Ameloblastic odontoma in a cynomolgus monkey (Macaca fascicularis)

An ameloblastic odontoma occurred in an adult cynomolgus monkey (Macaca fascicularis). The neoplasm involved the upper left maxilla as a disfiguring, fleshy growth. The tissue and cellular changes were consistent with an ameloblastic odontoma which is rare in man, nonhuman primates (NHP), and other vertebrate animals. The monkey was one of 50 adult, single-caged housed cynomolgus monkeys. No additional clinical signs of disease were present. Hematology and serum chemistries were within normal limits. There have been three reports in the literature of ameloblastic odontomas in NHP; however, this is the first reported case of an ameloblastic odontoma in a cynomolgus monkey.     

Persistent cloaca in a cynomolgus monkey (Macaca fascicularis).

A persistent cloaca was found to occur in a 15-year-old female cynomolgus monkey. This is the first case reported in a nonhuman primate. The embryological basis of this anomaly is discussed, and pertinent anatomical findings in this animal are reported which demonstrate the embryologic defect.     

Pulmonary cestodiasis in a cynomolgus monkey (Macaca fascicularis).

Cestodiasis in primates has been noted historically to occur quite frequently, although tissue damage and clinical signs may or may not be apparent. Larval cestodes, such as hydatid cysts or cysticercus cysts, are known to cause extensive tissue damage, while other larval cestodes, such as tetrathyridia, cause minimal damage to the host. This case history concerns an apparently healthy cynomolgus monkey that was part of a surgical study. During the study, all parameters were normal. The monkey died 3 hours postsurgery. The apparent cause of death was respiratory arrest. At necropsy, it was discovered there were 1- to 3-mm-diameter cysts, which on transection extruded 2- to 5-mm-long larvae. The larvae could not be positively identified; however, they resembled tetrathyridia of Mesocestoides sp.     

Cutaneous melanoma with metastasis in a cynomolgus monkey (Macaca fascicularis)

Background  A 3.3-year-old-male cynomolgus macaque ( Macaca fascicularis ) showed a focally extensive soft, dark, discoid dermal mass, 0.5 cm in diameter, on the dorsal surface of the right hind foot, over the fourth and fifth metatarsal bones.
Methods and results  Microscopic examination revealed a cutaneous melanoma with local lymphatic invasion, characterized by neoplastic melanocytes within the subcapsular sinus of popliteal and inguinal lymph nodes. The diagnosis was confirmed by immunohistochemistry and transmission electron microscopy.
Conclusions  To our knowledge, this is the first documented case of melanoma in a cynomolgus monkey.     

Squamous cell carcinoma with metastasis in a cynomolgus monkey (Macaca fascicularis)

A squamous cell carcinoma of the vulva with metastases to the inguinal lymph nodes and lung occurred in a female cynomolgus monkey (Maccaca fascicularis). The primary tumor was a pedunculated mass at the mucocutaneous junction of the left labium anterior to the clitoris.     

Early embryonal culture of the cynomolgus monkey (Macaca fascicularis)

Ovaries of ten female cynologus monkeys (Macaca fascicularis) were superstimulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). During this treatment, follicular development was monitored by ultrasonography. After three to four injections of PMSG, ovaries began to show an increase in their size. After seven to ten injections of PMSG and a hCG injection, a total of 183 oocytes (18.3±14.1/ animal, mean±SD) were recovered from these females by laparotomy. Five nulliparous females produced 24.2±18.2 oocytes per animal, and the remaining five parous females produced 12.5±5.46 oocytes per animal. In total, 133 (72.6%) of the 183 oocytes were classified morphologically as matured, and 130 of them were inseminated with cynomolgus monkey sperm for 18 hours in vitro. The second polar body was observed in 92 (71%) of the inseminated oocytes, and 54 (59%) of the 92 oocytes showed cleavage division at least once. When these oocytes were fertilized and cultured in serum-free media, they stopped their development at 4-cell stage. In contrast to this condition, about a half of fertilized oocytes in serum-free media were able to develop to morula stage 4 days after insemination by transferring them into serum-containing media after 2-cell stage.     

Triplet pregnancy in a cynomolgus monkey (Macaca fascicularis) after double embryo transfer

At our research center, cynomolgus monkeys (Macaca fascicularis) are bred by mating or intracytoplasmic sperm injection (ICSI) and embryo transfer. We typically transfer 2 embryos, because the pregnancy rate is better than that for single embryo transfer. In the case we present here, 2 embryos that had been frozen and thawed after ICSI were transplanted into a recipient female macaque, and a multiple pregnancy (3 fetuses) was confirmed. All 3 fetuses were miscarried between days 81 and 85 of pregnancy. One fetus, which was wrapped in the amnion, was expelled along with its own placenta and one other. Because the other placenta had 2 umbilical arteries, 2 fetuses may have shared it. Therefore, we believe this pregnancy was a case of triplets, including a set of twins from an embryo that divided after transfer.     

Study of cynomolgus monkey (Macaca fascicularis) DRA polymorphism in four populations

To describe the polymorphism of the DRA gene in Macaca fascicularis, we have studied 141 animals either at cDNA level (78 animals from Mauritius, the Philippines, and Vietnam) or genomic level (63 animals from the Philippines, Indonesia, and Vietnam). In total, we characterized 22 cDNA DRA alleles, 13 of which had not been described until now. In the Mauritius population, we confirmed the presence of three DRA alleles. In the Philippine and Vietnam populations, we observed 11 and 14 DRA alleles, respectively. Only two alleles were present in all three populations. All DRA alleles but one differ from the consensus sequence by one to three mutations, most being synonymous; so, only seven DR alpha proteins were deduced from the 22 cDNA alleles. One DRA cDNA allele, Mafa-DRA*02010101, differs from all other alleles by 11 to 14 mutations of which only four are non-synonymous. The two amino acid changes inside the peptide groove of Mafa-DRA*02010101 are highly conservative. The very low proportion of non-synonymous/synonymous mutations is compatible with a purifying selection which is comparable to all previous observations concerning the evolution of the DRA gene in mammals. Homologues of the allele Mafa-DRA*02010101 are also found in two other Asian macaques (Macaca mulatta and Macaca nemestrina). The forces able to maintain this highly divergent allele in three different macaque species remain hypothetical.     

Metabolism and pharmacokinetics of progesterone in the cynomolgus monkey (Macaca fascicularis)

[4-14C]Progesterone was administered to two cycling female monkeys during the luteal phase of the cycle, and blood and urine were sampled over a 24 h period. Progesterone had a volume of distribution of 1.75 +/- 0.3 L/kg, and a plasma elimination clearance of 0.06 +/- 0.03 L/kg/min. In comparison to the human, plasma progesterone binding was greater and progesterone clearance was slower in the cynomolgus monkey. The major unconjugated metabolite in plasma was 20 alpha-hydroxy-4-pregnen-3-one. In urine 6.2% of 14C-steroids were unconjugated, 2.3% of which were [14C]progesterone. Thin-layer chromatography (TLC) of conjugated metabolites in urine revealed that 24% had the mobility of sulfates, 19% that of glucuronides, and 52% were more polar. After hydrolysis of conjugates, a major fraction chromatographed with pregnanediol. However, despite evidence for the presence of a 20 alpha-hydroxyl group, none of the pregnanediol isomers could be identified among these 14C-steroids. Nevertheless, over 80% of urinary metabolites had sufficient analogy to pregnanediol to bind to an antiserum specific for ring D and the C-17 side-chain of pregnanediol.     

Urinary cystic calculi in a cynomolgus monkey (Macaca fascicularis): a case report.

An adult female Macaca fascicularis monkey became acutely anorexic and depressed and was found dead approximately 24 hours later. Necropsy revealed three hard brownish-yellow stones within the urinary bladder and urethra, a moderately shrunken left kidney, hemorrhage of the medulla of the left adrenal gland and a yellow liver. The stones, one of which was lodged in the urethra, were 1-2.5 cm in diameter, and their surfaces were rough and covered with spines. Chemical analysis of the stones revealed oxalates, phosphates, carbonates, ammonium salts, magnesium and calcium. Microscopic examination revealed chronic interstitial and glomerular nephritis and papillary hyperplasia of the transitional epithelium of the bladder.     

Isolation and culture of hepatocytes from the cynomolgus monkey (Macaca fascicularis)

Summary Isolation and culture techniques for hepatocytes from whole livers of the cynomolgus monkey,Macaca fascicularis, are described. Hepatocytes were isolated by two-step perfusion of livers, using collagenase with hyaluronidase; fructose and trypsin inhibitor were included to reduce cell loss. Yields from a single liver average 4×10⁹ cells with viabilities of 90.8±5.7%. Cells, plated on collagen substrates, were assessed for changes in morphology and various marker enzyme activities over a period of 7 d in culture. Cells exhibited a morphology similar to that observed for this species in vivo; little change in attached and spread cells was observed over the length of time monitored. Enzyme activities for catalase, succinate dehydrogenase, and tyrosine aminotransferase were observed to decrease significantly (though considerable activity remained), whereas acid phosphatase and 5′-nucleotide phosphodiesterase remained unchange. Activity of cytochrome P-450 reductase was observed to increase slightly for the first 2 d, then decrease to about 60% of initial levels. Activity of α-mannosidase was stable for 4 d but was observed to be increased at Day 7. Cells were observed to retain metabolic responsiveness demonstrated by glucose production by both gluconeogenesis and glycogenolysis in response to glucagon stimulation. The monkey hepatocytes obtained by methods described here thus retain hepatocellular morphology and activity through at least 1 wk in culture without medium or culture modification.     

The innervation of the myometrium of the cynomolgus monkey (Macaca fascicularis)

Summary The autonomic innervation of the myometrium of Macaca fascicularis consists of bundles of unmyelinated nerve fibres running between the smooth muscle cells, and is therefore considered to be of the fascicular (= unitary) type. Close contacts between nerve fibres and smooth muscle fibres were not found. Modification of the chromaffin method according to Tranzer and Richards made it possible to visualize the heterogeneity of the nerve fibres in a single bundle. The following fibre types were found to coexist: (1) noradrenergic fibres containing synaptic vesicles with a dense granule, (2) cholinergic fibres containing empty synaptic vesicles, and (3) non-adrenergic noncholinergic (NANC) fibres containing only or predominantly large dense-cored vesicles, which do not react with this method. Noradrenergic fibres are the most numerous (around 60%), followed by NANC fibres (30%) and cholinergic elements (around 10%). The distribution of these three types is similar in the cervix, the isthmus and the body of the uterus in pregnant and non-pregnant females.     

Comparison of casein of cynomolgus monkey (Macaca fascicularis) with human casein

Casein of cynomolgus monkey was compared with those from human and bovine milk. Cynomolgus monkey casein showed similar electrophoretical patterns to those of human casein on Disc- and SDS-electrophoresis. It consisted of beta- and kappa-casein-like components. The component corresponding to bovine alpha s1-casein was not detected. The beta-casein-like fraction of cynomolgus monkey showed 9 bands on Disc-PAGE. These were suggested to be the same protein binding different levels of phosphorus by dephosphorylation experiment using an acid phosphatase. The kappa-casein-like component of cynomolgus monkey was highly glycosylated (about 50% carbohydrate) similarly as human kappa-casein and the constituent carbohydrates were same as those detected in human kappa-casein (galactose, fucose, N-acetylgalactosamine, N-acetylglucosamine, and sialic acid). Amino acid composition of cynomolgus monkey kappa-casein bore a resemblance to those of both human and bovine kappa-caseins. Amino acid composition of cynomolgus monkey beta-casein was also similar to those of human and bovine beta-caseins.     

Ependymal cyst in a cynomolgus macaque (Macaca fascicularis)

Background A focal hypointense intracranial lesion was detected by magnetic resonance imaging in the right caudal occipital lobe of the cerebrum in an asymptomatic cynomolgus macaque (Macaca fascicularis). Results Following euthanasia, gross evaluation of the lesion revealed a 1 cm diameter, wedge‐shaped intracranial cavitation without apparent communication with the ventricles. Histologically, the lesion was lined by ciliated cuboidal to low columnar epithelium that showed immunopositivity for cytokeratin, S‐100, and GFAP. Conclusion Based upon the gross, histologic, and immunohistochemical findings, this lesion was classified as an ependymal cyst. In the human patients, ependymal cysts are benign, non‐infectious, non‐inflammatory lesions of the central nervous system that are believed to originate from aberrant migration of ependymal cells during development. To our knowledge, this is the first report of an ependymal cyst in a non‐rodent veterinary species and the first report of a benign intracranial cyst of any classification in a non‐human primate.     

Ultrasonographic findings of functioning renal allografts in the cynomolgus monkey (Macaca fascicularis)

PURPOSE: The purpose of this study was to describe the findings of serial ultrasound investigations of functioning and histologically normal renal allografts in the cynomolgus monkey. METHODS: Ten cyclosporine (Neoral) treated cynomolgus monkeys underwent renal allograft transplantation with bilateral nephrectomy, seven of which were examined serially with ultrasound. Ultrasound findings were compared to serum creatinine, and the results of histology from allograft biopsy on day 150 post-transplantation. RESULTS: Allografts increased in volume up to one and a half to twice that of their original volume and appeared morphologically similar to native kidneys. Allograft ureters were dilated postoperatively but decreased in size with time. Other than in two cases of ureter complications, the resistive index (RI) was normal in functioning grafts. CONCLUSIONS: Elevations in RI, as well as graft enlargement and increased cortical thickness, were related to graft pathology, but not necessarily to rejection histologically. The ultrasound findings of functioning grafts and of surgical complications after renal allograft transplantation in the cynomolgus monkey were similar to those in humans.     

Successful artificial insemination for indoor breeding in the Japanese monkey (Macaca fuscata) and the cynomolgus monkey (Macaca fascicularis)

Methods of artificial insemination (AI) for indoor breeding in the Japanese monkey and the Cynomolgus monkey were investigated. For the Japanese monkey AI was carried out in six females during the winter mating season and in six females during the summer non-mating season. During the mating season, semen was inseminated near ovulation time in natural menstrual cycles. In the mating season study, three females inseminated at the uterine cavity became pregnant. Three inseminated at the cervical canal failed to become pregnant. For the non-mating season study, ovulation was induced artificially by PMSG and hCG and AI was carried out near the induced ovulation time. In the non-mating season, no animals became pregnant. Of four Cynomolgus monkeys used, pregnancy occurred in two animals inseminated near ovulation time in natural menstrual cycles. AI occurred at the uterine cavity in one and cervical canal in the other. In both species ovulation was verified by laparoscopy. Semen was collected by penile electro-stimulation then diluted to 2.5 to 5.0×10⁷/ml with Whitten's medium. Diluted semen of 0.2l was inseminated at the uterine cavity or cervical canal. Our results indicate the usefulness of vaginal AI as a method of artificial indoor breeding.