Joseph William Kemnitz - US grants

Dietary restriction (DR) consistently slows the rate of aging, while reducing the incidence and delaying the onset of age-related disease in nonprimate species. The goal of this program is to determine the effects of DR on aging and disease in rhesus monkeys. This component research project is designed to evaluate the impact on DR on the regulation of metabolism during aging from an integrative, physiologic standpoint. Body composition and distribution of body fat will be measured and related to insulin sensitivity and to insulin and glucose levels. The relationship on insulin levels to metabolic rate will be assessed. The following hypotheses will be tested: 1) DR will result in reductions in body weight, body fat and lean body mass, followed by stabilization at lower levels. These changes will be accompanied by sustained alternations in both the level and efficiency of energy utilization. 2) DR-association changes in glucoregulation and metabolic rate represent fundamental aging processes that are at least partially independent of changes in body composition, and consequently will be associated with other measures of biologic aging. In this context, elucidating the effects of aging and DR on glucose, via nonenzymatic glycosylation of proteins and DNA, is a general mediator of age-related change. This project will also probe the cellular mechanisms of increased insulin sensitivity with DR using studies of the GLUT-4 glucose transporter levels in skeletal muscle. Improved understanding of the hyperinsulinemia and elevated glucose levels characteristic of middle age is important, because these conditions are associated with a greater risk for many age-related diseases, including hypertension, cardiovascular disease, cerebrovascular disease, peripheral vascular disease, glaucoma, cataract, and nephropathy.

nutrition; immunology; hormones; endocrine gland /system; ear; diabetes mellitus; cardiovascular system; carbohydrates; blood; Primates; Mammalia; aging;

Objective To test the hypothesis that moderate dietary restriction will slow the rate of functional aging as assessed by regular assessments of the monkeys in terms of body size and composition, glucose tolerance and insulin sensitivity, and energy expenditure. We are testing the hypothesis that moderate restriction of food intake will not only reduce the incidence and delay the onset of age-related diseases, but will also slow the rate of aging and prolong lifespan of primates, as has been shown for rodents and some other species. Adult rhesus monkeys are being assessed semi-annually in terms of body size and composition, insulin levels and blood glucose regulation, metabolic rate, and other measures as a component project of a Program Project Grant. After collection of baseline data, half of the animals underwent gradual food restriction so that they now eat 30% less than their individual baseline amounts, adjusted for changes (decreases) in levels of voluntary intake by the control subjects. After 60 months of restriction for Group 1 we find that animals on DR weigh less and have less body fat than controls, have increased insulin sensitivity, lower fasting insulin levels and insulin increments in response to glucose and tolbutamide challenges, lower fasting glucose levels and improved glucose tolerance, and reduced oxygen consumption. These differences between groups that have been observed thus far are consistent with the hypothesis that DR without malnutrition will improve metabolic efficiency and slow the rate of functional aging. Interim data analyses are in progress as the project continues. During the current report period we added 30 adult female and 16 adult male rhesus monkeys to the study to be evaluated in ways similar to those used for the initial group. These animals were given their baseline assessmemnts, restriction was imposed on the experimental groups, and six-month assessments were completed during this report period. Key words aging, dietary restriction, lifespan extension

women's health; epidemiology; model design /development; genome; genetics; endocrine gland /system; connective tissue; Primates; Mammalia; aging;

health care; nutrition; physical fitness; diabetes mellitus; Primates; aging; Mammalia; biological products; endocrine gland /system; behavioral /social science research tag;

health care; nutrition; physical fitness; diabetes mellitus; Primates; Mammalia; biological products; endocrine gland /system; behavioral /social science research tag;

OBJECTIVE: To assess the effect of growth and aging upon bone metabolism in rhesus monkeys. RESULTS Old world monkeys are often used as models for skeletal development and aging however, the age of peak bone mass and the effect of advancing age is not well known. The aim of this study was to use DXA and measurements of bone metabolism to more clearly characterize skeletal development and aging in rhesus monkeys making them better understood models for osteoporosis and aging research. Sixty female and 56 male rhesus monkeys (4-34 yr.-) were studied for the above endpoints. Peak bone mass was achieved by approximately 10 yrs. of age in both groups. In males, there was a significant decline (p<0.001) with age (based on regression analysis) in bone mineral content (BMC) and density (BMD) of the lateral lumbar spine, femur and distal radius. In addition, bone turnover decreased with age. Using endocrine data and menstrual cyclicity, females were divided into 3 groups, growing (G, n=12), adult (A, n=31) and old (O, n=17). O animals were lower (p<0.05) than A animals in total body BMC, anterior-posterior spine BMD and proximal radius BMC and BMD. Osteocalcin, 25-hydroxyvitamin D and calcium levels were also significantly (p<0.05) lower in O compared to A animals. In addition, lumbar spine radiographs were taken to adjust for the effect of osteoarthritis on measurements of BMC and BMD. In males and females, there was a significant (p<0.001) increase in the incidence of spinal osteoarthritis with age. FUTURE DIRECTIONS We plan to continue using DXA, radiographs and markers of bone metabolism to better characterize the skeletal aging process in rhesus monkeys making them better understood models for osteoporosis research. KEY WORDS Osteoporosis, bone density, aging, bone metabolism, DXA

OBJECTIVE: To determine the effect of central and peripheral leptin administration on food intake and energy expenditure in rhesus monkeys. RESULTS Four adult rhesus monkeys, cannulated in the left lateral cerebral ventricle, were studied during all phases of the experiment. The animals were allowed continuous access to food and water throughout the experiment and 24-hour food intake was measured daily. Indirect respiration calorimetry was used to determine energy expenditure. In the first phase of the study, food intake was measured following intracerebro-ventricular (ICV) injections of vehicle or three doses (500 ng, 2 g, 22 g) of leptin. Leptin administration resulted in a dose dependent decrease in food intake (p<0.05). Food intake decreased by an average of 36% at 500ng, 33% at 2 g, and 54% at 22 g of leptin compared to placebo. Energy expenditure was also measured at 500 ng and 22 g ICV doses of leptin. Energy expenditure was not different (p>0.10) between placebo and leptin at either dose or at any period of the day. Considering the expected decrease in thermic effect of feeding with a decrease in intake, leptin may have resulted in a slight increase in energy expenditure of less than 10%. In the second phase of the experiment, food intake was measured following IV injection of 3 mg of leptin. In this case, leptin did not alter food intake, despite increasing serum leptin levels by as much as one hundred fold. These results suggest that leptin is a potent inhibitor of food intake in rhesus monkeys, but this effect requires elevation of leptin concentrations in the cerebrospinal fluid or critical brain sites. The transport system for movement of leptin across the blood-brain barrier may limit the influence of circulating leptin on food intake in rhesus monkeys. FUTURE DIRECTIONS We plan to apply the methods used in this experiment to continue investigating the role leptin and other central-acting peptides play in regulating food intake and energy expenditure. We also plan to test these compounds for efficacy in treating obesity. KEY WORDS leptin, obesity, food intake, energy expenditure

OBJECTIVE: To determine the effect of PNU-91325, an insulin sensitizer from the Thiazolidinedione chemical class, on insulin and glucose metabolism in mildly to moderately obese rhesus monkeys. RESULTS Six adult male rhesus monkeys (body weight > 13 kg) were used for the experiment. The monkeys were studied during the following successive two week periods Placebo 1, Low Dose (0.3 mg/kg/day), Intermediate dose (3 mg/kg/day), High dose 1 (30 mg/kg/day), High dose 2 (30 mg/kg/day), and Placebo 2. Each treatment period was followed by a two week washout period, except for High Dose 1 which was immediately followed by High Dose 2. During all phases of the experiment, food intake was measured daily and body weight was measured weekly. Meal tolerance tests, frequently sampled glucose tolerance tests with minimal model analysis, blood pressure, heart rate, and plasma triglyeride and cholesterol subfractions were measured at the end of each assessment period. Body weight was not significantly (p > 0.05) changed by drug treatment. Systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate were all decreased (p < 0.05) following the Intermediate dose phase when compared to the Placebo phases. These blood pressure and heart changes, however, disappeared at the High dose treatments. No treatment related differences in insulin, glucose, or lactate were noticed during the meal tolerance test. Plasma triglyerides and HDL triglycerides, were consistently elevated (p < 0.05) during the meal tolerance test in the Placebo 2 phase when compared to the drug treatment phases. Basal insulin, basal glucose, second phase insulin response to glucose, insulin response to tolbutamide, glucose disappearance rate, insulin sensitivity, and glucose effectiveness were not significantly (p > 0.05) altered by drug treatment. PNU-91325 either had no effect or transient effects on measures of blood pressure or insulin and glucose parameters. Plasma triglycerides were dramatically increased following cessation of drug treatment, however, additional research will be needed to determine if PNU-91325 plays any role in regulating plasma triglyeride levels. FUTURE DIRECTIONS We are continuing to test novel insulin sensitizing agents for efficacy in treating non-insulin dependent diabetes . KEY WORDS insulin, glucose, triglycerides, diabetes

Beneficial alterations in energy expenditure, glucose metabolism, and cardiovascular health could be major contributors to the life-extending action of dietary restriction. We have shown that dietary restriction causes significant change sin all three of these areas in rhesus monkeys. Long-term changes in one or more of these areas could be extremely important to the overall effect of this intervention. We hypothesize that dietary restriction causes sustained changes in energy expenditure, glucose metabolism, and cardiovascular health which contribute to the retardation of disease and aging. In this renewal, we plan to continue investigating the effect of aging and dietary restriction on composition, we plan to continue measuring changes in body lean and fat mass with aging and dietary body mass. This will be done using several techniques including anthropometrics, dual-energy x-ray absorptiometry (DXA), computer assisted tomography (CT) and isotope dilution. Specific Aim 2 is to determine the effect of dietary restriction of whole-animal energy expenditure. Energy expenditure will be measured by indirect respiration calorimetry using calorimetry chambers and the doubly labeled water method. The calorimetry experiments will provide estimates of resting energy expenditure, the themic effect of feeding, activity, and total energy expenditure. Body composition data will be used to normalized energy expenditure for comparison between groups and among individuals. In addition to calorimetry derived measurements of activity, motion detectors will be used for further quantification of physical activity. Specific Aim 3 is to elucidate the effect of dietary restriction on insulin sensitivity and other parameters of glucose regulation by Minimal Modeling and quantitation of insulin receptor abundance. Minimal Modeling is performed on data derived from a frequently sampled intravenous glucose tolerance test and insulin receptor abundance will be measured in biopsies of skeletal muscle. In Specific Aim 4, we will further examine the effects of dietary restriction on composition and properties of plasma LDL that may affect their proteoglycan-binding and thus their atherogenicity, using blood samples, and in vitro systems for assessment.

OBJECTIVE To determine the effect of dietary restriction on insulin and glucose metabolism in aging macaques with the use of frequently sampled intravenous glucose tolerance tests (FSIGT). Secondly, to perform a small pilot study on the feasibility of conducting radiolabeled euglycemic hyperinsulinemic clamp procedures in dietary restricted and ad libitum-fed aging monkeys. RESULTS Sixty-eight male and female rhesus macaques in three experimental groups were studied as part of an ongoing multidimensional study of the effects of aging and dietary restriction. One half of the animals in each group, with adequate supplemental micronutrients in their diets, have been energy restricted by 20-30%. Restricted (R) compared to ad libitum-fed control (C) monkeys in group 1 studied since 1989 exhibited lower fasting glucose and insulin levels, lower insulin responses, and higher insulin sensitivity indices as determined from minimal model analysis of the semi-annual FSIGT data. Similar results are seen between R and C monkeys in the younger group 2 males and group 3 females studied since 1994. A small pilot study was also conducted with a separate group of eight rhesus macaques using a radio-labeled euglycemic hyperinsulinemic clamp procedure to determine steady state hepatic glucose production, and hepatic and peripheral insulin sensitivity FUTURE DIRECTIONS We intend to continue to perform FSIGT procedures on an annual basis in these three groups. We will also expand the FSIGT protocol to include the use of a stable-labeled glucose isotope, which, while not substantially altering the current protocol, will enable us to model insulin and C-peptide data, and to determine hepatic glucose production. KEY WORDS dietary restriction; aging; glucose metabolism; insulin sensitivity FUNDING NIH P01 AG11915 PUBLICATIONS Gresl, T., Roecker, E., Havighurst, T., Baum, S., and Kemnitz, J. Chronic dietary restriction protects against insulin resistance and type 2 diabetes in adult rhesus monkeys. Diabetes 47(Suppl. 1) A310, 1998. Gresl, T., Cartee, G., Gazdag, A., Roecker, E., Colman, R., Baum, S., Mason, L., and Kemnitz, J. Dietary restriction protects against the development of type 2 diabetes in rhesus monkeys. FASEB Journal 12(4) A254 , 1998.

This conference grant (R13) application requests funds to partially cover the cost of planning, organizing, publicizing and hosting the 18th Annual Symposium on Nonhuman Primate Models for AIDS. The symposium will be held October 4-7, 2000 at the Monona Terrace Convention Center in Madison, Wisconsin and will be hosted by the Wisconsin Regional Primate Research Center (WRPRC), University of Wisconsin--Madison. This meeting has become the premier forum for the presentation and exchange of the most recent scientific advances in AIDS research utilizing the nonhuman primate model. The latest findings in pathogenesis, primate immunology, vaccines and therapeutics will be presented. It is anticipated that more than 300 scientists from the United States, Puerto Rico and other countries will attend. The symposium will encompass five consecutive half-day scientific sessions, each devoted to a different theme. These will be: (1) Vaccines and Therapeutics, (2) Immunology, (3) Virology, (4) Pathogenesis, and (5) Technology and Resources. Each session will have an invited Chair who will give a 30-minute state-of- the-art presentation to open the session and a Co-Chair, who will moderate the session and entertain questions. In addition, there will be an invited keynote speaker and banquet speaker to address scientific approaches and concerns regarding the global AIDS crisis and related issues of public health A Scientific Program Committee consisting of nine members will review abstracts and select those for Oral vs. Poster presentation for each of the five scientific sessions. Committee members will include leaders in the field from a variety of scientific disciplines and research institutions. Criteria for selection of oral presentations will include relevance of the topic as well as originality and quality of the information contained in the abstract. Those giving talks will be invited to submit their presentations in manuscript form for publication in the Journal of Medical Primatology. A poster session will include meritorious presentations that cannot be accommodated in one of the five platform sessions. The conference will also include an opening reception on the day of arrival (Wednesday, October 4, 2000), an evening poster session (Thursday, October 5, 2000) with accompanying reception and an evening banquet on Friday, October 6, 2000, with a topical speaker.

OBJECTIVE To determine the effect of dietary restriction on insulin and glucose metabolism in aging macaques with the use of frequently sampled intravenous glucose tolerance tests (FSIGT). Secondly, to perform a small pilot study on the feasibility of conducting radiolabeled euglycemic hyperinsulinemic clamp procedures in dietary restricted and ad libitum-fed aging monkeys. RESULTS Sixty-eight male and female rhesus macaques in three experimental groups were studied as part of an ongoing multidimensional study of the effects of aging and dietary restriction. One half of the animals in each group, with adequate supplemental micronutrients in their diets, have been energy restricted by 20-30%. Restricted (R) compared to ad libitum-fed control (C) monkeys in group 1 studied since 1989 exhibited lower fasting glucose and insulin levels, lower insulin responses, and higher insulin sensitivity indices as determined from minimal model analysis of the semi-annual FSIGT data. Similar results are seen between R and C monkeys in the younger group 2 males and group 3 females studied since 1994. A small pilot study was also conducted with a separate group of eight rhesus macaques using a radio-labeled euglycemic hyperinsulinemic clamp procedure to determine steady state hepatic glucose production, and hepatic and peripheral insulin sensitivity FUTURE DIRECTIONS We intend to continue to perform FSIGT procedures on an annual basis in these three groups. We will also expand the FSIGT protocol to include the use of a stable-labeled glucose isotope, which, while not substantially altering the current protocol, will enable us to model insulin and C-peptide data, and to determine hepatic glucose production. KEY WORDS dietary restriction; aging; glucose metabolism; insulin sensitivity FUNDING NIH P01 AG11915 PUBLICATIONS Gresl, T., Roecker, E., Havighurst, T., Baum, S., and Kemnitz, J. Chronic dietary restriction protects against insulin resistance and type 2 diabetes in adult rhesus monkeys. Diabetes 47(Suppl. 1) A310, 1998. Gresl, T., Cartee, G., Gazdag, A., Roecker, E., Colman, R., Baum, S., Mason, L., and Kemnitz, J. Dietary restriction protects against the development of type 2 diabetes in rhesus monkeys. FASEB Journal 12(4) A254 , 1998.

This conference grant application (R13) requests support for planning, organizing, publicizing, and hosting a special workshop entitled, "Nonhuman Primate Models of Aging: Their Current Status and Future Potential." The workshop will be held May 31-June 1, 2001, at the Monona Terrace Convention Center in Madison, Wisconsin, and will be hosted by the Wisconsin Regional Primate Research Center (WRPRC), University of Wisconsin-Madison. The workshop will be held as a satellite event to the 30th annual meeting of the American Aging Association (AGE) to be convened June 2-4, 2001, at the same location. The AGE meeting will also include a special meeting and presentations by grantees of the American Federation for Aging Research (AFAR). The objective of the workshop proposed herein is to promote an exchange of information among researchers who use various species of nonhuman primates to model age-related disease and functional decline. The meeting will be organized across 1.5 days. On the afternoon of May 31, the session will consist of presentations on microcebus (Microcebus murinus), marmosets (Callithrix jacchus), squirrel monkeys (Saimiri sciureus), cynomolgus monkeys (Macaca fascicularis), baboons (Papio hamadryas), and chimpanzees (Pan troglodytes). A working dinner will be held on the evening of May 31. Because the vast majority of research in this area has been conducted in rhesus monkeys (Macaca mulatta), the entire second day will focus exclusively on studies using this species- The morning session will include presentations on reproductive, cardiovascular, and sensory function, the skeletal system, sarcopenia, oxidative stress, glucose regulation and diabetes. The afternoon session on June 1 will focus on neurobiological and behavioral studies of aging rhesus monkeys. A poster session will be held on the evening of June 1. Research concerning nonhuman primate models of aging has shown marked growth over the last decade. Continued progress requires cooperative and integrative approaches, because the relatively long lives of primates increase the time, as well as increase the cost, required for longitudinal studies. This workshop will permit investigators to learn about the research of others in the area and to engage in productive discussion, and it will promote collaborative studies. Holding the workshop as a satellite to the AGE meeting will provide extra benefits. Members of the workshop will be encouraged to attend the AGE meeting to learn about broad areas of gerontological research that might be relevant to their nonhuman primate studies. In addition, scientists planning to attend the AGE meeting will be invited to attend the workshop to learn about the growing value of nonhuman primates for gerontological research. The location in Madison is also beneficial because it will permit the dozens of scientists and students at the University of Wisconsin and the WRPRC who are interested in aging research to attend the workshop. A final objective of the workshop is to provide attendees information on the development of the Primate Aging Database (PAD), which is a joint project of the WRPRC, the National Center for Research Resources, and the National Institute on Aging. Attendees will be given a demonstration of the software for PAD and will be encouraged to participant in the project.

Aging; Animals; Appetite; Appetitive Behavior; CRISP; Caloric Intake; Computer Retrieval of Information on Scientific Projects Database; Desire for food; Developed Countries; Developed Nations; Developing Countries; Developing Nations; Diet; Energy Intake; Epidemic; Fats; Fatty acid glycerol esters; Feeding behaviors; Food Intake Regulation; Funding; Grant; Health; Healthcare Systems; Industrialized Countries; Industrialized Nations; Ingestive Behavior; Institution; Investigators; Less-Developed Countries; Less-Developed Nations; Macaca mulatta; Maintenance; Maintenances; Mammals, Primates; Modeling; NIH; National Institutes of Health; National Institutes of Health (U.S.); Obesity; Peptides; Peripheral; Primates; Research; Research Personnel; Research Resources; Researchers; Resources; Rhesus; Rhesus Macaque; Rhesus Monkey; Searching Behavior; Senescence; Services; Source; Substance administration; Systems, Health Care; Testing; Third-World Countries; Third-World Nations; Under-Developed Countries; Under-Developed Nations; United States National Institutes of Health; adiposity; caloric dietary content; corpulence; corpulency; corpulentia; feeding-related behaviors; nutrient intake activity; obese; obese people; obese person; obese population; senescent

disease /disorder model; AIDS; Primates; animal colony;

Primates; animal colony;

DESCRIPTION (Adapted from the applicant's abstract): Non human primates (NHPs) are essential in the study of genetic factors that influence susceptibility to AIDS, as well as other multifactorial diseases, such as cancer, osteoporosis, hypertension, atherosclerosis and psychological disorders. The ability to control genetic and environmental factors in captive NHP populations provides a powerful means for quantifying the influence of each on risk factors and outcomes of complex diseases. Use of ART will result in the production of completely MHC-defined and genetically identical macaques. The utility of MHC-defined and genetically identical animals in relevant viral challenge models would be enormous and have tremendous specific impact on the ability to assess vaccine efficiency, as well as having tremendous general implications for biomedical research and human health. In Specific Aim #1, the investigators will use blastomere biopsy and PCR in conjunction with in vitro fertilization (IVF) and selective embryo transfer, to produce approximately 150 MHC-defined offspring over the five year study period. In Specific Aim #2, they will develop strategies and techniques for the production of pairs or multiple sets of genetically identical monkeys by blastomere separation and will use these techniques to produce sets of age- matched, genetically identical MHC-defined monkeys. In Specific Aim #3, they will determine the optimal method of oocyte activation for production of developmentally competent rhesus monkey embryos by nuclear transfer, and use markers of nucleolar transcription and totipotency to determine whether incomplete nuclear reprogramming is a common feature of rhesus monkey embryos reconstituted with somatic cell nuclei. These advances will be crucial to the development of cloning technologies in the rhesus macaque. The investigators plan to develop a prototypic animal production program that will be central to the future of the Regional Primate Centers. MHC-defined animals produced using these techniques will complement recent developments in tetramer and ELISPOT technologies in rhesus macaques and provide valuable animals for AIDS vaccine research. Additionally, genetically identical macaques will have general utility in biomedical research, especially to the neuroscience community.

AIDS; Abscission; Accounting; Accounts Payable; Acquired Immune Deficiency; Acquired Immune Deficiency Syndrome; Acquired Immuno-Deficiency Syndrome; Acquired Immunodeficiency Syndrome; Aging; Agreement; Animal Experimental Use; Animal Experimentation; Animal Research; Animals; Applications Grants; Appointment; Area; Articulation; Asbestos; Assay; Award; Back; Bioassay; Biologic Assays; Biological Assay; Businesses; CRISP; Career Ladders; Caring; Categories; Certification; Charge; Class; Collaborations; Complex; Computer Retrieval of Information on Scientific Projects Database; Construction; Contracting Opportunities; Contracts; Data; Development; Documentation; Dorsum; Economic Income; Economical Income; Education; Educational aspects; Electronics; Employee; Equilibrium; Equipment; Equipment and supply inventories; Excision; Extirpation; Facility Construction; Facility Construction Funding Category; Facility Designs; Feedback; Financial Management; Flexibility; Floor; Funding; Future; Gays; Goals; Grant; Grant Proposals; Grants, Applications; Health Planning; Holidays; Human Resources; Hydrogen Oxide; IACUC; Immunologic Deficiency Syndrome, Acquired; Income; Individual; Information Technology; Infrastructure; Institution; Institutional Animal Care and Use Committee; Insurance, Life; Interdisciplinary Research; Interdisciplinary Study; Internet; Inventory; Investigators; Joints; Journal Article; Journal Article (PT); Journal Article [Publication Type]; Journals; Ladders, Career; Lead; Learning; Life Insurance; Light; Linguistic; Linguistics; Link; Long-Term Care; Macaca; Macaque; Magazine; Maintenance; Maintenances; Manpower; Manuals; Manufacturer; Manufacturer Name; Medical; Mentors; Modeling; Modification; Monitor; Monkeys; Movement; Multidisciplinary Collaboration; Multidisciplinary Research; NCRR; NIH; National Center for Research Resources; National Institutes of Health; National Institutes of Health (U.S.); Occupational activity of managing finances; On-Line Systems; Online Systems; Operation; Operative Procedures; Operative Surgical Procedures; Oral health; Organization Charts; Paint; Pathology; Pattern; Pb element; Pensions; Personal Satisfaction; Photoradiation; Plants; Plants, General; Plastics; Pliability; Plumbing; Position; Positioning Attribute; Pressure; Pressure- physical agent; Price; Principal Investigator; Process; Programs (PT); Programs [Publication Type]; Publications; R01 Mechanism; R01 Program; RPG; Recruitment Activity; Removal; Reporting; Research; Research Grants; Research Infrastructure; Research Personnel; Research Project Grants; Research Projects; Research Projects, R-Series; Research Resources; Research Support; Researchers; Resources; Retirement Benefits; Running; SCHED; Schedule; Schools; Scientific Publication; Senescence; Series; Services; Site; Solutions; Source; Staging; Structure; Students; Study, Interdisciplinary; Summary Reports; Surgical; Surgical Interventions; Surgical Procedure; Surgical Removal; System; System, LOINC Axis 4; Terminology; Testing; Time; Training; Training Programs; Translations; Tube; United States National Institutes of Health; Universities; Vendor; WWW; Water; Wisconsin; Work; animal care; animal resource; balance; balance function; body movement; college; court; day; dental health; design; designing; extended care; fiberglass; glass fibers; heavy metal Pb; heavy metal lead; improved; income insurance; instrument; journal article; member; online computer; organizational structure; personnel; pressure; pricing; programs; recruit; repair; repaired; resection; senescent; skills; surgery; tool; web; web based; well-being; world wide web

Coordinated Information Services for Primate Research The National Primate Research Center, University of Wisconsin-Madison, will work cooperatively with the National Center for Research Resources (NCRR), National Primate Research Centers (NPRC's) to coordinate information services and resourcesto more effectivelyserve researchers and staff of the NPRC's, and to promote resource sharing. The Wisconsin NPRC Library in partnership with the other NPRC libraries will 1) coordinate collections, resources and services where possible, 2) promote the rapid sharing of information among the NPRC's through electronic transfer of documents, 3) provide access to the unique NPRC library collections through participation in local, regional, and national interlibrary loan consortia, 4) continue to support and enhance the PrimateLit database (available via the Web), 5) continue developing Primate Info Net (PIN), the central Internet resource and repository of information relevant to primatology, and 6) share the research and educational expertise of NPRC staff with the scientific community and the general public. Collectively the libraries and PIC are able to effectively meet the needs of staff and researchers at all eight of the NPRC's, while being more efficient in managing scarce resources. PIN continues to be the primary building block supporting the coordination of services, functioning as a gateway and central resource. Through its support, NCRR will continue to realize more uniform availability of services and resources across the NPRC's. NCRR will solidify its essential role, much like the National Library of Medicine, as a provider of information not only to the scientists associated with the NPRC's, but also the biomedical community and members of the general public.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Associate Director for Research Services oversees activities in the Primate Center's five service units. As [unreadable] always, the organization and presence of different Units continues to be dynamic, and responsive to the needs of [unreadable] the investigators and cutting edge science. In 2005 the five Units consisted of Assay, Genetics, Pathology, Virology [unreadable] and Immunology, and Centralized Protocol Implementation (CPI) Services. The CPI Service Unit continues to [unreadable] expand and refine its operations. The Pathology Unit's confocal system with 4 visible light lasers and the pulsed near [unreadable] infrared laser for multiphoton excitation is being increasingly utilized by stem cell investigators and developmental [unreadable] biologists as well as AIDS investigators.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To 1) develop strategies for creating genetically identical monkeys using blastomere separation and 2) propagate a family of MHC-defined monkeys using assisted reproductive technologies. Genetically identical and MHC-defined monkeys would be extremely valuable models for biomedical studies of human disease. Progress early in the project was hampered by limited numbers of appropriate female rhesus monkeys for assignment. During the last reporting period, however, with a no cost extension of the grant, remarkable progress in the refinement of techniques was accomplished. There have been several successful transfers of split embryos with pregnancies in progress. This research used WNPRC Animal Services. Note: AIDS related

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: The primary objectives of the SIV program at the Wisconsin National Primate Research Center (WNPRC) are to understand the attributes of effective anti-immunodeficiency virus immune responses, develop novel AIDS vaccines, and expand the HIV animal model to include the unique genetic attributes of cynomolgus macaques (Macaca fasicularis) from Mauritius. The WNPRC is experiencing a critical shortage of animal housing which will directly affect continued advances in AIDS research. Our current SIV housing facility is near capacity and will be insufficient for our long-term housing needs. Inadequate housing will soon become a limiting factor when designing new studies. We currently have space for 120 SIV-infected macaques, and animals on active studies occupy 82 of those spaces. A conservative estimate of the number of additional animals needed in 2008 using funding already in place is 142. This estimate does not include large studies where pending funding could push this number well beyond 250 animals. The primary goal of this G20 grant proposal is to renovate an existing specimen storage area, which is adjacent to the existing SIV housing area, into three new animal housing rooms. Funding is also requested for sufficient caging and an automatic watering system to equip these new animal rooms. Completing this renovation will provide the critical space necessary for the SIV program to expand at the WNPRC and for the investigators to continue their ground-breaking research. The planning phase has been completed and renovation is now underway.

AIDS; Acquired Immune Deficiency; Acquired Immune Deficiency Syndrome; Acquired Immuno-Deficiency Syndrome; Acquired Immunodeficiency Syndrome; Advisory Committees; Aging; American; Animal Experimental Use; Animal Experimentation; Animal Research; Animal Rights; Animals; Appointment; Assay; Award; Bioassay; Biochemistry; Biologic Assays; Biological Assay; Biology; Biotechnology; Booklets; Brochures; CRISP; Caloric Restriction; Cells; Chemistry, Biological; Chicago; China; Clinical and Translational Science Awards; Communication; Communities; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; District of Columbia; ES cell; Electronics; Employee; Endowment; Female Health; Florida; Foundations; Funding; Generalized Growth; Genetic; Genomics; Goals; Grant; Growth; Hand; Head; Health; Health Care Research; Health Services Evaluation; Health Services Research; Healthcare Research; Housing; Human; Human, General; Idiopathic Parkinson Disease; Immunologic Deficiency Syndrome, Acquired; Informatics; Infrastructure; Institutes; Institution; International; Investigators; Jobs; Kinetic; Kinetics; Knowledge; Laboratories; Learning; Lewy Body Parkinson Disease; Mainland China; Mammals, Primates; Man (Taxonomy); Man, Modern; Medical Care Research; Mother Cells; NCI Director; NCI Office of the Director; NCRR; NIH; National Center for Research Resources; National Institutes of Health; National Institutes of Health (U.S.); Neurobiology; News; News (PT); News [Publication Type]; Newsletter; Nutrition; Nutritional Science; Occupations; Office of the Director; Pamphlets; Paralysis Agitans; Parkinson; Parkinson Disease; Parkinson's; Parkinson's disease; Parkinsons disease; Pathology; Personal Satisfaction; Physiologic; Physiological; Posters; Posters [Publication Type]; Primary Parkinsonism; Primates; Printing; Professional Postions; Progenitor Cells; Programs (PT); Programs [Publication Type]; QOL; Quality of life; Regenerative Medicine; Reporting; Research; Research Infrastructure; Research Personnel; Research Resources; Researchers; Resources; Review Committee; Schools; Science; Science of nutrition; Senescence; Services; Site; Site Visit; Societies; Source; Stem Cell Research; Stem cells; Task Forces; Technology; Tissue Growth; Training; United States National Institutes of Health; Universities; Visit; Washington, D.C.; Washington, DC; Wisconsin; Women's Health; Wood; Wood material; Work; animal care; base; calorie restriction; career; conference; diabetes; embryonic stem cell; improved; interest; member; neurobiological; news; non-human primate; nonhuman primate; nutrition; ontogeny; outreach; outreach program; posters; programs; senescent; services research; stem cell of embryonic origin; symposium; well-being

Access to Information; Address; Arts; Behavior; Bibliography; CRISP; Caribbean; Caribbean Sea Region; Caribbean natives; Caribbean region; Collaborations; Collection; Communities; Computer Retrieval of Information on Scientific Projects Database; Copyright; Data Banks; Data Bases; Databank, Electronic; Databanks; Database, Electronic; Databases; Deep; Depth; Development; Ecology; Electronic library; Environmental Science; Funding; Geographic Area; Geographic Locations; Geographic Region; Geographical Location; Grant; Image; Information Centers; Information Services; Institution; International; Internet; Investigators; Libraries; Link; Mammals, Primates; MeSH Descriptors Class 4; Morphology; NCRR; NIH; Names; National Center for Research Resources; National Institutes of Health; National Institutes of Health (U.S.); Natural History; Primates; Publications; Research; Research Personnel; Research Resources; Researchers; Resources; SIS; Scientific Publication; Scientist; Services; Sister; Site; Source; System; System, LOINC Axis 4; Taxonomy; Taxonomy, General; United States National Institutes of Health; Update; WWW; West Indies Region; career; clinical data repository; clinical data warehouse; data repository; digital; geographic site; imaging; indexing; outreach; outreach to information; relational database; web; world wide web

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To test efficacy and assess possible side effects of stem cell based therapies before proceeding to human trials. This service began in July 2007, with the launch of the new UW-Madison Stem Cell &Regenerative Medicine Center. Projects to develop cell replacement therapies may require that researchers implant stem cells into nonhuman primates to test efficacy and assess possible side effects before proceeding to human trials. In this context, nonhuman primates will be made available through the Nonhuman Primate Services core at the Wisconsin National Primate Research Center. Specific services include the provision of appropriate monkeys and primate tissue for projects, specialized animal husbandry, assistance with procedures such as surgeries and clinical assessments of monkeys, appropriate terminal procedures and preparation of tissues for analysis, and provision of specialized instruments.

AIDS; Acquired Immune Deficiency; Acquired Immune Deficiency Syndrome; Acquired Immuno-Deficiency Syndrome; Acquired Immunodeficiency Syndrome; Adopted; Applications Grants; CRISP; California; Collaborations; Communities; Computer Retrieval of Information on Scientific Projects Database; Consensus; Data; Data Banks; Data Bases; Databank, Electronic; Databanks; Database, Electronic; Databases; Development; Educational workshop; Environment; Focus Groups; Funding; Grant; Grant Proposals; Grants, Applications; Hand; IT Systems; Image; Immunologic Deficiency Syndrome, Acquired; Informatics; Information Services; Information Systems; Information Technology Systems; Institution; Internet; Investigators; Journal Article; Journal Article (PT); Journal Article [Publication Type]; Libraries; Mammals, Primates; Mission; Modeling; NCRR; NIH; National Center for Research Resources; National Institutes of Health; National Institutes of Health (U.S.); Ontology; Oregon; Pathologist; Pathology; Play; Primates; Process; Publications; Research; Research Activity; Research Personnel; Research Resources; Researchers; Resources; Role; SNOMED CT; SNOMED Clinical Terms; Scientific Publication; Services; Site Visit; Slide; Source; Strategic Planning; Support of Research; System; System, LOINC Axis 4; Systems, Data; Time; Training; United States National Institutes of Health; Vocabulary; Vocabulary Words; WWW; Wisconsin; Work; Workshop; clinical data repository; clinical data warehouse; conference; data repository; imaging; journal article; non-human primate; nonhuman primate; outreach; prototype; relational database; social role; symposium; tool; virtual; web; world wide web

DESCRIPTION (provided by applicant): The proposed project will establish a comprehensive web portal into Information pertaining to the use on nonhuman primates (NHR) in biomedical and translational research. The types of information to be linked through this "PrimatePortal" will include publicly funded resources providing access to the NHP themselves, as well as methods and facilities for specialized characterization of the animals in a research context. PrimatePortal will also provide links describing particular NHP models for human health and disease, tissue and DNA banks for NHP material and bibliographic data on previous research. In the first year of the project the emphasis will be on organizing and linking information pertaining to HIV/AIDS research, such as availability of specific pathogen-free NHP, resources for virological and immunologic testing, specialized reagents and other testing services, and funding opportunities for this research. In the second and third years the scope of PrimatePortal will be expanded to other areas of research, such as other infectious diseases, reproduction and development (including stem cells and regenerative medicine), aging, metabolic diseases, and neurosciences and behavioral research. The current activities of the Working Groups in the consortium of National Primate Research Centers (NPRCs) will be incorporated into PrimatePortal. The proposed work builds on initiatives in information technology and provision of information services, as well as data sharing and adoption of best practices, promoted by the Wisconsin National Primate Research Center in collaboration with other NPRCs and NCRR-supported NHP resources, as well as new programs through linkage with Clinical and Translational Science Institutes. PUBLIC HEALTH RELEVANCE (provided by applicant): The proposed project will facilitate the process of basic biomedical and translational research by enhancing the availability of information regarding the investigational use of nonhuman primates (NHP). Through the use of PrimatePortal, researchers will be able to acquire critical information regarding the appropriateness, availability and performance of studies benefiting from the use of NHP models.

Basic biomedical research is supported by the NIA through several programs that require animal models of the aging process. These programs include immunology, endocrinology, pharmacology, neurobiology, muscle physiology, behavior, genetics, and nutrition. Aged non-human primates (NHP) are an important model for determining how research findings from experiments in lower organisms translate to human biology and aging. From genetic, physiological and behavioral perspectives, NHP are our closest relatives in the animal world, making them a valuable tool in biomedical research. There are many drawbacks to using NHP in research. The availability of NHP is limited and NHP are expensive to obtain and to house. And there is strong public sentiment to reduce the number of NHP used in biomedical research. The Non-human Primate Tissue Bank allows investigators to make use of NHP biospecimens at relatively little cost, and provides a mechanism for multiple investigators to share tissue from a single animal, allowing more studies to be carried out with existing resources.

This is a searchable database developed to allow analysis of age-related traits in non-human primates (NHP). Currently, the database contains data from 20 species at 11 different institutions, comprising over 3000 individual animals and 500,000 data points. About 80% of the data is from rhesus monkeys. Current data fields are primarily lifespan, body composition parameters, and blood chemistry parameters, although addition of other parameters is possible. The PAD is useful for analyses of species differences in normal aging processes, studies on biomarkers of normal aging and age-related pathologies, and determination of baseline levels in geriatric NHP colonies.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To develop and maintain and aged nonhuman primate tissue bank. The objective of the Aged Non-human Primate Tissue Bank is to acquire, archive and distribute excess tissue from nonhuman primates that are being euthanized for research purposes at institutions around the country. Tissue will be both flash-frozen without fixation or fixed and embedded, to fit the needs of a wide-range of molecular and histochemical techniques.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To develop and maintain an aged nonhuman primate tissue bank. The objective of the Aged Non-human Primate Tissue Bank is to acquire, archive and distribute excess tissue from nonhuman primates that are being euthanized for research purposes at institutions around the country. Tissue are both flash-frozen without fixation or fixed and embedded, to fit the needs of a wide-range of molecular and histochemical techniques.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To develop and manage a database of primate biomarkers of aging to improve collaborative research on the biology of healthy aging in nonhuman primates. This project was jointly initiated by NIA, National Center for Research Resources (NCRR), and the WNPRC, and continues under contract from the NIA. The internet Primate Aging Database (iPAD) is a multi-center, relational database of biological variables in aging, captive nonhuman primates. The database included nearly 900,000 data points on 17 species at nine facilities during the 2008-2009 reporting period: the database now includes information from 13 facilities. An invaluable research, veterinary and clinical resource, iPAD features biomarkers on body weight, blood chemistry and hematology. This research used WNPRC Aging Resources and IT Services.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To develop a new web portal to assist researchers working with nonhuman primates. The Wisconsin National Primate Research Center (WNPRC) announced in February 2011 the release of Primate Portal, a new website that provides information for biomedical researchers who work, or plan to work, with the nonhuman primate as a human disease model. When a researcher is preparing to move to nonhuman primates from a smaller animal model, he or she can find it challenging to identify appropriate funding resources, collaborators, animal colonies and testing facilities. The Primate Portal website contains detailed information about programs and facilities funded by the National Institutes of Health, including the eight National Primate Research Centers, to aid researchers in finding the resources they need. The Primate Portal may be customized by the user to provide current information regarding funding opportunities, research articles, meetings and news stories in a specific research area. The Primate Portal also contains hundreds of links to other organizations engaged in biomedical research, categorized by disease model, described with abstracts, and searchable through an in-depth assignment of metadata terms. Researchers interested in primate research are invited to visit the Primate Portal at http://www.primateportal.org/ and create a user account at no cost. For more information, contact Dr. Joseph Kemnitz, WNPRC, kemnitz@primate.wisc.edu, (608) 263-3588 or Ray Hamel, Jacobsen Library, WNPRC, hamel@primate.wisc.edu, (608) 263-3512.

Basic biomedical research is supported by the NIA through several programs that require animal models of the aging process. These programs include immunology, endocrinology, pharmacology, neurobiology, muscle physiology, behavior, genetics, and nutrition. Aged non-human primates (NHP) are an important model for determining how research findings from experiments in lower organisms translate to human biology and aging. From genetic, physiological and behavioral perspectives, NHP are our closest relatives in the animal world, making them a valuable tool in biomedical research. There are many drawbacks to using NHP in research. The availability of NHP is limited and NHP are expensive to obtain and to house. And there is strong public sentiment to reduce the number of NHP used in biomedical research. The Non-human Primate Tissue Bank allows investigators to make use of NHP biospecimens at relatively little cost, and provides a mechanism for multiple investigators to share tissue from a single animal, allowing more studies to be carried out with existing resources.

This will provide a new research resource to many investigators and contribute to a reduction in the number of NHP needed by the research community since multiple investigators will be able to take advantage of each animal. The tissue will allow investigators to test hypotheses in a model closely related to humans by providing access to NHP tissue without the expense of obtaining and housing the animals. This is an extremely important aspect of this project, as the supply of NHP in general, and rhesus macaques in particular, is very limited. The tissues will be collected under strictly controlled protocols to ensure the integrity of the tissue. Tissue will be flash-frozen without fixation or fixed and embedded, to fit the needs of a wide-range of molecular and histochemical techniques.