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Fine structure of the langur monkey vas deferens and possible role of changes following vasectomy in the success or failure of the vasovasostomy.

Studies on the ultrastructure of the vas deferens have been carried out in control, vasectomized (6 and 24 months) and vasovasostomized (12 months) langur monkeys (Presbytis entellus entellus Dufresne). Vas deferens epithelium of the control animals depicted four types of cells, viz. the basal cells, principal cells, mitochondria-rich or apical cells and pencil or dark cells. The basal cells were short, cuboidal in nature with prominent nuclei, and contained sparse cytoplasmic organelles. The principal cells were characterized by the presence of nuclei with irregular outline and intranuclear electron-dense granules, well-developed Golgi bodies with prominent secretory vesicles, cisternae of rough endoplasmic reticulum, mitochondria, free ribosome particles, lysosomes and stereocilia in the cytoplasm, suggesting an active secretory role, as well as the absorptive functions of the cells. The mitochondria-rich cells consisted of numerous mitochondria, and other cytoplasmic organelles were sparse. The pencil cells were dark, slightly compressed and situated between the principal cells. Vasectomy resulted in reduction of cytoplasmic volume and vacuolization of the cytoplasm, especially in the Golgi region of the principal cells. Rough endoplasmic reticulum and mitochondria were poorly defined. Vasovasostomy showed no appreciable improvement in the configuration of the cytoplasmic organelles. The results suggest that a persistent reduced secretory activity of the cells following vasectomy and vasovasostomy might also be one of the factors responsible for unsuccessful vasovasostomy.

Animals↗

Conservation of human gamma-X centromeric satellite DNA among primates with an autosomal localization in certain Old World monkeys.

Gamma-X satellite DNA is a 220-bp tandemly arranged repetitive DNA with specificity for the centromeric region of the human X chromosome. The conservation of this human X centromeric satellite DNA sequence in primate species was evaluated by comparative fluorescence in-situ hybridization to metaphase chromosome preparations of the great apes and three Old World monkeys. Homologous gamma-X DNA were detected at centromeric locations in all six primate species. For the great apes, gamma-X was exclusively localized to the centromeric regions of the X chromosomes. Among the Old World monkeys studied, only the golden monkey exhibited localization to the X chromosome. In the black-and-white colobus and the pig-tailed macaque, human gamma-X sequences were localized to the pericentromeric regions of autosomes 1 and 4, respectively.

Animals↗

Spontaneous infection of lower primates with hepatitis C virus.

We present serological and virological evidence of spontaneous infection in Old World lower monkeys with human hepatitis C virus or, maybe, antigenically related but genetically different simian virus strain. These data is of both theoretical and practical importance and can serve as the basis for further development of experimental model of hepatitis C on lower monkeys.

Animals↗

Comparison of oral absorption and bioavailablity of drugs between monkey and human.

PURPOSE: To compare the oral absorption and bioavailability of numerous drugs with a wide variety of physicochemical and pharmacological properties between humans and monkeys and to explore potential reasons for the findings. METHODS: Data for fraction of dose absorbed (Fa) and oral absolute bioavailability (F) were obtained by an extensive Medline database search. Inclusion and exclusion criteria were the same as those reported in our previous studies. A total of 43 and 35 drugs were selected for Fa and F comparison, respectively. The time to reach peak concentration (t(max)), total clearance, and nonrenal clearance were evaluated for 15, 28, and 13 drugs, respectively. RESULTS: Fa values in monkeys were similar or identical to those in humans. Additionally, similar t(max) values were seen in monkeys and humans at comparable doses, thus indicating comparable absorption kinetics between the two species. Conversely, F values in monkeys were generally lower with coumarin being a marked exception. Both total and nonrenal clearances were evaluated and found to be generally greater in monkeys, supporting a generally higher first-pass metabolism and lower F in this species. This was also supported by published data suggesting greater in vitro hepatic drug metabolism for monkeys as compared to humans. CONCLUSIONS: Monkeys appear to be a good predictor of Fa in humans. However, a generally lower F makes monkeys a potentially poor predictor of human F. Higher reported metabolic clearances and hepatic enzyme activities in monkeys may account for this observation.

Administration, Oral↗

A probe generated by chromosome microdissection, useful for analyzing Y chromosome evolution in Old World monkeys.

We isolated a DNA probe, designated MMDYZ1, using a chromosome microdissection technique from the Y chromosome of the Rhesus monkey. The probe obtained from eight whole Y chromosomes shows higher specificity for the Y short arm of the Rhesus monkey, which consists totally of constitutive heterochromatin. Two microclones (MMY#3 and MMY#4) were constructed from the Y-specific primary PCR products. Sequence analysis of these two microclones revealed that both were essentially identical to each other and the sizes were 870 and 686 bp, respectively. From alignment analysis using the Genbank database of primates, the alphoid DNA has the highest affinity with the probe. However, the total composition of this probe has extremely high homology with the Y short arm of the Rhesus monkey, as demonstrated by fluorescence in-situ hybridization (FISH). Comparative FISH-mapping disclosed that this DNA-sequence cluster was located at extremely different sites on the Y chromosome in several species of the Old World monkey. Accordingly, this probe seems to be a high-quality tool, now established for the first time, for investigating Y chromosome evolution of the Old World monkey.

Animals↗

Intronic sequence motifs of HLA-DQB1 are shared between humans, apes and Old World monkeys, but a retroviral LTR element (DQLTR3) is human specific.

Long terminal repeats (LTRs) of the human endogenous retrovirus K (HERV-K) family have been found at several sites within the human genome, of which one is located in the vicinity of HLA-DQB1. Since this DQLTR3 is only present on some haplotypes, we performed a linkage analysis in 130 Caucasian families. In order to date the integration event we also investigated the presence of this DQLTR3 in apes and Old World monkeys. Additionally, we sequenced the adjacent region of DQLTR3-positive and -negative haplotypes in humans, apes and old world monkeys to elucidate their evolution. Linkage analysis revealed a differential integration of DQLTR3 on specific HLA-DQ haploypes: there was a high frequency of this LTR on haplotypes containing HLA-DQB1*0302 (0.96) and a moderate frequency on HLA-DQB1*0402 (0.78), HLA-DQB1*0303 (0.44), HLA-DQB1*0502 (0.38) and HLA-DQB1*0301 (0.35). HLA-DQB1*0201 (0.18), HLA-DQB1*0503 (0.15), HLA-DQB1*0603 (0.15), HLA-DQB1*0602 (0.04), HLA-DQB1*0501 (0.03) and HLA-DQB1*0604 were rarely positive or devoid of DQLTR3. In apes and Old World primates there was no DQLTR3 rendering it a human specific insertion. Sequence analysis of the adjacent region showed two different motifs in humans corresponding to either presence or absence of DQLTR3. Two different motifs were observed within three sequences of Macaca mulatta: One motif is closely related to the sequence from Macaca nemestrina and Macaca fascicularis whereas the other sequence is more closely related with that of Papio papio and Cercopithecus aethiops. Therefore the analysis of retroviral elements as well as intronic sequences of MHC-DQB1 could help to clarify the evolution of this gene region as well the phylogenic relationship between humans, apes and Old World monkeys.

Animals↗

Alpha1 and alpha2 domains of Aotus MHC class I and Catarrhini MHC class Ia share similar characteristics.

Functional and structural analyses of major histocompatibility complex (MHC) class I molecules of the Aotus genus are necessary to validate it as a solid animal model for biomedical research. We thus isolated, cloned and sequenced exons 2 and 3 from three Aotus species (A. nancymaae, A. nigriceps and A. vociferans). We found 24 sequences, which divided into two different groups (Ao-g1 and Ao-g2). A further sequence was identified as a processed pseudogene (Aona-PS2). Both sequence evolution and variability analyses showed that Ao-g1 and Ao-g2 display similar characteristics to Catarrhini's classical loci, such as positive selection pressure at the peptide binding region (PBR) high variability and a trans-specific evolution pattern.

Amino Acid Sequence↗

Anti-Gal alpha 1-3Gal IgM and IgG antibody levels in sera of humans and old world non-human primates.

Organs transplanted from pig to primate are rejected within minutes or hours by an antibody-dependent, complement-mediated mechanism [hyperacute rejection (HAR)]. Even after depletion of anti-Gal alpha 1-3Gal (Gal) antibody (Ab), for example by extracorporeal immunoadsorption, return of natural Ab is believed to be a major factor in the initiation of acute humoral xenograft rejection. Various non-human primates are used as recipients of pig organs in experimental discordant xenotransplantation (XTx) models. However, anti-Gal IgM and IgG levels in non-human primates may differ from those in humans. Serum levels of anti-Gal IgM and IgG were measured by enzyme-linked immunosorbent assay (ELISA) in humans (n=14), chimpanzees (n=8), baboons (n=214), cynomolgus monkeys (n=29), rhesus monkeys (n=23) and Japanese monkeys (n=6). The mean level of anti-Gal IgM was significantly higher in chimpanzees than in other groups, while in rhesus monkeys it was significantly lower than in other groups, except baboons and Japanese monkeys. The mean human anti-Gal IgG level was higher than in other groups and this difference reached statistical significance except with regard to chimpanzees. The mean anti-Gal IgG level in baboons was significantly lower than that in humans, chimpanzees and cynomolgus monkeys. The measured differences in anti-Gal IgM and IgG levels may affect the kinetics of Ab removal and rate of return in different species, and thus may have relevance for translating work in non-human primate models to the clinical setting.

Animals↗

Species-specific evolution of MHC class I genes in the higher primates.

Humans express three highly polymorphic 'classical' (HLA-A,B and C) and three conserved 'non-classical' (HLA-E, F and G) MHC class I genes. Their comparison with the MHC class I genes of apes and monkeys reveals the differential extent to which MHC class I genes have been preserved during primate evolution. African apes have orthologues of all six human genes, and although allelic lineages of the A and C loci are shared, these species share none of the human alleles. In Asian apes, several MHC class I genes show significant differences from the human genes, a trend which continues with the Old World monkeys, and even more so in the New World monkeys, where E and F are the only human gene orthologues. The C locus is confined to humans and apes. Multiple A-related and B-related loci have been identified in apes and Old World monkeys showing that duplication of these loci has been a common event during primate evolution. Certain of the daughter loci exhibit low polymorphism, suggesting they have adopted a non-classical function. The differing rates at which MHC class I genes have evolved during primate evolution likely reflects their differing functions in the immune response.

Animals↗

The evolution of the MHC-G gene does not support a functional role for the complete protein.

The study of the MHC-G gene evolution during nearly 40 million years does not support a role for the full molecule. The MHC-G-like proteins of New World monkeys are probably classical presenting molecules. Old World Cercopithecinae monkeys do not have a full MHC-G molecule and human individuals homozygous for the HLA-G null allele are healthy and do not show birth pathologies.

Amino Acid Sequence↗

Preclinical evaluation of tolerance induction protocols and islet transplantation in non-human primates.

Non-human primate studies of tolerance induction strategies in solid organ transplantation represent a critical bridge between studies in rodents and humans. Our work demonstrates that strategies involving the blockade of co-stimulatory molecules, especially the CD40-CD154 pathway, have great potential for clinical adaptation. While the combination of anti-CD154 antibody with blockade of the CD28 pathway reduced donor antibody production, graft survival was not significantly improved over that achieved with anti-CD154 antibody alone. Moreover, although long courses of steroids seem to interfere with this approach, it may be possible to combine blockade of the CD40-CD154 pathway with other conventional immunosuppressants without sacrificing efficacy. This is a key issue for reducing the risk associated with eventual clinical trials. Work in the non-human primate islet transplant model demonstrates that viable islets can be recovered, isolated and infused in a reliable fashion. It also confirms the efficacy of a steroid sparing approach to immunosuppression for islet transplantation. These data have been expanded to the kidney allograft model, setting the stage for kidney islet transplantation studies. Overall, tolerance induction and islet transplant studies in non-human primates permit the preclinical screening of promising immunomodulatory approaches developed in rodents and reduce the inherent uncertainties associated with adapting new regimens to the clinic.

Animals↗

Recognition of heterospecific alarm vocalizations by bonnet macaques (Macaca radiata).

Recognition of heterospecific alarm vocalizations is an essential component of antipredator behavior in several prey species. The authors examined the role of learning in the discrimination of heterospecific vocalizations by wild bonnet macaques (Macaca radiata) in southern India The bonnet macaques' flight and scanning responses to playbacks of their own alarm vocalizations were compared with their responses to playbacks of vocalizations of Nilgiri langurs (Trachypithecus johnii), Hanuman langurs (Semnopithecus entellus), and sambar deer (Cervus unicolor). The study was conducted in 3 regions that differed in the frequency with which bonnet macaques encountered these species and included an urban setting. Call recognition was highest in adults and in regions where individuals were frequently exposed to the calling species; calls were not recognized by urban monkeys. Thus, age and experience are important factors in heterospecific call recognition by bonnet macaques.

Animals↗

From Pan to pandemic.

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Acquired Immunodeficiency Syndrome↗

Human T-lymphotropic retroviruses.

The first human retroviruses have been discovered during the past six years. They cause two diseases which involve disturbances of the growth of the T4 lymphocyte, a remarkably specific target cell type. This cell, which is central to the regulation of the immune system, is induced by human T-lymphotropic virus type I (HTLV-I) to excessive proliferation (leukaemia) and by HTLV-III to premature death (acquired immune deficiency syndrome, AIDS). Both also seem to be indirectly involved in several other disorders. The genetic structures of these retroviruses and the mechanisms by which they usurp host-cell functions are novel among retroviruses.

Acquired Immunodeficiency Syndrome↗

Isolation of an HTLV-III-related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys.

Acquired immune deficiency syndrome (AIDS) has become a worldwide epidemic, so the development of vaccines and antiviral agents effective against the causative agent, human T-lymphotropic virus type III (HTLV-III), is vital. This work would be greatly simplified if a suitable animal model could be developed. Here we report the isolation of an HTLV-III-related retrovirus, STLV-III/Delta, from rhesus macaques (Macaca mulatta) with transmissible simian AIDS (SAIDS) and from asymptomatic sooty mangabeys (Cercocebus atys). SAIDS was initially diagnosed in several macaques previously inoculated with tissue homogenates of mangabey origin. Western blot analysis of both the mangabey and macaque sera demonstrated the presence of antibody cross-reactive primarily with the HTLV-III proteins p24 and p61. In a related experiment, analysis of these same sera revealed simian antibody to STLV-III/Delta proteins similar, but not identical, to those of HTLV-III with estimated relative molecular masses (Mrs) of 16,000 (16K), 26K, 35K, 45K, 60K and 110K. Infection of the mangabey, an African primate, with an HTLV-III-related virus may provide a clue to the origin of HTLV-III in humans. The apparent difference in susceptibility to SAIDS-like disease between infected macaques and mangabeys suggests that these species may respond differently to STLV-III infection.

Acquired Immunodeficiency Syndrome↗

Sequence of simian immunodeficiency virus and its relationship to the human immunodeficiency viruses.

The characterization of HIV-1 (HTLV-III/LAV), the human retrovirus associated with AIDS (acquired immune deficiency syndrome) has led to the identification of a group of related human and simian retroviruses which also infect CD4-bearing T lymphocytes. Simian T-lymphotropic virus type III (simian immodeficiency virus) from macaques (STLV-IIIMAC) induces symptoms similar to those of AIDS in infected macaques, but isolates from African green monkeys (STLV-IIIAGM) and mangabeys (STLV-IIMM) appear to be non-pathogenic in these animals. A human virus immunologically related to STLV-IIIAGM (HTLV-IV), reported to have been isolated from healthy humans, has been shown to be almost identical to STLV-IIIAGM, which has called into question the independent origin of these viruses. Here we report the complete DNA sequence of STLV-IIIAGM and analyse its relationship with the genomes of the HTLV-IIIB strain of HIV-1, HIV-2ROD (previously called LAV-2) and several ungulate lentiretroviruses. STLV-IIIAGM and HIV-2 are closely related, and more distantly related to HIV-1.

Acquired Immunodeficiency Syndrome↗