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Utilization of s35-cystine in rats fed protein deficient diets
Western
Society
for Clinical
and cortisone administration. (2) The proportional increase in urinary sugar was significantly greater than the increase in urinary nitrogen. In numerous instances during the course of each of the three studies the D/N ratio greatly exceeded 3.65. At times the ratio actually exceeded 6.25. (3) In two of the patients major insulin resistance resulted from the administration of ACTH and cortisone. In the third patient (in whom the experimental procedures were modified) no insulin resistance occurred despite progressive hyperglycemia and glycosuria. One may conclude that cortisone-like steroids resulting from adrenocortical stimulation accelerate the formation of carbohydrate from fatty acid. Observations upon the possible mechanism of steroid hormone-induced insulin resistance will be discussed as time permits. UTILIZATION OF S35-~~~~~~~IN RATS FED PROTEIN DEFICIENT DIETS. jlrorman D. Lee and Robert H. Williams, * Department of Medicine, University of Washington School of Medicine, Seattle, Wash. Female Sprague-Dawley rats, weighing approximately 165 gm., were placed on various artificial diets for seven days and were allowed to feed ad libitum. The dietary variation was concerned with the quantity and biologic value of the protein constituent and with non-protein diets supplemented with non-radioactive Lcystine. On the eighth day a standard dose of S 35labeled DL-cystine was administered intraperitoneally and the animals were sacrificed eight hours later. The extent of incorporation of the label into liver and plasma protein was then determined. It was found that increasing the dietary content of protein-bound cystine resulted in a decrease in the incorporation of isotopic cystine. When the non-protein diet was supplemented with L-cystine, the incorporation of the isotopic amino acid was increased. Furthermore, if nutritionally incomplete proteins such as zein and gelatin were the sole source of dietary protein, the incorporation of isotopic cystine was increased in comparison to similar diets containing complete proteins. The data were analyzed with respect to the effect of protein depletion and surfeit on the control of the rate of protein synthesis in the liver. Evidence is presented consistent with the hypothesis that the rat adapts to protein depletion by increasing its rate of protein anabolism. JULY,
1952
Research
97
OCCLUSION OF THE THORACIC AORTA FOR LONG PERIODSBY MEANS OF A MECHANICAL SHUNT. Sanford E. Leeds* and Morris Culiner, Harold Brunn Institute for Cardiovascular Research, Mount Zion Hospital, San Francisco, Calif. Prolonged occlusion of the normal thoracic aorta in dogs is followed by severe damage to vital structures and death. In order to avoid the deleterious effects of the occlusion the clamped portion of the aorta was by-passed using a roller-type pump with a carotid-femoral artery shunt. By this means a controlled flow of blood from an artery proximal to the occlusion can be shunted to an artery distal to the occlusion thus supplying the spinal cord and viscera with oxygenated blood in adequate amounts. In the experimental animals it was found that if a plastic tube was inserted through the femoral artery into the thoracic aorta below the occlusion the mortality was reduced remarkably compared to the use of a metal cannula in the femoral artery. Division and suture of the aorta were carried out while occluding the aorta in some animals. This required reversal of the action of the heparin which is required during the mechanical shunting of the blood. STUDIESIN SULFUR METABOLISM.VII. THE PROTEIN METABOLIC ABNORMALITY OF THE NEPHROTIC SYNDROME As STUDIED WITH S35LABELED METHIONINE. Sheldon Margen, Judith Lange, Harold Carver, Roy DeLaney and Laurance Kinsell, * Institute for Metabolic Research, Highland Alameda County Hospital, Oakland, and the Department of Biochemistry, University of California, Berkeley, Calif. A male patient age eighteen years with severe nephrotic syndrome was studied as follows: (1) Following intravenous administration of a tracer dose of S35-labeled methionine, incorporation of the isotope into plasma protein and the urinary excretion of the isotope were determined. (2) Following the administration of sufficient serum albumin to bring the serum level to approximately 3 gm. per 100 cc. (from a pretreatment level of 0.92 gm. per 100 cc.), a second S35 study was carried out. (3) The study was continued during ACTH therapy, which in this patient induced complete remission. One may conclude the following in the nephrotic patient : (1) The rates of both albumin and globulin synthesis are greatly increased as compared to the normal. (2) The rate of synthesis of albumin and the rate of urinary loss of albumin are almost identical. This is true with
Society
for Clinical
and cortisone administration. (2) The proportional increase in urinary sugar was significantly greater than the increase in urinary nitrogen. In numerous instances during the course of each of the three studies the D/N ratio greatly exceeded 3.65. At times the ratio actually exceeded 6.25. (3) In two of the patients major insulin resistance resulted from the administration of ACTH and cortisone. In the third patient (in whom the experimental procedures were modified) no insulin resistance occurred despite progressive hyperglycemia and glycosuria. One may conclude that cortisone-like steroids resulting from adrenocortical stimulation accelerate the formation of carbohydrate from fatty acid. Observations upon the possible mechanism of steroid hormone-induced insulin resistance will be discussed as time permits. UTILIZATION OF S35-~~~~~~~IN RATS FED PROTEIN DEFICIENT DIETS. jlrorman D. Lee and Robert H. Williams, * Department of Medicine, University of Washington School of Medicine, Seattle, Wash. Female Sprague-Dawley rats, weighing approximately 165 gm., were placed on various artificial diets for seven days and were allowed to feed ad libitum. The dietary variation was concerned with the quantity and biologic value of the protein constituent and with non-protein diets supplemented with non-radioactive Lcystine. On the eighth day a standard dose of S 35labeled DL-cystine was administered intraperitoneally and the animals were sacrificed eight hours later. The extent of incorporation of the label into liver and plasma protein was then determined. It was found that increasing the dietary content of protein-bound cystine resulted in a decrease in the incorporation of isotopic cystine. When the non-protein diet was supplemented with L-cystine, the incorporation of the isotopic amino acid was increased. Furthermore, if nutritionally incomplete proteins such as zein and gelatin were the sole source of dietary protein, the incorporation of isotopic cystine was increased in comparison to similar diets containing complete proteins. The data were analyzed with respect to the effect of protein depletion and surfeit on the control of the rate of protein synthesis in the liver. Evidence is presented consistent with the hypothesis that the rat adapts to protein depletion by increasing its rate of protein anabolism. JULY,
1952
Research
97
OCCLUSION OF THE THORACIC AORTA FOR LONG PERIODSBY MEANS OF A MECHANICAL SHUNT. Sanford E. Leeds* and Morris Culiner, Harold Brunn Institute for Cardiovascular Research, Mount Zion Hospital, San Francisco, Calif. Prolonged occlusion of the normal thoracic aorta in dogs is followed by severe damage to vital structures and death. In order to avoid the deleterious effects of the occlusion the clamped portion of the aorta was by-passed using a roller-type pump with a carotid-femoral artery shunt. By this means a controlled flow of blood from an artery proximal to the occlusion can be shunted to an artery distal to the occlusion thus supplying the spinal cord and viscera with oxygenated blood in adequate amounts. In the experimental animals it was found that if a plastic tube was inserted through the femoral artery into the thoracic aorta below the occlusion the mortality was reduced remarkably compared to the use of a metal cannula in the femoral artery. Division and suture of the aorta were carried out while occluding the aorta in some animals. This required reversal of the action of the heparin which is required during the mechanical shunting of the blood. STUDIESIN SULFUR METABOLISM.VII. THE PROTEIN METABOLIC ABNORMALITY OF THE NEPHROTIC SYNDROME As STUDIED WITH S35LABELED METHIONINE. Sheldon Margen, Judith Lange, Harold Carver, Roy DeLaney and Laurance Kinsell, * Institute for Metabolic Research, Highland Alameda County Hospital, Oakland, and the Department of Biochemistry, University of California, Berkeley, Calif. A male patient age eighteen years with severe nephrotic syndrome was studied as follows: (1) Following intravenous administration of a tracer dose of S35-labeled methionine, incorporation of the isotope into plasma protein and the urinary excretion of the isotope were determined. (2) Following the administration of sufficient serum albumin to bring the serum level to approximately 3 gm. per 100 cc. (from a pretreatment level of 0.92 gm. per 100 cc.), a second S35 study was carried out. (3) The study was continued during ACTH therapy, which in this patient induced complete remission. One may conclude the following in the nephrotic patient : (1) The rates of both albumin and globulin synthesis are greatly increased as compared to the normal. (2) The rate of synthesis of albumin and the rate of urinary loss of albumin are almost identical. This is true with