Craniorachischisis and omphalocele in a stillborn cynomolgus monkey (Macaca fascicularis).

Nonhuman primates have been a common animal model to evaluate experimentally induced malformations. Reports on spontaneous malformations are important in determining the background incidence of congenital anomalies in specific species and in evaluating experimental results. Here we report on a stillborn cynomolgus monkey (Macaca fascicularis) with multiple congenital anomalies from the colony maintained at the Southwest National Primate Research Center at the Texas Biomedical Research Institute, San Antonio, Texas. Physical findings included low birth weight, craniorachischisis, facial abnormalities, omphalocele, malrotation of the gut with areas of atresia and intussusception, a Meckel diverticulum, arthrogryposis, patent ductus arteriosus, and patent foramen ovale. The macaque had normal male external genitalia, but undescended testes. Gestational age was unknown but was estimated from measurements of the limbs and other developmental criteria. Although cytogenetic analysis was not possible due to the tissues being in an advanced state of decomposition, array Comparative Genomic Hybridization analysis using human bacterial artificial chromosome clones was successful in effectively eliminating aneuploidy or any copy number changes greater than approximately 3-5 Mb as a cause of the malformations. Further evaluation of the animal included extensive imaging of the skeletal and neural tissue defects. The animal's congenital anomalies are discussed in relation to the current hypotheses attempting to explain the frequent association of neural tube defects with other abnormalities.

Experiencing Body Worlds: voyeurism, education, or enlightenment?

Until the advent of plastinated cadavers, few outside the medical professions have had firsthand experience with human corpses. Such opportunities are now available at the Body Worlds exhibits of Gunther von Hagens. After an overview of these exhibits, we explore visitor responses as revealed in comment books available upon exiting the exhibit. Cultural, philosophical, and religious issues raised in the comments serve as a microcosm of society at large. The conclusion considers the challenge of such exhibits in introducing the public to science education, notes the image of the body as machine-so prevalent in the West-reflected in visitor comments, and finds hope that the exhibits promote, for many visitors, a sense of community among all humankind.

Applied neuroanatomy elective to reinforce and promote engagement with neurosensory pathways using interactive and artistic activities.

One in six Americans is currently affected by neurologic disease. As the United States population ages, the number of neurologic complaints is expected to increase. Thus, there is a pressing need for more neurologists as well as more neurology training in other specialties. Often interest in neurology begins during medical school, so improving education in medical neural courses is a critical step toward producing more neurologists and better neurology training in other specialists. To this end, a novel applied neuroanatomy elective was designed at the University of Texas Health Science Center at San Antonio (UTHSCSA) to complement the traditional first-year medical neuroscience course and promote engagement and deep learning of the material with a focus on neurosensory pathways. The elective covered four neurosensory modalities (proprioception/balance, vision, auditory, and taste/olfaction) over four sessions, each with a short classroom component and a much longer activity component. At each session, students reviewed the neurosensory pathways through structured presentations and then applied them to preplanned interactive activities, many of which allowed students to utilize their artistic talents. Students were required to complete subjective pre-course and post-course surveys and reflections. The survey results and positive student comments suggest that the elective was a valuable tool when used in parallel with the traditional medical neuroscience course in promoting engagement and reinforcement of the neurosensory material.

A kidney epithelial cell line from a Bolivian squirrel monkey.

Squirrel monkeys are the most commonly used New World primates in biomedical research, but in vitro studies are restricted by the limited number of cell lines available from this species. We report here the development and characterization of a continuous, kidney epithelial cell line (SQMK-FP cells) derived from a newborn squirrel monkey. Karyotype was consistent with Bolivian squirrel monkey (submetacentric chromosome pair 15 and acrocentric chromosome pair 16). All cells examined were hyperdiploid with chromosome numbers ranging from 52 to 57. Ultrastructural analysis of SQMK-FP cells revealed the presence of cell junctions with radiating filaments, indicating desmosomes and numerous surface projections containing longitudinally oriented filaments typical of tubular epithelium. Biochemically, SQMK-FP cells exhibit glucocorticoid resistance typical of the squirrel monkey. Glucocorticoid receptor (GR) binding is low in SQMK-FP cells because of high expression of the FK506-binding immunophilin FKBP51 that inhibits GR binding. SQMK-FP cells constitute a tubular epithelial cell line that has biochemical properties characteristic of squirrel monkeys and represents an alternate cell model to B-lymphoblast SML cells to study the biology of the squirrel monkey in vitro.

Gunther von Hagens and Body Worlds part 2: The anatomist as priest and prophet.

Part 1 of this two-part series highlighted tensions between the anatomical quest for scientific knowledge about the human interior and artistic representations of the anatomized body, contrasting the roles of Goethe's scientific Prosektor and humanistic Proplastiker-roles disturbingly fused in Gunther von Hagens. Part 2 first examines religious interpretations of the human body that fuel the tensions manifest in anatomy art. The body in Western cultures is a sacred text amenable to interpretation as handiwork of God, habitation for the soul, and vehicle for resurrection. As handiwork of God the body beckons the anatomist's scalpel, helping establish dissection as the hallmark of Western medicine. The body as divinely designed machine encompasses the idea of an indwelling soul expressing its will in actions mediated through the intricate network of muscles-an understanding reflected in the oft occurring muscle men of early anatomical textbooks. Interconnections of body and soul in medieval somatic spirituality are examined with reference to ideas of resurrection and their impact on anatomical illustration. Part 2 concludes with consideration of von Hagens as priest and prophet, culminating in the Promethean impulse that recognizes not God but ourselves as proper owners and molders of our destiny, embodied in the plastinator's visionary quest to create the superhuman.

Gunther von Hagens and Body Worlds Part 1: the anatomist as prosektor and proplastiker.

Recent calls to reintegrate the sciences and humanities are challenged by the contemporary work of anatomist Gunther von Hagens and his Body Worlds exhibits of plastinated cadavers. The anatomical quest to understand our physical interior has long been in tension both with aesthetic ideals and religious sensitivities regarding the metaphysical significance of the human body. Part I of this two-part Historical Note examines tensions epitomized by Goethe's figures of the prosektor and proplastiker. The former, driven by scientific curiosity, is willing to destroy, even desecrate, the human form to obtain knowledge. The latter demurs at such mutilation of our physical body, wondrous even in death--seeking instead to rejoin what the prosektor has pulled apart, to restore human dignity. In the confrontation between prosektor and proplastiker, roles disturbingly fused in the person of von Hagens himself, questions arise regarding the authenticity of models as well as the appropriate recipients of such mediated yet intimate anatomical knowledge. Part II will focus on religious perspectives on the human body, variously interpreted as God's handiwork, habitation for the soul, and vehicle of resurrection. Consideration also is given to the role of anatomist as priest, prophet, and Promethean creator, roles self-consciously embraced by von Hagens.

Genetic relationships among three squirrel monkey types: Implications for taxonomy, biomedical research, and captive breeding.

Fourteen electrophoretically variable and 12 monomorphic erythrocytic and serum proteins were used to determine the genetic relationships among Bolivian squirrel monkeys (Saimiri boliviensis boliviensis), Peruvian squirrel monkeys (Saimiri boliviensis peruviensis), and Guyanese squirrel monkeys (Saimiri sciureus sciureus). The results supported the classification scheme of Hershkovitz (AMERICAN JOURNAL OF PRIMATOLOGY 7:155-210, 1984), which is used above. A profile of marker phenotypes can unambiguously discriminate between the two species examined, and can discriminate most S. b. boliviensis from most S. b. peruviensis. All three groups can be distinguished unambiguously by the location of the centromeres (acrocentric or submetacentric) on chromosomes 15 and 16; however, the biochemical genetic markers provide a powerful means of detecting admixture that might not be detected cytogenetically in instances where hybridization occurred earlier than the preceding generation. The use of this panel of biochemical genetic markers, combined with karyotypic analysis, can ensure a high degree of certainty that animals selected for experimental protocols are uniform with respect to unique physiological characteristics of each species and subspecies. They also can ensure that animals selected to be members of breeding colonies are of a single species/subspecies type and reproductively compatible.

Trisomy 16 in a pigtailed macaque (M. nemestrina) with multiple anomalies and developmental delays.

A female pigtailed macaque (Macaca nemestrina) with unusual physical characteristics, deficits in learning and cognitive tasks, abnormal social behavior, and abnormal reflexes and motor control was followed from birth until 3 years of age and found to have trisomy 16, which is homologous to trisomy 13 in humans. The animal described here showed similar features to cases of trisomy 16 and 18 (human trisomy 13 and 18, respectively) reported previously in nonhuman primates. However, both significant differences and similarities were found when compared with the homologous human trisomy. Evaluation of the genetic components of these disorders as well as systematic developmental evaluation can lead to new insights into the genetic basis of speciation, development, and the underlying differences between humans and their closest living relatives.

Polyostotic fibrous dysplasia in a cynomolgus Macaque (Macaca fascicularis).

A 2.3-y-old female cynomolgus macaque (Macaca fascicularis) presented with a broken right tibia and fibula. Radiographs showed multiple cyst-like defects in all long bones. We suspected that both fractures were pathologic because they occurred through these defects. Ultrasonography, MRI, and dual X-ray absorptiometry revealed that the defects were filled with soft tissue. Grossly, the bones were abnormal in shape, and a gelatinous material filled the defects and the surrounding marrow cavity. Histologically, the gelatinous material was composed of fibrin and cartilage; few normal bone cells were seen. Genetic testing revealed extra material on the short arm of chromosome 8 in all tissues examined, but no copy number alterations of likely clinical significance were observed, and no abnormalities were found that were unique to the lesions. In light of the clinical signs and radiographic and pathologic findings, polyostotic fibrous dysplasia was diagnosed. This report represents the first documented case of fibrous dysplasia in a cynomolgus macaque.

Developing observational skills and knowledge of anatomical relationships in an art and anatomy workshop using plastinated specimens.

One of the strong trends in medical education today is the integration of the humanities into the basic medical curriculum. The anatomy program is an obvious choice for using the humanities to develop professionalism and ethical values. They can also be used to develop close observational skills. Many medical schools have developed formal art observation training in conjunction with nearby art museums to enhance the visual diagnostic skills of their medical students. We report here on an art and anatomy workshop that paired medical and art students who did drawing exercises from plastinated anatomical specimens and the animated face to hone observational skills. Each member of the pair brought a different perspective and expertise to the work that allowed each to be a mentor to the other. The workshop had three sessions: the first involved drawings of plastinated specimens that allowed an intimate experience with authentic human material; the second involved drawings of the human face; and the third included examination of anatomical texts of important anatomist-artists, a lecture on contemporary artists whose work involves anatomy, and a film demonstrating the facial muscles. We propose workshops such as these will help students increase their ability to detect details. This will assist the medical student in developing diagnostic skills for identifying disease and the art student in using the human body as subject. We further propose that these programs will help students develop humanistic sensitivities and provide an outlet for expression of the emotional aspects of dealing with disease and mortality.

The baboon model (Papio hamadryas) of fetal loss: maternal weight, age, reproductive history and pregnancy outcome.

BACKGROUND: Several risk factors are associated with the incidence of human stillbirths. The prevention of stillbirths in women is a pressing clinical problem. METHODS: We reviewed 402 pathology records of fetal loss occurring in a large baboon (Papio spp.) colony during a 15-year period. Clinical histories of 565 female baboons with one or more fetal losses during a 20-year period were analyzed for weight, age, and reproductive history. RESULTS: Fetal loss was most common at term (35.57%) and preterm (28.61%) and less common in the first half of gestation (11.20%) and post-term (5.22%). Greater maternal weight, older age, history of stillbirth and higher parity were independent predictors for stillbirth. An exponential increase in the incidence of fetal loss was observed beginning at age 14 years in baboons. CONCLUSIONS: Fetal loss and maternal risk factors associated with stillbirths in baboons were similar to those documented in women.

Effects of calorie restriction on chromosomal stability in rhesus monkeys (Macaca mulatta).

The basic tenet of several theories on aging is increasing genomic instability resulting from interactions with the environment. Chromosomal aberrations have been used as classic examples of increasing genomic instability since they demonstrate an increase in numerical and structural abnormalities with age in many species including humans. This accumulating damage may augment many aging processes and initiate age-related diseases, such as neoplasias. Calorie restriction (CR) is one of the most robust interventions for reducing the frequency of age-related diseases and for extending life span in many short-lived organisms. However, the mechanisms for the anti-aging effects of CR are not yet well understood. A study of rhesus monkeys was begun in 1987 to determine if CR is also effective in reducing the frequency of age-related diseases and retarding aging in a long-lived mammal. Male monkeys were begun on the diet in 1987, and females were added in 1992 to examine a possible difference in response to CR by sex. The CR monkeys have been maintained for over 10 years on a low-fat nutritional diet that provides a 30% calorie reduction compared to a control (CON) group. Because of the greater similarity of nonhuman primates to humans in life span and environmental responses to diet compared with those of rodents, the rhesus monkey provides an excellent model for the effects of CR in humans. This study examined the effects of CR on chromosomal instability with aging. Significant age effects were found in both CR and CON groups for the number of cells with aneuploidy: old animals had a higher loss and a higher gain than young animals. However, there was no effect of age on chromosomal breakage or structural aberrations in either diet group. Diet had only one significant effect: the CR group had a higher frequency of chromatid gaps than did the CON group. CR, implemented in adult rhesus monkeys, does not have a major effect on the reduction of numerical or structural aberrations related to aging.

Trisomy 17 in a baboon (Papio hamadryas) with polydactyly, patent foramen ovale and pyelectasis.

Trisomy 13 in humans is the third most common autosomal abnormality at birth, after trisomy 21 and trisomy 18. It has a reported incidence of between 1:5,000 and 1:30,000 live births. It is associated with multiple abnormalities, many of which shorten lifespan. We describe here the first reported case of a baboon (Papio hamadryas) with trisomy of chromosome 17, which is homologous to human chromosome 13. The trisomic infant was born to a consanguineous pair of baboons and had morphological characteristics similar to those observed in human trisomy 13, including bilateral polydactyly in the upper limbs, a patent foramen ovale, and pyelectasis. Molecular DNA analysis using human chromosome 13 markers was consistent with the affected infant inheriting two copies of chromosome 17 derived from the same parental chromosome. This trisomy was, therefore, due to either an error in meiosis II or the result of postzygotic nondisjunction. The parental origin, however, could not be determined.

Primary amenorrhea associated with ovarian leiomyoma in a baboon (Papio hamadryas).

A 6-y-old female baboon was examined due to absence of menstrual cycling and secondary sex characteristics and failure to reproduce. The mammary glands and vaginal introitus were hypoplastic, the clitoris was prominent, and the perineal skin was immature with lack of cyclic color alterations and sexual swelling. Evaluation of the reproductive tract revealed a hypoplastic uterus and rudimentary ovaries with the presence of an ovarian leiomyoma within the right ovary. Hormonal values (estradiol, progesterone) were low and comparable to those of adult males or ovariectomized females. Adrenal and pituitary hormones (dehydroepiandrosterone, luteinizing and follicular stimulating hormones) and pituitary structure were within normal limits for this species. The baboon had a normal 42,XX karyotype. These findings suggest primary amenorrhea due to ovarian dysgenesis. This is the first report of a case of primary amenorrhea due to ovarian dysgenesis with a normal karyotype associated with a unilateral ovarian leiomyoma in the baboon. Continued studies of noncycling female nonhuman primates in captive breeding colonies may lead to a greater understanding of the underlying causes of this condition.

Nephroblastomatosis and nephroblastoma in nonhuman primates.

Wilms' tumors, or nephroblastomas, are renal embryonal malignancies with a high incidence in humans. Nephroblastomas are uncommon in nonhuman primates. This report describes three cases of spontaneous proliferative renal tumors in young monkeys: two cases of unilateral kidney nephroblastomas in baboons and a nephroblastomatosis in a cynomolgus macaque. Histologically, both baboon tumors were typical of Wilms' tumors found in humans, with proliferative epithelial cells forming tubules and aborted glomeruli, nephrogenic rests and proliferative fibrovascular tissue. The left kidney of the macaque was markedly enlarged and histologically similar to the baboon tumors, although normal kidney architecture was completely effaced by primitive tubules and occasional glomeruli surrounded by edematous stromal tissue. Cytogenetic analysis did not detect any macaque or baboon equivalents to human Wilms' tumor chromosomal abnormalities. By human pathology classification, the diffuse nature of the macaque tumor is more consistent with nephroblastomatosis than nephroblastoma. This differentiation is the first to be reported in a species other than human. The nephroblastomas described here are the first nephroblastomas to be reported in baboons. Our observations indicate that nonhuman primate nephroblastomatosis and nephroblastomas develop in a similar way to Wilms' tumors in humans, although no genetic marker has been associated with nephroblastomas of nonhuman primates thus far.

Spontaneous ovarian tumors in twelve baboons: a review of ovarian neoplasms in non-human primates.

Twelve spontaneous ovarian tumors were found in the Southwest Foundation for Biomedical Research baboon colony. These included four granulosa cell tumors, three teratomas, two endometrioid carcinomas, one seromucinous cystadenofibroma, a cystic papillary adenocarcinoma, and an ovarian carcinoma. Age was a pre-disposing factor. With one exception, the tumors of surface epithelial- and sex cordstromal origin occurred in baboons over 17 years of age. The exceptional animal was 7 years of age when a malignant granulosa cell tumor with Sertoli cell differentiation was identified. The two endometrioid tumors, which were found in 17- and 30-year-old animals, were both associated with endometriosis. In contrast, the teratomas, which are tumors of germ cell origin, were found in younger animals, i.e. 17 years of age or younger. One case of an ovarian carcinoma with metastases was observed in a 6-month-old infant. Cases of spontaneous ovarian tumors from the literature are reviewed.