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PubMedDate not supplied

The metabolism of (2-cyclopentyl-6,7-dichloro-2-methyl-1-oxo-5-indanyloxy)acetic acid in chimpanzee and man.

The metabolism of the polyvalent saluretic agent (2-cyclopentyl-6,7-dichloro-2-methyl-1-oxo-5-indanyloxy)acetic acid was studied in chimpanzee and man. The drug was well absorbed and extensively metabolized by man. Peak levels of drug (5--8 microgram/ml) occurred within 1.5--4.5 hr of drug administration. The plasma half-life was estimated to be 2 hr; a similar half-life was observed in the chimpanzee. Little unchanged drug (less than 10%) was excreted in the urine of either species. Similar metabolic profiles were obtained for man and chimpanzee. The major urinary metabolites resulted from hydroxylation of the cyclopentyl moiety, giving rise to a number of diastereomers. The alcohol metabolites were subsequently oxidized to the ketone. The excretion of the metabolites coincided with maximal excretion of sodium and chloride ions. The hydroxylated metabolites have intrinsic pharmacological activity.

Animals↗
PubMed1989

Human immunodeficiency virus (HIV) from experimentally infected chimpanzees: isolation and characterization.

Human immunodeficiency virus-1 (HIV-1) isolates obtained from chimpanzees that had undergone various immunosuppressive treatments were characterized by growth on various primary cells and cell lines as well as by restriction endonuclease analysis. Viruses recovered from animals inoculated with uncloned HIV showed genetic variation from the original inoculum, whereas viruses isolated from an animal infected with a molecular clone of HIV did not. In some cases, virus recovery was possible only after enrichment for CD4+ cells by panning, inoculation with a chimpanzee cytomegalovirus, or a combination of these procedures. These findings indicate a role for viral and host cofactors in the control of virus replication and suggest explanations for the absence of clinical manifestations in HIV-infected chimpanzees.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Non-A, non-B hepatitis-related hepatocellular carcinoma in a chimpanzee.

Epidemiology has indicated the possible association of non-A, non-B hepatitis (NANBH) with hepatocellular carcinoma (HCC) in man, but there are no means for confirmation. Chimpanzees are recognized models for studying hepatitis B and NANBH, and may become carriers of both. The first case of HCC to be reported in chimpanzees was found after longitudinal study of a hepatitis B-free chimpanzee 7 years after inoculation with human plasma from a patient reported to have chronic NANBH.

Animals↗
PubMed1986

[Veterinary aspects of raising chimpanzees].

The problems involved in chimpanzee husbandry are mainly baised on their behaviour, intelligence and psychical sensitivity. The most suitable species-specific conditions of keeping, feeding and veterinary welfare are fundamental demands for physical and mental health as well as for successful reproduction of chimpanzees living in captivity. In spite of different possibilities and motives of chimpanzee husbandry in each particular case, the general statements given in this article may be useful concerning these requirements.

Animal Feed↗
PubMed1987

Summation in the chimpanzee (Pan troglodytes).

In this research, we asked whether 2 chimpanzee (Pan troglodytes) subjects could reliably sum across pairs of quantities to select the greater total. Subjects were allowed to choose between two trays of chocolates. Each tray contained two food wells. To select the tray containing the greater number of chocolates, it was necessary to sum the contents of the food wells on each tray. In experiments where food wells contained from zero to four chocolates, the chimpanzees chose the greater value of the summed wells on more than 90% of the trials. In the final experiment, the maximum number of chocolates assigned to a food well was increased to five. Choice of the tray containing the greater sum still remained above 90%. In all experiments, subjects reliably chose the greater sum, even though on many trials a food well on the "incorrect" tray held more chocolates than either single well on the "correct" tray. It was concluded that without any known ability to count, these chimpanzees used some process of summation to combine spatially separated quantities. Speculation regarding the basis for summation includes consideration of perceptual fusion of pairs of quantities and subitization.

Animals↗
PubMed1986

Cardiac correlates of individual recognition in the chimpanzee (Pan troglodytes).

The ability of a chimpanzee to recognize individuals depicted in photographs was evaluated through the use of heart rate measures. Heart rate was recorded before and during photographic projections of human caregivers, familiar individuals, strangers, and blank control slides. In the absence of explicit training or reinforcement, the chimpanzee displayed a differential pattern of heart rate response to the stimulus categories. Although heart rate responses to all stimuli were predominantly deceleratory, the photographs of caregivers yielded consistently larger responses than other stimuli. Results indicate that the chimpanzee is able to recognize individual humans from novel photographic representations and that heart rate can provide an objective measure of such recognition.

Animals↗
PubMed1985

Longitudinal study of HTLV-III-infected chimpanzees by lymphocyte subpopulation analysis.

Following inoculation with plasma from human patients with AIDS, two chimpanzees demonstrated specific antihuman T-cell leukemia virus type 3 (HTLV-III) antibodies. One of the two chimpanzees also developed massive lymphadenopathy that persisted for 32 weeks and demonstrated a concurrent and more frequent depression of total T cells (T3) and T helper cells (T4) with a decrease in the ratios of T4 to T suppressor cells (T8). These results indicate that chimpanzees demonstrate a range of T-cell subpopulations during infection and disease induced by HTLV-III.

Acquired Immunodeficiency Syndrome↗
PubMed1977

Chimpanzee livers after infection with human hepatitis viruses A and B: Ultrastructural studies.

Electron microscopical studies were carried out on coded liver biopsy specimens from chimpanzees inoculated with human hepatitis A or B virus. Hepatitis B was recognized by the presence of hepatitis B core particles in hepatocellular nuclei. Hepatitis A was characterized by unidentified large, dense, and more irregular heterochromatin-like particles in hepatocellular nuclei coincidental with peak aminotransferase activities. As type A hepatitis illness became manifest in the chimpanzees, mitochondrial cristae were curled and attenuated, and clusters of endoplasmic reticulum were tightly packed. In contrast, the livers in viral hepatitis B showed mainly hypertrophy of tubular smooth endoplasmic reticulum. This suggested different pathogenetic mechanisms in A and B chimpanzee viral hepatitis.

Animals↗
PubMed1982

Flexible fiberoptic bronchoscopy of chimpanzees.

Five 10- to 12-year-old, male chimpanzees were used in a study that required repeated flexible fiberoptic bronchoscopic procedures. The combination of ketamine and inhalation anesthesia was satisfactory for these procedures. The gross anatomy of the airways of the chimpanzee resembled those of man more than those of the dog or rhesus monkey. The bronchoscope could be easily maneuvered into the main bronchi, lobar bronchi, and at least two branches of the lobar airways. Sublobar lavages were performed to obtain cells from the deep lung. Histologic examination of a lung showed that generous numbers of bronchial glands extended down to the tertiary bronchi in chimpanzees explaining the copius amounts of mucous observed during bronchoscopy.

Anesthesia, Endotracheal↗
PubMed1993

Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C.

Hepatitis C virus (HCV)-specific CTL responses were evaluated in two chimpanzees (Pan troglodytes) during the acute and chronic phases of HCV infection. CD8+ T lymphocytes were isolated from liver tissue homogenates using anti-CD8 antibody-coated magnetic beads and then stimulated with anti-CD3 antibodies, IL-2, and irradiated human PBMC using limiting dilution culture conditions. HCV-specific cytotoxic activity of expanding CD8+ cell lines was assessed against autologous lymphoblastoid cell lines infected with recombinant vaccinia virus vectors encoding HCV Ag. CD8+ T cell lines specific for structural and nonstructural proteins of HCV were established from both animals. Cytolytic activity was blocked with anti-CD8 or anti-class I MHC antibodies, indicating that class I MHC molecules were involved in presentation of viral Ag to the CTL. Overlapping synthetic peptides were used to define a 12 amino acid segment of the nonstructural 3 (NS3) protein recognized by CTL lines from both chimpanzees. Studies with truncated peptides revealed that these CD8+ cell lines were directed against overlapping epitopes presented by distinct class I restriction elements of the chimpanzee MHC complex. CD8+ cell lines with identical specificities for an NS3 epitope were generated from one chronically infected animal at 16 and 28 wk postinfection. These results indicate that virus-specific CTL populations persist in the liver for months, but are unable to resolve chronic HCV infection.

Acute Disease↗
PubMed1993

Quantitative study of chimpanzee and gorilla counterparts of the human D antigen.

The reactivities of three human anti-D monoclonal antibodies (mAbs) with human, chimpanzee, and gorilla red blood cells (RBCs) were compared by quantitative radioimmunology and indirect immunofluorescence methods. The number of antigenic sites varies widely in gorillas (from 48,000-283,000), while in chimpanzees this number is very close to that observed in human R1R2 RBCs. The affinity of the anti-D antibodies was slightly lower with ape RBCs than with D-positive human RBCs. In chimpanzee, the D-like epitopes recognition is enhanced by papain while the gorilla D-like epitopes are destroyed by enzyme treatment.

Animals↗
PubMed1993

Relationship between chimpanzee Rh-like genes and the R-C-E-F blood group system.

The antigenic closeness between the chimpanzee alloantigen Rc of the R-C-E-F system, and the human alloantigen Rho(D) suggests a phyloge-connection between their genes. To confirm at the molecular level the common origin of these genes, genomic DNA from 16 unrelated chimpanzees of various R-C-E-F phenotypes were digested by three restriction enzymes and analyzed by Southern blot using a human Rh cDNA probe and three exon-specific probes. Restrictions profiles displayed reach polymorphism. Correlations between some bands and certain R-C-E-F phenotypes demonstrate that the human Rh cDNA probe defines in chimpanzee genomic DNA some genes of the R-C-E-F system.

Animals↗
PubMed1993

Major histocompatibility complex class II polymorphisms in humans and chimpanzees.

Allelic variation at the MhcPatr-DR and -DQ loci was studied by molecular biological techniques and compared to available HLA data. With regard to the number of allelic lineages, the chimpanzee shows a condensation of its major histocompatibility complex (MHC) class II repertoire as compared to humans. This does not have an impact on the overall degree of MHC class II polymorphism in the chimpanzee since a few lineages that are oligomorphic in humans display an extensive degree of polymorphism in the chimpanzee.

Alleles↗
PubMed1975

Conversations with a chimpanzee in a computer-controlled environment.

The linguistic-type skills of a young chimpanzee (Pan) acquired in a computer-controlled language-training situation are reviewed. Those skills include facile acquisition of vocabulary, object naming, color naming, appropriate use of "yes" and "no" in response to certain questions, and conversation. In conversations the subject has formulated novel sentences and without special training has asked that objects be named, whereupon requests were made that they be given to her. These findings are interpreted in terms of how enriched environments can serve to bring forth novel communication skills in the chimpanzee, which is otherwise alinguistic; how the challenge of the environment can serve to limit manifest intelligence; and how a cognitive, rather than the traditional stimulus-response, framework is required for understanding the communication skills and psychological processes of the chimpanzee.

Animals↗
PubMed1976

Immunity in infection with Neisseria gonorrhoeae: duration and serological response in the chimpanzee.

Relative and absolute resistance to urethral and pharyngeal infection with Neisseria gonorrhoeae persisted for up to two years in male chimpanzees parenterally immunized with a colony type 2 gonococcal antigen. Twelve additional adult males were immunized with either a colony type 1 gonococcal antigen or a sham diluent before being challenged with the immunizing isolate of N. gonorrhoeae. Serum specimens were obtained throughout the immunization procedure and tested for indirect fluorescent, bactericidal, microhemagglutinating, and complement-fixing antibody to the immunizing isolate of N. gonorrhoeae. The serological response measured by the indirect fluorescent antibody and serum bactericidal tests correlated most closely with the resistance of individual chimpanzees when they were challenged in the pharynx and urethra with graduated doses of N. gonorrhoeae one month after the last immunization. In this study, the resistance of the immunized chimpanzees to urethral infection with N. gonorrhoeae varied from one to greater than 1,000 times that of sham-injected controls.

Animals↗
PubMed1993

Pentoxifylline attenuates neutrophil activation in experimental endotoxemia in chimpanzees.

Costimulation of neutrophils and cytokines may play an important role in organ injury in sepsis. Pentoxifylline inhibits various neutrophil functions in vitro, and attenuates endotoxin-induced production of TNF in both in vitro and in vivo models. To assess the effect of pentoxifylline on neutrophil activation in endotoxemia, nine adult chimpanzees (Pan troglodytes) were i.v. injected with saline (n = 2), Escherichia coli endotoxin (4 ng/kg; n = 4), or E. coli endotoxin (4 ng/kg) in combination with pentoxifylline (500 mg/3 h, starting 30 min before the endotoxin injection; n = 3). Serial blood samples were obtained for measurements of leukocyte counts and the granulocytic proteinases elastase complexed with alpha 1-antitrypsin and lactoferrin, and cytokines during the next 5 h. No changes were observed in the saline-treated chimpanzees. Endotoxin induced a marked leukocytosis and neutrophilia, which were slightly reduced by pentoxifylline. In contrast, pentoxifylline almost completely prevented endotoxin-induced neutrophil degranulation: peak elastase-alpha 1-antitrypsin was 164 +/- 21 ng/ml (mean +/- SE) after endotoxin alone, vs 71 +/- 7 ng/ml after endotoxin with pentoxifylline (t = 3 h; p < 0.05); peak lactoferrin was 329 +/- 15 and 182 +/- 5 ng/ml, respectively (t = 5 h; p < 0.05). Pentoxifylline also inhibited the endotoxin-induced release of TNF (271 +/- 26 vs 55 +/- 23 pg/ml at t = 1.5 h; p < 0.05) and IL-6 (225 +/- 42 vs 73 +/- 25 pg/ml at t = 2 h; p < 0.05). IL-8 release was not significantly inhibited by pentoxifylline. In none of the animals activation of the C system could be detected. We conclude that pentoxifylline attenuates neutrophil activation in endotoxemia in chimpanzees, probably in part by inhibiting the release of TNF.

Animals↗
PubMed1995

Disposition of DMP 811 (L-708,404), a potent angiotensin II receptor antagonist, in the rat, monkey, and chimpanzee.

DMP 811 {4-ethyl-2-n-propyl-1-[(2'-(1H-tetrazole-5-yl)biphenyl-4-yl) methyl]imidazole-5-carboxylic acid; L-708,404} is a highly potent angiotensin II receptor antagonist. The physiological disposition of DMP 811 was examined in the Sprague-Dawley rat, rhesus monkey, and pan troglodytes chimpanzee. Plasma concentrations of DMP 811 were determined by an HPLC assay with fluorescence detection. After intravenous administration of DMP 811 to rats (1 mg/kg), monkeys (0.5 mg/kg), and chimpanzees (0.5 mg/kg), the plasma clearance was 1.3, 1.8, and 0.3 ml/min/kg, respectively. The corresponding volumes of distribution were 0.16, 0.10, and 0.10 liters/kg, and the value for the terminal half-life was 3.0, 2.4, and 10.1 hr in the respective species. After oral administration to rats (5 mg/kg), monkeys (2 mg/kg), and chimpanzees (2 mg/kg), DMP 811 was 8.4%, 10.2%, and 8.0% bioavailable, respectively. The mass balance of [14C]DMP 811 was investigated in rats and monkeys. In rats, the radiolabeled dose was excreted primarily in feces (79% intravenous; 99% oral) with <1% of the dose in urine. In monkeys, the intravenous radiolabeled dose was excreted in both urine (48%) and feces (42%), whereas the oral dose was excreted largely in feces (79%), with an additional 6% in urine. In summary, DMP 811 was cleared slowly in all three species. The oral bioavailability of DMP 811 was low, but consistent across species. Pharmacokinetic data suggest that the low oral bioavailability was not caused by first-pass metabolism, but probably caused by limited absorption.

Angiotensin II↗