恒河猴乳酸脱氢酶同工酶等的血清学调查

本文应用琼脂糖凝胶电泳技术分离恒河猴血清LDH同工酶区带，其百分比为（x±S）LDH_127．56±9．57、LDH_241．14±7．27、LDH_315．57±3．70、LDH_49．97±4．76和LDH_55．58±3．83。正常猴血清ICD的水平（x±S）是853．15～310．83单位，其范围为921．37～793．93单位。猴血清的ALT的含量水平均值为20．55U／L，S为4．22，变异系数为20．54％，性别之间无显著性差异。     

猕猴实验感染人乙型肝炎病毒的研究

目的建立猕猴实验感染人乙型肝炎病毒 (HBV)的动物模型。方法无自然感染HBV的健康熊猴5只 (其中2只预先经环磷酰胺处理 ) ,经 60Co全身照射处理的恒河猴2只 ,分别接种HBV携带者血清。给动物每周定期采血 ,用改良赖氏法、ELISA、PCR、原位杂交、免疫组化及电镜分别检测血清ALT、HBV标志物、HBV_DNA及肝组织中HBsAg 和HBV_DNA ,以及观察病毒颗粒。结果4只熊猴、2只恒河猴血清中ALT出现短期低水平的升高 ,延长了血清中HBsAg 阳性时限。肝组织有类似人乙型肝炎的病理改变 ,部分肝组织切片、免疫组化、原位杂交为阳性。结论改变实验猴免疫状态可提高其对HBV的易感性使感染成功 ,但能否作为合适的动物模型有待进一步研究     

猕猴感染人乙肝病毒动物模型病理学研究

目的：观察猕猴感染人乙型肝炎病毒（HBV）后肝脏的病理学改变。方法：采用HE染色、免疫组化、原位杂交技术对实际及对照组猕猴肝组织进行研究分析。结果：部分猕猴感染人HBV后,肝组织可出现病理改变,具备动物模型的条件,但是否为适合的动物模型有待进一步研究。     

Immunogenicity of a DNA vaccine against herpes B virus in mice and rhesus macaques

Herpes B virus (Cercopithecine herpesvirus 1) is endemic in captive macaque populations and poses a serious threat to humans who work with macaques or their tissues. A vaccine that could prevent or limit B virus infection in macaques would lessen occupational risk. To that end, a DNA vaccine plasmid expressing the B virus glycoprotein B (gB) was constructed and tested for immunogenicity in mice and macaques. Intramuscular (IM) or intradermal (ID) immunization in mice elicited antibodies to gB that were relatively stable over time and predominately of the IgG2a isotype. Five juvenile macaques were immunized by either IM+ID (n=2) or IM (n=3) routes, with two booster immunizations at 10 and 30 weeks. All five animals developed antibodies to B virus gB, with detectable neutralizing activity in the IM+ID immunized animals. These results demonstrated that DNA immunization can be used to generate an immune response against a B virus glycoprotein in uninfected macaques.     

恒河猴细菌感染性子宫出血模型内膜组织NF-κB活性及TNF-α、IL-1mRNA表达的实验研究

目的:探讨核因子κB(NF-κB)及肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1)在恒河猴细菌感染性子宫出血模型中的变化。方法:选择月经正常的雌性育龄恒河猴7只,随机分为模型组4只和正常对照组3只,通过官腔细菌接种制作细菌感染性子宫出血模型。用电泳迁移率改变分析法(EMSA)检测模型组及正常对照组恒河猴子宫内膜组织NF-κB与靶基因DNA的结合活性,用反转录-多聚酶链式反应(RT-PCR)法检测两组恒河猴子宫内膜组织TNF-α、IL-1mRNA的表达。结果:模型组NF-κB活性及TNF-α、IL-1mRNA的表达量均明显高于正常对照组,差异有显著性意义(P<0.01)。结论:NF-κB活化及TNF-α、IL-1mRNA的高度表达可能参与了恒河猴细菌感染性子宫出血发病机制。     

食蟹猴精原干细胞分离纯化及鉴定

目的掌握食蟹猴精原干细胞 (spermatogonial stem cells,SSCs) 体外培养生长特性,建立食蟹猴精原干细胞分离、纯化、培养及初步鉴定的方法。 方法经手术获取2岁14天食蟹雄猴单侧睾丸,采用三步酶消化法分离获得单细胞悬液和差异贴壁法富集精原干细胞。将细胞培养于经丝裂酶素C处理的STO细胞层上,使用添加神经胶质细胞源性的神经营养因子(GDNF)、碱性成纤维细胞生长因子(bFGF)、GDNF家族受体α (GFRa1) 三种重要生长因子的无血清培养液体外培养,20d后采用CDH1标记分子免疫荧光染色和RT-PCR对培养的食蟹猴细胞进行SSCs初步鉴定。 结果通过差异贴壁法分离纯化富集的SSCs,接种到丝裂霉素C处理的STO饲养层细胞上,第2天开始分裂增殖。用含有生长因子的培养基培养2 d细胞形成小集落,5 d后细胞集落明显。培养20 d后,SSCs呈葡萄串状细胞簇,符合SSCs的形态特征,这些细胞经CDH1标记分子免疫荧光染色和RT-PCR均呈阳性表达。 结论本研究成功建立食蟹猴精原干细胞的分离纯化及鉴定体系。基于STO饲养细胞的添加GDNF、bFGF和GFRa1三种生长因子的无血清培养体系可用于食蟹猴精原干细胞培养,CDH1可作为食蟹猴精原干细胞鉴定的标志物。     

Determinants of sexual behavior ofMacaca arctoides in a laboratory colony

Copulatory behavior of wild-born individually caged laboratory stumptail monkeys (Macaca arctoides) was investigated. The monkeys were paired daily for 20 min, and altogether 536 pairings were observed. The influence of the female's menstrual cycle and social factors on male sexual activity was determined. The reactions of the other monkeys during a pairing, and masturbation behavior of the males were observed and described. It was found that when a male and female were paired daily their sexual activity remained on a rather constant and high level for months provided the pair could not see, touch, or smell each other between the pairings. In these conditions the most common copulatory behavior consisted of 3–4 ejaculations. When the couple lived continuously in adjacent cages, which allowed them visual, tactual, and olfactory communication between pairings, the male ejaculated, on the average, only once during five successive pairings. Thus separation and reunion was potent in triggering sexual activity. When the couple was visually separated between sessions the male's sexual activity did not depend on the menstrual cycle of the female. The males initiated copulation and the females were always willing, except in later stages of pregnancy, to cooperate. All males masturbated to ejaculation and it was often triggered by copulation, masturbation, or any happening causing arousal in the colony. The females were never seen to masturbate outside of the heterosexual context.     

Asynchronous Onset of Clinical Disease in BSE-Infected Macaques

To estimate the effect of the variability of prion disease onset on primary bovine spongiform encephalopathy transmission to humans, we studied 6 cynomolgus macaques. The preclinical incubation period was significantly prolonged in 2 animals, implying that onset of variant Creutzfeldt-Jacob disease in humans could be more diverse than previously expected.     

Grooming and consort partner selection in a troop of Japanese monkeys (Macaca fuscata)

The Arashiyama West troop of Macaca fuscataconsists of 150 monkeys transported from Kyoto, Japan, in February 1972 to their present location near Laredo, Texas. At this site the animals range over 108 acres and during the study period were only minimally provisioned and disturbed. In the report of a 3-year study of consort partner selection it was suggested that yearlong social bonds within the troop appeared to be distinct from consort bonds formed during mating season. Like Sade, we consider grooming to be a good measure of yearround affinitive bonding in macaques. This study compares the pairs formed for consorting with those formed for yearlong grooming activities, by the 94 individuals who formed consort relationships during the mating season of 1973–1974. It was found that yearlong grooming involved pairs of monkeys which were significantly different from those for consorting. Grooming was relatively frequent between related monkeys, while consort partners were seldom related. In addition, yearlong grooming patterns were not disrupted during mating season. These results suggest that consort and grooming activities are behavioral expressions of two important social networks, involving mutually exclusive social bonds. This research was supported in part by grants-in-aid of research from the Explorers Club and the Society of the Sigma XI and by a National Science Foundation Fellowship (No. 26-1140-5850).     

Non-clinical immuno-toxicological evaluation of HER1 cancer vaccine in non-human primates: a 12-month study

Human epidermal growth factor receptor (HER1) constitutes a tumor associated antigen. Its overexpression in many epithelial tumors has been associated with bad prognosis and poor survival. Cancer vaccine based on the extracellular domain (ECD) of HER1 and adjuvated in very small sized proteoliposomes (VSSP) and Montanide ISA 51-VG is a new and complementary approach for the treatment of epithelial tumors. The present study deals with the immunogenicity of this vaccine in Macaca fascicularis monkeys and evaluation of its toxicity during 12 months. Twelve monkeys were randomized into two groups of 3 animals per sex: control and vaccinated. Treated monkeys received 9 doses of vaccination and were daily inspected for clinical signs. Body weight, rectal temperature, cardiac and respiratory rates were measured during the study. Humoral immune response, clinical pathology parameters and delayed type hypensensitivity were analyzed. Skin biopsy was performed at the end of the study in all animals. Animal's survival in the study was 100% (n = 12). Local reactions were observed at the administration site of four treated animals (n = 6), with two showing slight inflammatory cutaneous damage. Clinical pathology parameters were not affected. HER1 vaccine induced high IgG antibodies titers in the treated animals even when DTH was not observed. The induced antibodies recognized HER1+ tumor cell lines, decreased HER1 phosphorylation and showed anti-proliferative and pro-apoptotic effects in H125 cells. In general the present study showed that HER1 vaccine induced specific immune response in M. fascicularis monkeys and was well tolerated, suggesting it could be safely used in clinical studies in epithelial cancer patients.     

Primate-to-human retroviral transmission in Asia

We describe the first reported transmission to a human of simian foamy virus (SFV) from a free-ranging population of nonhuman primates in Asia. The transmission of an exogenous retrovirus, SFV, from macaques (Macaca fascicularis) to a human at a monkey temple in Bali, Indonesia, was investigated with molecular and serologic techniques. Antibodies to SFV were detected by Western blotting of serum from 1 of 82 humans tested. SFV DNA was detected by nested polymerase chain reaction (PCR) from the blood of the same person. Cloning and sequencing of PCR products confirmed the virus's close phylogenetic relationship to SFV isolated from macaques at the same temple. This study raises concerns that persons who work at or live around monkey temples are at risk for infection with SFV.     

Tickborne encephalitis in naturally exposed monkey (Macaca sylvanus)

We describe tickborne encephalitis (TBE) in a monkey (Macaca sylvanus) after natural exposure in an area at risk for TBE. TBE virus was present in the brain and could be identified as closely related to the European subtype, strain Neudoerfl.     

Alcohol response and consumption in adolescent rhesus macaques: life history and genetic influences

The use of alcohol by adolescents is a growing problem and has become an important research topic in the etiology of the alcohol use disorders. A key component of this research has been the development of animal models of adolescent alcohol consumption and alcohol response. Because of their extended period of adolescence, rhesus macaques are especially well suited for modeling alcohol-related phenotypes that contribute to the adolescent propensity for alcohol consumption. In this review, we discuss studies from our laboratory that have investigated both the initial response to acute alcohol administration and the consumption of alcohol in voluntary self-administration paradigms in adolescent rhesus macaques. These studies confirm that adolescence is a time of dynamic change both behaviorally and physiologically, and that alcohol response and alcohol consumption are influenced by life history variables, such as age, sex, and adverse early experience in the form of peer-rearing. Furthermore, genetic variants that alter functioning of the serotonin, endogenous opioid, and corticotropin-releasing hormone systems are shown to influence both physiological and behavioral outcomes, in some cases interacting with early experience to indicate gene by environment interactions. These findings highlight several of the pathways involved in alcohol response and consumption, namely reward, behavioral dyscontrol, and vulnerability to stress, and demonstrate a role for these pathways during the early stages of alcohol exposure in adolescence.     

Environmental pollutant Aroclor 1242 (PCB) disrupts reproduction in adult male rhesus monkeys (Macaca mulatta)

Adult male rhesus monkeys (Macaca mulatta) were given oral treatment of either Aroclor 1242 or vehicle (corn oil and glycerol) at a dose of 200 microg/kg body wt/day for 6 months to investigate the effects of the pollutant on plasma testosterone and the morphology of testes and accessory glands. Aroclor 1242 treatment significantly decreased testicular size and testosterone levels in plasma and adversely affected spermatogenic activity by disrupting epithelial organization. All components of the germinal epithelium were greatly reduced. The spermatogonia were either hypertrophied or had shrunken vesiculated cytoplasm with distorted mitochondria and nuclear pyknosis. Changes were milder in the Sertoli cells, where nuclear infoldings were reduced. Characteristic features of treated Leydig cells were the presence of electron-dense and electron-opaque zones, appearing as plaques, cell membrane abnormalities, and high variability in nuclear shape and heterochromatin distribution. All the Aroclor 1242-treated accessory glands contained more connective tissue than their vehicle-treated counterparts. The epithelium contained many layers of irregularly shaped necrotic cells possessing stereocilia in the epididymides, either hypochromic and hypertrophied or hyperchromic and hypotrophied cells in the prostate and shrunken cuboidal cells with elongated nuclei in the seminal vesicles. In conclusion, Aroclor 1242 treatment causes severe structural alterations on gonads and accessory organs in adult male rhesus monkeys, and these effects could be mediated through both estrogen and Ah receptors.     

Endogenous opiate systems and primate reproduction: Inability of naloxone to induce sexual activity in rhesus males

The opiate antagonist naloxone was tested for its effectiveness in inducing sexual behavior in sexually inactive male rhesus macaques (Macaca mulatta).Naloxone was administered to males directly into the carotid artery via a T-tube implant. Naloxone-treated males and sexually receptive females were pair tested for sexual behavior. Despite the positive behavioral cues of the females, the males failed to initiate heterosexual interactions at any level of naloxone therapy. The implications of this finding for the role of the endogenous opiate system in primate reproduction are discussed in relation to the homeostatic nature of the system.     

Tetanus as Cause of Mass Die-off of Captive Japanese Macaques, Japan, 2008

In 2008 in Japan, 15/60 captive Japanese macaques died. Clostridium tetani was isolated from 1 monkey, and 11 had tetanus-specific symptoms. We conclude the outbreak resulted from severe environmental C. tetani contamination. Similar outbreaks could be prevented by vaccinating all monkeys, disinfecting housing areas/play equipment, replacing highly C. tetani–contaminated soil, and conducting epidemiologic surveys.     

Homosexual behavior in a laboratory group of stumptail monkeys (Macaca arctoides): Forms,contexts, and possible social functions

Observations of stumptail monkeys revealed frequent prolonged, intensive genital stimulation between individuals of the same sex, both males and females, adults and infants, These homosexual interactions occurred in positive emotional contexts, were accompanied by positive emotional facial expressions, and often were evidently elicited by the observation of heterosexual behavior. Infants' first copulations were performed with adults of the same or opposite sex who actively aided them. This suggests that homosexual and heterosexual encounters function as training for adult sexual roles, and that homosexual behavior is a basic primate pattern not exclusive to man.This research was supported in part by the Interdisciplinary Training Program, Langley Porter Neuropsychiatric Institute, University of California, San Francisco, and by United States Public Health Service Training Grant MH-7082, from the National Institutes of Public Health.The stumptail macaque,Macaca arctoides, was formerly designatedMacaca speciosa I. Geoffroy, 1926. For nomenclature, see Fooden (1967a,b) and International Commission on Zoological Nomenclature (1970).This article was part of the symposium Biological and Cultural Bases of Sex Role Differentiation, presented at the Meetings of the American Association for the Advancement of Science, December 1971, in Philadelphia.     

Age and sexual behavior of Japanese macaques (Macaca Fuscata)

The sexual behavior of the Arashiyama West troop, a natural semi-free-ranging troop of Japanese macaques, was studied during the 1973–1974 and 1974–1975 breeding seasons. The troop was transported intact from Japan to its current location in South Texas. There they have been free to move about in a 42.2-hectare electric fence enclosure. This report describes the relationships among age, aging, and sexual behavior. Males beginning at the age of 2.5 years were observed to series-mount estrous females in the double foot clasp mount position. Mounting in series in the double foot position is the normal pattern for Japanese macaque males. The ejaculation of semen with concomitant body movements indicative of orgasm begins at age 4.5 years at the earliest and continues until death. Males 4.5 and 5.5 years of age, sexually mature in the physiological sense, were not consistently sexually mature in the behavioral sense. The oldest male displayed traits that appear analogous to traits observed in aging human males. Females begin to experience estrus at 3.5 years of age. However, like pubescent males, pubescent females display behavioral patterns of sexual immaturity. The oldest female of the troop has remained sexually active. The attainment of sexual maturity by adulthood can be viewed as a learned process leading to efficiency and prowess, followed in old age by sexual involution.This study was partially supported by a University of Oregon Department of Anthropology PHS Biomedical Science Grant No. 50-262-1112.     

Oral contraceptive administration,interfemale relationships,and sexual behavior inMacaca fascicularis

The effects of oral contraceptive administration on the social relationships of adult female cynomolgus monkeys (Macaca fascicularis) were examined. Ten females were administered ethinyl estradiol/ethynodiol diacetate (Demulen), 10 were administered ethinyl estradiol/norgestrel (Ovral), and 10 served as a control group. The monkeys lived in social groups of 5 females each, and patterns of social interaction and social status were recorded. Interfemale relationships were also observed when a vasectomized male was placed in each social group for 50 min, once/week. During the latter observations, preliminary data on the effects of oral contraceptive treatment on sexual interaction were also collected. In the absence of the male, interfemale agonistic interactions and time spent alone were influenced by social status but not by oral contraceptive treatment. Time spent in passive body contact, an affiliative state, was reduced by Ovral treatment. In the presence of the male, dominant females aggressively interfered with the sexual interactions of subordinates. This aggression resulted in the termination of a greater proportion of the sexual interactions of subordinates than dominants in the control group only, indicating suppression of this type of interaction by oral contraceptive treatment. Other effects included a decreased frequency of ejaculation with Ovral-treated females. These results suggest that oral contraceptives may suppress certain types of female agonistic behavior (e.g., in the context of mate competition) and some oral contraceptives may interfere with sexual activity. More broadly, these findings indicate that intrasexual competition for access to mates may occur in females as well as males. This study was supported in part by NICHD Contract #N01-HD-32800 and by Grant #HL14164 from the National Heart, Lung and Blood Institute.