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Serial serum levels of gonadotropins, prolactin and sex steroids in the nonpregnant and pregnant chimpanzee.

Serum levels of FSH, LH, chorionic gonadotropin (CG), prolactin, estrone (E1), estradiol-17Beta (E2), estriol (E3) and progesterone were measured at 2-3-day intervals in 4 chimpanzees through 2-3 menstrual cycles, and serially through subsequent pregnancies. The hormone patterns of the menstrual cycles were similar to those in man, with high levels of FSH in the early follicular phase, followed by rising E2 concentrations to a peak (up to 35 ng/dl) at or just before a midcycle LH/FSH peak. In most cycles there was a secondary E2 rise and progesterone rose to values above 500 ng/dl during the luteal phase. There was no consistent pattern in prolactine levels through 3 menstrual cycles. A simultaneous increase in E2 and LH/CG levels and a fall in FSH about 10 days postovulation indicated fertilization and implantation. Other early signs of pregnancy were persistent luteal range progesterone concentrations and rising levels of E1 and E3. Peak CG levels (56-154 IU/ml) occurred 30-50 days after the midcycle LH/FSH peak, followed by a decline and then a small secondary rise to (to 1 IU/ml) before term. E1, E2 and E3 levels rose more rapidly after 80 days to a peak at term (E1: 180-300 ng/dl; E2: 500-800 ng/dl; and E3:400-1000 ng/dl). Progesterone levels showed one peak coincident with the CG peak, and a secondary rise after about 80 days to maximal values at term of 49-120 ng/ml. Prolactin levels increased during pregnancy with irregular fluctuations (7-127 ng/ml). These findings indicate in contrast to observations in rhesus monkeys and baboons, that the hormonal patterns during pregnancy in the chimpanzee are remarkably similar to those in man. Thus, the chimpanzee should prove to be an ideal model for research directly applicable to human reproduction.

Animals↗

KIT-positive gastrointestinal stromal tumor in a 22-year-old male chimpanzee (Pan troglodites).

Gastrointestinal stromal tumors (GIST), KIT-positive and KIT signaling driven or platelet-derived growth factor receptor alpha (PDGFRA) signaling driven mesenchymal tumors, are poorly known in nonhuman primates. Availability of KIT- and PDGFRA-inhibitor drug imatinib mesylate has greatly raised the interest for these tumors. At necropsy of a 22-year-old male chimpanzee, a round, firm 2-cm intramural tumor was incidentally found in the midbody of the stomach and diagnosed as a GIST. Histologically, the mass was composed of spindle to polygonal epithelioid cells arranged in short to intermediate-length, interlacing streams, bundles, and nodular whorls often separated by hyalinized eosinophilic matrix. The mitotic rate was a maximum 1/50 high-power field. Immunohistochemically, the tumor cells were diffusely positive for KIT and CD34, focally positive for alpha-smooth muscle actin, and negative for muscle specific actin, desmin, S-100 protein, synaptophysin, and glial fibrillary acidic protein. Because the majority of human GISTs have gain-of-function KIT or PDGFRA mutations, genomic sequences of KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 from this chimpanzee GIST were polymerase chain reaction amplified and sequenced. However, no mutation was identified in the analyzed "mutational hot spots." This study is the first extensive histomorphologic, immunohistochemical, and molecular genetic analysis of a chimpanzee GIST. More cases of nonhuman primate GISTs should be analyzed to discover the clinicopathologic spectrum of GISTs in these species.

Animals↗

Comparative study on toxicokinetics of bisphenol A in F344 rats, monkeys (Macaca fascicularis), and chimpanzees (Pan troglodytes).

We compared the toxicokinetics of bisphenol A (BPA) among three animal species: rats, cynomolgus monkeys and chimpanzees. Rats and monkeys were administered BPA orally or subcutaneously at 10 or 100 mg/kg body weight, while chimpanzees were administered only 10 mg/kg of BPA. BPA in serum was measured by ELISA. In oral administration of BPA at 10 mg/kg, both C(max) and AUC were rats < chimpanzee < monkeys. In oral administration of BPA at 100 mg/kg, both C(max) and AUC were rats < monkeys. Subcutaneous BPA administrations also revealed similar results, although the values of toxicokinetic parameters in subcutaneous administration were higher than those in oral administration. These results suggest that orally or subcutaneously administered BPA in primates is more easily absorbed than that in rats. We conclude that there are considerable differences in distribution, metabolism, and excretion of BPA between rodents and primates.

Animals↗

Intestinal parasites of baboons (Papio cynocephalus anubis) and chimpanzees (Pan troglodytes) in Gombe National Park.

A survey of gastrointestinal parasites of nonhuman primates in Gombe National Park, Tanzania, was conducted during July and August 1989. Fresh fecal samples collected from 35 baboons (Papio cynocephalus anubis) and 20 chimpanzees (Pan troglodytes) were analyzed for intestinal parasites. Parasite identifications were based upon the size and appearance of eggs and larvae on both direct and fecal flotation examinations. Seven species of helminths and three species of protozoa were noted in the chimpanzees, and seven species of helminths, two species of trematodes, and one species of protozoa were noted in baboons. An unidentified parasite, with a thick egg shell similar to that of ascarids, was noted in both the chimpanzee and baboon population. Unfortunately a definitive identification of this parasite could not be made based upon egg size and morphology alone and insufficient numbers of larva were present to aid identification. One previously unreported parasite, Schistosoma mansoni, was identified in the baboon population. This is the first report of a schistosome in Gombe's nonhuman primate population.

Animals↗

Management and prevention of vitamin D deficiency rickets in captive-born juvenile chimpanzees (Pan troglodytes).

Vitamin D deficiency rickets was diagnosed in three juvenile chimpanzees (Pan troglodytes) raised indoors under skylights and consuming only breast milk. Two cases detected early had mild but characteristic radiographic changes. More advanced disease presented with florid x-ray features of rickets and pathologic fractures, as well as hypocalcemia, hypophosphatemia, and low serum 25-hydroxyvitamin D levels. Treatment by a single injection of vitamin D2 in sesame oil (slow release) followed by daily oral supplementation with vitamin D2 corrected the condition. On the basis of experience with these cases and comparison with rickets in humans, a prevention protocol for mother-reared, inside-housed, chimpanzee juveniles was developed. Injection with slow release vitamin D2 (5,000 IU i.m. once) at 4 mo of age, followed by oral supplementation of 400 IU vitamin D2 daily until weaning, prevents rickets in juvenile chimpanzees raised indoors.

Administration, Oral↗

Effects of repeated anthelmintic treatment on Enterobius vermicularis infection in chimpanzees.

Effects of repeated treatment with pyrantel pamoate on Enterobius vermicularis infection in chimpanzees were assessed by observing worms discharged in the feces after administration of anthelmintic treatment. Three of 9 chimpanzees reared in a zoological garden in Japan were subjected to fecal worm count and morphometric observation, and all were given oral pyrantel pamoate 6 times at 10-day intervals simultaneously. Following the first and second treatments, more than 30,000 pinworms were discharged from 1 chimpanzee. The number of discharged worms abruptly decreased after the third treatment, and only a few worms were recovered after the fifth treatment, indicating that repeated treatment at short intervals was very effective. Complete eradication was not achieved, however, presumably because of reinfection. The female proportion among discharged worms tended to increase as the treatment was repeated.

Animals↗

Characterization of two relaxin genes in the chimpanzee.

Relaxin is a peptide hormone which has a variety of physiological effects on tissues of the reproductive tract as well as other organs such as the heart and brain. Whereas all non-primates so far examined have only a single relaxin gene, humans have two genes (H1 and H2, or gene 1 and gene 2). H2 relaxin is synthesized in the corpus luteum during pregnancy and is also found in the placenta and prostate, whereas expression of H1 has been very difficult to detect. We have begun a study of relaxin genes in the chimpanzee to assess whether this species may provide a suitable model in which to examine the roles of gene 1 relaxin. We find that the chimpanzee has two relaxin genes, one of which is very similar to H2. The second gene has an gene 1 type A chain but the B chain is of the gene 2 type, possibly due to a gene conversion event. The authentic chimpanzee gene 2 (Ch2) is expressed in the corpus luteum of pregnancy and in the placenta. Ch1 is not expressed in the placenta, but the mRNA can be detected by polymerase chain reaction in the corpus luteum.

Amino Acid Sequence↗

DEVELOPMENT OF A COMPLEX MULTIPLE SCHEDULE IN THE CHIMPANZEE.

The development of chimpanzee behavior on a four-component, three-lever multiple schedule is described. Component schedules included the Sidman avoidance procedure with a concurrent discriminated avoidance schedule on a second lever, fixed ratio performance for food, differential reinforcement of low rate for water requiring a dual response chain, and a symbol discrimination task for continuous food reinforcement using three levers. The avoidance component of this schedule was employed during the January 31, 1961 suborbital space flight of the chimpanzee "Ham." On November 29, 1961, the chimpanzee "Enos" performed on the multiple schedule during three orbits around the earth in a Mercury capsule.

Animals↗

Emotional behavior during the learning of a contingency task in a chimpanzee.

A female chimpanzee's behavior was videotaped during the learning of contingency tasks and used to code her facial expressions, vocal expressions, and other behavior. The chimpanzee showed negative emotional behaviors to negative feedback and seemed to depend not only on the lack of food as reward. The most negative emotional situation for the chimpanzee seemed to be one in which she made an error.

Animals↗

A search for search asymmetry in chimpanzees (Pan troglodytes).

Two chimpanzees and two humans were trained on visual search tasks with several sets of geometric forms composed of 1 and 2 elements (graphemes). When the double-grapheme item was the target and single grapheme item was the distractor, both chimpanzees and humans searched the target quickly irrespective of the display size. On the other hand, when the single-grapheme item was the target and double-grapheme item was the distractor, they showed an increase in response times as a function of the display size on some sets of stimuli. These results were considered as evidence for search asymmetry by chimpanzees.

Adult↗

Manual action in infant chimpanzees: a preliminary study.

In human infants, index finger extension is shown frequently even from 3 months old, and it is considered that such pointing develops into deictic and communicative pointing however, there are many reports that chimpanzees do not point with the index finger. In the present study the manual actions of two infant chimpanzees were observed when the experimenter was trying to make eye contact with them. The result shows that pointing was shown very rarely by these infant chimpanzees even morphologically.

Aging↗

Intracytoplasmic crystalline inclusions in the hepatocytes of humans and chimpanzees.

Intracytoplasmic crystalline inclusions (CCIs) were observed in liver biopsy specimens taken from three patients and three chimpanzees. CCIs are rare in human hepatocytes and have never been described in chimpanzees. All three human cases were connected with alcoholic liver disease; no viral infection was noted. The histologies of the two liver biopsy specimens obtained from healthy chimpanzees were normal, but hepatitis B virus (HBV) infection was demonstrated in the third case by immunohistochemistry and radioimmunoassay. In the last biopsy specimen a large accumulation of HBV core particles was present in the nuclei and among the filaments of CCIs of the hepatocytes. This finding suggests that crystallizations of viral proteins may form intracytoplasmic inclusions in hepatocytes, whereas in other cases toxic effects (alcohol) or normal conditions (storage) may lead to the formation of similar structures.

Animals↗

Development and chimpanzee testing of a vaccine against human hepatitis B.

Highly purified hepatitis B virus surface antigen (Australia antigen) purified by physical and chemical procedures from infected human plasma was used to prepare hepatitis B vaccine. The purified antigen was treated with formalin and the vaccine was tested exhaustively for safety by ordinary procedures and additionally in marmosets (for live hepatitis B virus). The vaccine was highly potent, inducing antibody in guinea pigs, grivet monkeys, and chimpanzees given three doses of vaccine containing up to 20 mug of hepatitis B antigen per dose. A protective efficacy trial was carried out in chimpanzees that were given three doses of vaccine subcutaneously and then challenged intravenously with 1000 chimpanzee infectious doses of human hepatitis B virus. All of five unvaccinated control animals developed hepatitis B virus antigenemia following challenge and all of six vaccinated animals were protected, including one animal that had failed to develop detectable antibody following vaccination.

Animals↗

Studies in chimpanzees of live, attenuated hepatitis A vaccine candidates.

Human hepatitis A virus was attenuated in virulence for chimpanzees by passage in FRhK6 and human diploid lung fibroblast cell cultures. A number of variants were developed by passage in cell cultures which showed different levels of virulence/attenuation for chimpanzees. These results were compared to those obtained with marmosets and reported previously. In general, most variants behaved similarly in the two animal types. Two chimpanzees which gave vaccine-like responses following inoculation with HAV cell culture variants were challenged with virulent HAV. Both animals were immune to HAV infection. These findings provide further evidence for the feasibility of developing live, attenuated vaccines against human hepatitis A.

Animals↗

Chimpanzee adenovirus antibodies in humans, sub-Saharan Africa.

Human sera from the United States, Thailand, and sub-Saharan Africa and chimpanzee sera were tested for neutralizing antibodies to 3 chimpanzee adenoviruses. Antibodies were more common in humans residing in sub-Saharan Africa than in humans living in the United States or Thailand. This finding suggests cross-species transmission of chimpanzee adenoviruses.

Adenoviridae Infections↗

Methodological-conceptual problems in the study of chimpanzees' folk physics: how studies with adult humans can help.

In three experiments, we examined humans' folk physics (i.e., a naturally occurring and spontaneous understanding of the physical world), using variations of problems used to study chimpanzees' folk physics. Presented with trap-tube problems in two experiments, adult humans showed an unnecessary bias to insert a stick into the end of the tube farthest from the reward to push it out the other end. When presented with trap-table problems with ineffective trapping holes, people unnecessarily avoided the side with the hole. The similarity of humans' and chimpanzees' behavior on these tasks highlights methodological and conceptual problems in studies of chimpanzees' folk physics and suggests alternative explanations for their behavior.

Adult↗

Observations on early and late post-sporozoite tissue stages in primate malaria. IV. Pre-erythrocytic schizonts and/or hypnozoites of Chesson and North Korean strains of Plasmodium vivax in the chimpanzee.

In a continuing reexamination of plasmodial tissue stages within the context of the hypnozoite theory of malarial relapse, 2 strains of Plasmodium vivax with distinct and disparate relapse characteristics in humans were studied in chimpanzees. Following intravenous inoculation of massive numbers of salivary gland sporozoites, both the frequently relapsing Chesson strain and a North Korean strain characterized by predominantly delayed relapses exhibited relapse patterns and antimalarial sensitivity in the splenectomized chimpanzee essentially indistinguishable from those seen in humans. Examination of hepatic biopsies obtained at 7 and 10 days after infection revealed both pre-erythrocytic (pre-e) schizonts and hypnozoites in tissue obtained from the animal infected with the Chesson strain, but only rare hypnozoites (no pre-e schizonts) at 7 days in the animal infected with the North Korean strain. These findings, combined with the comparability of relapse behavior--which indicates the suitability of the chimpanzee as a model for the natural (human) host-parasite relationship--are essentially as predicted by the hypnozoite theory, despite the small numbers of tissue forms seen. Pre-erythrocytic schizogony of the Chesson strain in the liver was essentially indistinguishable from that of other strains studied, also underlining the suitability of this model system for tissue stage studies of P. vivax.

Animals↗

Infection of chimpanzees with Nigerian I/CDC strain of Plasmodium ovale.

Seven splenectomized chimpanzees were infected with the Nigerian I/CDC strain of Plasmodium ovale. Two of the animals had no history of previous malarial infection whereas three had been infected with P. vivax, one with P. malariae, and one with P. vivax and P. malariae. The two animals with no previous malarial experience had maximum parasitemias of 88,700 and 127,000 per mm3 while the other animals had maximum parasitemias ranging from 10,100 to 60,600 per mm3. Anopheles freeborni, An. dirus, An. stephensi, and An. gambiae were readily infected via membrane feeding on heparinized blood obtained from these chimpanzees during the ascending phases of their primary attacks. The parasitemias in the chimpanzees with previous malarial experience were transient.

Animals↗