Recognition of the role of the adrenal cortex in electrolyte metabolism dates back to 1927 (1,2). Since then, a great deal has been learned about the effects ot adrenalectomy, and replacement therapy, on electrolyte metabolism. A number of adrenal cortical compounds have been isolated, and their biological activity in adrenalectomized animals, and in patients with Addison’s disease, has been ascertained. No attempt will be made, in this section, to cover all of the findings reported on the subject of the adrenal cortex and electrolytes, as several excellent reviews have appeared in recent years (3,4,5). However, some findings, pertinent to the present study, are presented below. In 1932, Loeb (6) found that there was a fall in plasma sodium in Addisonian crisis, and that the administration of sodium chloride would render the patient symptom-free (7). The fall in plasma sodium following adrenalectomy in the dog was related to the abnormally large quantity of sodium in the urine (8). This urinary loss of sodium was attributed, by Harrison and Darrow (9), to a disturbance in the tubular reabsorption of this ion from the glomerular filtrate. Anderson and co-warkers noted that adrenalectomized rats, unsupported by salt treatment, had increased total sodium excretion, and an increased rate of excretion of administered sodium-24, as compared with normal animals (10,11,12). They found the reverse to be true for potassium.[...]

Harris (1) has postulated a neurohumoral theory for the control of ACTH (adrenocortiocotrophin) release in which the hypothalamis elaborates a chemical, a neurohumor. This neurohumor passes down the nerve axons to a capillary bed located in the pituitary stalk. By the blood that the neurohumor reaches the anterior pituitary where it exerts its ACTH-releasing effect. [...]

The second world war greatly stimulated investigations on the preservation and use of blood. Numerous groups of workers directed their attention to this problem and rapidly improved methods of preservation and methods for following the survival of red blood cells after transfusion. By the end of the war these studies had advanced to a point where it was evident that further progress in the field of blood preservation could be achieved only through detailed studies of the enzymes, expecially of the formed elements, and the chemical changes that take place during preservation of the blood. The research which has continued in the department of Biochemistry at McGill University since January 1940 has been under the direction of Dr. O.F. Denstedt, and has covered numerous physical and chemical aspects of the preservation of the erythrocytes. It has been supported financially by the National Research Council of Canada, the Markle Foundation and the Baxter Company of Canada. The enzyme studies were begun in 1944 by Rocklin, who studied the glycolytic activity of the red cells. The work was continued the following year by Andreae, and later by Kwiecinska and Woodford. The results obtained, especially by the latter two workers, fit in well with the Meyerhof scheme, but there have been some interesting discrepancies with certain individual bloods. It was of interest, therefore, to investogate certain other enzyme systems, particularly the glyoxalase system [...]

The production in vivo of antibodies to pathogenic antigens, such as influenza virus, polio virus and diphtheria, or to non-pathogenic substances, such as serum proteins, constitutes the basis of immunity (1). The antibodies produced to pathogenic antigens serve as a specific defense against these antigens, and the immunized host, if reexposed to the same pathogens resists their harmful effects (1). In contrast to immunity, some animals and humans develop hypersensitivity to either a toxic or innocuous antigen: i.e., following the initial formation of antibodies to an antigen, the host reacts in an abnormal manner if reexposed to the same substance (1). The well known condition of hay fever represents just such a hypersensitivity reaction to the pollens of trees, grasses and weeds. Of the pollen sensitivities occurring on the North American continent, that caused by ragweed is the most prevalent. The present study forms a continuation of investigations made in this laboratory on the chemical nature of constituents of ragweed pollen involved in eliciting ragweed hypersensitivity. A brief survey of work done in this and other laboratories on the isolation and characterization of these constituents is presented in Sections C and D of this chapter. It is appropriate to preface this survey with a discussion of immune and hypersensitive reactions (Section A) and of hypersensitivity to ragweed pollen (Section B). [...]

Helminthiasis is widespread and has involved a medical and veterinary problem since ancient times. Stoll (1947) has estimated that at least eight hundred million human beings are infested with more than two billion helminths. There are also thousands of species of parasites which do not infest man, but which have as their natural hosts other animals, or plants. Despite the extensive distribution of parasitic worms and their enormous economic and medical importance, little is known concerning their life processes.

The development of this research program, designed to study some new aspects of intracellular oxidations and reductions, had its origin in the writer's observation that many in vitro studies concerning the reported metabolism of certain steroids, had one fact in common. This fact was that the enzymatic changes undergone by these steroids were the consequences of either hydrogen addition or removal. These enzymatic reactions had been observed with tissue slices, tissue homogenates, bacterial suspensions or fungi.

In surgical procedures, where there is need for profound muscular relaxation, the use of adjuncts in anaesthesia has been enthusiastically received by the surgeon, anaesthetist and the patient. Among these adjuncts, which have been adequately tested, are curare and myanesin. They relax the muscles of the body to a degree depending on the dosage, the nature of the anaesthetic gases and the general physical condition of the patient. Benzimidazole also belongs to this group of substances which cause muscular relaxation. Curare was first introduced as a muscle relaxant in anaesthesia by Griffith and Johnson of Montreal in 1942. It is now very widely used.

The peripheral circulation has long been an object of intense study. Besides its obvious medical importance, for example, in shock and hypertension, it is a fundamental factor in the integration of the various organs of the vertebrate body. A great amount of knowledge has been obtained by indirect means, such as the effects of various pharmacological agents on the blood pressure or on the rate of flow through isolated perfused organs. In addition, a number of ingenious techniques have been developed for the direct observation of the peripheral circulation. In all such studies the peripheral circulation is of interest as the site acted upon by the stimulus, chemical or physical, in question.

The present investigation arose out of a study on blood preservation which was begun in the Department of Biochemistry at McGill in January, 1940 by Collip and Denstedt. In the course of the investigation it became necessary to evaluate the efficiency of various methods of preservation and the viability of the preserved red cells. The only satisfactory method at that time, and even at the present date, was to transfuse the preserved blood and follow the elimination of the donor cells from the circulation of the recipient.

PCSK9 is the third gene implicated in autosomal dominant hypercholesterolemia, due to its role in promoting the degradation of the low density lipoprotein receptor (LDLR). Little is known regarding the mechanism by which it promotes the degradation of LDLR, nor the effects PCSK9 has on other cellular proteins. I report here the first quantitative subcellular proteomic study of proteins affected by the expression of a variant of PCSK9. I show that the expression levels of 293 proteins were affected by the expression of the PCSK9-ACE2-V5 construct. Of particular interest, is a protein involved in receptor recycling, EHBP1, which shows reduced protein levels by both PCSK9-ACE2-V5 and the PCSK9-D374Y mutant. I show that an EHBP1 binding protein, EHD4, binds with PCSK9 and LDLR. These results establish novel effects of PCSK9 on liver cell protein levels, of which some relating to endosomal sorting are shown to bind to PCSK9 and LDLR in complex, providing insight into the mechanism of PCSK9 mediated LDLR degradation.