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Genetic homology between man and the chimpanzee: syntenic relationships of genes for galactokinase and thymidine kinase and adenovirus-12-induced gaps using chimpanzee-mouse somatic cell hybrids.

The induction by adenovirus-12 of a site-specific gap and assignment of the chimpanzee genes for thymidine kinase and galactokinase were studied by utilizing chimpanzee-mouse hybrid cells. It has been shown that adenovirus-12 induces a specific gap in the long arm of human chromosome 17 (HS 17); with chimpanzee-mouse hybrid cells the specific gap appears on the short arm of the chimpanzee homolog [PTR 19 (HS 17)] of HS 17. This result supports the proposed relationship of HS 17 to PTR 19 (HS 17) by means of a pericentric inversion. The chimpanzee thymidine kinase and galactokinase genes were assigned to PTR 19 (HS 17), further confirming the homology to HS 17. Other syntenic relationships and gene assignments were consistent with proposed homologies between chimpanzee and human chromosomes.

Adenoviridae

Rh antibodies produced by an isoimmunized chimpanzee; reciprocal relationship between chimpanzee simian-type isoimmune sera and human anti-Rho reagents.

An isoimmune chimpanzee serum was found to contain, in addition to expected antibodies of the simian-type specificity anti-Lc, a fraction of anti-Rho specificity, as proved by parallel tests with standard human anti-Rho sera as well as by absorption experiments using human and chimpanzee red cells. On the other hand, the two human anti-Rho sera tested in parallel were found to contain not only antibodies of specificity anti-Rho but also antibodies capable of detecting Lc specificity on the chimpanzee red cells. The reciprocal relationship between human and chimpanzee isoimmune sera constitutes the first example of symmetrical cross-reactivity between closely related species. The new source of anti-Rho reagents is expected to contribute additional information on the human Rh-Hr blood group system.

Animals

Experimental infection of chimpanzees with hepatitis A virus.

The susceptibility of chimpanzees to viral hepatitis type A was examined with immine electron microscopy. Of four seronegative infant chimpanzees, two were inoculated with a hepatitis A acute-phase stool filtrate rich in 27 nm virus-like hepatitis A antigen (HA Ag) particles, and two were inoculated with an HA Ag-negative preinfection stool filtrate. One of each pair of chimpanzees was inoculated intravenously, the other orally. One month later both chimpanzees that had received the HA Ag-positive filtrate developed biochemical, histologic, and clinical evidence of acute viral hepatitis. HA Ag particle (27 nm) were detected in their stools by immune electron microscopy; particle shedding followed a pattern similar to that in human volunteers. Immune electron microscopy also showed that antibody HA Ag had developed in the convalescent-phase sera of the infected chimpanzees. Control animals remained free of illness at this time but did develop hepatitis three to five weeks after exposure to the two infected chimpanzee-. The infectious inoculum was titrated in two additional seronegative chimpanzees. It was concluded that hepatitis a can be successfully transmitted to seronegative chimpanzees. Moreover, these studies provide further evidence that the 27-nm virus-like HA Ag particle is the etiologic agent of viral hepatitis type A.

Animals

The nonhuman primates as models for studying human atherosclerosis: studies on the chimpanzee, the baboon and the rhesus macacus.

There is no dearth of experimental techniques for producing the hyperlipoproteinemia resulting in atherosclerotic complications and for myocardial infarction in the non human primates. Most of the recent experiments which have given information of great value have been studied with relatively expensive animals for a long period of time up to 6-7 years. It is evident that no animal model perfectly duplicates the human disease or satisfies all desirable requirements. The chimpanzees, representatives of the New World monkeys, have circulating plasma lipoproteins identical to man in composition as well as in function. The results reported above indicate that the compositional changes of chimpanzee plasma lipoproteins in response to dietary changes reflect the appearance of type II and type IV hyperlipoproteinemia similar to the human disease. Moreover, there are more indications about the existence of genotype II a in the chimpanzee, and also on the influence of stress on the plasma lipids, so that the developed intimal lesions similar to the human pathology are in this sense multifactorially influenced. From a phylogenetic point of view the chimpanzee is closer to man than any other non human primate. Furthermore, the chimpanzee lipoproteins are useful models for understanding the relationship between function and structure of the plasma lipoproteins in health and disease. Baboon and rhesus monkeys show similar results, but more differences to the human lipoproteins in health and disease were observed. At present it appears that the most useful models of human atherosclerosis are those induced in the non human primates, especially in the chimpanzee.

Animals

Biologic and antigenic characteristics of Epstein-Barr virus-related Herpesviruses of chimpanzees and baboons.

Leukocyte-transforming agents were isolated in baboon leukocytes inoculated with oral excretions from immunosuppressed chimpanzees. The transformed lymphoblasts had B cell surface markers and harbored herpes-type virus particles; 5-10% of the cells contained cytoplasmic antigens reactive with Epstein-Barr virus (EBV)-antibody-positive chimpanzee, human and baboon sera. These sera also neutralized the transforming activity of the chimpanzee virus. Long-term lymphoid cell lines were established from circulating lymphocytes of normal baboons: two from Papio cynocephalus and three from P. hamadryas. The cells had B cell surface markers, contained herpes-type virus particles and produced virus with leukocyte-transforming activity. No virus-associated nuclear antigen was detectable with reference baboon and chimpanzee sera; however, the cells reacted with selected human sera containing antibodies to EBV nuclear antigen (EBNA). Absorption experiments confirmed the specificity of this reaction. Baboon lymphoblasts produced baboon virus-associated soluble complement-fixing (CF/S) antigen. Baboon sera had CF antibodies to viral (CF/V) antigen derived from EBV but failed to react with EBV-associated CF/S antigen. Chimpanzee and baboon herpesviruses had similar in vitro host cell ranges but were different from those of EBV. Inoculation of baboons, rhesus monkeys and cottontop marmosets failed to produce detectable illness or palpable tumors.

Animals

Transmission of non-A, non-B hepatitis from man to chimpanzee.

Non-A, non-B hepatitis was transmitted to four colony-born chimpanzees by intravenous inoculation of human sera. Two chimpanzees were inoculated with serum from a patient with a clinical and serological diagnosis of chronic non-A, non-B hepatitis whose blood appeared to transmit this disease to a nurse following accidental needle-stick, and the other two chimpanzees were inoculated with serum from either of two former blood-donors whose HBsAg-negative blood appeared to transmit clinically recognisable hepatitis, and who were found to have raised serum-aminotransferase levels 1 1/2 and 5 years later. Serum-aminotransferase levels rose in all four chimpanzees, beginning 2--4 weeks after inoculation: peak alanine-aminotransferase values were 210 to 328 I.U./l. Evidence of hepatitis was present in liver biopsy specimens from all four chimpanzees, beginning 8--10 weeks after inoculation. None showed serological evidence of infection with hepatitis A virus, hepatitis B virus, cytomegalovirus, or Epstein-Barr virus.

Alanine Transaminase

Non-A, non-B hepatitis: ultrastructural evidence for two agents in experimentally infected chimpanzees.

Two different ultrastructural alterations were observed in liver cells of chimpanzees inoculated with plasma derived from two different patients with non-A, non-B hepatitis. During the acute phase of illness in one group of four chimpanzees, peculiar tubular structures, composed of two unit membranes with electron-opaque material in between, were observed in the cytoplasm of hepatocytes. In contrast, these structures were never detected in the liver cells of the second group of five chimpanzees that received the second inoculum, However, nuclear changes, usually associated with aggregates of 20- to 27-nanometer particles, were found in hepatocytes of the latter animals. Although these particles resembled viruses, they were not as uniform as small virus particles often appear. In five other chimpanzees inoculated with non-A, non-B hepatitis material not known to be related to the first two inocula, cytoplasmic structures were found in four, and nuclear structures were found in the remaining one. Thus, all 14 chimpanzees inoculated with transmissible non-A, non-B hepatitis agents could be classified as having either nuclear or cytoplasmic changes. These observations add support to epidemiologic data suggesting that there may be more than one agent of non-A, non-B hepatitis.

Animals

Antibodies in urine of chimpanzees with chronic adenoviral viruria.

Many chimpanzees have naturally occurring chronic intermittent viruria with an adenovirus of a new type called Pan 11. Small amounts of neutralizing antibodies to Pan 11 adenovirus were found in the urine of chimpanzees. Urinary antibodies to adenovirus were mainly of the immunoglobulin G (IgG) class with some IgA antibodies also present. There was no neutralizing activity in urine against another adenovirus, Pan 9, which has been isolated from lymph nodes, but not from urine, of chimpanzees; however, sera of all chimpanzees had neutralizing antibodies to Pan 9 virus, some with titers similar to those of antibodies against Pan 11 virus. Antibodies reacting with simian cytomegalovirus by indirect immunofluorescence were found in sera of all chimpanzees tested and in two of six urines. There was no correlation between levels of antiviral IgG antibodies in serum and urine by immunofluorescence. These findings suggest that both IgG and IgA antibodies may be locally produced in response to viral infection of the urinary tract in primates.

Adenoviridae Infections

Comparative physical and immunological aspects of the chimpanzee and guinea-pig subcutaneous chamber models of Neisseria gonorrhoeae infection.

Physical and immunological characteristics of the chimpanzee and guinea-pig subcutaneous chamber models for Neisseria gonorrhoeae infection were compared to evaluate their usefulness for gonococcal research. Urethral infection in chimpanzees anatomically resembled the human infection; however, individual variation in response, limited availability, and the presence of interfering micro-organisms in the urethra were found to limit the usefulness of the chimpanzee in immunological research. Although the guinea-pig subcutaneous chamber model may not be suitable for studying the attachment of gonococci to host cells or for the local production of IgA, it does have the immunological advantages of being more sensitive to infection, less variable in response, free of interfering micro-organisms, and is readily available to investigators. Except for differences in sensitivity and variability, results with the guinea-pig model paralleled results obtained in experiments with chimpanzees. Unlike chimpanzees, guinea-pigs are a comparatively inexpensive, rapidly replenishable animal, which after subcutaneous implantation with small porous chambers provide a convenient model for studying most immunological aspects of gonococcal infections.

Animals

Acid-base curve nomogram for chimpanzee blood and comparison with human blood characteristics.

An acid-base nomogram for chimpanzee blood was constructed. Blood was drawn from eight lightly anesthetized chimpanzees. Each sample of blood was oxygenated and nine aliquots were prepared with three different concentrations of hemoglobin and three different amounts of added acid or base. Each aliquot was equilibrated at two PCO2 levels and the pH was measured and plotted on pH-logPCO2 coordinates. Using the intersection point of these pH-logPCO2 lines as a point of equal hemoglobin-independent "base excess" for each condition, values for true base excess were plotted. Connecting these values provided a Cartesian PCO2-pH base excess nomogram for the chimpanzee comparable to that devised by Siggaard-Andersen for humans. Examination of blood from normal human subjects by the same methods showed no appreciable differences from the original Siggaard-Andersen nomogram. However, the PCO2-pH-base excess nomogram for chimpanzee blood deviated slightly from that for human blood. It is possible that the deviation is related to an arterial bicarbonate concentration in the chimpanzee slightly higher than that in human.

Acid-Base Equilibrium

Experimental infection of chimpanzees with antihemophilic (factor VIII) materials: recovery of virus-like particles associated with non-A, non-B hepatitis.

Non-A, non-B viral hepatitis was transmitted to four colony-born chimpanzees by infusion of three lots of antihemophilic factor (factor VIII) implicated in the transmission of non-A, non-B hepatitis to two human recipients. All four inoculated animals showed histopathological evidence of viral hepatitis, and all demonstrated significant ALT elevations between seven and one-half weeks after inoculation. Acute-phase plasma from one of the infected chimpanzees (no. 771) was shown to induce non-A, non-B hepatitis in two other chimpanzees approximately three weeks after their inoculation. In addition, an acute-phase open liver wedge biopsy obtained from animal no. 771 was processed and examined by immune electron microscopy (IEM) for virus-like particles with convalescent serum from a serologically confirmed case of non-A, non-B hepatitis. Twenty-five to 30 nm (mean = 27 nm) diameter virus-like particles that were either "full" or "empty" were identified in this liver preparation by IEM. Two additional chimpanzees inoculated with a cesium chloride gradient fraction of an isopycnically banded liver homogenate (animal no. 771) also developed elevated ALT activity two to two and one-half weeks later. Our findings have experimentally verified that commercially produced factor VIII materials can induce non-A, non-B hepatitis in champanzees and that the disease can be subpassaged in these animals by inoculation of either acute-phase plasma or liver. These results also provide evidence for the association of 27 nm-diameter virus-like particles with non-A, non-B viral hepatitis.

Adult

Sex differences, dominance, and personality in the chimpanzee.

This study demonstrates a useful methodology for judging the personality of chimpanzees (Pan troglodytes schweinfurthi). Observers rated the chimpanzees on a forced-choice rating scale which yielded measures on eight emotion dimensions. The rating scale, Emotions Profile Index, is derived from a theory of personality which stresses the adaptive significance of emotions at all evolutionary levels. This method has theoretical generality, having been successfully applied previously to humans, baboons and dolphins. Observers were able to rate chimpanzees with reasonable reliability. Sex differences in personality were evident in this chimpanzee sample. In addition, dominance rank was found to correlate with certain emotion dimensions.

Aggression

Object sorting by chimpanzees and monkeys.

Chimpanzees and two species of monkey were compared on sorting tasks. When the sets of objects differed in multiple ways, most chimpanzees learnt to sort whereas only a few monkeys performed better than chance (and then inconsistently). When the objects within a set differed in one or two respects, so that sorting by one principle entailed "unsorting" by one or more alternative principles, chimpanzees had greater difficulty. Two young animals did rapidly learn to sort by color and size ("unsorting" by size and shape or by color and shape). They did not sort pictorial material and had difficulty in sorting by shape if "unsorting" by both color and size. The sorting task differentiated between the cognitive capacities of chimpanzees and monkeys whereas other tasks did not.

Animals

Hepatitis B outbreak among chimpanzees at the London Zoo.

Persistent carriage of hepatitis B virus in extremely high titre was identified in 5 out of 9 chimpanzees kept at the London Zoo. Antibody to this virus was present in the other 4 chimpanzees. Serological survey of the other primates in the Regent's Park collection did not reveal the presence of the surface antigen in 2 gorillas, 11 orang-utans, and 2 gibbons, although surface antibody was present in the serum of 1 gorilla and 2 orang-utans. 3 of the carrier chimpanzees were born at the Zoo and were the offspring of either a carrier mother or a carrier father, and perinatal transmission may have occurred. A strict safety code of practice was introduced and hepatitis B immunoglobulin was given at intervals to designated staff members. Sero-conversion did not occur in any of the 38 staff members under surveillance for more than 2 years. Treatment of the carrier state in the chimpanzees was attempted with human leucocyte interferon, with and without ribavirin ('Virazole'), and with adenine arabinoside, but the effects were mostly temporary.

Animals

Simultaneous acute infections with hepatitis A and hepatitis B viruses in a chimpanzee.

The unexpected occurrence of a hepatitis B virus (HBV) infection in a chimpanzee experimentally inoculated with hepatitis A virus (HAV) provided an opportunity to examine the course of simultaneous acute infections with both agents. A chimpanzee inoculated intravenously with HAV developed elevated levels of aminotransferases in serum, detectable excretion of hepatitis A antigen in feces, and a marked antibody response to HAV. During the acute phase of this experimentally induced infection with HAV, the chimpanzee simultaneously developed an HBV infection. The latter was characterized by jaundice, a second increase in levels of aminotransferases in serum, and the appearance in serum of hepatitis B surface antigen (HBsAg), hepatitis B e antigen, antibody to hepatitis B core antigen, and, later, antibody to HBsAg. During the acute phase of both HAV and HBV infections, marked histopathologic inflammatory changes were observed in serial liver biopsy specimens. In this chimpanzee, the concurrent acute infection with both HAV and HBV occurred in association with marked liver damage.

Acute Disease

Feeding behaviour and diet of chimpanzees (Pan troglodytes troglodytes) in the Okorobikó Mountains of Rio Muni (West Africa).

Some aspects of the nutritional behaviour of the Okorobikó-Matama (Rio Muni, West Africa) chimpanzees have been studied over two periods--from June 1963 to September 1964 and from July 1966 to February 1969. This research totaled 640 h, 119 of which were in sustained contact with the animals. We have complied a list of 43 plant and two termite species consumed by the chimpanzees. We studied the relative importance of the plants consumed in terms of the four principal biotopes and seasonal cycles, the feeding behavior, the rhythm of activity and chimpanzees' vertical stratification during feeding. We also took into accout group dynamics as a function of feeding, communication and polyspecific associations with other primates. We finally compared some aspects of the nutrition of these chimpanzees with that of gorillas living in nearby zones.

Africa, Western

Persistent shedding of adenovirus in urine of chimpanzees.

A new adenovirus, designated Pan 11, was isolated repeatedly from the urine of several chimpanzees for more than 1 year. One chimpanzee had chronic interstitial nephritis; the others were healthy. Most chimpanzees tested had neutralizing antibodies to Pan 11 virus in the serum; three people who worked with chimpanzees also acquired antibodies. Transplantable rhabdomyosarcomas developed in hamsters inoculated as newborns with Pan 11 virus.

Adenoviridae

Cytomegalovirus isolation from a chimpanzee with acute demyelinating disease after inoculation of multiple sclerosis brain cells.

A strain of cytomegalovirus (CMV) was isolated during the third subcultivation of explants from the left frontal lobe of a chimpanzee that developed paralysis more than 3 years after intracerebral inoculation at birth with brain cell cultures derived from a patient with multiple sclerosis. Another strain of CMV was also isolated from a lymph node culture taken from the same chimp. The isolates, designated MZM-13 and MZM-14, produced a cytopathic effect characteristic for CMV when inoculated into brain, ganglion, or fibroblast cultures of human or simian origin. Infected cells contained characteristic Cowdry A intranuclear as well as intracytoplasmic inclusion bodies, and 100-nm spherical herpes-like virus particles were detected by electron microscopy in the nucleus and cytoplasm of infected cells. Virus was further identified as CMV with convalescent human anti-CMV serum. Complement-fixing antibody to CMV was present at a titer of 1:32 when the acutely ill chimpanzee was sacrificed. No antibody was detected at birth or at 1 or 2 years of age. A newborn chimpanzee inoculated intracerebrally with MZM-13 developed clinically asymptomatic lesions in the central nervous system characterized by acute and chronic inflammation and degeneration of myelin in cranial and spinal nerve roots. Restriction endonuclease analysis of viral deoxyribonucleic acid isolated from these two viruses indicated that MZM-13 and MZM-14 are identical and are closely related to chimpanzee CMV. No similarity in restriction endonuclease fragment patterns was found between MZM virus and the Towne and Clegg strains of human CMV.

Animals