Mary Beth Glendening

Plasma Throinboplastin Component (PTC) Deficiency A New Disease Resembling Hemophilia

Summary1. A severe hemorrhagic disease, characterized by a prolonged whole blood coagulation time due to the delayed formation of thrombin, has been described. The patient with this disease was found to have normal plasma concentrations of all the previously described coagulation factors. 2. The corrective factor in normal plasma or serum can be removed by barium sulfate adsorption. A method for the partial purification and concentration of the patients missing factor has been outlined. The defect in the patients blood may be corrected by the addition of plasma free of previously described thromboplastin components (e.g. platelet-free hemophilic plasma), as well as by small amounts of tissue thromboplastin. The name plasma thromboplastin component (PTC) has been assigned to this previously undescribed coagulation factor.Summary 1. A severe hemorrhagic disease, characterized by a prolonged whole blood coagulation time due to the delayed formation of thrombin, has been described. The patient with this disease was found to have normal plasma concentrations of all the previously described coagulation factors. 2. The corrective factor in normal plasma or serum can be removed by barium sulfate adsorption. A method for the partial purification and concentration of the patients missing factor has been outlined. The defect in the patients blood may be corrected by the addition of plasma free of previously described thromboplastin components (e.g. platelet-free hemophilic plasma), as well as by small amounts of tissue thromboplastin. The name plasma thromboplastin component (PTC) has been assigned to this previously undescribed coagulation factor.

The cause of the blood coagulation defect following abruptio placentae.

Abstract Abruptio placentae is sometimes followed by a hemorrhagic syndrome which results from a sudden depletion of plasma fibrinogen. This defibrination is probably due to the escape of placental or decidual thromboplastin into the maternal circulation. This converts prothrombin to thrombin, which in turn converts fibrinogen to fibrin, and the latter is deposited spottily over a very large vascular surface, sometimes producing serious visceral lesions. The syndrome was reproduced in 18 dogs by the intravenous infusion of human placental thromboplastin. This resulted in fibrinolysin depletion, a variable reduction in prothrombin and accelerator globulin concentrations, an inability of the blood to clot, focal lesions in the liver and kidneys, and oliguria. All of these findings are sometimes encountered in severe cases of abruptio placentae. The administered thromboplastin disappeared almost immediately from the blood and was probably incorporated with the fibrin and fixed by the tissues. No fibrinolytic activity was demonstrated in the undiluted plasma samples from 10 of the dogs in which the syndrome was produced nor in 5 clinical cases of abruptio placentae. Reasons are given for rejecting the hypothesis that an activation of a plasma fibrinolytic enzyme could account for the observed reductions of fibrinogen.

Amino acid concentrations in fetal and maternal plasma

Summary Fetal and maternal plasma samples, obtained at the time of cesarean section, were analyzed by column ion exchange chromatography for individual amino acids. The oncentrations of 9 individual and 3 paired amino acids, plus taurine and urea, are compared. Each amino acid with the exception of proline was found to exist in higher concentration in the fetal blood. This was found to be true when fetal and maternal blood samples were drawn simultaneously and also when maternal samples were compared to blood samples obtained from the newborn infants of other mothers. The data are presumed to be evidence favoring an active, mediated transport of the amino acids across the placental barrier. The relationship of these findings to the rate of fetal protein synthesis and to the endocrine control of the cellular uptake of free amino acids is discussed.

Cyclic biochemical changes in the human endometrium: With special reference to the fibrinolytic enzyme☆

Abstract The biochemical changes occurring in the human endometrium during a menstrual cycle have been reviewed and classified into four patterns. The amount of beta-glucuronidase parallels the estrogen curve, whereas the content of protease is greatest during the regressive phase of estrogen withdrawal. The intracellular concentration of fat and of glycogen follows the progresterone pattern, while the amount of ribonucleic acid and alkaline phosphatase present in the endometrium increases under the influence of estrogen, then declines with the addition of progesterone. A method for measuring the concentration of fibrinolytic enzyme in tissue is described. When applied to human endometrial samples, it was found that the fibrinolytic activity increased in the latter part of the menstrual cycle, regardless of progesterone influence, and was highest during the bleeding phase. The stimulative influence of estrogens and of estrogen withdrawal upon the fibrinolytic activity of uterine extracts was confirmed in rabbits. Increased activity following estrogen administration is due to an increase in total enzyme concentration and not to a reduction of antifibrinolysin. Endometrial fibrinolysin bears a relation to the fluidity of menstrual blood and might be concerned with the process of endometrial disintegration and shedding.

Plasma aminopeptidase activity (oxytocinase) in pregnancy and labor

Abstract The primary oxytocinase activity of pregnancy plasma is apparently due to a cystine aminopeptidase. The latter activity may be measured by a chemical procedure which utilizes the synthetic substrate cystine-di-β-naphthylamide. The results of 110 determinations during pregnancy indicate a progressive rise of this aminopeptidase activity in plasma, paralleling the oxytocinase curves obtained by biologic assay methods. Contrary to some reports, there is no decline of activity during early or late labor, parturition, or the early puerperium. The onset of spontaneous labor in women can hardly be attributed to a diminished ability of the plasma to inactivate endogenous oxytocin.

Influence of pyridoxine on transaminase activity of human placenta, maternal and fetal blood.

Summary 1. The glutamic-aspartic transaminase activity of whole blood from normal pregnant subjects is essentially the same as in non-pregnant subjects. Activity is significantly increased by supplementing the diet with 10 mg of pyridoxine daily. Transaminase activity of fetal blood is twice as great as in maternal blood in mothers not receiving additional vit. B6. The transaminase activity of placental tissue is not altered by prior administration of pyridoxine for several weeks. 2. The results suggest that fetal tissues contain optimal quantities of B6 whereas adults, both pregnant and non-pregnant, contain sub-optimal concentrations for peak enzymatic activity. The method employed is not sufficiently sensitive to demonstrate a reduced “reserve” of B6 in normal gestation, but the data are compatible with the view that pyridoxine supplementation is desirable in human pregnancy.

Calcium and phosphorus dynamics in pregnancy.

Abstract 1. The renal handling of calcium and of phosphorus was studied in 24 women in the sixth, seventh, or eighth month of pregnancy. 2. Serum calcium levels were lower than in nongravid women; the reduction of serum calcium was quantitatively accounted for by a decrease in serum albumin. Protein-binding was not altered by pregnancy. 3. The filtered calcium load, tubular resorption of calcium, and urinary excretion of calcium were not significantly altered by pregnancy. 4. Phosphate filtration and net tubular reabsorption were likewise not altered by pregnancy. 5. Effects of 2 Gm. of calcium taken by mouth varied with the preparation used: (a) calcium lactate produced hypercalcemia with the increment of serum calcium being normally distributed between the protein-bound and free fractions; (b) nonfat milk increased urinary calcium excretion but not the serum calcium level; (c) calcium sulfate and dicalcium phosphate effected no change in serum or urine calcium content; (d) all of the oral calcium preparations raised serum phosphate levels and decreased phosphaturia, with the most potent compound being calcium lactate; and (e) the cause of the phosphate antidiuresis without discernible hypercalcemia at a time when phosphaturia is normally maximal is unknown.

Studies of the isolated perfused human placenta

Summary Methods of perfusing the isolated, surviving human placenta under nearly physiologic circumstances are presented. During periods up to 12 hours, the rate of glucose utilization is about 1 Gm. per kilogram per hour. The production of organic acids causes a steady rise in hydrogen ion concentration with a parallel rise in potassium concentration. No conjugation of bilirubin with glucuronic acid could be observed. Hypoxia results in vasodilatation with increased rates of flow through the fetal vascular bed, whereas high oxygen pressures cause the reverse. It is believed that similar responses occur in utero. The fetal circulation is not responsive to epinephrine or norepinephrine but responds with vigorous vasoconstriction to serotonin and histamine.

Influence of Pregnancy upon Hypertension Induced in Rats by Sodium Chloride and Desoxycorticosterone.

Conclusions 1. Desoxycorticosterone acetate (DCA) and sodium choloride, in amounts sufficient to cause hypetension do not interfere with conception, implantation or normal delivery in rats. 2. When pregnancy in superimposed upon DCA-sodium hypertension, the blood pressure and fluid balance are not affected. There may be a transient increase of proteinuria during the last third of pregnancy. 3. The failure of the elevated blood pressure to fall during late pregnancy, as it regularly does in experimenta renal hypertension, suggests a differece in the chemical mediation of the 2 types of hypertension.

Does monozol stimulate elaboration of pituitary gonadotrophin

Summary Administration of Monozol, 1.5-6.0 mg/day, to 8 hypogonadotrophic human subjects resulted in estrogenic phenomena and the excretion of estrogen in the urine, but did not induce elaboration of pituitary gonadotrophin.