Adrenal myelolipoma in the cottontop tamarin (Saguinus o. oedipus)

Two cases of myelolipoma in the cottontop tamarin (Saguinus o. oedipus) were found unequivocally within the adrenal gland, supporting an earlier suggestion that the adrenal gland was the possible origin of a juxtarenal myelolipoma in the same species. In the present study a 30-mm-diameter myelolipoma was present in the adrenal gland in case 1, whereas in case 2 the myelolipoma was only detected on histological examination. In case 1, changes in the adrenal gland were considered to be of minor clinical significance, whereas in case 2 the myelolipoma was an incidental finding.     

The regulation of maternal behaviour in marmosets and tamarins

This article reviews a long-term investigation into the roles of (1) experience obtained with infants during development and postnatally, and (2) levels of reproductive-steroid hormones during late pregnancy, in the regulation of maternal caregiving motivation and behaviour in the red-bellied tamarin (Saguinus labiatus) and the common marmoset (Callithrix jacchus) (family Callitrichidae, Order Primates). Both observational studies, e.g. post hoc analysis of the relationship between developmental caregiving experience and infant-rearing success, and manipulative studies, e.g. direct analysis of the effects of sex-steroid administration on maternal motivation, were performed. In red-bellied tamarins, a breeding female's infant-rearing success was related to its caregiving experience obtained during development and postpartum/postnatally. In multiparous females lacking developmental caregiving experience, postpartum maternal caregiving behaviour and infant-rearing success were related to prepartum urinary oestradiol levels. In nulliparous common marmosets, caregiving of infant-siblings increased as a consequence of physical interaction with parent-infant dyads, late pregnancy, and exposure to late pregnancy-like levels of progesterone and oestradiol. The evidence for a dual mechanism of endocrine and experiential regulation of caregiving in these monkeys is discussed in terms its evolution and function.     

Visual monitoring of threatening objects by captive tamarins (Saguinus labiatus)

Captive social groups of red-bellied tamarins (Saguinus labiatus) were observed in the presence of threatening, inanimate objects. The tamarins monitored the stimuli over the course of the 20-minute trials by conducting brief, periodic visual checks of the objects. The average number of checks per subject per trial was stable both across trials and between groups, and individual differences in rates varied relatively little around the group means. These data generate the hypothesis that there is a species-typical execution of vigilance in the presence of mildly threatening objects. This execution takes the form of brief visual inspections of the stimulus, usually by one tamarin at a time, at a fairly consistent rate. The discussion of the data takes place in the context of the behavioral ecology of callitrichid species.     

Murine embryonic stem cell-derived hepatocytes correct metabolic liver disease after serial liver repopulation

Although embryonic stem (ES) cell-derived hepatocytes have the capacity for liver engraftment and repopulation, their in vivo hepatic function has not been analyzed yet. We aimed to determine the metabolic function and therapeutic action of ES cell-derived hepatocytes after serial liver repopulations in fumaryl acetoacetate hydrolase knockout (Fah(-/-)) mice. Albumin expressing (Alb(+)) cells were obtained by hepatic differentiation of ES cells using two frequently reported methods. After transplantation, variable levels of liver repopulation were found in Fah(-/-) mice recipients. FAH expressing (FAH(+)) hepatocytes were found either as single cells or as nodules with multiple hepatocytes. After serial transplantation, the proportion of the liver that was repopulated by the re-transplanted FAH(+) hepatocytes increased significantly. ES cell-derived FAH(+) hepatocytes were found in homogenous nodules and corrected the liver metabolic disorder of Fah(-/-) recipients and rescued them from death. ES cell-derived hepatocytes had normal karyotype, hepatocytic morphology and metabolic function both in vitro and in vivo. In conclusion, ES cell-derived hepatocytes were capable of liver repopulation and correction of metabolic defects after serial transplantation. Our results are an important piece of evidence to support future clinical applications of ES cell-derived hepatocytes in treating liver diseases.     

A juxtarenal myelolipoma in a cottontop marmoset (Saguinus oedipus): A case report

A myelolipoma was surgically removed from the abdomen of a 15-year-old female cottontop marmoset (Saguinus oedipus). Because of its close adherence to the right kidney, a unilateral nephrectomy was performed. The post-surgical recovery was uneventful. A myelolipoma is a circumscribed mass of bone marrow elements embedded in mature adipose tissue. These masses have been reported in the adrenal glands, paravertebral tissue, intrathoracic tissues, and mesentery of man. A similar condition has been observed in the liver and spleen of both captive and wild felidae. This report documents the first observation of this tumor-like condition in nonhuman primates with the possible exception of a subcutaneous myeloliposarcoma in a potto.     

A case report of hepatocellular carcinoma and focal nodular hyperplasia with a myelolipoma in two chimpanzees and a review of spontaneous hepatobiliary tumors in non-human primates

Spontaneous hepatobiliary tumors in non-human primates are uncommon. Here we report a case of hepatic carcinoma and a case of hepatic focal nodular hyperplasia (FNH) and myelolipoma in two captive chimpanzees. A 16-year-old male chimpanzee (4X0392) died after an 8-month history of hepatic amyloidosis and low-grade anemia. Necropsy findings included a hepatic neoplasm with highly pleomorphic hepatocytes arranged into irregular thickened trabeculae. The diagnosis was high-grade hepatocellular carcinoma. A second male chimpanzee (4X0080), 23 years of age, died suddenly of heart failure secondary to cardiomyopathy. An incidental finding at necropsy was a liver mass characterized by multinodularity, prominent fibrous septa, and biliary hyperplasia. These features were consistent with FNH. While 4X0392 had no history of experimental viral exposure, 4X0080 was vaccinated with inactivated hepatitis B virus, an attenuated hepatitis A virus, and was experimentally infected with hepatitis C virus and human immunodeficiency virus. A survey of the literature revealed 68 reported cases of hepatobiliary tumors in non-human primates, including 12 hepatocellular adenomas, eight cholangiocellular adenomas/cystadenomas, 22 hepatocellular carcinomas, seven cholangiocarcinomas, and seven gallbladder adenocarcinomas. The majority of reported cases have been in prosimians and Old World monkeys. Hepatic neoplasia is rare in chimpanzees. Only four hepatic neoplasms have been reported in chimpanzees, three of which were associated with viral hepatitis. FNH has not been previously described in any non-human primate.     

Expression of N-acetylglucosaminyltransferase III in hepatic nodules during rat liver carcinogenesis promoted by orotic acid

The activity of N-acetylglucosaminyltransferase III, which adds a "bisecting" GlcNAc in beta 1,4 linkage to the beta-linked Man of the core of Asn-linked oligosaccharides (Narasimhan, S. (1982) J. Biol. Chem. 257, 10235-10242), was determined in hepatic nodules of rats initiated by administration of a single dose of carcinogen 1,2-dimethylhydrazine.2HCl (100 mg/kg, intraperitoneal) 18 h after partial hepatectomy and promoted by feeding a diet supplemented with 1% orotic acid for 32-40 weeks. N-Acetylglucosaminyltransferase III was assayed using glycopeptide GlcNAc beta 1,2Man alpha 1,6(GlcNAc beta 1,2Man alpha 1,3)Man beta 1, 4GlcNAc beta 1,4GlcNAc-Asn as substrate and, as enzyme sources, microsomal membranes of the hepatic nodules, surrounding liver, regenerating liver, and age- and sex-matched control liver. The nodules had significant N-acetylglucosaminyltransferase III activity (0.78-2.18 nmol GlcNAc transferred/h/mg of protein), while the surrounding liver, the regenerating liver (24 h after partial hepatectomy), and the control liver had negligible activity (0.02-0.03 nmol/h/mg of protein). Product isolated from a large scale N-acetylglucosaminyltransferase III incubation with hepatic nodules as enzyme source showed the presence of the bisecting GlcNAc residue by 500 MHz proton NMR spectroscopy. Concomitant with the appearance of N-acetylglucosaminyltransferase III activity in the preneoplastic nodules, the activities of N-acetylglucosaminyltransferase I and II were decreased in these membranes when compared to those from surrounding liver, regenerating liver, and control liver. These results suggest that N-acetylglucosaminyltransferase III is induced at the preneoplastic stage in liver carcinogenesis promoted by orotic acid and are consistent with the reported presence of bisecting GlcNAc residues in the Asn-linked oligosaccharides of rat and human hepatoma gamma-glutamyl transpeptidase and their absence in enzyme from normal liver of rats and humans (Kobata, A., and Yamashita, K. (1984) Pure Appl. Chem. 56, 821-832).     

Effects of colchicine on liver functions of cirrhotic rats: beneficial effects result from stellate cell inactivation and inhibition of TGF beta1 expression

Liver cirrhosis (LC) is a chronic disease with high mortality rate and its pathophysiology includes hepatic parenchymal cell destruction, connective tissue formation, and nodular regeneration. Colchicine has been used in liver diseases as an anti-inflammatory and anti-fibrotic drug. However, there is controversy over the beneficial effects of colchicine in LC treatment. In the present study, we injected rats with multiple doses of dimethylnitrosamine for 4 weeks and used rats with severe LC to determine whether colchicine treatment improved liver functions and resolved cirrhotic nodules. Colchicine (30-150microg/kg per day, i.p., for 4 weeks) failed to significantly increase the survival rate of LC rats. Animals were subjected to blood biochemical, liver histopathological and immunochemical analyses. The plasma albumin level, decreased in cirrhotic rats, was restored by colchicine treatment along with reduction of ascites. Colchicine decreased the accumulated extracellular matrix and the multiple fibrotic nodules formed in cirrhotic liver, and eliminated alpha-smooth muscle actin (alpha-SMA)-positive cells. In activated stellate cells, colchicine inhibited alpha-SMA and transforming growth factor-beta1 (TGFbeta1) expression. The results of the present study showed that colchicine resolves cirrhotic nodules and accumulated fibers in the liver of LC rats, but failed to significantly improve the survival rate of LC animals, and that the beneficial effects of colchicine in cirrhotic animals result from stellate cell inactivation and inhibition of TGFbeta1 expression.     

自体骨髓间充质干细胞对二甲基甲酰胺中毒肝衰竭患者肝功能恢复的促进作用

目的探讨自体骨髓间充质干细胞（BM-MSCs）对二甲基甲酰胺（DMF）中毒致急性肝衰竭后肝功能延迟恢复患者的疗效和安全性。 方法1例DMF中毒性急性肝衰竭患者,在人工肝为主的内科综合治疗后肝功能持续得不到恢复时,采取患者骨髓,分离、培养制备BM-MSCs,经肝动脉介入输注到患者肝内,观察其临床表现、肝功生化、凝血、肝脏影像学、肝组织病理学等改变及BM-MSCs近期不良反应和远期的安全性。 结果BM-MSCs治疗后,患者持续不见好转的肝功生化指标开始改善,凝血功能恢复速度加快,凝血酶原活动度（PTA）逐渐恢复到40%以上,上腹部CT见肝脏再生结节较前增大,Child-Pugh分级由C级转为A级,终末期肝病模型（MELD）评分由21分降到7分;干细胞输注早期未出现相关的不良反应,8周后再生结节穿刺活检其病理特征为：肝细胞变性、坏死、纤维化、胆汁淤积与再生并存。随访3年患者肝功生化正常、肝硬化结节影像学观察无明显变化,未发生癌变。 结论BM-MSCs肝动脉介入治疗对DMF中毒致急性肝衰竭肝功能延迟恢复患者的肝功能改善具有一定促进作用,近期无明显不良反应,中远期安全性好。     

Primary hepatic neuroendocrine carcinoma in a baboon (Papio sp.)

Background  Primary neuroendocrine carcinomas of the liver have rarely been reported in humans and domestic animals, but not in non-human primates.
Methods  We describe the morphologic and immunohistochemical features of a primary hepatic neuroendocrine carcinoma found in a 29-year-old female baboon.
Results and conclusions  The neoplasm was characterized by multiple solid nodules that were multifocally distributed in the liver. Metastases were not observed. Histologically, the neoplasm was composed of cords and nests of epithelial cells arranged in a neuroendocrine pattern, occasionally forming glandular and rosette-like structures. On immunohistochemical evaluation, the neoplastic cells were immunopositive for pancytokeratin, chromogranin A, neuron-specific endolase, and synaptophysin and were negative for vimentin, S100 protein, glucagon, and insulin.     

Cutting edge: inhibition of experimental tumor metastasis by dendritic cells pulsed with alpha-galactosylceramide.

A unique lymphoid lineage, Valpha14 NKT cells, bearing an invariant Ag receptor encoded by Valpha14 and Jalpha281 gene segments, play crucial roles in various immune responses, including protective immunity against malignant tumors. A specific ligand of Valpha14 NKT cells is determined to be alpha-galactosylceramide (alpha-GalCer) which is presented by the CD1d molecule. Here, we report that dendritic cells (DCs) pulsed with alpha-GalCer effectively induce potent antitumor cytotoxic activity by specific activation of Valpha14 NKT cells, resulting in the inhibition of tumor metastasis in vivo. Moreover, a complete inhibition of B16 melanoma metastasis in the liver was observed when alpha-GalCer-pulsed DCs were injected even 7 days after transfer of tumor cells to syngeneic mice where small but multiple metastatic nodules were already formed. The potential utility of DCs pulsed with alpha-GalCer for tumor immunotherapy is discussed.     

Environmental Enrichment for New World Primates: Introducing Food-Irrelevant Objects and Direct and Secondary Effects

This study examined methods of environmental enrichment for zoo animals for 4 New World primate species: pygmy and Geoffrey's marmosets (Cebuella pygmaea and Callithrix geoffroyi), red-bellied tamarins (Saguinus labiatus), and golden- headed lion tamarins (Leontopithecus chrysomelus). Subjects were housed in groups at the Philadelphia Zoo. Baseline behavioral time budget data were collected, and stimulus objects were then introduced in succession to each enclosure. Each object included multiple manipulable subcomponents. Time budget data were collected while objects were in the enclosures, and subjects' contacts with objects were videotaped. Overall time budgets were significantly altered in only the red-bellied tamarins, the least active of the species, solely due to a shift from social grooming to passive social contact; when categories were collapsed into broader categories, this effect disappeared. Object contact occurred within the 1st hr for all species and ranged over nearly 2 orders of magnitude, from approximately 10 sec per subject (red-bellied tamarins) to approximately 700 sec per subject (Geoffrey's marmosets). Habituation was not evident within any 1st hr of observation but was shown when 1st hr observations were compared with those from subsequent days. This article discusses implications for environmental enrichment in zoos.     

Non-random association of opsin alleles in wild groups of red-bellied tamarins (Saguinus labiatus) and maintenance of the colour vision polymorphism

The remarkable X-linked colour vision polymorphism observed in many New World primates is thought to be maintained by balancing selection. Behavioural tests support a hypothesis of heterozygote advantage, as heterozygous females (with trichromatic vision) exhibit foraging benefits over homozygous females and males (with dichromatic vision) when detecting ripe fruit on a background of leaves. Whilst most studies to date have examined the functional relevance of polymorphic colour vision in the context of foraging behaviour, alternative hypotheses proposed to explain the polymorphism have remained unexplored. In this study we examine colour vision polymorphism, social group composition and breeding success in wild red-bellied tamarins Saguinus labiatus. We find that the association of males and females within tamarin social groups is non-random with respect to colour vision genotype, with identified mating partners having the greatest allelic diversity. The observed distribution of alleles may be driven by inbreeding avoidance and implies an important new mechanism for maintaining colour vision polymorphism. This study also provides the first preliminary evidence that wild trichromatic females may have increased fitness compared with dichromatic counterparts, as measured by breeding success and longevity.     

Butanol-extractable and detergent-solubilized cell surface components from murine large cell lymphoma cells associated with adhesion to organ microvessel endothelial cells.

Metastatic variant cell lines of the murine RAW117 large cell lymphoma were used to study the cell surface components involved in syngeneic tumor cell/microvessel endothelial cell interactions. Poorly liver-metastatic parental RAW117-P cell line adhered to murine hepatic sinusoidal endothelial cell monolayers at significantly lower rates than the liver-selected, highly liver-metastatic RAW117-H10 line and both cell lines were poorly adherent to lung microvessel and bovine aorta endothelial cells. Viable, 2% 1-butanol-treated RAW117-H10 tumor cells formed fewer liver tumor nodules in experimental metastasis assays than untreated H10 cells and were significantly less adherent to murine hepatic sinusoidal endothelial cell monolayers. When 2% 1-butanol extracts of metabolically labeled or CHAPS detergent lysates of cell surface-labeled tumor cells were analyzed for their ability to bind to fixed microvessel endothelial cell monolayers, quantitative differences were found in the extractable tumor cell surface components that bound to the different organ-derived microvessel endothelial cells. Cell surface components (1-butanol extractable), of Mr approximately 85,000-90,000 and approximately 37,000-40,000 bound to hepatic sinusoidal endothelial cell monolayers to a greater extent than to murine lung microvessel endothelial or bovine aortic endothelial cell monolayers, whereas tumor cell surface components of Mr approximately 45,000, approximately 33,000, and approximately 25,000 bound similarly to endothelial cells regardless of origin. The results suggest but do not prove that tumor cell/endothelial cell adhesion involves multiple tumor cell surface components, some of which commonly bind to various endothelial cells and others for which binding may be dictated by the tissue origin and type of endothelial cell. Particular RAW117 butanol-extractable cell membrane components were associated with tumor cell-endothelial cell adhesion, and these components could be responsible, in part, for the preferential adhesion of RAW117 cells to liver sinusoidal endothelial cells and metastasis to liver.     

Pre‐conditions for eliminating mitochondrial dysfunction and maintaining liver function after hepatic ischaemia reperfusion

The liver, the largest organ with multiple synthesis and secretion functions in mammals, consists of hepatocytes and Kupffer, stem, endothelial, stellate and other parenchymal cells. Because of early and extensive contact with the external environment, hepatic ischaemia reperfusion (IR) may result in mitochondrial dysfunction, autophagy and apoptosis of cells and tissues under various pathological conditions. Because the liver requires a high oxygen supply to maintain normal detoxification and synthesis functions, it is extremely susceptible to ischaemia and subsequent reperfusion with blood. Consequently, hepatic IR leads to acute or chronic liver failure and significantly increases the total rate of morbidity and mortality through multiple regulatory mechanisms. An increasing number of studies indicate that mitochondrial structure and function are impaired after hepatic IR, but that the health of liver tissues or liver grafts can be effectively rescued by attenuation of mitochondrial dysfunction. In this review, we mainly focus on the subsequent therapeutic interventions related to the conservation of mitochondrial function involved in mitigating hepatic IR injury and the potential mechanisms of protection. Because mitochondria are abundant in liver tissue, clarification of the regulatory mechanisms between mitochondrial dysfunction and hepatic IR should shed light on clinical therapies for alleviating hepatic IR‐induced injury.     

Characterization of the proteolytic compartment in rat hepatocyte nodules

Persistent liver nodules (hepatocyte nodules, neoplastic nodules) were produced in rat liver by intermittent feeding with 2-acetylaminofluorene. Dense bodies (secondary lysosomes) were purified and characterized from the nodules. The purity of the dense body fraction was 90%. The levels of various lysosomal enzyme activities were lower in these dense bodies in comparison with dense bodies from control liver. Similarly, protein degradation was 50% lower in dense bodies from liver nodules than in control liver. The number of autophagic vacuoles (AVs) in the nodular tissue increased considerably after 3 h vinblastine treatment. We have taken advantage of this expansion in an effort to isolate these organelles from liver nodules. Autophagic vacuoles have been isolated recently from liver and kidney but not from putatively premalignant liver nodules. Fraction purity of AVs from liver nodules was 95%. As with dense bodies, AVs from nodular tissue displayed lower activities of proteinases and lower rates of protein degradation when compared with their counterparts from normal liver tissue. Accordingly, the lower rate of overall protein degradation in liver nodules can be ascribed to a decrease in lysosomal activity. A diminished autophagic sequestration capacity is the most plausible explanation for the decreased rate of proteolysis in cells. This could conceivably give these nodular cells a growth advantage and assist in their selective outgrowth as well as in their transformation from neoplastic into true cancer cells.     

Hepatic carcinoma with spleen metastasis in a California sea lion from the Gulf of California.

A primary hepatic carcinoma with a neuroendocrine pattern was detected in an adult female California sea lion (Zalophus californianus) found dead on Granito Island in the Gulf of California (Mexico) in January 1996. At necropsy, several light yellow nodules of different sizes were observed on the entire surface of the liver and spleen. Microscopic examination of these nodules using routine haematoxylin-eosin stain, revealed cubic, polyhedral and pleomorphic cells with three to four bizarre mitotic figures per field (40X). An immunohistochemistry test revealed a positive reaction of indirect immunoperoxide to cytokeratin (CK2). This is the first known case of a primary hepatic carcinoma in free-ranging California sea lions from Mexican waters.     

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV) DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry). Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV) and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.     

Hepatic myelolipoma in two Goeldi's monkeys from South America held captive

Two cases of hepatic myelolipoma in Goeldi's monkeys from South America are described. One was a female evaluated due progressive abdominal distension. Ultrasound and computed tomography detected hepatic mass. Partial hepatectomy was performed, but the monkey died after surgery. Case 2 was a male that died suddenly, showing non‐specific clinical signs.