Department of Department of Anatomy, Cell Biology and Physiology Works

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    WKY Fatty Rat as a Model of Obesity and Non-insulin-dependent Diabetes Mellitus
    (Oxford, 1990-07) Peterson, Richard G.; Little, Leah A.; Neel, Mary-Ann; Anatomy and Cell Biology, School of Medicine
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    Constructing a new nigrostriatal pathway in the Parkinsonian model with bridged neural transplantation in substantia nigra
    (Society for Neuroscience, 1996-11-01) Zhou, Feng C.; Chiang, Yung H.; Wang, Yun; Anatomy and Cell Biology, School of Medicine
    The physical repair and restoration of a completely damaged pathway in the brain has not been achieved previously. In a previous study, using excitatory amino acid bridging and fetal neural transplantation, we demonstrated that a bridged mesencephalic transplant in the substantia nigra generated an artificial nerve pathway that reinnervated the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rats. In the current study, we report that a bridged mesencephalic transplant can anatomically, neurochemically, and functionally reinstate the 6-OHDA-eradicated nigro-striatal pathway. An excitatory amino acid, kainic acid, laid down in a track during the transplant generated a trophic environment that effectively guided the robust growth of transplanted neuronal fibers in a bundle to innervate the distal striatum. Growth occurred at the remarkable speed of approximately 200 microm/d. Two separate and distinct types of dopamine (DA) innervation from the transplant have been achieved for the first time: (1) DA innervation of the striatum, and (2) DA innervation of the pars reticularis of the substantia nigra. In addition, neuronal tracing revealed that reciprocal connections were achieved. The grafted DA neurons in the SNr innervated the host's striatum, whereas the host's striatal neurons, in turn, innervated the graft within 3-8 weeks. Electrochemical volt- ammetry recording revealed the restoration of DA release and clearance in a broad striatal area associated with the DA reinnervation. Furthermore, the amphetamine-induced rotation was attenuated, which indicates that the artificial pathways were motor functional. This study provides additional evidences that our bridged transplantation technique is a potential means for the repair of a completely damaged neuronal pathway.
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    Skeletal loading in animals
    (2001) Robling, Alexander G; Burr, David B.; Turner, Charles H
    A number of in vivo skeletal loading models have been developed to test specific hypotheses addressing the key mechanical and biochemical signals involved in bone’s adaptive response to loading. Exercise protocols, osteotomy procedures, loading of surgically implanted pins, and force application through the soft tissues are common approaches to alter the mechanical environment of a bone. Although each animal overload model has a number of assets and limitations, models employing extrinsic forces allow greater control of the mechanical environment. Sham controls, for both surgical intervention (when performed) and loading, are required to unequivocally demonstrate that responses to loading are mechanically adaptive. Collectively, extrinsic loading models have fostered a greater understanding of the mechanical signals important for stimulating bone cells, and highlighted the roles of key signaling molecules in the adaptive response.
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    Harold M. Frost T J Musculoskel Neuron Interact 2001; 2(2):117-119 William F. Neuman Awardee 2001
    (2001-12) Recker, Robert R; Jee, Webster S; Burr, David B.; Forwood, Mark R; Talmage, Roy V
    Tribute to Harold M. Frost, honorary president of ISMNI, who received the William F. Neuman Award from the American Society of Bone and Mineral Research October 2001.
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    Bone material properties and mineral matrix contributions to fracture risk or age in women and men
    (2002) Burr, David B.
    The strength of bone is related to its mass and geometry, but also to the physical properties of the tissue itself. Bone tissue is composed primarily of collagen and mineral, each of which changes with age, and each of which can be affected by pharmaceutical treatments designed to prevent or reverse the loss of bone. With age, there is a decrease in collagen content, which is associated with an increased mean tissue mineralization, but there is no difference in cross-link levels compared to younger adult bone. In osteoporosis, however, there is a decrease in the reducible collagen cross-links without an alteration in collagen concentration; this would tend to increase bone fragility. In older people, the mean tissue age (MTA) increases, causing the tissue to become more highly mineralized. The increased bone turnover following menopause may reduce global MTA, and would reduce overall tissue mineralization. Bone strength and toughness are positively correlated to bone mineral content, but when bone tissue becomes too highly mineralized, it tends to become brittle. This reduces its toughness, and makes it more prone to fracture from repeated loads and accumulated microcracking. Most approved pharmaceutical treatments for osteoporosis suppress bone turnover, increasing MTA and mineralization of the tissue. This might have either or both of two effects. It could increase bone volume from refilling of the remodeling space, reducing the risk for fracture. Alternatively, the increased MTA could increase the propensity to develop microcracks, and reduce the toughness of bone, making it more likely to fracture. There may also be changes in the morphology of the mineral crystals that could affect the homogeneity of the tissue and impact mechanical properties. These changes might have large positive or negative effects on fracture incidence, and could contribute to the paradox that both large and small increases in density have about the same effect on fracture risk. Bone mineral density measured by DXA does not discriminate between density differences caused by volume changes, and those caused by changes in mineralization. As such, it does not entirely reflect material property changes in aging or osteoporotic bone that contribute to bone's risk for fracture.
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    Osteoporosis and fracture risk: bone matrix quality
    (2002-08) Burr, David B.
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    Depression of fast excitatory synaptic transmission in large aspiny neurons of the neostriatum after transient forebrain ischemia
    (Society for Neuroscience, 2002-12) Pang, Zhi-Ping; Deng, Ping; Ruan, Yi-Wen; Xu, Zao C.; Anatomy and Cell Biology, School of Medicine
    Spiny neurons in the neostriatum die within 24 hr after transient global ischemia, whereas large aspiny (LA) neurons remain intact. To reveal the mechanisms of such selective cell death after ischemia, excitatory neurotransmission was studied in LA neurons before and after ischemia. The intrastriatally evoked fast EPSCs in LA neurons were depressed < or =24 hr after ischemia. The concentration-response curves generated by application of exogenous glutamate in these neurons were approximately the same before and after ischemia. A train of five stimuli (100 Hz) induced progressively smaller EPSCs, but the proportion of decrease in EPSC amplitude at 4 hr after ischemia was significantly smaller compared with control and at 24 hr after ischemia. Parallel depression of NMDA receptor and AMPA receptor-mediated EPSCs was also observed after ischemia, supporting the involvement of presynaptic mechanisms. The adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked the inhibition of evoked EPSCs at 4 hr after ischemia but not at 24 hr after ischemia. Electron microscopic studies demonstrated that the most presynaptic terminals in the striatum had a normal appearance at 4 hr after ischemia but showed degenerating signs at 24 hr after ischemia. These results indicated that the excitatory neurotransmission in LA neurons was depressed after ischemia via presynaptic mechanisms. The depression of EPSCs shortly after ischemia might be attributable to the enhanced adenosine A1 receptor function on synaptic transmission, and the depression at late time points might result from the degeneration of presynaptic terminals.
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    Effects of physical training on proprioception in older women
    (2003) Thompson, KR; Mikesky, Alan; Bahamonde, Rafael E.; Burr, David B.
    Older adulthood is accompanied by declines in muscular strength, coordination, function, and increased risk of falling. Resistance training increases muscular strength in this population but its effect on proprioception is unknown. To evaluate the effect of resistance training on proprioception, community dwelling older women completed a three-month exercise study. A resistance training (RT) group (N=19) underwent supervised weight training three times per week while a non-strength trained control (NSTC) group (N=19) performed range-of-motion activities that mimicked the movements of the RT group without the benefit of muscle loading. Subjects were evaluated at baseline, 6, and 12 weeks for strength and proprioception. Muscular strength was assessed by measuring the subject’s one repetition maximum performance on four different exercises. Static proprioception was measured by the subject’s ability to reproduce a target knee joint angle while dynamic proprioception was measured by the subject’s ability to detect passive knee motion. The RT group made significant strength improvements compared to the NSTC group. Proprioception significantly improved in both groups by 6 weeks. Our findings suggest that improvements in proprioception can be obtained via regular activity that is independent of heavy muscle loading.
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    Essentials of Complementary and Alternative Medicine for Medical Students and Residents: A Web-Based Course for Self-Instruction
    (2003) Brokaw, James J.; McConnell, Elizabeth J.; Raess, Beat U.
    Because physicians are increasingly seeing patients who use CAM therapies, they need to be aware of the potential harm some of these therapies pose. The objective of this project was to develop brief, self-contained lessons that teach the fundamental concepts of CAM and the use of herbal medicines. Each PowerPoint® lesson presents basic information about major aspects of CAM, which can usually be completed in less than 30 minutes. The course will be made available via ANGEL, an internet-based course presentation and management system. To assess understanding of the material, students have the option of taking a brief online quiz at the conclusion of each lesson. The first six lessons comprise a general overview of CAM that exposes the student to a broad variety of “popular” CAM topics: Introduction, Alternative Medical Systems, Mind-Body Interventions, Manipulative Therapies, Energy Therapies and Biologically-Based Therapies. The last four lessons focus on herbal remedies, their uses, actions, and precautions: Pharmacological and Clinical Aspects of Botanicals, Botanical and Herbal Medicines, Herbal Medicines and Drug Interactions, and Patient Education and Advising. This course simply presents information and neither promotes nor condemns the use of CAM. The intent is to expose physicians-in-training to CAM information in a self-paced, time-efficient manner that will enable them to practice safe and effective medicine in a population that typically uses one or more forms of CAM.