Date of Award

8-1958

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biochemistry and Cellular and Molecular Biology

Major Professor

D. F. Holtman

Committee Members

J. Orvis Mundt, John M. Woodward, Frank E. Staudt, Samuel R. Tipton

Abstract

The literature concerning the pathology accompanying infectious diseases has concerned, predominantly, gross and microscopic pathology. The biochemical changes in pathologic conditions have had little attention except for the generally accepted clinical procedures. Within the last decade, however, a change in emphasis has begun. A number on investigators have reported studies of enzymatic changes observed in infected animals. Many of these observations, however, have been with unnatural host-parasite systems.

The desirability of using a natural host-parasite system is obvious. Among the Enterobacteriaceae there are a limited number of complexes which are suitable for study with experimental animals. One of these is the well documented pullorm disease, a malady which has been accepted as being specific for chicks.

The etiologic agent has been known for over half a century, during which the epidemiology and control methods have been worked out in detail. The biochemical pathology has, on the contrary, been studied in detail only in recent years.

Reports from this laboratory have described alteration in nitrogen and carbohydrate metabolism. Chromatographic procedures have shown qualitative changes in amino acids occur in the disease. Nitrogen excretion is altered as demonstrated by the high levels of urea in the blood of normally uricotelic animals. The carbohydrate studies have been concerned largely with the components of the Krebs cycle. This has been accomplished by enzyme studies, assay of the concentration of intermediates and by using inhibitors of enzyme activity.

Many of these alterations were similar to those encountered in carbon tetrachloride poisoning. One of the most characteristic results of poisoning with carbon tetrachloride is deposition of fat in the liver. Such a change has been observed in histologic preparations of liver from chicks infected with Salmonella pullorum. This and the fact that methionine, an amino acid which exerts a marked lipotropic effect, disappears in the diseased bird led to the study of changes in the lipids which is reported in this thesis. This study has been correlated, in part, with previous studies of amino acid therapy. Certain lipotropic agents have been used similarly in order to compare therapeutic effects and to arrive at a cause for the variations in the fat from the liver

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