Regional Primate Research Center Research Articles

Arthur J. Riopelle (1920–2012).

Presents an obituary for Arthur (Art) J. Riopelle. After graduating from the University of Wisconsin in 1942, Art joined the U.S. Army. He returned to the university after the war as a graduate student in psychology and earned a doctorate in experimental psychology under the supervision of Dave Grant and Fred Mote. In 1950, Art completed his degree and moved to the Psychology Department of Emory University in Georgia. This was the beginning of an unusual and eventful career. At Emory, Art worked with Harlow W. Ades, but when Ades eventually left, Art established a small colony of monkeys to pursue his own projects. Art moved from Emory to Fort Knox, Kentucky, in 1957 to become director of the Psychology Division of the U.S. Army Medical Laboratories. He continued to be involved with primates, including on a well-publicized project that entailed launching monkeys into space. In 1959, Art left Fort Knox to become the new director of what was then known as the Yerkes Laboratories of Primate Biology. Art played an important part in the history of regional primate research centers, which have benefited the nation in numerous ways. He had many admirable qualities. He was a tolerant, supportive, fair-minded, and principled administrator, a careful and dedicated scientist, and a steadfast friend who loved a good joke.

Maternal and Neonatal Exposure to Environmental Tobacco Smoke Targets Pro-Inflammatory Genes in Neonatal Arteries

Maternal mainstream tobacco smoking is known to have adverse outcomes on fetal respiratory function; however, no data is currently available on the effects of passive exposure to tobacco smoking and environmental tobacco smoke (ETS) on fetal systemic arterial structure and function. Eight pregnant rhesus macaque monkeys were studied at the California Regional Primate Research Center breeding colony. The estimated gestational age for each dam was established by sonography performed before gestational day 40. Two inhalation chambers were used, each with an air capacity of 3.5 m3, and each housed two dams. Aged and diluted sidestream smoke was used as a surrogate for ETS. Exposure to ETS (1 mg/m3) occurred for 6 h/day, 5 days/week, beginning on gestational day 100. All dams were allowed to give birth spontaneously and then ETS exposure continued 70–80 days postnatally with the chamber containing both the mother and infant. Carotid arteries from four control (C) and four ETS-treated newborns were analyzed for mRNA by gene macroarray and for protein by Western blotting. A total of 588 cardiovascular genes were studied. Four genes were upregulated by ETS compared to C, and nine genes were downregulated (≥2-fold change). Three genes were selected for further study. Following ETS exposure, neonatal carotid arteries of non-human primates manifested evidence of inflammation with increased gene and protein expression of LFA-1 and RANTES, proteins that are recognized to be important in vascular adhesion and inflammation, and downregulation of expression for the receptor for VEGF, which has a key role in angiogenesis. Prenatal and postnatal exposure to ETS increases expression of pro-inflammatory genes and may be responsible for early arterial vascular remodeling that is predisposing to a subsequent vascular disease.

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Basic and applied biology of the primate reproductive tract – a symposium in honor of the career of Dr Robert M Brenner: Introduction and overview

In 1962, the National Institutes of Health dedicated the first Primate Center in the United States, located in Beaverton, Oregon and closely associated with what was then called the University of Oregon Medical School, now known as Oregon Health & Science University. Within a few years, the Oregon Regional Primate Research Center was followed by 6 others in various cities across the country that were affiliated with many distinguished universities. In recent years another institution has joined the unique club now known as the National Primate Centers. The key aim of these centers was to explore the biology of nonhuman primates with the ultimate goal of improving human health. The original planners at NIH who conceived the Primate Centers deserve great credit, and this symposium is in part a testament to their foresight. While no animal model is perfect, all agree that nonhuman primates are superbly useful for probing key aspects of human biological systems. Early on it was recognized that the reproductive system in female nonhuman primates was almost identical to that of women. Consequently, the Oregon Center focused its efforts on reproductive physiology. Evidence accumulated that numerous gynecological problems that afflict women such as premature birth, pelvic disorders, dysfunctional bleeding and endometriosis had their counterparts in female nonhuman primates. Consequently, strong collaborations developed between Primate Center scientists and Ob-Gyn physicians, nationally and internationally, to probe the mechanisms underlying these disorders. Many of the papers presented at this symposium provide summaries of such collaborative efforts, and all the reviews provide helpful perspectives and important insights into the field of endometrial physiology, with examples drawn from both human and nonhuman primates.

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Structural and Spectroscopic Studies Shed Light on the Mechanism of Oxalate Oxidase

Oxalate oxidase (EC 1.2.3.4) catalyzes the conversion of oxalate and dioxygen to hydrogen peroxide and carbon dioxide. In this study, glycolate was used as a structural analogue of oxalate to investigate substrate binding in the crystalline enzyme. The observed monodentate binding of glycolate to the active site manganese ion of oxalate oxidase is consistent with a mechanism involving C-C bond cleavage driven by superoxide anion attack on a monodentate coordinated substrate. In this mechanism, the metal serves two functions: to organize the substrates (oxalate and dioxygen) and to transiently reduce dioxygen. The observed structure further implies important roles for specific active site residues (two asparagines and one glutamine) in correctly orientating the substrates and reaction intermediates for catalysis. Combined spectroscopic, biochemical, and structural analyses of mutants confirms the importance of the asparagine residues in organizing a functional active site complex.

Andrology: Pursuit of the Scientific Trinity

It is a great honor to accept the opportunity to serve the American Society of Andrology and the Journal of Andrology as the new Section Editor of the Journal of Andrology Lab Corner. Previous section editors have served the Journal extremely well, and I will strive to do so also. I would first like to thank the Co-Editors-in-Chief, Drs Matthew Hardy and Peter Schlegel, for this privilege. Within this brief editorial, I will take the occasion to 1) introduce myself, 2) provide a philosophical view of the Journal of Andrology Lab Corner focus during upcoming months, 3) provide a schematic vision for manuscript submission and review, and last, 4) implore you, the individuals of the Andrological Society, to share ideas and manuscripts that will serve our readers well. As a graduate student, I was fortunate to be mentored in Reproductive Biology and Endocrinology by Drs Fredrick Stormshak and Jerry Reeves at Oregon State and Washington State Universities, respectively. These individuals made great impressions on me in areas of scientific imagination, rigor, experimental design, and the use of statistical analytical tools. After my doctoral training, I found myself at a crossroad, desiring a quest for scientific knowledge and also the ability to translate these findings to practices that would impact patient care. Quite serendipitously, the opportunity arose to conduct a postdoctoral fellowship with Dr Donald P. Wolf at the Oregon Regional Primate Research Center. This amazing experience profoundly molded my passion for basic science studies of gamete and embryo biology with an emphasis on assisted reproductive technologies (ART). At comple-

Restoration of liver surface area correlated to KI-67 expression following 60% partial hepatectomy in a rhesus macaque: Paul J Gaglio, Huifeng J Liu, Shrikanta Dash, Bruce Dunne, Tulane University Medical School, New Orleans, LA; Marion Ratterree, Tulane Regional Primate Research Center, Covington, LA

Restoration of liver surface area correlated to KI-67 expression following 60% partial hepatectomy in a rhesus macaque: Paul J Gaglio, Huifeng J Liu, Shrikanta Dash, Bruce Dunne, Tulane University Medical School, New Orleans, LA; Marion Ratterree, Tulane Regional Primate Research Center, Covington, LA

Evaluation of a possible interaction between hyperhomocyst(E)inemia & elevated soluble vascular cell adhesion molecule-1 in predicting preeclampsia

HYPERHOMOCYST(E)INEMIA & ELEVATED SOLUBLE VASCULAR CELL ADHESION MOLECULE-1 IN PREDICTING PREECLAMPSIA SURAB VADACHKORIA, SANCHEZ SIXTO, CHUNFANG QIU, MARTIN MUY-RIVERA, M. RENE MALINOW, MICHELLE WILLIAMS, Swedish Medical Center, Center for Perinatal Studies, Seattle, WA Dos de Mayo Hospital, Lima-1, Peru Oregon Regional Primate Research Center, Beaverton, OR OBJECTIVE: Hyperhomocystinemia (HHcy) is a risk factor of endothelial dysfunction and preeclampsia (PE). Soluble vascular cell adhesion molecule-1 (sVCAM-1), a specific marker of endothelial dysfunction, is elevated in PE. Few have assessed the joint contribution of these biomarkers in predicting PE. We assessed the extent to whichHHcy and elevated sVCAM-1 are independently and jointly associated with PE risk. STUDY DESIGN: We used information from a case-control study of 100 PE cases and 100 controls to test our study hypothesis. Maternal plasma was collected before labor onset. Total plasma homocysteine (tHcy) was measured using high-performance liquid chromatography with electrochemical detection procedures. Plasma sVCAM-1 was determined using ELISA. Using the distribution of each analyte among controls, elevated tHcy was defined as plasma tHcy > 6.6 lmol/L and elevated sVCAM-1 was defined as plasma concentrations >845 ng/mL (i.e., values above the median). Odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Plasma tHcy was weakly correlated with sVCAM-1 in cases (r = 0.18, P = 0.08), but not in controls (r = 0.04, P = 0.70). Compared with women without elevated tHcy and without elevated sVCAM-1 (the referent group), those with elevated sVCAM-1 alone experienced a 4.1-fold increased risk of PE (CI 1.2-13.8). Women with elevated tHcy alone experienced a 2.2-fold increased risk of PE (OR = 2.2; CI 0.6-7.9). Women who had elevated tHcy and sVCAM-1 were 13.2 times more likely to experience PE (CI 4.1-42.2). CONCLUSION: Elevated tHcy and sVCAM-1 concentrations together are strongly associated with an increased risk of PE. Our results suggest that combining these two biomarkers may be particularly powerful in predicting the risk of PE. Future larger, prospective studies are needed to confirm these findings.

Endocrine-related resources from the National Institutes of Health.

Endocrine-related resources from the National Institutes of Health.