Testicular steroidogenesis in the baboon Papio anubis.

We recently reported that the baboon testis converts pregnenolone to testosterone through the delta-4 pathway. The present studies were to determine the metabolism of intermediates of the delta-4 and delta-5 pathway by the baboon testis. Fragments (50 mg) were incubated for 3 hr with 10 muCi of the following tritium-labelled substrates: pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, or testosterone. Pregnenolone was converted to testosterone primarily through the delta-4 pathway, with accumulation of progesterone, 17-hydroxyprogesterone and 20alpha-dihydroprogesterone as predominant intermediates. Similar results were obtained in progesterone incubations. 17-hydroxyprogesterone was not efficiently metabolized by the fragments, while 17-hydroxypregnenolone and dehydroepiandrosterone were efficiently converted into testosterone and androstenedione. Androstenedione was metabolized primarily to testosterone, while testosterone was not a suitable substrate. Some 5alpha-androstanediol was identified in each incubate. These results suggest that although testosterone is formed from pregnenolone through the delta-4 pathway, the delta-5 intermediates are more suitable substrates for testosterone synthesis in the baboon testis.     

Comparison of cortisol-cortisone interconversion in vitro by the human and baboon placenta

The kinetics of 11 beta-hydroxysteroid dehydrogenase (11HSD) catalyzing the interconversion of cortisol (F) and cortisone (E) were compared in vitro following incubation of homogenates of human (N = 7) and baboon (N = 2) placenta. In both species, enzyme activity catalyzing the conversion of F to E was associated with the membrane fraction of the cell, was greater in the presence of NAD+ than NADP+, was of similar concentration within the placenta, and exhibited a similar Km for F. Moreover, there was no conversion of E to F in either the baboon or human placenta indicating that in both species, term placenta lacks the 11HSD enzyme catalyzing the reduction of the 11-oxo group of corticosteroids. Significantly, the conversion of F to E by both the baboon and human placenta was inhibited when progesterone was added to the reaction mixture at concentrations equimolar to the substrate. We conclude that 11HSD enzyme kinetics in term baboon placental homogenates are similar to those measured in human term placenta. Moreover, progesterone may be a physiologic regulator of 11HSD in both the human and baboon placenta. Collectively, our findings support the use of the baboon as a model for studies of the regulation of placental corticosteroid metabolism during human pregnancy.     

Immunohistochemical localisation of TRA-1-60, TRA-1-81, GCTM-2 and podocalyxin in the developing baboon kidney

The baboon is an ideal animal model to study human kidney development. The aim of the current study was to use immunohistochemistry to localise the antigens TRA-1-60, TRA-1-81, GCTM-2 and podocalyxin in the developing baboon kidney where nephrogenesis was still on-going and in kidneys where nephrogenesis was complete. Fixed kidney sections from baboons delivered at 125, 140, 175 and 185 days gestation (term = 185 days) were immuno-labelled with antibodies directed against TRA-1-60, TRA-1-81, GCTM-2 and podocalyxin. In kidneys with on-going nephrogenesis (125 and 140 days gestation), TRA-1-60, TRA-1-81 and GCTM-2 were specifically localised to the apical plasma membrane of the epithelium of the ureteric ampullae and the collecting ducts, while podocalyxin immunostaining was not detected. In kidneys where nephrogenesis was complete (175 and 185 days gestation) localisation of these markers was again very specifically localised to the collecting ducts. In conclusion, although further experimentation is required to confirm the identity of the specific cell types marked by these antibodies, this study provides new insight into the distribution of commonly utilised stem cell antibodies in the developing baboon kidney.     

Electron-microscopic localization of baboon acrosomal antigens using antisperm monoclonal antibody.

A sperm antigen corresponding to baboon sperm monoclonal antibody 1A9 was localized in the testis and ejaculated sperm in this animal, using the immunofluorescence technique and immunogold labelling. Immunohistochemical studies of the baboon testis showed that the antigenic determinant was localized in the late spermatid cells and spermatozoa close to the seminiferous tubules. Immunofluorescence studies indicate that the protein was localized on the acrosome region of ejaculated baboon sperm. At the electron-microscopic level, gold particles indicative of the presence of this determinant recognized by 1A9 monoclonal antibody were detected on the inner acrosomal region of ejaculated baboon sperm.     

Characterization of baboon pregnancy-specific beta 1-glycoprotein

Immunostaining of baboon placental tissues with anti-human pregnancy-specific beta 1-glycoprotein (SPI) antibodies demonstrated that an SP1-like molecule was present in the syncytiotrophoblasts. Staining was observed on the membrane and in the cytoplasm, but the nucleus was devoid of any staining. Western blot analysis further demonstrated the presence of five protein species in baboon placental extract, whereas four protein bands were detected in human placental extract. Culture medium of baboon placental villi also contained five SP1-like molecules with sizes slightly different from those present in the placental extract. Amniotic fluid and culture medium of decidua basalis and chorioamniotic tissue contained lesser quantities and fewer species of SP1-like molecules. However, an 87 kDa band was present in all samples examined. Northern blot analysis of baboon placenta with a human placental SP1 cDNA probe demonstrated the presence of a 1.65 Kb band, whereas two hybridizing bands (1.65 Kb and 2.25 Kb) were present in human placenta. Southern blot analysis of baboon genomic DNA further demonstrated the presence of multiple bands hybridizing with a human placental SP1 cDNA probe. These results showed the presence in baboons of multiple genes encoding mRNAs and proteins highly similar to human placental SP1.     

Congenital anomalies in the baboon (Papio spp.)

Background A comprehensive survey of the prevalence of congenital anomalies in baboons has not been previously reported. We report the congenital anomalies observed over a 26‐year period in a large captive baboon colony. Methods A computer search was performed for all baboon congenital anomalies identified at necropsy and recorded on necropsy submissions. Results We identified 198 congenital anomalies in 166 baboons from 9972 necropsies (1.66% of total necropsies). The nervous, urogenital, musculoskeletal, and cardiovascular systems were most commonly affected. The most common organs affected were the brain, bone, heart, testicle, kidney, penis, aorta, and skeletal muscle. The most frequent congenital anomalies were blindness, seizures, and hydrocephalus. Conclusions The baboon has an overall frequency of congenital anomalies similar to humans and other non‐human primates. Although the most frequently affected systems are similar, congenital anomalies involving the digestive system appear to be less common in the baboon.     

Expression of baboon endogenous virus in exogenously infected baboon cells.

Strains of low-passage, fetal diploid, baboon (Papio cynocephalus) fibroblasts were susceptible to exogenous infection with three independent isolates of baboon endogenous virus, as measured by an immunofluorescence assay specific for viral p28. Infectivity of the M7 strain of baboon endogenous virus for baboon cells of fetal skin muscle origin was equivalent to that for human and dog cells in that similar, linear, single-hit titration patterns were obtained. The assay for supernatant RNA-dependent DNA polymerase, however, showed that baboon cells produced only low levels of virus after infection compared with the production by heterologous cells. The results showed that baboon endogenous virus was capable of penetrating baboon cells and that viral genes were expressed in infected cells. Replication of complete infectious virus was restricted, however, indicating that in this primate system homologous cells differentially regulated the expression of viral genes.     

Radioimmunoassay of somatomedin-C in the baboon (Papio cynocephalus): A comparison of multiple techniques of measurement

This study was undertaken to assess the nature of somatomedin-C (SM-C) in baboon (Papio cynocephalus) blood and to compare various methods for estimating SM-C concentrations. Parallel dose-response curves were obtained with normal baboon serum, normal human serum, and purified SM-C. Recovery of purified SM-C added to baboon serum over a wide dosage range (n = 17) was 111 ± 12%, with slightly better recovery at higher potencies. Chromatography of normal baboon serum on Sephadex G-200 at neutral pH produced a profile similar to that observed in the human, as did samples chromatographed on Sephadex G-50 in acid. Although the SM-C content in acid chromatographed plasma was approximately 2.5 times higher than in native unprocessed plasma, there was excellent correlation between the values (r = 0.9143, p < 0.0001). The SM-C in baboon plasma which had been preincubated with glycine HCl was approximately twice that of unprocessed plasma, but the correlation between the two methods was excellent (r = 0.9593, p < 0.0001). The correlation between values obtained after simple acid-ethanol extraction and those observed in unextracted plasma were also significant (r = 0.7689, p < 0.0001). Following a series of four injections of human growth hormone (hGH) to a normal baboon, plasma SM-C rose approximately sevenfold above the initial concentration and returned to basal levels five days after the final injection. These studies show that although the radioimmunoassay (RIA) for SM-C in unprocessed baboon plasma does not measure all of the SM-C present, it provides a reliable index of the total SM-C concentration and reflects GH status in the baboon.     

Phospholipid binding and self-association of the major apoprotein of human and baboon high-density lipoproteins.

The purpose of this study was to establish a relationship between self-association and phospholipid binding of the human and the baboon apoA-I protein. The enthalpy changes on binding dimyristoyl lecithin and lysolecithin to either the human or the baboon native apoA-I protein were measured in a microcalorimeter. An endothermal process, most pronounced for the human apoprotein, was observed at low phospholipid levels. At higher phospholipid to protein ratios the binding was exothermal. Gel filtration experiments on Sephadex G-200 showed that the native apoprotein of both species consists of dimers and tetramers. The baboon native apoA-I protein contained a higher amount of dimers. After preincubation of the apoA-I protein with lysolecithin, the enthalpy changes measured on subsequent binding of dimyristoyl lecithin were shifted towards more exothermal values compared to the curve for the native apoprotein. The amplitude of this shift corresponds to that of the endothermal process observed on binding dimyristoyl lecithin to the native apoprotein. This process was attributed to a phospholipid-induced disaggregation of the apoA-I protein. Gel filtration data showed a decreased extent of aggregation in the apoA-I protein preincubated with lysolecithin. This sample consisted exclusively of dimers. Ultracentrifugal flotation of the complexes formed between the apoA-I protein, and respectively dimyristoyl lecithin and sphingomyelin indicated that preincubation with lysolecithin increased the extent of complex formation. These results suggest that the dimeric form of the apoA-I protein possesses the highest affinity for phospholipids. Any dissociation of higher polymers enhances the phospholipid-binding capacity of the human and the baboon apoA-I protein.     

Increased frequency of acetaldehyde-induced sister-chromatid exchanges in human lymphocytes treated with an aldehyde dehydrogenase inhibitor

Acetaldehyde, the first metabolite of ethanol oxidation, in concentrations ranging from 100 microM to 400 microM caused a dose-dependent linear increase in the frequency of sister-chromatid exchanges (SCE) in cultured human peripheral lymphocytes. The SCE frequency was on an average 2-fold higher when the cells were exposed to the acetaldehyde after 24 h incubation instead of at the time of mitogen stimulation (0 h). When acetaldehyde was added together with the potent aldehyde dehydrogenase inhibitor 1-aminocyclopropanol (0.1 mM), the SCE response was significantly (p less than 0.05) increased. The present results indicate that acetaldehyde is metabolized within human lymphocytes, and, moreover, that alcohol consumption during treatment with drugs that inactivate aldehyde dehydrogenase may cause a further increased incidence of acetaldehyde-induced SCE and concomitant lesions.     

A new genetic locus, Bevi, on human chromosome 6 which controls the replication of baboon type C virus in human cells.

Somatic cell hybrids derived from seven independent fusions between mouse X human and hamster X human parental cells were examined for their ability to support the replication of the baboon endogenous type C virus. These hybrids preferentially segregated human chromosomes while retaining rodent chromosomes, as demonstrated by karyotypic and isozyme analysis. A total of 41 primary colonies and 33 secondary subclones were analyzed for viral replication, as well as for the presence of enzyme structural gene markers for 19 of 23 human chromosomes. A syntenic association was seen between the ability of the baboon type C virus to infect and replicate in hybrid cultures and the expression of human malic enzyme-1 (assigned to human chromosome 6). Analysis of 86 highly segregated subclones derived from cells preinfected with baboon type C virus showed that the continued production of baboon type C virus segregated concordantly with the expression of three enzyme genes assigned to human chromosome 6 (malic enzyme-1, phosphoglucomutase-3 and superoxide dismutase-2). Subclones of infected hybrids which lost chromosome 6 and failed to release virus also failed to synthesize the virus-coded major structural protein p30. No syntenic association between baboon virus expression and any of 18 other human chromosomes was observed. These studies define a new gene (designated Bevi) on human chromosome 6 which dominantly controls the replication of baboon type C virus. The data suggest that Bevi may be a preferred integration site for the baboon type C DNA provirus in the human genome.     

Human–hamadryas baboon (Papio hamadryas) conflict in the Wonchit Valley,South Wollo,Ethiopia

Understanding the extent of human–primate conflict is crucial to the development of conservation and management strategies. We carried out this study in an unprotected area of central Ethiopia to examine the magnitude of human–hamadryas baboon (Papio hamadryas) conflict and to assess the attitude of local farmers towards baboons in Wonchit Valley. In 2014, we interviewed 119 adult respondents using a structured questionnaire. Local farmers considered hamadryas baboons to be the major pest in the area. All respondents reported that hamadryas baboons caused crop raiding and small livestock predation in the region. Respondents reported that a shortage of fruit producing wild trees and ready availability of crops were the main causes of conflict between farmers and hamadryas baboons. We found that hamadryas baboons damaged cereal crops at dusk and dawn during full moonlight, and most (89.9%) respondents claimed that they were not interested in hamadryas baboon conservation. Our results indicate that human–hamadryas baboon conflict has a strongly negative impact on both baboon conservation and local farmers. We suggest that to mitigate the human–hamadryas baboon conflict, job opportunities such as beekeeping should be introduced in the region.     

Immunobiology of the reproductive tract in a female baboon

The aim of this study was to assess the suitability of various antihuman antibodies directed against immunocomponent cells to identify components involved in cellular and humoral immune responses in the immune organs of a female baboon, and to use these reagents to analyze the immunobiology of its reproductive tract. A female baboon of reproductive age was euthanized in the luteal phase of the menstrual cycle, and samples of spleen, intestines, tonsil, lymph nodes, Fallopian tube, uterus, cervix, and vagina were removed. Tissues were either fixed in 10% unbuffered formaldehyde, Bouin's fluid, or 95% ethanol containing 5% glacial acetic acid, and embedded in paraffin, or frozen unfixed. Frozen sections were then fixed in 100% acetone. Subsequently, tissue sections were reacted with the following antihuman antibodies directed against CD3, CD45RA, CD45RO, CD4, CD8, CD20, CD68, HLA-DR, CD57, CD103, CD15, and TIA-1: IgA, IgG, IgM, J-chain, secretory component, and neutrophil elastase, using routine immunohistology techniques. Human tissues (spleen, small intestine, lymph node, and tonsil) were used as positive controls. All antihuman antibodies crossreacted with baboon tissues, except neutrophil elastase, CD15, CD45RO, CD57, and CD1A. The distribution of immune cells in the reproductive tract of the female baboon was comparable to that in the human and offers the potential for this primate to be used as a model for the study of human reproductive immunology.     

Susceptibility of baboon aorta elastin to proteolysis

Elastin was purified from baboon aorta using Achromobacter collagenase and its susceptibility to proteolysis by various enzymes was studied. Human leukocyte elastase (HLE) hydrolysed baboon aortic elastin 8 times faster than human cathepsin G. Bovine chymotrypsin had virtually no activity against this substrate. The kinetic constants V and [S50] of aortic elastin hydrolysis by HLE (0.15 microM) were 0.00286 mg x ml-1 x min-1 and 0.158 mg x ml-1, respectively. One mg of this elastin could be saturated with 5.6 micrograms of HLE. As with elastins isolated from other sources, the hydrolysis of baboon aortic elastin by HLE was highly sensitive to ionic strength, and a biphasic effect was obtained with increasing NaCl concentrations. A nearly 2-fold stimulation of elastolysis was observed at a 0.15M NaCl concentration. Further increase in ionic strength led to a continuous decrease of the rate of elastolysis which paralleled the decrease of adsorption of elastase to baboon aortic elastin. Cathepsin G, but not bovine alpha-chymotrypsin, was able to stimulate the rate of hydrolysis of baboon aortic elastin by HLE. A 1.7 fold stimulation was observed for a 1:1 molar ratio of the two proteinases and rose to 2.1 for a HLE/Cat. G ratio equal to 8.     

Carbon 13 NMR study of glycogen metabolism in the baboon liver in vivo.

In vivo glycogen metabolism was investigated at 2 Tesla by 13C NMR in the baboon liver. Two concentric surface coils were used for 13C observation and proton decoupling, respectively. Spectra were acquired in 2 to 10 minutes with a 60 ms repetition time. After 3 hours of glucose infusion in the 48 hr fasted animal, 3 g of 99%-enriched [1-13C]glucose were injected. The distribution of the label on C-1 and also C-2, C-5 and C-6 of glycogen indicated 65% and 35% contributions of the direct and indirect pathways to glycogen synthesis from glucose, respectively. The results show that hepatic metabolic pathways and rates can be followed in vivo in large animals by 13C NMR at 2 Tesla.