the following hypotheses: (1) Betamethasone-induced hyperinsulinemia impairs acceleration of surfactant production but does not negate increases in maximum lung volume; (2) betamethasone-induced increases in maximum lung volume occur through mechanisms other than alveolar surfactant alterations.

A rapidly fatal neoplastic disease with histological and clinical features resembling gestational choriocarcinoma in humans has been observed in patas monkeys. Timed pregnant females were given ethylnitrosourea (ENU) intravenously at doses of 0.1 to 0.4 mmol/kg body weight, beginning on day 30 of gestation and continuing weekly for a total of 12 injections. Of 59 monkeys given ENU during pregnancy, four of 12 subjected to the highest dose and three of the remaining 47 given lower doses died of choriocarcinoma within six months of cessation of ENU exposure. Death was usually caused by exsanguinating haemorrhage. At necropsy, tumour deposits were always numerous in the lungs and were frequently observed in abdominal viscera. An obvious primary uterine tumour was never found, and only one small primary was detected grossly. Sub-endometrial masses of tumour cells were generally observed microscopically, invading the endometrial stroma and forming endovascular tumour deposits in the veins. Both uterine and extrauterine tumour deposits were highly haemorrhagic, often partially necrotic, and consisted of cytotrophoblast-like cells with frequent mitoses, a high degree of cellular pleomorphism and variable but often prominent cytoplasmic glycogen. This tumour was never seen in males or non-gravid adult females. Chorionic gonadotrophin assays conventionally used for human and macaque samples were negative in both normally pregnant and tumour-bearing patas, and did not contribute to the diagnosis. Trophoblast of patas monkeys appears highly susceptible to the carcinogenic effects of ENU and provides an animal model for gestational choriocarcinoma.

In previous studies, we noted that treatment of pregnant rhesus monkeys with betamethasone resulted in a marked increase in fetal lung distensibility. The purpose of the present study was to determine whether these changes persisted during subsequent in utero development. Pregnant rhesus monkeys were treated with 2 mg of betamethasone intramuscularly from day 120 to day 133 and underwent delivery by cesarean section one month later. The treated fetuses were found to have smaller lungs (-31%; p less than 0.005), and lower alveolar stability (-14%; p less than 0.025) than the control fetuses. Additional findings included smaller weights for the brain (p less than 0.01), liver, pancreas, and heart (p less than 0.05). Smaller adrenal (p less than 0.025) and larger pituitary weights (p less than 0.05) and lower plasma corticoid concentrations (p less than 0.001) indicated long-standing adrenal insufficiency in the treated fetuses. These persistent sequelae caution the indiscriminate and prolonged use of these potent glucocorticoids during pregnancy.

A laboratory-passaged genital strain of Chlamydia trachomatis and two unpassaged genital strains from patients with nongonococcal urethritis were inoculated intraurethrally into three young male chimpanzees. Chlamydia were recovered from the urethra of two animals and specific antibody responses were detected in all of them. Furthermore, a urethral polymorphonuclear leucocyte response, but not an overt discharge, occurred in all the chimpanzees about 1-2 weeks after inoculation. None of these events occurred in a chimpanzee inoculated with medium only. At necropsy three months after inoculation the submucosa of the urethra of one chimpanzee was densely infiltrated with small round cells. This suggests that a similar chronic lymphocytic response may occur in human chlamydial infection of the urethra.

Inoculation of hepatitis B surface antigen (HBsAg)-positive sera from patients with chronic liver disease and intrahepatic delta (delta) into chimpanzees susceptible to infection with hepatitis B virus (HBV) resulted in type B hepatitis and delta markers (delta antigen and antibody to delta) in recipient animals. A dilution (10(-8)) of serum induced type B hepatitis without delta markers in another HBV-susceptible animal. HBV infection and delta markers did not develop in animals with preexisting titers of antibody of HBsAg. In chimpanzees with circulating HBsAg at the time of inoculation, synthesis of delta occurred earlier and its extent and duration were greater than in animals previously unexposed to HBV; coincident with synthesis of delta, hepatitis occurred in chronic HBsAg carriers, and synthesis of preexisting HBV gene products (HBsAg and hepatitis B core antigen) was diminished. Delta appears to be a marker of a transmissible pathogenic agent, either an HBV variant or another agent that requires the helper functions of HBV, that is defective and interferes with HBV replication.