Walter L. Bloom

Course of experimental tuberculosis in the albino rat as influenced by cortisone.

Summary 1. Rats injected with virulent tubercle bacilli did not die of tuberculous infection. A majority of rats similarly infected with tubercle bacilli but treated with cortisone died of tuberculosis. 2. Striking histologic differences were noted. Localized granu-lomatas were seen in the organs of rats injected only with tubercle bacilli, whereas the lesions in the animals also receiving cortisone were diffuse and contained fewer inflammatory cells. 3. The influence of cortisone on experimental tuberculosis appears to be a lowering of the hosts natural resistance. The possible modes of action resulting in this are discussed.

Hemodynamic Effects of Anemia with and without Plasma Volume Expansion

Hypervolemic anemia and normovolemic anemia were produced in dogs. Cardiac outputs increased comparably with similar degrees of anemia in the hypervolemic and normovolemic animals. No significant association between right atrial mean pressure and cardiac output was found. Right atrial and pulmonary arterial pressures increased in a degree comparable to blood volume increase. Systemic mean pressures did not change significantly; there was a significant decrease in total peripheral resistance. The results are consistent with the concept that the increase in cardiac output occurring with hypervolemic anemia is related primarily to the anemia and not to the increase in blood volume.

Hemodynamic Effects of Hypervolemia with and without Anemia

Hypervolemia was produced in dogs by infusion of matched whole blood or of red cells suspended in dextran. In the dogs which had received matched whole blood, bleeding with simultaneous volume replacement with dextran produced acute hypervolemic anemia. This was associated with increased cardiac output, whereas no increase of cardiac output was seen in the same animals with a comparable amount of hypervolemia without anemia. The results suggest that anemia rather than hypervolemia was the important factor in causing an increase of cardiac output in these experiments.

Antimicrobial Activity of a Natural and a Synthetic Polypeptide.

Summary The antibacterial and antiviral properties of a tissue polypeptide were compared with the activity of a synthetic lysine polypeptide. On a weight basis, the activity of the synthetic peptide was approximately 4 times greater than that of the natural peptide. From the fact that the tissue peptide contains 30% lysine, it is possible to conclude that the activity resides within the lysine portion of the molecule. Additional evidence to support the implication of lysine was obtained from a comparative study on the mode of inactivation of these peptides by desoxy-ribonucleic acid (DRNA) and ribonucleic acid (RNA). Both peptides combine stoich-iometrically, at pH 6.5 with DRNA but not with RNA; it is apparent that both peptides combine with RNA in multiple proportions depending upon the relative concentrations of the reactants. In this respect, the similarity between the RNA-peptide interaction and antigen-antibody reactions is pointed out. A mechanism by which the tissue polypeptide could take part in the natural resistance of animals to infection and the possible role of these basic peptides in fibrinoid degeneration is discussed.

Systolic and diastolic pressure relationships in the isolated rat heart.

This report deals with variations in intraventricular pressure in the excised, beating rat heart. A negative early diastolic pressure developed, the magnitude of which correlated with the vigor of contraction.

Influence of diet on serum alkaline phosphatase in rats and men.

Summary 1. Serum alkaline phosphatase in albino rats was found to be lowered on fasting and was increased by the ingestion of fat. Carbohydrates and proteins had no effect. 2. The same phenomenon was found in human beings and factors influencing alkaline phosphatase serum levels are discussed.

Macrophage content of oil-induced peritoneal exudate in rats and rabbits.

Summary 1. Albino rats and rabbits were injected intraperitoneally with sterile mineral oil to produce peritoneal exudates. 2. Peritoneal exudates of rats contained greater numbers of white blood cells than rabbit exudates. 3. There was a significantly greater mononuclear phagocyte response to the same stimulus in rats than in rabbits. It can be postulated that this response may be related to the native resistance of the rat to tuberculosis. We wish to thank Miss Mary Louise Wilcox for her technical assistance throughout this study.

Effects of Intravenous Administration of Dextran on Renal Function.

Summary Following the intravenous administration of 500-1500 cc of 6% dextran solution in 13 normal subjects there were no marked changes in clearance of PAH and creatinine or in TmPAH.

Dextran as a Source of Liver Glycogen and Blood Reducing Substance.

In earlier experiments in this laboratory it has been observed that dextran, fed to human subjects, is not recovered in the stools. Engstrom and Aberg 1 have suggested that some of the dextran administered intravenously might be excreted into the gastrointestinal tract where it could be destroyed by bacterial action. Our own observations on dextran incubated with stools suggested that dextran disappears only very slowly, but Hehre 2 has since shown that there are large numbers of anaerobic bacteria present in the intestinal flora, and that it is these, rather than the aerobes, that are capable of splitting dextran. Although ingested dextran may be in part degraded and consumed by the intestinal bacteria, it still seemed to us of interest to learn more about the disappearance of dextran fed by mouth. The following experiments show that dextran feeding leads to a sustained increase in blood sugar and a rise in liver glycogen in the fasted rat, and brings about an increase in the blood sugar of human subjects. Experimental. Male albino rats of the Sprague-Dawley strain, weighing 250-350 g were fasted for 24 hours. A group of 10 control animals were killed and both fractions of liver glycogen were determined by the method of Bloom, Lewis and Schumpert 3 . Glycogen was determined (as glucose equivalent) by means of the anthrone reaction. The fasted experimental animals were given 5 ml of 18% dextran in 0.9% saline by stomach tube. An initial blood sample was taken from the cut end of the tail and additional samples were taken at intervals after feeding. Copper tungstate filtrates were prepared and reducing substances were determined by the method of Nelson 4 . In a series of four rats, both total and fermentable reducing substances were determined. Two or four hours after feeding, the rats were anesthetized with Nembutal and the liver was removed and immediately frozen and powdered. Trichloroacetic acid-extractable and total glycogen was determined on aliquots of the well-mixed liver powder. In order to determine whether glycogen or dextran might be present, other samples were allowed to stand at room temperature for 1.5 to 2 hours in order that glycogenolysis might occur. Dextran was added to parallel samples in order to determine whether dextranolysis could occur in the liver preparation.

Hydrodextran: preparation, and study on blood level and excretion rate.

Summary Hydrodextran was prepared by high-pressure catalytic hydrogenation of dextran. The 6% solution prepared for intravenous use was found to be essentially stable over a 6-month period of storage. The preliminary studies on blood level and urine excretion showed no specific effect from hydrogenation of the terminal groups of the dextran chain.