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Biomedical subjects

M E Keeling

Publications and source records attributed to M E Keeling.

At least 19 recordsLinked to original sources
PubMed1999

Oral transmission of primate lentiviruses.

Oral transmission of human immunodeficiency virus type 1 (HIV-1) is well documented in children who become infected postnatally through breast milk. In contrast, epidemiologic surveys have yielded conflicting data regarding oral HIV-1 transmission among adults, even though case reports have described seroconversion and the development of AIDS in adults whose only risk was oral-genital contact. To study oral virus transmission in primate models, we exposed rhesus macaques of various ages to cell-free simian immunodeficiency virus (SIV), including uncloned and molecularly cloned viruses. In neonates, viremia and AIDS developed after nontraumatic oral exposure to several SIV strains. Furthermore, chimeric simian human immunodeficiency viruses containing the HIV-1 envelope can also cross intact upper gastrointestinal mucosal surfaces in neonates. In adult macaques, infection and AIDS have resulted from well-controlled, nontraumatic, experimental oral exposure to different strains of SIV. These findings have implications for the risks of HIV-1 transmission during oral-genital contact.

Age Factors↗
PubMed1996

Rev/RRE-independent Mason-Pfizer monkey virus constitutive transport element-dependent propagation of SIVmac239 vectors using a single round of replication assay.

In a step toward creating live-attenuated or DNA subunit vaccines for AIDS, the replication of simian immunodeficiency virus (SIV) was studied independently of the Rev and RRE (Rev-responsive element) regulatory system, over a single round. To accomplish this, the env gene of an SIV vector was made defective by the insertion of a SV40 promoter/enhancer hygromycin B phosphotransferase gene cassette. Using this vector as the backbone, molecular clones of SIV were generated that contained a mutated Rev, Rev(-), a deleted RRE, RRE(-), or both, Rev(-)RRE(-). It has been shown recently that human immunodeficiency virus type 1 (HIV-1) Rev and RRE functions can be replaced in vitro by a cis-acting sequence, constitutive transport element (CTE), from simian type D retroviruses. To determine whether such a cis-acting element from Mason-Pfizer monkey virus (MPMV) would substitute for SIV Rev and RRE functions, the MPMV CTE was inserted either into the Nef ORF or at the junction of vpx and vpr of our Rev(-), RRE(-), and Rev(-)RRE(-) SIV molecular clones. Cell-free viral stocks harvested from Cos cells following transfections of these molecular clones revealed that these stocks were infectious over a single round of replication; however, their replication was attenuated 16-fold compared to that of wild-type virus. In addition, our experiments revealed that CTE functions in a position-dependent manner such that its insertion at the junction of vpx and vpr attenuated SIV replication 8- to 12-fold compared to the attenuation observed when it was inserted in the nef region. Our results demonstrate that MPMV CTE is capable of substituting for SIV Rev and RRE functions, resulting in an attenuated ability to produce infectious virus.

Animals↗
PubMed1994

Maintenance of genetic variability in a specific pathogen-free breeding colony.

We used 18 genetic loci including blood groups, isozymes, and a serum protein to evaluate our efforts to preserve genetic variability in a specific pathogen-free (SPF) colony of rhesus monkeys. We compared genetic variability in the SPF population to the virally contaminated, non-SPF population from which it was derived. There was no change in the average gene diversity between the SPF and non-SPF populations. However, gene diversity at blood group Q locus increased significantly in the SPF population, while blood group M locus showed an insignificant trend toward decreased gene diversity. Allele frequencies changed significantly at blood group Q locus, although no alleles were lost from the population. We hypothesized that this change was due to extensive overreproduction by a small number of founder males that possessed the initially rare allele, Q1. There was no evidence that this change was associated with genes involved in viral infection.

Alleles↗
PubMed1984

Predisposition to invasive pneumococcal illness following parainfluenza type 3 virus infection in chimpanzees.

An outbreak of invasive disease, including pneumococcal bacteremia, meningitis, and pneumonia, involved 17 of 83 (20.5%) chimpanzees at a primate rehabilitation unit. Invasive disease was more common in splenectomized than in nonsplenectomized animals (42.9% vs 18.4%), but the difference was not statistically significant. The outbreak followed closely an outbreak of upper respiratory tract infection (URTI) that occurred with equal frequency in splenectomized and nonsplenectomized chimpanzees. Those with URTI were 5.7 times as likely to develop invasive disease than those without URTI (P less than 0.005). Fourteen of 20 (70%) chimpanzees with recent URTI and serologically examined had a 4-fold or greater rise in titer to parainfluenza type 3 virus. The outbreak of invasive disease occurred despite the fact that most of the chimpanzees had been vaccinated with pneumococcal vaccine. Efficacy of pneumococcal vaccine could not be demonstrated among any segment of the chimpanzee population, and testing of sera from 23 vaccinated chimpanzees against 4 pneumococcal serotypes (3, 6, 8, and 14) failed to show a meaningful immune response. The findings demonstrated that viral URTI can predispose primates to invasive infections and suggested that pneumococcal vaccine is not protective in chimpanzees.

Adult↗
PubMed1982

Chimpanzee holding, rehabilitation and breeding: facilities design and colony management.

A multipurpose chimpanzee facility was designed and constructed to provide the unique housing requirements of rehabilitating laboratory-raised, behaviorally-deficient chimpanzees. The housing complex provided quarantine facilities, single or group housing for long-term holding, and semi-free-ranging compounds for established breeding groups. The facilities were designed to accommodate 170 animals of diverse ages and group configurations. Reproductive performance of the chimpanzees resulted in the production of 0.41 live infants per adult female year. Information was also given on the care, diet, maintenance, health status, handling, and rehabilitation of the chimpanzee. Development of this facility has made it practical to house large numbers of chimpanzees economically and conveniently in an enriched environment which promotes breeding and contributes to the survival of this irreplaceable animal model.

Animal Husbandry↗
PubMed1975

A quantitative and morphological study of the pigmentary system of the chimpanzee with the light and electron microscope.

The epidermal melanocyte system of the chimpaneze was studied by the combined skin-splitting DOPA, and electron microscopic techniques. It is very similar to man. There are DOPA-positive epidermal melanocytes in all body regions regradless of the degree of macroscopic skin pigmentation or hirsutism. Furthermore, as in man, but in contrast to rodents, chimpanzee skin contains a very high level of melanocytes in the epidermis; approximately 3,320+/-350 per square millimeter skin. Chimpanzee melanosomes are long, wide, and fully melanized. In keratinocytes, these organelles are individually dispersed in all body regions, regardless of the degree of skin color, as is true for other mammalian species with large melanosomes.

Animals↗
PubMed1975

Reproductive, gestational, and newborn physiology of the chimpanzee.

The Yerkes Regional Primate Research Center has successfully bred chimpanzees since 1930. Breeding statistics for the last 6 yr and problems of fetal waste and infant mortality are presented here. Experience with a potential advantages of semi-free-ranging breeding systems are presented. This 6-yr study period also produced considerable information on gestational and newborn physiology.

Abortion, Veterinary↗