Plasma Proteins: Their Source, Production and Utilization

Madden, S. C.; Whipple, G. H.

doi:10.1152/physrev.1940.20.2.194

Cited by 254 publications

(61 citation statements)

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“…The latter portion is believed to represent a readily available source of needed plasma protein in the hypoproteinemic animal. Operation of this equilibrium and the draining and replenishment of dispensable fractions have been frequently observed in this laboratory (23). Rittenberg, Schoenheimer, and others (27,28) have reported excellent evidence for the rapid interchange of tissue and plasma proteins, and have found varying planes of metabolic activity among body proteins.…”

Section: ~16mentioning

confidence: 75%

“…Patterns of normal dogs and successive analyses in the same dog (Tables 2 and 3) indicate a range of variation no greater than that reported for human plasmas (7,24). Suitably designed experiments in the dog may thus prove applicable to problems of general interest in plasma protein metabolism and may be of aid in studying some of the interesting pathological Constant plasma protein concentration in the normal animal reflects a steady state between tissue proteins on the one hand and plasma proteins on the other (12,23,35). In plasmapheresis experiments we disturb the steady state and observe the process of its restoration toward normal.…”

Section: Discussionmentioning

confidence: 99%

“…~LECTROPIIOI~ETIC STUDIIES ON PLASMA PROTEIN M~TA.BOLIS~ tissue reserves on the one hand and plasma proteins on the other has been formulated to explain such observations (23,34,35). This concept pictures cellular protein as consisting, in a physiological sense, of three portions--an indispensable fraction, a dispensable fraction, and a labile fraction (34).…”

Section: ~16mentioning

confidence: 99%

“…Madden and Whipple (23) in reviewing their data, find that the tissues of a fasting dog may furnish to the plasma in acute depletion an amount of protein equal to 40 to 60 per cent of the original eirculating protein. In more prolonged depletion experiments they find evidence that the total reserve stores comprise a pool from which may be formed a quantity of plasma protein equal to one or two times that normally circulating in a well nourished dog.…”

Section: ~16mentioning

confidence: 99%

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Plasma Protein Metabolism—electrophoretic Studies

Zeldis

Alling

1945

Journal of Experimental Medicine

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Electrophoretic patterns of normal dog plasma in veronal buffer at pH 8.5 are shown to be essentially similar to patterns of human plasma. Dog albumin has a higher mobility than human albumin and in a mixture of dog and human plasmas migrates as a partially separated peak. Normal dog plasma frequently shows four alpha globulin peaks. Rates of restoration of plasma protein components in dogs subjected to acute plasmapheresis have been studied by electrophoresis. During the first 24 hours following such acute depletion, appreciable quantities of all electrophoretic components of the plasma proteins enter the circulating blood stream even when food is not given and has not been given for 12 hours before plasmapheresis. In such fasting periods albumin and total globulin appear in approximately the proportions present in normal plasma. Alpha and beta globulins continue relatively elevated during subsequent days in which caloric and protein intakes are adequate for weight and nitrogen gains. Initial albumin levels, however, are regained more slowly than those of total globulin. The relative proportions of the electrophoretic components of plasma proteins may be disturbed from normal following a single acute depletion for as long as 2 to 3 weeks after the total protein level has returned to normal. Abnormally high beta globulin and fibrinogen, but a low albumin, were found in a dog with an acute and chronic cholangitis and hepatitis. Similar elevation of gamma globulin was noted in a dog in which a hemolytic reaction occurred.

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Section: ~16mentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: ~16mentioning

confidence: 99%

Section: ~16mentioning

confidence: 99%

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Plasma Protein Metabolism—electrophoretic Studies

Zeldis

Alling

1945

Journal of Experimental Medicine

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“…For 30 consecutive weeks, (210 days), Dog 41-187 was maintained in nitrogen and weight balance and produced considerable blood plasma protein from amino acids injected intravenously, subcutaneously, or intraperitoneally. The amount of plasma protein produced was comparable to that which might be obtained from feeding any one of several good proteins by mouth (12 Tables 1 and l-a) produced no consistent change in plasma production so that the Vj mixture should he considered the most efficient, having the lowest total content. The Vt mixture of periods 16 to 20…”

Section: Experimental Observationsmentioning

confidence: 75%

Amino Acid Mixtures Effective Parenterally for Long Continued Plasma Protein Production. Casein Digests Compared

Madden

Woods

Shull

et al. 1944

Journal of Experimental Medicine

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Our objective in the experiments tabulated below is a better understanding of the amino acid requirements for plasma protein production. It is important to determine the optimal make-up of mixtures which are used by the plasma-depleted dog to produce new plasma proteins. Briefly it may be said that the better mixtures of amino acids rate with the best food proteins in the production of new plasma protein in dogs standardized as described below under Methods. They are better tolerated when given intravenously than are casein digests, producing no clinical disturbance when given several times faster than the tolerable rate for such digests. They provide nitrogen balance as well as plasma protein production over periods of several months.In a previous report (11) it was found that good plasma protein regeneration was obtained from feeding or injecting the ten amino acids determined by Rose (21) to be essential for the growth of rats. Further tests have now been made of various mixtures of these ten acids and of non-essential amino acids. Similar mixtures of the ten essential amino acids plus glycine have appeared similarly well used and tolerated in the first trial in a human patient recently reported (2) as well as in other trials in patients to be reported soon. These mixtures appear not to have the undesirable vomiting and pyrogenic effects noted in an earlier report regarding the use in infants of an amino acid mixture containing more of the non-essential amino acids (25).Subcutaneous administration of the better mixtures of amino acids in 10 per cent solution in distilled water produces no clinical disturbance in dogs or in man and is accompanied by good utilization. The availability of the subcutaneous route is a great boon in many instances where repeated daffy injections are indicated. It is particularly fortunate that solutions of high concentration are so well tolerated.* We are indebted to Merck and Company, Inc., for the crystalline amino acids used in these experiments.We are indebted to Eli Lilly and Company for aid in conducting this work and for valuable materials. 6O7

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