The objective is to help satisfy an important need, the need to know the biochemical nature of the different kinds of cells in muscle and nervous system. Brain function depends on the interplay of diverse kinds of cells, grandly entangled with each other. The admixture of the many cell types and the fact that the functional state differs from cell to cell, and from moment to moment, means that macroscopic chemical approaches are limited in usefulness. Muscle is also an intimate mixture of cells which differ greatly in chemical composition. Muscle fibers lying next to each other vary as much as 50-fold in the ratios between particular enzymes, and the differences can be exaggerated in muscle disease. Therefore, here also macroscopic studies are inadequate. To attack this situation, an analytical methodology is available which has virtually unlimited sensitivity and which makes it possible to measure nearly any enzyme or metabolite in single nerve cell bodies, in nuclei of large neurons, in other neuronal structures of similar size, and in small pieces of individual muscle fibers. It is the purpose of this project to exploit this analytical capability in the study of muscle and the nervous system. In some cases, single neurons or portions thereof are examined; in other cases, small groups of cells are studied. In the case of muscle, the technique is such that the same individual fibers can be analyzed for a great many enzymes, metabolites and cofactors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS008862-21
Application #
3393845
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1974-10-04
Project End
1995-02-28
Budget Start
1990-03-01
Budget End
1991-02-28
Support Year
21
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Chi, M M; Manchester, J K; Lowry, O H (1998) Effect of centrifugation at 2G for 14 days on metabolic enzymes of the tibialis anterior and soleus muscles. Aviat Space Environ Med 69:A9-11
Manchester, J; Kong, X; Lowry, O H et al. (1994) Ras signaling in the activation of glucose transport by insulin. Proc Natl Acad Sci U S A 91:4644-8
Manchester, J; Kong, X; Nerbonne, J et al. (1994) Glucose transport and phosphorylation in single cardiac myocytes: rate-limiting steps in glucose metabolism. Am J Physiol 266:E326-33
Michel, R N; Cowper, G; Chi, M M et al. (1994) Effects of tetrodotoxin-induced neural inactivation on single muscle fiber metabolic enzymes. Am J Physiol 267:C55-66
Lowry, O H (1994) The evolution of analytical biochemistry (1933-1983). A biased 50-year review. FASEB J 8:262-4
Date, H; Matsumura, A; Manchester, J K et al. (1993) Changes in alveolar oxygen and carbon dioxide concentration and oxygen consumption during lung preservation. The maintenance of aerobic metabolism during lung preservation. J Thorac Cardiovasc Surg 105:492-501
Chi, M M; Manchester, J K; Carter, J G et al. (1993) A refinement of the Akabayashi-Saito-Kato modification of the enzymatic methods for 2-deoxyglucose and 2-deoxyglucose 6-phosphate. Anal Biochem 209:335-8
McDougal Jr, D B; Carter, J G; Pusateri, M E et al. (1992) Glucose metabolism assessed with 2-deoxyglucose and the effect of glutamate in subdivisions of rat hippocampal slices. J Neurochem 59:1915-24
Chi, M M; Choksi, R; Nemeth, P et al. (1992) Effects of microgravity and tail suspension on enzymes of individual soleus and tibialis anterior fibers. J Appl Physiol 73:66S-73S
Yip, V; Carter, J G; Pusateri, M E et al. (1991) Distribution in brain and retina of four enzymes of acetyl CoA synthesis in relation to choline acetyl transferase and acetylcholine esterase. Neurochem Res 16:629-35

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