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[Prevention and therapy of viral diseases with special reference to interferon].

Human leukocyte interferon (HLI) was used for treatment of human diploid fibroblasts before and after infection with vaccinia virus, herpes simplex virus type 1 (HSV 1), herpes simplex virus type 2 (HSV 2), and varicella zoster virus (VZV). Vero cells were infected with Medical Lake macaque herpes virus (MLMV), and treated with HLI in the same way. In all of these systems HLI exhibited an antiviral effect when administered before infection, and this effect could be increased by additional HLI treatment after infection. In vivo studies with HLI treatment were performed in monkeys experimentally infected with vaccinia virus, HSV 1, and MLMV. Vaccinia and herpes keratitis were prevented by local, prophylactic administration of HLI. Generalized infections with vaccinia virus and MLMV in monkeys immunosuppressed by antilymphocyte globulin, were significantly modified by either prophylactic or therapeutic systemic treatment with HLI.

Animals↗

[Tumors of the liver, biliary tracts and pancreas in monkeys].

The article deals with spontaneous tumours of the liver, biliary tract, and pancreas observed in monkeys of the Sukhumi Simian Nursery during the period of 1960--1974. Among tumours of the liver hepatoadenomas predominated: they were revealed in 4 macaco rhesuses, one green marmoset. In a young baboon hamadryad adenomatous hyperplasia was observed to be developed against the background of hepatocirrhosis. All three cases of tumours of the biliary tract in baboons hamadryad were classified as adenocarcinomas. Descriptions of liver cell anaplastic carcinoma with extensive metastasizing in Macaco rhesus, those of insuloma of the pancreas in the same species, and of papilary duct carcinoma of the head of the pancreas in a red ape (Erythrocebus patas) are presented for the first time. All the monkeys with tumours, but one, were at the age over 10 years and were born in the Nursery, or had been brought to it more than 7 years before.

Adenocarcinoma↗

Effect of adsorbents on IgM and IgG measles antibodies.

Sera from rabbits immunized with L-16 measles virus absorded with monkey blood cells; kaolin and blood cells; and MnCl2 and heparin were examined in haemagglutination inhibition (HI) and neutralization tests. Kaolin and MnCl2 adsorbed primarily HI IgM antibodies from the early immunization period. The adsorbents used had no influence on HI and neutralization IgG antibodies. Human convalescent serum gave similar results, i.e. only IgG antibodies were found and they were not affected by kaolin and MnCl2 with heparin.

Adsorption↗

Characterization of Nigerian strains of West Nile virus by plaque formation.

Seven strains of West nile virus isolated in Nigeria were investigated for their ability to form plaques in monkey kidney cell monolayers. Five strains antigenically related to one another produced plaques of about the same size 3 to 4 days after the addition of the overlay medium. The two other strains closely related to each other produced no plaques. Their inability to produce plaques was regarded as a significant characteristic of the intratypic group to which the two strains belong.

Animals↗

Poxvirus in West African nonhuman primates: serological survey results.

Ten species of nonhuman primates in West African habitat were analysed for variolavaccinia subgroup haemagglutination-inhibition (HI) and neutralization antibodies. The animals were taken in 27 different sampling zones in parts of the Ivory Coast, Mali, and Upper Volta. Of the 195 tested, 15 (8%) had elevated HI antibodies after nonspecific reactions were reduced with potassium periodate pretreatment. Positive neutralization antibodies were found in 21% (44 of 206). Antibodies were detected in serum from monkeys living near two areas where monkeypox cases in humans had occurred. Four samples were tested for monkeypox specific antibodies using an indirect immunofluorescent test; 3 were positive. Despite the prevalence of poxvirus antibodies in monkeys (and other animals) in West Africa, smallpox eradication has been maintained in the area since 1970; thus, animal reservoirs of poxvirus appear to pose no threat to the worldwide smallpox eradication programme.

Africa, Western↗

Histopathology of hyperacute rejection of the heart: experimental and clinical observations in allografts and xenografts.

The histologic findings in a total of 112 experimental heart transplants comprising allografts (baboon to baboon: n = 37), concordant xenografts (vervet monkey to baboon: n = 52), and discordant xenografts (pig to baboon: n = 23), in which the roles of ABO blood group incompatibility, corcordance, and immunosuppression were evaluated, are described. Hyperacute (vascular, humoral) rejection was characterized by disruption of the microcirculation, with interstitial hemorrhage and edema, rather than by intravascular thrombosis; the features were basically similar whether hyperacute rejection occurred in an ABO-incompatible allograft, concordant xenograft, or discordant xenograft. Hyperacute rejection was noted in all 23 discordant xenografts, in 12 to 52 concordant xenografts, and in four of 17 ABO-incompatible allografts. A unique mixture of acute and hyperacute rejection was observed in three ABO-incompatible allografts and in 10 concordant xenografts. Intensive antirejection therapy was associated with a reduced incidence of hyperacute rejection in corcordant xenografts but also with a significant number of fatal treatment-related complications.

ABO Blood-Group System↗

Experimental infection of African green monkeys and cynomolgus monkeys with a SIVAGM strain isolated from a healthy African green monkey.

An infection occurred in all African green monkeys and cynomolgus monkeys experimentally inoculated with SIVAGM [TYO-1], as demonstrated by the appearance of an antibody to SIVAGM [TYO-1] and the isolation of the virus. No monkey exhibited overt clinical disorders throughout the experimental period of 42 weeks. Thus, SIVAGM was not pathogenic to its original host or to macaques. This system is proposed as a model for HIV infection manifesting no overt disease.

Animals↗

[Application of a TRICIN-buffered modification of the CMRL-1969 medium in cell and virus cultivation (author's transl)].

CMRL-1969 medium (Healy et al., 1971) was modified by using 0.02 molar N-[Tris-(hydroxymethyl)-methyl]-glycin (= TRICIN) instead of bicarbonate as the buffer substance. Several permanent cell lines and primary cell cultures did not show growth differences in the two medium variants. Like other non volatile buffers TRICIN abolishes the initial increase of the Ph in freshly split or newly fed closed vessel cultures, but in 0.02 M concentration maintains the same buffering capacity of the medium as compared to bicarbonate. Multiplication of Entero-, Adeno-, Herpes-, Influenza-A-, and Vaccinia-viruses was also not altered. The medium allows open vessel methods like microtiter- and plaque-tests to be conducted under normal atmosphere and seems especially useful when initial pH-values are to be set in the rank of 7.5 to 8.6. For microtiter neutralization tests with enteroviruses a medium adjusted to pH 7.6 and a cell density of 10(5) cells/cm2 was found optimal. Plaque formation of Coxsackie-B-viruses reached a maximal plaque-size and -number when the pH of the double concentrated medium was beyond 8.2.

Animals↗

Infection of macaque monkeys with simian immunodeficiency virus from African green monkeys: virulence and activation of latent infection.

The virulence of three isolates of simian immunodeficiency virus from African green monkeys (SIVagm) was studied in rhesus and pigtailed macaques. None of 15 rhesus monkeys and one of four pigtailed monkeys died from infection during the time they were studied (up to 33 months). SIVagm was only isolated from rhesus monkeys for up to 2 months after inoculation. However, when these animals were secondarily infected with Simian acquired immunodeficiency syndrome retrovirus type 1 (SRV-1), SIVagm was activated and isolated. Dual infection caused increased mortality.

Animals↗

Genetic analysis and infection of SIVAGM and SIVMND.

Recently, the authors determined the partial sequence of simian immunodeficiency virus (SIV) from the mandrill (SIVMND) and found SIVMND to be a new member of the HIV/SIV group, equidistant from other members, including SIVAGM. Experimentally, the African green monkey and cynomolgus monkey could be infected with SIVAGM and the cottontop tamarin with SIVMND. However, no clinical sign of an AIDS-like disease was observed in these monkeys.

Animals↗

The role of ABO blood group compatibility in heart transplantation between closely related animal species. An experimental study using the vervet monkey to baboon cardiac xenograft model.

The role of ABO blood group compatibility on graft survival when transplantation is performed between closely related animal species is uncertain. Heart transplants (in the neck) were performed between donor vervet monkeys and recipient baboons; no immunosuppressive therapy was given. Survival in ABO-compatible pairs (group 1, n = 9) was for a mean of 10.3 (+/- 5.2) days, which was not significantly different from that in ABO-incompatible pairs (group 2, n = 9: mean survival 7.3 +/- 5.6 days). In group 2, however, three hearts were rejected hyperacutely within 60 minutes, whereas in group 1 only one heart was rejected within 24 hours (not significant). Preformed anti-vervet monkey antibody was present in only one of 18 baboons, but developed in eight others. ABO-specific antibodies were present in all nine group 2 baboons and increased in titer in six cases. Histopathologic features of vascular (humoral) rejection, sometimes associated with cellular infiltration, were seen in a majority of hearts in both groups. Though the number of animals in this study was small, ABO-incompatibility would not appear to be a major factor in cardiac xenograft survival when transplantation is performed between closely related primate species, though early hyperacute rejection would seem more likely to occur when blood group incompatibility is present.

ABO Blood-Group System↗

Changes in lipopolysaccharide concentrations in hepatic portal and systemic arterial plasma during intestinal ischemia in monkeys.

The time course of changes in the level of plasma lipopolysaccharides (LPS) in both the hepatic portal and the systemic arterial circulations, together with changes in cardiovascular parameters, was ascertained during a 1 hr occlusion of the superior mesenteric artery (SMA) in six primates. The LPS concentrations before occlusion of the SMA in the hepatic portal and systemic arterial circulation were 0.051 +/- 0.009 and 0.065 +/- 0.011 ng/ml, respectively (NS). At the end of the occlusion period, there was no significant increase in either the hepatic portal or systemic arterial plasma LPS concentrations. Immediately on removal of the occlusion, however, the LPS concentration in the portal plasma increased and peaked at 0.431 +/- 0.124 ng/ml (P less than 0.01) within 17.5 +/- 1.71 min, whereas in the systemic arterial circulation the LPS concentration began to rise but only after a delay of approximately 10 min to peak at 0.287 +/- 0.126 ng/ml (P less than 0.05) within 32.5 +/- 4.23 min of reperfusion. The mean arterial pressure (MAP) declined during the reperfusion period from 98.6 +/- 6.89 to 65.0 +/- 9.5 mm Hg (P less than 0.05). The heart rate showed a small but not significant increase (P greater than 0.2) after about 80 min of reperfusion. These data indicate that the gut is the source of the increased plasma LPS concentration following occlusion of the SMA.

Animals↗

Metabolic behavior of hepatic VLDL and plasma LDL apoB-100 in African green monkeys.

Recently, evidence has accumulated suggesting that significant amounts of plasma low density lipoproteins (LDL) may be derived by direct production. These plasma very low density lipoprotein (VLDL)-independent sources include the production and secretion of LDL-like particles directly by the liver, and/or a small pool of nascent precursor particles that are converted rapidly to LDL. The current studies were designed to test the hypothesis that hepatic VLDL represent a rapidly turning over precursor pool to plasma LDL in African green monkeys. Livers from African green monkeys were perfused with serum-free medium containing [3H]leucine or 3H-labeled amino acids for 4-6 hr. Hepatic [3H]VLDL and autologous plasma 125I-labeled LDL were injected simultaneously into recipient animals and density gradient ultracentrifugation and gel filtration were used to characterize the distribution of 3H and 125I radioactivity at selected times after injection. These studies show that 4 to 66% of the injected dose of hepatic VLDL [3H]apoB-100 was metabolized extremely rapidly into particles that resembled the recipient's plasma LDL by size and density. Based on the kinetic model developed to describe the metabolic behavior of hepatic VLDL [3H]apoB-100, the estimated maximal pool size of hepatic VLDL apoB-100 in these animals was very small (0.042 and 0.112 mg) and represented, at best, approximately 10% of the average plasma VLDL apoB-100 mass found in cholesterol-fed African green monkeys. In addition, the radiolabeled hepatic LDL appear to be metabolized similarly to plasma LDL. That is, the rapid conversion of hepatic VLDL as well as the direct production of hepatic particles within the LDL density range appear to contribute to plasma LDL. Metabolic heterogeneity was also seen within the LDL class. The more buoyant subfraction (LDL1) had a higher turnover rate than the more dense subfraction (LDL2) and hepatic VLDL-derived [3H]LDL1 had a slower final rate of plasma disappearance than the plasma-derived 125I-labeled LDL1 in most animals. The results from these studies suggest that a small pool of hepatic VLDL can be converted very rapidly to plasma LDL and may contribute significantly to the large plasma pool of LDL seen in cholesterol-fed African green monkeys. This pathway may be analogous to the pathway in some human subjects in which a portion of human plasma VLDL is converted rapidly into LDL without passing through a delipidation cascade, often referred to as direct LDL production.

Animals↗

Cell- and antibody-mediated responses to measles and mumps viruses in experimental animals.

Monkeys and guinea pigs were immunized with various doses of measles and mumps viruses. A cell-mediated response measured by leukocyte migration inhibition occured during the first two weeks after immunization. In case of measles virus, marked migration inhibition occurred already on the 7th day in monkeys and guinea pigs immunized with high virus doses. The response declined as early as 14 days after immunization in contrast to the group of guinea pigs inoculated with a lower virus dose. In these animals the response sustained for up to 50 days. Immunization of animals with various doses of mumps virus was similar and positive responses were obtained in the absence of detectable antibodies. Even 2.5 TCID50 of mumps virus induced the response although more irregularly than 250 or 2500 TCID50 virus.

Animals↗