scholarly journals TRAUMATIC SHOCK. I. THE PRODUCTION OF RADIOACTIVE PLASMA PROTEIN FROM AMINO ACIDS CONTAINING RADIOACTIVE SULFUR

1943 ◽  
Vol 22 (2) ◽  
pp. 265-273 ◽  
Author(s):  
Arnold M. Seligman ◽  
Jacob Fine
Keyword(s):  
Amino Acids ◽  
Plasma Protein ◽  
Traumatic Shock

Purification of Antihemophilic Factor (Factor VIII) by Amino Acid Precipitation*

1964 ◽  
Vol 11 (01) ◽  
pp. 064-074 ◽  
Author(s):  
Robert H Wagner ◽  
William D McLester ◽  
Marion Smith ◽  
K. M Brinkhous
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Factor Viii ◽  
Plasma Protein ◽  
Acid Precipitation ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Specific Procedure ◽  
Beta Alanine ◽  
Antihemophilic Factor

Summary1. The use of several amino acids, glycine, alpha-aminobutyric acid, alanine, beta-alanine, and gamma-aminobutyric acid, as plasma protein precipitants is described.2. A specific procedure is detailed for the preparation of canine antihemophilic factor (AHF, Factor VIII) in which glycine, beta-alanine, and gammaaminobutyric acid serve as the protein precipitants.3. Preliminary results are reported for the precipitation of bovine and human AHF with amino acids.

scholarly journals Albumin, fibrinogen and transferrin synthesis in isolated rat hepatocyte suspensions. A model for the study of plasma protein synthesis

1975 ◽  
Vol 146 (1) ◽  
pp. 141-155 ◽  
Author(s):  
K N Jeejeebhoy ◽  
J Ho ◽  
G R Greenberg ◽  
M J Phillips ◽  
A Bruce-Robertson ◽  
...  
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Plasma Protein ◽  
Plasma Proteins ◽  
Horse Serum ◽  
Rat Hepatocyte ◽  
Isolated Rat

A system using hepatocyte suspensions in vitro was developed for studying the synthesis of albumin, fibrinogen and transferrin. Conditions for optimum survival of the hepatocyte and for synthesis of these plasma proteins were defined for this system. These conditions included the use of horse serum (17.5 percent, v/v, heat-inactivated), an enriched medium (Waymouth's MB 752/1), an O2 tension of between 18.7 times 10(3) and 26.7 times 10(3) Pa and constant stirring. Albumin, fibrinogen and transferrin synthesis rates were obtained of 0.32 p 0.094(10), 0.12 p 0.030(11) and 0.097 p 0.017(10) [mean p S.D. (n)]mg/h per g of hepatocytes respectively. These rates were maintained for the first 12h of study and synthesis continued at a diminished rate up to 48h. The synthesis of albumin was decreased in a medium containing less amino acids and glucose, but that of fibrinogen was substantially unaffected. ATP concentrations up to 12h and RNA/DNA ratios up to 24h were comparable with values in vivo. The ability to study cells up to 48h permitted us to find that the addition of a mixture of hormones consisting of glucagon, cortisol, tri-iodothyronine and growth hormone enhanced fibrinogen synthesis. Addition of insulin to the above mixture resulted in increased synthesis for albumin and transferrin but not for fibrinogen.

scholarly journals AMINO ACID MIXTURES EFFECTIVE PARENTERALLY FOR LONG CONTINUED PLASMA PROTEIN PRODUCTION. CASEIN DIGESTS COMPARED

1944 ◽  
Vol 79 (6) ◽  
pp. 607-624 ◽  
Author(s):  
S. C. Madden ◽  
R. R. Woods ◽  
F. W. Shull ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Intravenous Injection ◽  
Plasma Protein ◽  
Nitrogen Balance ◽  
Protein Production ◽  
Nitrogen Retention ◽  
Essential Amino Acids ◽  
Skin Lesions ◽  
Good Utilization ◽  
Rapid Injection

When blood plasma proteins are depleted by bleeding with return of red cells suspended in saline (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications. The ten growth essential amino acids of Rose plus glycine will maintain nitrogen balance and produce as much new plasma protein as will good diet proteins. This good utilization is demonstrated over periods of several months when the amino acids are given either orally or parenterally. There is no evidence of toxicity in general nor to unnatural forms of these synthetic amino acids in particular. Given parenterally appropriate mixtures of these amino acids are well tolerated even upon rapid injection. The minimal daily requirements for a 10 kilo dog may be given intravenously in 10 minutes without reaction. Subcutaneously a 10 per cent solution may be given rapidly without reaction. Among various mixtures tested Vt approximates a minimum for a 10 kilo dog. It contains in grams (dl-threonine 0.7, dl-valine 1.5, l-(-) leucine 1.5, dl-isoleucine 1.4, dl-lysine hydrochloride 1.5, l(-) tryptophane 0.4, dl-phenylalanine 1.0, dl-methionine 0.6, l(+)-histidine hydrochloride 0.5, l(+)-arginine hydrochloride 0.5, and glycine 1.0. The presence of glycine improves tolerance to rapid intravenous injection, but excess glycine does not improve utilization of the mixture. Over a long period this mixture appears suboptimal in quantity. Doubled it is more than ample. Of two casein digests tested the one prepared by enzymatic hydrolysis provided good nitrogen retention and fairly good plasma protein production but was much less tolerable upon intravenous injection than certain mixtures of pure amino acids. The other one prepared by acid hydrolysis and tryptophane fortification afforded bare nitrogen equilibrium and produced virtually no plasma protein. Skin lesions observed after 10 to 20 weeks of synthetic diet probably reflect a deficiency of some member or members of the vitamin B2 group. A persistent slight weight loss in the face of a strongly positive nitrogen balance may accompany this deficiency.

scholarly journals ANEMIA AND HYPOPROTEINEMIA

1947 ◽  
Vol 85 (3) ◽  
pp. 267-275 ◽  
Author(s):  
L. L. Miller ◽  
F. S. Robscheit-Robbins ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Body Weight ◽  
Plasma Protein ◽  
Nitrogen Balance ◽  
Essential Amino Acids ◽  
The Body ◽  
Liver Protein ◽  
Food Proteins ◽  
Positive Nitrogen Balance ◽  
Maintain Body Weight

Dogs with sustained anemia and hypoproteinemia due to bleeding and a continuing low protein or protein-free diet with abundant iron are used to test the value of food proteins as contrasted with mixtures of pure amino acids. The stimulus of double depletion (anemia and hypoproteinemia) drives the body to use every source of protein and all protein-building materials with the utmost conservation. Raiding of body tissue protein to produce plasma protein and hemoglobin is a factor when protein-building factors are supplied in small amounts. In this severe test (double depletion) the good food proteins in adequate amounts are able to maintain body weight, a strongly positive nitrogen balance, and produce considerable amounts of new hemoglobin and plasma protein. Casein, lactalbumin, whole egg protein, liver protein are all adequate in amounts of 150 to 250 gm. protein per week. Under comparable conditions mixtures of pure amino acids (essential for growth) do produce large amounts of new hemoglobin and plasma protein and a positive nitrogen balance but do not maintain body weight. The loss of weight is conspicuous even with large amounts of amino acids (200 to 300 gm. protein equivalent per week). Methionine, threonine, and phenylalanine are related to nitrogen conservation in growth mixtures of essential amino acids (Paper I) but when these three are given together they have little influence on the doubly depleted dog (Table 3). Some unidentified substance or compound present in certain proteins but absent in mixtures of the essential amino acids may be responsible for these differences in the response of the doubly depleted dog.

scholarly journals TEN AMINO ACIDS ESSENTIAL FOR PLASMA PROTEIN PRODUCTION EFFECTIVE ORALLY OR INTRAVENOUSLY

1943 ◽  
Vol 77 (3) ◽  
pp. 277-295 ◽  
Author(s):  
S. C. Madden ◽  
J. R. Carter ◽  
A. A. Kattus ◽  
L. L. Miller ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Protein ◽  
Nitrogen Balance ◽  
Protein Intake ◽  
Protein Production ◽  
The Body ◽  
Acid Mixture ◽  
Negative Nitrogen Balance ◽  
Growth Mixture

When blood plasma proteins are depleted by bleeding with return of the washed red cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet protein intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications. When the protein intake of such dogs is completely replaced by the growth mixture (Rose) of crystalline amino acids, plasma protein production is excellent, weight and nitrogen balance are maintained. This growth mixture consists of ten amino acids, threonine, valine, leucine, isoleucine, tryptophane, lysine, phenylalanine, methionine, histidine, arginine, and is as effective as most diet proteins in plasma protein production. The above amino acid mixture in aqueous solution may be given by vein with equally good plasma protein production and no apparent clinical disturbance even when given rapidly. Cystine may replace methionine in the above mixture with equally good plasma protein production for 7 to 10 days but at the expense of the body tissues, that is, with weight loss and a negative nitrogen balance. The addition of cystine to the protein-free, otherwise adequate diet may result in the production of considerable new plasma protein during a period as long as 1 week (cystine effect). This reaction may depend upon the amino acid constitution of the preceding diet protein in that it occurred following a liver feeding but did not occur after pancreas feeding. Arginine is required in the diet of the protein depleted dog for fabrication of plasma protein. It is apparently not needed for nitrogen balance for as long as 1 or 2 weeks. The omission of either threonine or valine from the growth mixture is quickly followed by a sharp decline in plasma protein formation and by a negative nitrogen balance. When histidine, arginine, and most of the lysine are omitted from the growth mixture, nitrogen balance and weight may be maintained for as long as 1 week but plasma protein production falls off markedly. The findings indicate that the growth mixture of amino acids should be a valuable addition to transfusion and infusion therapy in disease states associated with deficient nitrogen intake or tissue injury and accelerated nitrogen loss, including shock, burns, and major operative procedures.

scholarly journals PLASMA PROTEIN PRODUCTION INFLUENCED BY AMINO ACID MIXTURES AND LACK OF ESSENTIAL AMINO ACIDS

1945 ◽  
Vol 82 (2) ◽  
pp. 77-92 ◽  
Author(s):  
S. C. Madden ◽  
F. W. Anderson ◽  
J. C. Donovan ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Protein ◽  
Protein Production ◽  
Daily Intake ◽  
Essential Amino Acids ◽  
Nitrogen Excretion ◽  
Acid Mixture ◽  
Rapid Weight Loss ◽  
Urinary Nitrogen

When blood plasma proteins are depleted by bleeding with return of red cells suspended in saline (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and intoxication and probably to vitamin deficiency. When the diet nitrogen is provided by certain mixtures of the ten growth essential amino acids plus glycine, given intravenously at a rapid rate, plasma protein production is good. The same mixture absorbed subcutaneously at a slower rate may be slightly better utilized. Fed orally the same mixture is better utilized and associated with a lower urinary nitrogen excretion. An ample amino acid mixture for the daily intake of a 10 kilo dog may contain in grams dl-threonine 1.4, dl-valine 3, dl-leucine 3, dl-isoleucine 2, l(+)-lysine·HCl·H2O 2.2, dl-tryptophane 0.3, dl-phenylalanine 2, dl-methionine 1.2, l(+)-histidine·HCl·H2O 1, l(+)-arginine·HCl 1, and glycine 2. Half this quantity is inadequate and not improved by addition of a mixture of alanine, serine, norleucine, proline, hydroxyproline, and tyrosine totalling 1.4 gm. Aspartic acid appears to induce vomiting when added to a mixture of amino acids. The same response has been reported for glutamic acid (8). Omission from the intake of leucine or of leucine and isoleucine results in negative nitrogen balance and rapid weight loss but plasma protein production may be temporarily maintained. It is possible that leucine may be captured from red blood cell destruction. Tryptophane deficiency causes an abrupt decline in plasma protein production. No decline occurred during 2 weeks of histidine deficiency but the urinary nitrogen increased to negative balance. Plasma protein production may be impaired during conditions of dietary deficiency not related to the protein or amino acid intake. Skin lesions and liver function impairment are described. Unidentified factors present in liver and yeast appear to be involved.

scholarly journals HEMOGLOBIN AND PLASMA PROTEIN

1943 ◽  
Vol 77 (4) ◽  
pp. 375-396 ◽  
Author(s):  
F. S. Robscheit-Robbins ◽  
L. L. Miller ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Protein ◽  
The Body ◽  
Acid Mixture ◽  
Blood Proteins ◽  
Body Protein ◽  
Growth Mixture ◽  
Amino Acid Mixtures ◽  
Hemoglobin Production

Given healthy dogs, fed abundant iron and protein-free or low protein diets, with sustained anemia due to bleeding, we can study the capacity of these animals to produce simultaneously new hemoglobin and plasma protein. The reserve stores of blood protein producing materials in this way are very largely depleted, and levels of 6 to 8 gm. per cent for hemoglobin and 4 to 5 gm. per cent for plasma protein can be maintained for considerable periods of time. These dogs are very susceptible to infection and to injury by many poisons. Under such conditions, these anemic and hypoproteinemic dogs will use very efficiently a variety of digests (serum, hemoglobin, and casein) and the growth mixture (Rose) of pure amino acids. Nitrogen balance is maintained and considerable new blood proteins are produced. Dog plasma by vein is used freely in these doubly depleted dogs to make new hemoglobin in abundance (Table 1). Serum digests by vein are well utilized to make new hemoglobin and plasma protein in the same dogs (Table 1). Serum digests by mouth are effectively used to make new blood proteins (Table 5). Dog or sheep hemoglobin given in large amounts intraperitoneally are remarkably well utilized to form hemoglobin and plasma protein (Table 6). It must be obvious that the globin of the hemoglobin is saved in these protein-depleted dogs and used to make large amounts of hemoglobin and plasma protein. Hemoglobin digests are also well utilized whether given by mouth (Table 7) or by vein (Table 8) and liberal amounts of plasma protein are manufactured from digests presumably ideally suited for hemoglobin production. Casein digests are well used (Table 8) and form as much new plasma protein as any material tested—even serum digests. Amino acid mixtures are of especial interest. The growth mixture of 10 amino acids (Rose) is well utilized by mouth or by vein and favors new hemoglobin production more than any material tested (Table 2). Cystine replacing methionine in the amino acid mixture increases the plasma protein—hemoglobin output ratio, that is it favors plasma protein production. Digests of various sorts and amino acid mixtures or combinations of digests and amino acid mixtures can be used rapidly and effectively to build new hemoglobin or plasma protein, to maintain nitrogen equilibrium, and to replete reserve protein stores. These experiments point to clinical problems. The unexplained preference given to hemoglobin production in these hypoproteinemic dogs is observed under all conditions, even when whole plasma or serum digests are given by vein. In general, 2 to 4 gm. of hemoglobin are formed for every gram of plasma protein. This all adds up to a remarkable fluidity in the use of plasma protein or hemoglobin which can contribute directly to the body protein pool from which are evolved, without waste of nitrogen, the needed proteins, whether hemoglobin, plasma protein, or tissue proteins.

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