The applicant, after completion of medical school training at U. of Miami, and clinical training in medicine at U. of Tennessee, began subspecialty training in gastroenterology at the U. of Florida. During the fellowship, sufficient clinical time was devoted to patient care, consultations, and learning endoscopy, colonoscopy and other related procedures. The applicant studied in the basic laboratories of John Mathias, MD and Charles Sninsky, MD, investigating the enteric nervous system and small bowel motility. Some of those studies involved the effects of microtubule altering agents on intestinal myoelectric activity and generated a need for further study and training in order to more fully investigate the area of cytoskeletal proteins in the enteric nervous system. The environment at the U. of Florida is ideal for such studies by the applicant. Collaboration with and sponsorship of Daniel Purich, PhD, who is chairman of Biochemistry and Molecular Biology, and internationally respected expert in microtubule interactions, has led the applicant to graduate course work in cellular biology and investigations of microtubule polymerization. Gerry Shaw, PhD, the secondary sponsor, respected for his work with neurofilament proteins, helped direct studies using immunolocalization to examine neurofilaments in enteric neurons. The proposed project involves the study of cytoskeletal proteins in enteric neurons. Based on their unique location between muscle layers and constant mechanical stress, we hypothesized that cytoskeletal structural proteins in enteric neurons might be modified. Preliminary studies on neurofilament protein immunoreactivity in enteric neurons suggests that they are different as compared to brain neurons. we propose to 1) continue the immunoreactivity studies of neurofilaments and 2) to study other cytoskeletal proteins within enteric neurons, in both 3) developing as well as adult intestine. 4) We will establish enteric neuron cell cultures to take these studies beyond the confines of the intestinal wall and 5) isolate and purify neurofilament and microtubule proteins from enteric neurons for further structural characterization.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK002007-05
Application #
2133645
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1991-07-01
Project End
1996-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Florida
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Eaker, E Y; Sallustio, J E; Marchand, S D et al. (1996) Differential increase in neuropeptide Y-like levels and myenteric neuronal staining in diabetic rat intestine. Regul Pept 61:77-84
Valentine, J F; Tannahill, C L; Stevenot, S A et al. (1996) Colitis and interleukin 1beta up-regulate inducible nitric oxide synthase and superoxide dismutase in rat myenteric neurons. Gastroenterology 111:56-64
Eaker, E; Sallustio, J; Kohler, J et al. (1995) Endothelin-1 expression in myenteric neurons cultured from rat small intestine. Regul Pept 55:167-77
Howe, S; Eaker, E Y; Sallustio, J E et al. (1994) Antimyenteric neuronal antibodies in scleroderma. J Clin Invest 94:761-70
Eaker, E Y; Sallustio, J E (1994) The distribution of novel intermediate filament proteins defines subpopulations of myenteric neurons in rat intestine. Gastroenterology 107:666-74
Eaker, E Y; Sallustio, J E; Harris, J M et al. (1993) Myenteric plexus neurons have developmentally acquired differences in the medium molecular weight subunit of neurofilament protein. Neuroscience 53:561-70