The Baboon in Biomedical Research (eBook)

Preface 7
Contents 9
Contributors 11
Introduction 16
The Development and Status of the Baboon Genetic Linkage Map 23
Introduction 23
Early Linkage Studies in Macaques and Baboons 23
Initial Studies of Microsatellite Polymorphisms in Nonhuman Primates 24
Development of the Baboon Whole Genome Linkage Map 25
Current Status of the Baboon Linkage Map 26
Locating Quantitative Trait Loci Using the Baboon Linkage Map 37
Future Directions for Research 38
The Study of Captive Baboon Behavior 42
Introduction 42
A Primer on Baboon Behavior 43
Behavioral Measures of Baboons in Biomedical Research 43
The Study of Behavior 45
Behavioral Management of Captive Baboons 47
Spontaneous Pathology of Baboons 56
Introduction 56
Integumental System 63
Alimentary System 64
Genitourinary System 65
Central Nervous System 66
Musculoskeletal System 66
Hematopoietic and Lymphoid Systems 67
Cardiovascular System 68
Respiratory System 68
Endocrine System 69
Growth and Development of Baboons 77
Introduction 77
Materials and Methods 78
2.1 Materials 78
2.2 Methods 79
Results 82
3.1 General Features of Growth 82
Growth Curves 92
4.1 Body Mass 92
4.2 Body Surface Area 92
4.3 Head Dimensions 94
4.4 Other Axial Dimensions 94
4.5 Limb Dimensions 99
4.6 Testes Volume 102
Discussion 102
5.1 Growth Patterns 102
5.2 Growth Spurts 104
Conclusions 105
Reproductive Biology of Baboons 109
Introduction 109
Social Structure and Life History in Relation to Reproduction 109
Female 113
3.1 Reproductive Anatomy 113
3.2 Reproductive Physiology 116
3.3 Menopause 120
Male 121
4.1 Reproductive Anatomy 121
4.2 Reproductive Physiology 123
Potential of the Baboon as a Model for Studies of Human Reproductive Biology 125
Microbiology of Captive Baboons 131
Introduction 131
Bacterial Infections 131
2.1 Mycobacterium 131
2.2 Streptococcus 132
2.3 Staphylococcus 133
2.4 Shigella 133
2.5 Salmonella 134
2.6 Clostridium 135
2.7 Klebsiella 136
2.8 Bordetella 136
2.9 Pasteurella 136
2.10 Francisella 136
2.11 Campylobacter 137
2.12 Helicobacter 137
2.13 Yersinia 137
2.14 Pseudomonas 138
2.15 Nocardia 138
Parasitology 138
3.1 Arthropods 139
3.2 Cestodes 139
3.3 Nematodes 140
3.3.1 Intestinal Nematodes 140
3.3.2 Filarid Nematodes 140
3.4 Protozoa 141
3.4.1 Enteric Protozoans 141
3.4.2 Hemoprotozoans 142
3.5 Trematodes 142
Viruses 142
4.1 Herpesviruses 143
4.1.1 Alpha-Herpesviruses 144
4.1.2 Beta-Herpesviruses 145
4.1.3 Gamma-Herpesviruses 146
4.2 Retroviruses 147
4.2.1 Simian Foamy Virus 147
4.2.2 Simian T Cell Lymphotropic Virus 147
4.2.3 Endogenous Retroviruses 148
4.2.4 Simian Immunodeficiency Virus 149
4.3 Papovaviruses 150
Summary 150
Baboon Model for Endometriosis 159
Introduction 159
1.1 Why Is There Limited Progress in Endometriosis Research? 159
Advantages of the Baboon Model for the Study of Endometriosis 160
Development of the Baboon as a Model for Research in Endometriosis (Institute of Primate Research, Nairobi, Kenya) 162
3.1 Prevalence of Macroscopic and Microscopic Endometriosis in Baboons 162
3.2 Prevalence of Spontaneous Retrograde Menstruation in Baboons 163
3.3 Pathogenesis of Endometriosis: Retrograde Menstruation 163
3.3.1 Experimental Retrograde Menstruation 163
3.3.2 Intraperitoneal Transplantation of Menstrual Endometrium 164
3.3.3 Menstruation, Transplantation, and Inflammation 164
3.3.4 Conclusion 165
3.4 Pathogenesis of Endometriosis: Immunological Aspects 166
3.4.1 White Blood Cell Populations in Peritoneal Fluid and Peripheral Blood 166
3.4.2 High-Dose Immunosuppression and Development of Endometriosis 167
3.5 Spontaneous Evolution of Endometriosis in Baboons 167
3.6 Endometriosis and Subfertility 168
3.7 Endometriosis, Subfertility, and the Role of the Luteinized Unruptured Follicle Syndrome 169
3.7.1 Re-epithelialization of Ovulation Stigma in the Early Luteal Phase 169
3.7.2 Luteinized Unruptured Follicle Syndrome 169
3.8 Baboon as a Preclinical Model for Prevention and Treatment of Endometriosis 170
Conclusion 172
The Baboon in Embryology and Teratology Research 177
Introduction 177
Embryology 178
2.1 Nervous System (Stages 8--16) 178
2.2 Eye (Optic Vesicle, Stages 10--23) 180
2.3 Ear (Otic Vesicle, Stages 10--23) 181
2.4 Nose/Palate (Stages 12--23) 181
2.5 Urinary Tract Development 182
2.6 Limb Development 182
2.7 Development of the Placenta 183
2.8 Comparative Features 183
2.9 Spontaneous Incidence of Prenatal Loss 186
Teratology 186
3.1 Thalidomide 187
3.2 Sex Hormones 187
3.3 Triamcinolone Acetonide 189
3.4 Bendectin ® 189
3.5 Rubella Virus 190
3.6 Comparative Features 191
3.7 Protocols for Safety Evaluation 192
3.8 Spontaneous Malformations 192
Baboon Models for Neonatal Lung Disease 199
Introduction 199
Primate Neonatal Lung Research 200
2.1 Fetal Lung Development 200
2.1.1 Stages of Lung Development 200
2.1.2 Vasculogenesis 200
2.1.3 Bombesin-Like Protein 201
2.1.4 Extracellular Matrix 202
2.2 Hyaline Membrane Disease 202
2.2.1 Early Model Development 202
2.2.2 Surfactant Metabolism and Replacement 203
2.2.3 Nitric Oxide Metabolism 205
2.2.4 Antioxidants and Free Oxygen Radicals 205
2.3 Bronchopulmonary Dysplasia 206
2.3.1 140-day Model ("Old BPD") 206
2.3.2 125-day Model ("New" BPD) 207
2.3.3 Infection 208
2.4 Interventional Studies 208
2.4.1 High-Frequency Ventilation 208
2.4.2 Inhaled Nitric Oxide 210
2.4.3 Superoxide Dismutase Mimetic 210
2.4.4 Hypoxia-Inducible Factor (HIF) 210
2.4.5 Nasal CPAP 211
Cardiopulmonary Aspects of Neonatal Lung Disease 211
3.1 Patent Ductus Arteriosus (PDA) 211
3.1.1 Closure of the Ductus Arteriosus 211
3.1.2 Cardiopulmonary Effects of PDA 212
3.1.3 Surgical/Medical Closure of the PDA 213
3.2 Cardiac Function 214
Brain Development and Injury in the Premature Baboon Model For Lung Disease 214
4.1 MRI and Histology 217
4.2 Brain Activity 217
Summary 218
The Baboon Model for Dental Development 226
Introduction 226
Development of the Dental Formula 227
Development of Tooth Crown Morphology 229
Tooth Crown Mineralization 232
Dental Eruption Schedule 233
Conclusions 235
Baboon Model for Dyslipidemia and Atherosclerosis 243
Introduction 243
Atherosclerosis in Baboons 243
2.1 Pathology of Atherosclerosis 244
2.2 Experimental Atherosclerosis 244
Genetic and Dietary Effects 244
3.1 High-Density Lipoproteins (HDLs) 245
3.1.1 Genetic Effects 245
3.1.2 Diet Effects 245
3.2 Low-Density Lipoproteins (LDLs) 246
3.2.1 Genetic Effects 246
3.2.2 Diet Effects 246
3.3 Lipoprotein (a) 'Lp(a)' 247
3.3.1 Genetic Effects 247
3.3.2 Diet Effects 248
3.4 Oxidative Damage 248
3.4.1 Genetic Effects 248
3.4.2 Diet Effects 248
3.5 Endothelial Cell Damage 249
3.5.1 Endothelial Cell Responses to Cytokines 249
3.5.2 Endothelial Cell Responses to Atherogenic Diet 250
Conclusion 250
Baboon Model for the Study of Nutritional Influences on Pregnancy 255
Introduction 255
The Need for a Nonhuman Primate Model to Study the Effects of Undernutrition in Pregnancy 257
Design and Implementation of a System to Control Dietary Intake of the Pregnant Baboon 257
3.1 Description of the Group Housing System 259
3.2 Formation of Stable Groupings 259
3.3 General Observations 260
3.4 Diet 260
3.5 Training for Individual Feeding 260
3.6 Weight Measurements and Food Consumption Over the First 60 Days 261
3.7 Dominance Testing 261
3.8 Association of Dominance Rank and Feeding Behaviors and Food Intake 264
3.9 Other Procedures that Can Be Conducted with This System 266
Effects of Alteration of Feed Intake During Pregnancy 266
4.1 Maternal Physical Activity 266
4.2 Maternal and Fetal Morphometry 266
4.3 Development of Fetal Organs 267
Summary 268
Baboon Model for Infant Nutrition 272
Introduction 272
Nutritional Studies with Premature Baboons 272
Nutritional Studies During the Preweaning Period 273
3.1 Long-Chain Fatty Acid Accretion in the Brains of Neonatal Baboons 273
3.2 Responses to Dietary Fat and Cholesterol in Infancy 274
3.3 Neonatal Responses to Caloric Intake 275
Studies of Neonatal Nutritional Programming 276
4.1 Long-Term Effects of Infant Diet on Cholesterol Homeostasis and Thyroid Hormones 276
4.2 Long-Term Effects of Caloric Intake on Obesity 277
Experimental Malnutrition 279
Conclusion 279
Baboon Model for Ingestive Behaviors 282
Introduction 282
Approach 282
Background 283
3.1 Stress Hormones and Restraint Stress 285
3.2 Brain Angiotensin and Brain Sodium 290
Achievements and Perspectives 297
Baboon Model for Alcoholic Liver Disease: 1973-2003 301
Introduction 301
Model of Alcoholic Liver Disease in the Baboon 302
2.1 Alcohol-Containing Baboon Liquid Diet 302
2.2 Animals Used and Lesions Produced 304
2.3 Summary 307
Special Studies 307
3.1 Prevention of Alcoholic Liver Cirrhosis by Supplementation with Polyenylphosphatidylcholine 307
3.2 Effects of Ethanol and Polyenlyphosphatidylcholine on Hepatic Phosphatidylethanolamine Methyltransferase Activity 309
3.3 Impaired Oxygen Utilization: A New Mechanism for the Hepatotoxicity of Ethanol 310
3.4 Effect of S -adenosyl- l -methionine on Alcohol-Induced Liver Injury 311
3.5 Silymarin Retards the Progression of Alcohol-Induced Hepatic Fibrosis 313
Conclusion 315
Baboons in Drug Abuse Research 318
Introduction 318
Eliciting Functions of Drugs 318
2.1 Methods for Evaluating Drug Effects on Motor and Sensory Function 319
2.2 Drug Effects on Motor Function 319
2.2.1 Basic Drug Effects and Drug Time Course 319
2.2.2 Effects of Drug Dose 321
2.2.3 Drug Time Course and Dosing Schedule Effects 321
2.3 Drug Effects on Sensory Function 321
2.4 Parceling Out Drug Effects on Sensory and Motor Function 325
2.5 Drug Effects on Perceptual Discriminations 325
2.5.1 Human Speech Sound Discriminations 325
2.5.2 Drug Effects and Discrimination Difficulty 328
2.5.3 Drug Effects and Procedural Differences Versus Stimulus Differences 329
2.5.4 Drug Effects on the Discrimination of Species-Specific Baboon Calls 330
Reinforcing Functions of Drugs 331
3.1 Motivational Strength of Self-Administered Drugs 331
3.2 Models of Drug Craving and Relapse in Baboons 332
3.3 Methods for Testing Dependence Potential of Abused Drugs 333
Future Developments 338
Neuroimaging in Baboons 341
Introduction 341
Methods Development 342
2.1 Positron Emission Tomography (PET) 342
2.1.1 Blood Flow, Blood Volume, Metabolism 342
2.1.2 Radiopharmaceutical Development for Receptor Imaging 342
2.2 Evaluation of SPECT Radiopharmaceuticals 346
2.3 Imaging 347
2.3.1 MRI:PET Registration 347
2.3.2 Population Functional Neuroimaging in Baboons: Brain Atlas Methods 348
2.4 Animal Model of Dystonia 349
Asymmetric Resting rCBF in Baboons and Humans 349
Pharmacologic Activation PET Studies 350
4.1 Introduction 350
4.1.1 Rationale and Face Validity 350
4.1.2 Background (2DG) 351
4.2 Quinpirole, A Dopamine D2-Like Receptor Agonist 351
4.3 U91356a, A D2-Preferring Dopamine D2-Like Receptor Agonist 351
4.4 Levodopa, the Dopamine Precursor 352
4.4.1 Baboon and Macaque 352
4.4.2 Effects of Sedation 352
4.4.3 Humans with Parkinson's Disease 353
4.5 SKF82958, a Dopamine D1 Receptor Agonist 356
4.6 Pramipexole, a D3-Preferring Dopamine D2-Like Receptor Agonist 356
4.7 Model Validity vs. Comparison to Awake 357
Summary 357
The Baboon Model of Epilepsy: Current Applications in Biomedical Research 365
Epilepsy Classification 365
Natural Models of Epilepsy in Animals 366
Baboon Model of Photosensitive Epilepsy 366
3.1 Photosensitivity of the Baboon 367
3.1.1 Origins 367
3.1.2 Early Studies 367
3.1.3 EEG Findings 367
3.1.4 Physical Parameters 369
3.1.5 Environmental Factors 369
3.1.6 Interspecies and Intraspecies Differences 370
3.1.7 Invasive Electrophysiological Studies 370
3.1.8 Lesion Studies 372
3.1.9 Functional Neuroimaging 372
3.1.10 Pharmacological Studies 374
3.2 Electroclinical Features of Idiopathic Generalized Epilepsy in the Baboon 375
3.2.1 Clinical Findings 375
3.2.2 Scalp EEG Findings 376
3.2.3 Invasive Electrophysiology 377
3.2.4 Pathological Studies 378
Summary 379
Future Directions 380
5.1 Genetic Studies 380
5.2 Longitudinal Studies 380
5.3 Invasive Electrophysiological Studies 381
The Baboon in Xenotransplant Research 385
Introduction 385
Scope of Experimental Use of Baboons 386
Technical Considerations 388
Xenotransplantation Survival Patterns 389
Baboons as Potential Organ Donors 390
Ethics Applied to Use of Baboons in Xenotransplantation Research 390
Summary 391
Index 395