Publications via PubMed Central
James received his Ph.D. in Human Nutrition from Iowa State University. Following his extensive work on iron binding proteins, Dr. Swain conducted research on the efficacy of novel iron fortificants at a U.S. Department of Agriculture, Agricultural Research Service center in Grand Forks, North Dakota.
Dr. Swain is a registered, licensed dietitian and has clinical experience in many areas of patient care. His primary areas of interests are in oncology nutrition and anemia. Please see Dr. Swain's section on RESEARCH INTERESTS below for additional information.
He joined the Nutrition faculty at Case Western Reserve University as Assistant Professor in August 2003. In addition to his teaching and research activities, he is director of the Nutrition Department nationally accredited (CADE) Didactic Program in Dietetics (DPD). Dr. Swain serves as student mentor and advisor and teaches courses in undergraduate and graduate nutrition and dietetics, including food science and medical nutrition therapy.
He conducts research in the area of iron absorption and the influence of dietary iron on intestinal cancer. He is a program reviewer with CADE, is the current Chair of the Vitamins and Minerals Research Interest Section of the American Society for Nutrition, and a Ohio State Representative for the Oncology Nutrition Dietetic Practice Group.
2001- 2003 Post-Doctoral Fellow
USDA Human Nutrition Research Center
2000 Ph.D. | Major: Nutrition
Iowa State University2000 Dietetic Internship
Clinical Rotation Mercy Hospital (Des Moines, IA)
1996 M.S. | Major: Human Nutrition
California State University (Northridge)
1993 B.A. | Major: Biological Sciences
University of California (Santa Barbara)
My research interests are in the areas of food safety, nutritional status and hematology/anemia, iron absorption and metabolism, as well as pathophysiology of diseases involving iron. My research also focuses on understanding the influence of dietary iron on intestinal tumorigenesis, using immunohistochemistry, proteomics, and gene expression analysis.
ONGOING RESEARCH in Dr. SWAIN's LABORATORY:
Recently, a study was conducted to determine the effect of excess dietary iron on intestinal tumorigenesis using histological and proteomic analyses of tumor and normal intestinal tissue in Apc1638N mice fed different concentrations of dietary iron.
Six weanlings were fed adequate (n=6) and six weanlings were fed excess (n=6) amounts of iron (ferrous sulfate: 45 vs. 450 mg iron/kg AIN-93M[M] diet). After 24 wk, mice were sacrificed and intestines removed. Portions of the small intestine and both the proximal and distal colon were subjected to histological analyses.
Tumors and adjacent normal (non-tumor) intestinal tissue were excised for proteomic analysis and network/pathway analyses to relate histological findings to inflammatory regulators. Findings reveal that excess dietary iron stimulates polyp (tumor) growth, induces significant differences in the proteome of tumor cells, and modulates the activity of antioxidant enzymes, such as glutathione-S-transferase, in intestinal tumors, possibly in response to the pro-oxidative, pro-inflammatory effects of excess intraluminal iron.
Weight gain of mice did not differ (p<0.05) between the groups. Food intake also did not significantly differ (p<0.05) between the treatment groups throughout the study.
Figure 1. Intestinal segment -stained with methylene blue- showing
tumor and normal (non-tumor) tissue. Diameter grid measurements
overlay each tumor.
Figure 2. No significant difference was seen in polyp number in the colon. However, there was a significant difference in mean size of tumors. Thus, tumor “burden” or total area of coverage by polyps was approximately 2-fold greater in mice fed the high iron diet vs. controls.
Proteins extracted from tumor and non-tumor tissue samples were labeled with fluorescence dye, cy3 and cy5. Those two labeled samples were then mixed with an internal control generated by pooling all samples and labeling with fluorescence dye, cy2. In addition, all samples were reversely labeled to eliminate dye bias. All mixed samples were separated by isoelectric point in pH 3-10 gradient IPG strip and then by molecular weight in 12.5% homogeneous SDS-PAGE gel. Image analysis was performed using DeCyder software and average values for same sample were taken for differential analysis. One way anova followed by posthoc test (Tukey test) using R identified proteins differentially expressed. P value for each protein spots shows in attached excel file.
Figure 4. Proteomic Data: 2-D gel electrophoresis image of protein spots, using 3-in-1 (Cy-Dye) technique. Includes tumor, non-tumor, and control intestinal tissue samples, each with different dye.
Of 980 analyzed protein spots, 78 spots were differentially expressed among normal and tumor tissues (AFe vs. High Fe (p<0.05)). Among these spots, 36 changed in tumor vs. normal tissue (12↓; 24^) and 18 differed between tumors in mice fed AFe vs. High Fe (5↓; 13^).
Figure 5. Network/pathway signaling analyses: Based on proteomic data (see Fig. 3 and Fig. 4), one of the network/protein signaling pathways determined involved modulation of the antioxidant enzyme, Glutathione-S-transferase. Tumor (T) vs. normal (non-tumor; NT) intestinal tissue.
Excess dietary iron is associated with changes in expression of proteins in tumors involved in generation or reduction of reactive oxygen species and proteins involved in protein degradation. Using Ingenuity Pathways Analysis, we found 4 highly significant functional networks in tumor as compared to normal tissue and 2 in tumors from mice fed adequate as compared to high iron. Notably, the top networks in both cases were associated with functions implicated in cancer, GI disease, and inflammatory disease. (See Figure 6, below)
Figure 6. Biological pathways, modulated by excess dietary iron (iron supplementation), include cancer and inflammatory disease.
Sean R Lynch, Thomas Bothwell, and the SUSTAIN Task Force on Iron Powders (Lou Campbell, Kristina Cowan, Ray Glahn, Leif Hallberg, Michael Hoppe, Lena Hulthen, Janet R Hunt, Richard F Hurrell, Dennis Miller, James H. Swain, Liz Turner, Pattanee Winichagoon, C.K. Yeung, Christophe Zeder, and Michael B Zimmermann).. (2007) "A Comparison of Physical Properties, Screening Procedures and a Human Efficacy Trial for Predicting the Bioavailability of Commercial Elemental Iron Powders Used for Food Fortification." Int. J. Vitam. Nutr. Res.; 77 (2):107-124, 2007.
James H Swain, Johnson LK, Penland JG and Hunt JR. (2007) "Combating Iron Deficiency: Electrolytic Iron or Ferrous Sulfate Increase Body Iron in Women with Moderate to Low Iron Stores" J. Nutr.; 137:620-627. PMID: 17311950
James H Swain, Johnson, LK and Hunt, JR. (2006) "An irradiated electrolytic iron fortificant is poorly absorbed by humans and is less responsive than FeSO4 to the enhancing effect of ascorbic acid." J Nutr. 2006 Aug;136(8):2167-74. PMID: 16857836
Petersen HL, Peterson CT, Reddy MB, Hanson KB, Swain JH, Sharp RL, Alekel DL. (2006) "Body composition, dietary intake and iron status of female collegiate swimmers." Int J Sport Nutr Exerc Metab. 2006 Jun;16(3):281-95. PMID: 16948484
Swain JH, Newman SM, Hunt JR.. (2003) "Bioavailability of elemental iron powders to rats is less than bakery-grade ferrous sulfate and predicted by iron solubility and particle surface area." J Nutr. 2003 Nov;133(11):3546-52. PMID: 14608072
Swain JH, Alekel DL, Dent SB, Peterson CT, Reddy MB (2002) "Iron indexes and total antioxidant status in response to soy protein intake in perimenopausal women." Am J Clin Nutr. 2002 Jul;76(1):165-71. PMID: 12081830
Swain JH, Tabatabai LB, Reddy MB (2002) "Histidine content of low-molecular-weight beef proteins influences nonheme iron bioavailability in Caco-2 cells." J Nutr. 2002 Feb;132(2):245-51. PMID: 11823585
Dent SB, Peterson CT, Brace LD, Swain JH, Reddy MB, Hanson KB, Robinson JG, Alekel DL (2001) "Soy protein intake by perimenopausal women does not affect circulating lipids and lipoproteins or coagulation and fibrinolytic factors." J Nutr. 2001 Sep;131(9):2280-7. PMID: 11533267
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