Date of Award

12-1960

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biochemistry and Cellular and Molecular Biology

Major Professor

John M. Woodward

Committee Members

Samuel R. Tipton, Gerald E. Hunt, Raymond W. Beck, J. O. Mundt, D. F. Holtman

Abstract

Introduction: Although tularemia is generally considered to be a disease of rodents and of small ground animals, man is an occasional host. The early workers in this field succeeded in isolating and describing the causative organism, and in a relatively short time its nutritional requirements and cultural characteristics were fairly well understood. In slightly more than a decade after Pasteurella tularensis was first isolated (McCoy and Chapin, 1912), both American and Japanese workers had reported on its symptomatology, pathology, and epidemiology.

In more recent years, efforts have been directed to studies of the bacterium itself in an attempt to understand its virulence (Fleming and Foshay, 1955; Fleming and Foshay 1956; Rendina and Mills, 1957). The literature, however, is meager concerning a systematic host-parasite study with tularemia.

Since the rat and P. tularensis afford a host-parasite system suitable for the investigation in the laboratory, studies employing this model could elucidate the interaction of these two agents, namely, the invading organism on the one hand and the host on the other. It is conceivable that any knowledge so obtained could be pertinent to the understanding of other infections in mammals by gram-negative bacteria.

Previous studies have shown disturbances in the nitrogen metabolism and in enzymes concerned with amino acid utilization. Liver dysfunction and the reduction in activity of certain tricarboxylic acid cycle enzymes in the liver of the host have also been reported.

An analysis of these outward manifestations of the disease is of worth not only for its intrinsic value but also because this understanding may serve as a basis for the exploration of more fundamental disturbances of the host from which many other abnormalities follow, possibly through a series of complex and intricately related reactions.

The purpose of this thesis has been to follow the course of tularemia in rats with the aid of biochemical methods. An attempt was made to alleviate disease symptoms by administering the appropriate chemical substances, and to study the disease anew from this vantage point.

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