UTERINE PEROXIDASE ACTIVITY IN HUMAN ENDOMETRIUM.
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Biomedical subjects
Publications and source records attributed to F V LUCAS.
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During protein depletion produced by plasmapheresis and a very low protein diet there is a proportionately greater decrease in extravascular, extracellular fluid protein than in plasma protein. A shift in the normal ratio of protein in these 2 compartments, approximately 1 to 1 in the dog, to over 2 to 1 as a result of depletion indicates an important, labile source of reserve protein for the plasma in the interstitial fluids. This reserve source is limited since a maximum drop of 50 per cent in the total exchangeable pool and of 75 per cent in the extravascular, extracellular protein occurred after both shorter and longer periods of depletion. Under the rigid conditions of these experiments additional plasma protein removal was associated with loss of weight despite adequate caloric intake. Investigation of the status of the interstitial fluid proteins in other conditions associated with disturbed protein metabolism seems warranted.
The rate of plasma protein turnover is more rapid in dogs receiving adequate dietary protein than when a diet devoid of protein is fed. Both albumin and combined globulins are involved in this change. The difference in turnover is reflected in a total protein half-life of 4.8 days with protein feeding versus 7.8 days without protein in the diet and in the metabolism of 1.0 and 0.65 gm. per kilogram of body weight per day on the respective diets. Additions of dietary protein from 10 to 30 per cent caused no further increase in the rate of plasma protein turnover. With protein depletion due to plasmapheresis and a very low protein diet there is evidence of reduced protein metabolism as indicated by nitrogen retention as well as a reduction in total plasma protein breakdown and interchange of isotope between plasma and tissue proteins. Following introduction of labeled plasma protein into the circulation the net amount of isotope transferred to tissues has been computed from the difference between total plasma protein breakdown and combined C(14) excretion in urine and expired air. In animals receiving adequate dietary protein, tissue transfer amounts to 70 per cent of the total lost from the plasma proteins each day while the percentage rises to 85 in depleted dogs deprived of protein. In dogs with both plasma and tissue proteins labeled it can be estimated that, under conditions of protein feeding, an amount of C(14) approximately equal to that lost from the plasma must recycle to account for the observed decrease in Apparent plasma protein turnover rate, (t(1/2) of 15 versus 5 days). Without protein in the diet the isotope contribution of the tissues to the maintenance of plasma protein levels must be as great as or greater than that transferred in the opposite direction.
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Plasma proteins tagged in vivo by feeding D-L-lysine-epsilon-C(14) to donor dogs have been administered to pregnant dogs by both oral and intravenous routes. A relatively small percentage of the C(14) activity originally incorporated in these proteins is found to pass from mother to fetus after intravenous injection. The amount transferred tends to increase with the length of gestation period and total number of fetuses. Plasma protein labeled with I(131) does not cross the placenta in the dog, but does in the rabbit. Evans blue dye does not cross the placenta of the dog. After oral administration of labeled plasma protein or lysine, C(14) is transferred promptly and in considerable quantity to the fetus. Labeled plasma proteins disappear more rapidly from the circulation of pregnant than of normal dogs. This increased metabolic turnover occurs without excretion of any excess waste metabolites. The chorionic epithelium, gram for gram, is probably 2 to 3 times as active as the hepatic epithelium in protein metabolism. These findings indicate an important placental function related to maternal and fetal protein metabolism. While the placenta utilizes maternal plasma proteins and amino acids, in a quantitative sense the latter appear to supply the major nitrogen needs of the growing fetus.
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Carbon-14-labeled plasma proteins given by mouth to dogs with sterile abscesses undergo decreased absorption, presumably owing to impaired digestion of protein. The turnover of plasma albumin is greatly accelerated but the globulins, excluding fibrinogen, show little change during the acute stage of the sterile inflammation. Fibrinogen shows very rapid production and utilization during acute inflammation. Large amounts of C(14) are incorporated in fibrinogen within a few hours after ingestion of the labeled material. The labeled fibrinogen largely disappears within 2 to 4 days after its production. The appearance of C(14) in new red cells from labeled protein or amino acid sources is reduced by inflammation-evidence of impaired synthesis. The pus of the sterile abscess contains a good deal of C(14) activity which at times is as much as that found in the liver. Pus cell C(14) activity per milliliter is similar after injection of labeled plasma and ingestion of labeled plasma or lysine. However, the pus cell fraction contains 3 to 4 times more C(14) activity per milliliter than does the supernatant fluid when the isotope is fed. In the supernatant fluid the activity is all within precipitable protein, much of which is probably derived from the blood plasma. In spite of increased loss of C(14) as CO(2) in the expired air and in the pus, there is evidence of conservation of protein-building materials for maintenance of new plasma proteins and tissue proteins in the more active organs (e.g. liver)-a shift of protein C(14) from the less active tissues (muscle and skin).
The metabolism of homologous plasma proteins, labeled with lysine-epsilon-C(14), after oral administration to dogs has been investigated. The speed of the various processes involved is indicated by the maximum rate of C(14) O(2) excretion which is attained within 1 to 4 hours, the prompt appearance of protein activity in the plasma and disappearance of non-protein activity from it, both virtually complete in 7 to 10 hours, as well as the rapid incorporation of a large percentage of the fed-C(14) into tissues. There are no essential differences between the behavior of labeled plasma and that of an amino acid digest containing epsilon-C(14) labeled lysine when these two materials are given orally. At the end of 48 hours after labeled plasma feeding, a CO(2) elimination of 16 to 28 per cent of the fed C(14) is noted. In contrast, after 48 hours following labeled plasma by vein, a CO(2) elimination of only 2.5 per cent is recorded-almost a 10 to 1 ratio. We believe this, together with the data concerning plasma and tissue protein activity, represents a significant difference in the metabolic process. The evidence favors a complete breakdown of plasma protein to the amino acid level when given orally but not when given by vein.