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Issue published May 1, 1969 Previous issue | Next issue

  • Volume 48, Issue 5
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  • Research Articles
Research Articles
Metabolic dependence of red cell deformability
Robert I. Weed, … , Paul L. LaCelle, Edward W. Merrill
Robert I. Weed, … , Paul L. LaCelle, Edward W. Merrill
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):795-809. https://doi.org/10.1172/JCI106038.
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Metabolic dependence of red cell deformability

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Abstract

The contribution of the metabolic state of human erythrocytes to maintenance of cellular deformability was studied during and after in vitro incubation in serum for periods up to 28 hr. An initial loss of membrane deformability became apparent between 4 and 6 hr when cellular adenosine triphosphate (ATP) levels were approximately 70% of initial values. Membrane deformability then remained stable between 6 and 10 hr.

Authors

Robert I. Weed, Paul L. LaCelle, Edward W. Merrill

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The role of aminogenic glucagon secretion in blood glucose homeostasis
Roger H. Unger, … , Eugenio Aguilar-Parada, Anna M. Eisentraut
Roger H. Unger, … , Eugenio Aguilar-Parada, Anna M. Eisentraut
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):810-822. https://doi.org/10.1172/JCI106039.
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The role of aminogenic glucagon secretion in blood glucose homeostasis

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Abstract

Hyperaminoacidemia is a powerful stimulus of pancreatic glucagon secretion. These studies were designed to elucidate the role of aminogenic hyperglucagonemia in glucoregulation. Conscious dogs with previously implanted indwelling venous catheters were employed. The results support the view that a role of glucagon is to limit blood glucose decline during hyperaminoacidemia.

Authors

Roger H. Unger, Akira Ohneda, Eugenio Aguilar-Parada, Anna M. Eisentraut

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Effect of Adrenal steroid hormones on the response of the toad's urinary bladder to vasopressin
J. S. Handler, … , A. S. Preston, J. Orloff
J. S. Handler, … , A. S. Preston, J. Orloff
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):823-833. https://doi.org/10.1172/JCI106040.
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Effect of Adrenal steroid hormones on the response of the toad's urinary bladder to vasopressin

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Abstract

This study was designed to examine the effect of adrenal steroid hormones on the response of the toad bladder to vasopressin. Aldosterone enhanced the short-circuit current response, the osmotic water flow response, and the urea permeability response to vasopressin. Since aldosterone also enhanced the short-circuit current response and the osmotic water flow response to adenosine 3′,5′-monophosphate, the steroid effect on the bladder's response to vasopressin appears to be at a step beyond the stimulation of adenyl cyclase.

Authors

J. S. Handler, A. S. Preston, J. Orloff

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Hemoglobin Hasharon (α247 his(CD5)β2): a hemoglobin found in low concentration
S. Charache, … , A. M. Mondzac, U. Gessner
S. Charache, … , A. M. Mondzac, U. Gessner
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):834-847. https://doi.org/10.1172/JCI106041.
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Hemoglobin Hasharon (α247 his(CD5)β2): a hemoglobin found in low concentration

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Abstract

Hemoglobin Hasharon (α247 his(CD5)β2) was found to comprise only 16-19% of hemolysates of carriers. These heterozygotes appeared to have mild, compensated, hemolytic anemia. Hb Hasharon was more heat-labile than hemoglobins A, S, or C. Its specific activity was higher than that of Hb A after administration of 59Fe to two carriers. When hemoglobin synthesis by bone marrow cells was studied in vitro, about 18% of incorporated leucine appeared in the Hb Hasharon fraction. It is suggested that Hb Hasharon is unstable in vivo, and that mild hemolytic anemia and a relatively small decrease in its concentration in hemolysates result from its denaturation within red cells. Decreased synthesis, which appears to be the major cause of the small amount of abnormal hemoglobin, may protect heterozygotes from clinically significant hemolytic anemia.

Authors

S. Charache, A. M. Mondzac, U. Gessner

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Parotid fluid cortisol and cortisone
Fred H. Katz, Ira L. Shannon
Fred H. Katz, Ira L. Shannon
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):848-855. https://doi.org/10.1172/JCI106042.
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Parotid fluid cortisol and cortisone

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Abstract

Parotid fluid corticosteroids, substantially comprised of cortisol and cortisone, were previously demonstrated to rise to far greater levels 4 hr after administration of ACTH than they did in the third trimester of pregnancy, although the plasma total corticosteroid concentrations were similar in these two states. It was therefore suggested that only nonproteinbound corticosteroid gains access to parotid fluid. In the present study parotid fluid cortisol and cortisone and plasma dialyzable cortisol concentrations have been measured in normal men before and 2 hr after 40 U ACTH, and, in another group, before and after 10 days of diethystilbestrol (5 mg daily). Total plasma cortisol rose from a mean of 6.3 to 17.9 μg/100 ml after ACTH and from 14.6 to 39.4 mg/100 ml after the estrogen. However parotid fluid cortisol plus cortisone rose from 0.8 to 2.6 μg/100 ml after ACTH and to only 2.2 after estrogen. This rise resembled that of the plasma dialyzable cortisol (control 0.4, ACTH 1.8, estrogen 1.2 μg/100 ml) rather than the increase in total plasma cortisol which was over twice as high after estrogen as after ACTH. Thus parotid fluid corticosteroids seem to be a good measure of nonprotein-bound corticosteroid, the cortisol available to the cell. The total amount of cortisol plus cortisone excreted is approximately constant, independent of parotid fluid flow rate. Cortisone exceeds cortisol in parotid fluid in the basal state, but after ACTH the situation is reversed.

Authors

Fred H. Katz, Ira L. Shannon

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Serum kynurenine in rheumatoid arthritis
Harry Spiera, Ramon Vallarino
Harry Spiera, Ramon Vallarino
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):856-859. https://doi.org/10.1172/JCI106043.
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Serum kynurenine in rheumatoid arthritis

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Abstract

The concentration of kynurenine has been measured in the serum of patients with rheumatoid arthritis and in a control group. The mean serum concentration was 2.27 ± 0.688 μg/ml for patients with rheumatoid arthritis and 2.95 ± 0.825 μg/ml for the control group.

Authors

Harry Spiera, Ramon Vallarino

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Cardiac hemodynamics in alcoholic patients with chronic liver disease and a presystolic gallop
Lawrence Gould, … , Mohammad Zahir, Mary Di Lieto
Lawrence Gould, … , Mohammad Zahir, Mary Di Lieto
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):860-868. https://doi.org/10.1172/JCI106044.
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Cardiac hemodynamics in alcoholic patients with chronic liver disease and a presystolic gallop

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Abstract

10 male subjects with chronic liver disease and with normal cardiovascular findings, except for the presence of a presystolic gallop, underwent right and left heart catheterization. In general, all of the patients had a high resting cardiac output, narrow arteriovenous oxygen difference, a low peripheral vascular resistance, and normal left ventricular end-diastolic pressures and volumes. The plasma volume was increased in the seven patients in which it was determined.

Authors

Lawrence Gould, Mahmood Shariff, Mohammad Zahir, Mary Di Lieto

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Studies on the control of sodium excretion in experimental uremia
Raymond G. Schultze, … , Howard S. Shapiro, Neal S. Bricker
Raymond G. Schultze, … , Howard S. Shapiro, Neal S. Bricker
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):869-877. https://doi.org/10.1172/JCI106045.
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Studies on the control of sodium excretion in experimental uremia

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Abstract

A study of the mechanisms governing the high rate of sodium excretion per nephron characteristic of patients with chronic renal disease has been made in dogs. A “remnant kidney” was produced by 85% infarction of the left kidney while the right kidney was left intact. A bladder-splitting procedure allowed simultaneous measurement of glomerular filtration rate and the rate of sodium excretion by each kidney. The animals were fed a constant known amount of sodium chloride and 0.1 mg of 9 α-fluorohydrocortisone twice daily throughout the study.

Authors

Raymond G. Schultze, Howard S. Shapiro, Neal S. Bricker

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Effect of physiological variations in free fatty acid concentration on the binding of thyroxine in the serum of euthyroid and thyrotoxic subjects
Lewis E. Braverman, … , Angela E. Foster, Sidney H. Ingbar
Lewis E. Braverman, … , Angela E. Foster, Sidney H. Ingbar
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):878-884. https://doi.org/10.1172/JCI106046.
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Effect of physiological variations in free fatty acid concentration on the binding of thyroxine in the serum of euthyroid and thyrotoxic subjects

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Abstract

The effect of variations in the concentration of free fatty acids (FFA) on the binding of thyroid hormones in serum has been studied in 20 euthyroid subjects and 19 thyrotoxic patients. In the euthyroid group, neither the pronounced decreases in FFA induced by the oral administration of glucose or the intravenous administration of nicotinic acid, nor the marked increases in FFA which followed the administration of nicotinic acid or 2-deoxyglucose were accompanied by significant changes in the per cent of free thyroxine (T4), the protein-bound iodine (PBI), the per cent of endogenous T4 bound by the T4-binding globulin (TBG) or T4-binding prealbumin (TBPA), or the resin sponge uptake of triiodothyronine (T3).

Authors

Lewis E. Braverman, Ronald A. Arky, Angela E. Foster, Sidney H. Ingbar

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Plasma and urinary amino acids in primary gout, with special reference to glutamine
Ts'Ai-Fan Yü, … , Elias Bobrow, Alexander B. Gutman
Ts'Ai-Fan Yü, … , Elias Bobrow, Alexander B. Gutman
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):885-894. https://doi.org/10.1172/JCI106047.
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Plasma and urinary amino acids in primary gout, with special reference to glutamine

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Abstract

Measurement of the plasma free amino acids by column chromatography (AutoAnalyzer) in 32 patients with primary gout showed statistically significant increases or decreases in several components when compared with the spectrum in 18 control subjects, but the absolute amounts involved were small and the mean total plasma amino acid concentrations in both groups were the same. In the urine all major amino acid components, notably glutamine, serine, threonine, and leucine, were lower in our gouty than in our nongouty subjects, as were also the corresponding renal clearance ratios. These deficits could be reproduced by restricting dietary protein, so appear to be due largely to the some-what reduced mean dietary protein intake of our gouty subjects. However, the low renal clearance of glutamine, the most striking and consistent of the deficits in urinary amino acids noted, could not be accounted for by dietary or other relevant factors, and is interpreted as indicating increased tubular reabsorption of glutamine in primary gout. This interpretation was supported by the results of glutamine loading. The possible compensatory relationship of the abnormality in renal handling of glutamine to the deficiency in renal production of ammonia previously reported is discussed.

Authors

Ts'Ai-Fan Yü, Max Adler, Elias Bobrow, Alexander B. Gutman

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Pressure-flow studies in man. An evaluation of the duration of the phases of systole
Alexander Harley, … , C. Frank Starmer, Joseph C. Greenfield Jr.
Alexander Harley, … , C. Frank Starmer, Joseph C. Greenfield Jr.
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):895-905. https://doi.org/10.1172/JCI106048.
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Pressure-flow studies in man. An evaluation of the duration of the phases of systole

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Abstract

This study was designed to assess the independent effects of stroke volume and heart rate on the phases of systole and other selected hemodynamic parameters. By means of the pressure gradient technique instantaneous blood pressure and flow were recorded in the ascending aorta at fixed ventricular rates in five patients with complete heart block and in four patients with atrio-ventricular dissociation induced by ventricular pacing. Because of the variable contribution of atrial systole to ventricular filling, a wide range of stroke volumes were observed at each heart rate. The results indicate that the duration of ejection bears a close direct linear relationship to stroke volume while heart rate has only a weak but independent relation. On the other hand, the duration of total systole is related chiefly to the heart rate but stroke volume exerts an important independent effect. In a given patient, both duration of ejection and pulse pressure reflect changes of stroke volume and the product of the duration of ejection and the pulse pressure shows a good correlation with the stroke volume.

Authors

Alexander Harley, C. Frank Starmer, Joseph C. Greenfield Jr.

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The selective and conjoint loss of red cell lipids
Richard A. Cooper, James H. Jandl
Richard A. Cooper, James H. Jandl
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):906-914. https://doi.org/10.1172/JCI106049.
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The selective and conjoint loss of red cell lipids

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Abstract

The pattern of lipid loss from the membrane of red cells incubated in serum is influenced by the availability of glucose. Under homeostatic conditions with respect to glucose, cholesterol alone is lost. This results from esterification of free cholesterol in serum by the serum enzyme, lecithin:cholesterol acyltransferase, and is associated with a proportional decrease in membrane surface area, reflected by an increased osmotic fragility. This selective loss of membrane cholesterol also occurs in hereditary spherocytosis (HS) red cells, even after incubation for 65 hr in the presence of glucose. The loss of free cholesterol from red cells relative to its loss from serum, under these conditions, is greatest at higher hematocrits, similar to those found in the spleen.

Authors

Richard A. Cooper, James H. Jandl

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Role of the sympathetic nervous system in the renal response to hemorrhage
John R. Gill Jr., Alfred G. T. Casper
John R. Gill Jr., Alfred G. T. Casper
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):915-922. https://doi.org/10.1172/JCI106050.
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Role of the sympathetic nervous system in the renal response to hemorrhage

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Abstract

In 12 studies, a femoral artery and vein of a donor dog treated with desoxycorticosterone were connected by tubing to a renal artery and vein of a recipient dog treated with desoxycorticosterone, and the kidney with its nerve supply intact was perfused at femoral arterial pressure. Infusion of normal saline, which contained albumin, from 2.7 to 3.1 g/100 ml, in the donor produced significant natriuresis in a kidney of the donor (from 112 to 532 μEq/min) and in the perfused kidney (from 60 to 301 μEq/min) of the recipient. Increased sodium excretion in the perfused kidney was associated with an increase in the clearances of inulin and para-aminohippurate (P < 0.01) and a decrease in hematocrit of perfusing blood (P < 0.01).

Authors

John R. Gill Jr., Alfred G. T. Casper

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Extraction and characterization of a thyrotropic material from the human placenta
Jerome M. Hershman, Willard R. Starnes
Jerome M. Hershman, Willard R. Starnes
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):923-929. https://doi.org/10.1172/JCI106051.
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Extraction and characterization of a thyrotropic material from the human placenta

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Abstract

A material with thyrotropic activity was extracted from fresh human placentas. After chromatography of the extract on carboxymethyl cellulose, thyroid-stimulating activity ranged from 0.12 to 1.06 mU of thyroid-stimulating hormone (TSH) per mg of protein in bioassays of eight preparations. The amount of TSH per placenta varied from 113 to 2200 mU and approximated the content of the pituitary gland. Additional purification by gel filtration on Sephadex G-100 gave a maximum activity of 8 mU/mg. The most active portion was eluted in the same position as 125I-labeled bovine or human TSH, a fact suggesting that the molecular size of this thyrotropic substance was similar to that of pituitary TSH. Another placental fraction with weaker activity was eluted earlier indicating that the placental material was heterogeneous.

Authors

Jerome M. Hershman, Willard R. Starnes

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Plasma Progesterone and 17-hydroxyprogesterone in normal men and children with congenital adrenal hyperplasia
Charles A. Strott, … , Teruya Yoshimi, Mortimer B. Lipsett
Charles A. Strott, … , Teruya Yoshimi, Mortimer B. Lipsett
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):930-939. https://doi.org/10.1172/JCI106052.
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Plasma Progesterone and 17-hydroxyprogesterone in normal men and children with congenital adrenal hyperplasia

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Abstract

Plasma 17-hydroxyprogesterone (17-OHP) concentrations in normal men averaged 0.094 μg/100 ml. Studies using suppressive doses of androgens and glucocorticoids showed that 90% of the 17-OHP originated from the Leydig cell. The 17-OHP production rate was 1.8 mg/24 hr. Plasma 17-OHP has a marked circadian variation, the 8 p.m. values being only 40% of the 8 a.m. values. Plasma luteinizing hormone measured in the same samples did not vary.

Authors

Charles A. Strott, Teruya Yoshimi, Mortimer B. Lipsett

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Factor XIII in human plasma and platelets
Jan McDonagh, … , J.-M. Delâge, Robert H. Wagner
Jan McDonagh, … , J.-M. Delâge, Robert H. Wagner
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):940-946. https://doi.org/10.1172/JCI106053.
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Factor XIII in human plasma and platelets

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Abstract

Plasma and platelet factor XIII levels were measured in normal human donors and in a patient congenitally deficient in factor XIII. The purpose of these experiments was to study the role of platelet factor XIII in blood coagulation. On polyacrylamide disc electrophoresis, factor XIII activity in extracts of washed normal platelets appeared as a single peak. This peak was missing or very low when factor XIII-deficient platelet extract was used. The patient was also studied before and after transfusion of fresh frozen plasma. Before transfusion, factor XIII activity could not be detected in the patient's plasma or platelet extracts. 24 hr after transfusion the plasma factor XIII level was still at the anticipated value, but factor XIII activity could not be detected in the platelet extracts. These experiments imply that plasma factor XIII was not transported across the platelet membrane in measurable quantities in vivo. This suggests that platelet factor XIII is a true platelet component and originates in the platelet precursor, the megakaryocyte. Thrombelastographic studies suggest that platelet factor XIII participates in the coagulation process. Thrombelastograms of factor XIII-deficient samples had decreased maximum amplitude and clot elasticity values. The abnormalities were fully corrected by the addition of washed normal platelets to factor XIII-deficient plasma; preincubation of the normal platelets in the deficient plasma had no additional effect. This indicates that platelet factor XIII is immediately available during clot formation.

Authors

Jan McDonagh, R. P. McDonagh Jr., J.-M. Delâge, Robert H. Wagner

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Effect of hypotonic expansion on sodium, water, and urea excretion in late pregnancy: the influence of posture on these results
Marshall D. Lindheimer, Peter V. Weston
Marshall D. Lindheimer, Peter V. Weston
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):947-956. https://doi.org/10.1172/JCI106054.
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Effect of hypotonic expansion on sodium, water, and urea excretion in late pregnancy: the influence of posture on these results

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Abstract

Mineralocorticoid-treated, normotensive third trimester subjects positioned in lateral recumbency were studied before and during the infusion of 300 mEq of hypotonic saline. Urinary sodium excretion increased in all subjects from a mean value of 199 to 416 μEq/min. In 12 maximally hydrated subjects free water clearance (CH2O) and urine flow (V) increased from means of 7.54 and 9.50 to 11.6 and 14.5 ml/100 ml of glomerular filtrate (GFR) Also the ratio of urea to inulin clearance (Curea/Cinulin) increased from 0.59 to 0.64. The changes in the renal handling of water and urea suggest that fractional sodium reabsorption decreased at proximal nephron sites.

Authors

Marshall D. Lindheimer, Peter V. Weston

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Studies on the purification of antihemophilic factor (factor VIII): II. Separation of partially purified antihemophilic factor by gel filtration of plasma
Oscar D. Ratnoff, … , Lawrence Kass, P. Dieter Lang
Oscar D. Ratnoff, … , Lawrence Kass, P. Dieter Lang
Published May 1, 1969
Citation Information: J Clin Invest. 1969;48(5):957-962. https://doi.org/10.1172/JCI106055.
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Studies on the purification of antihemophilic factor (factor VIII): II. Separation of partially purified antihemophilic factor by gel filtration of plasma

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Abstract

A high degree of purification of antihemophilic factor was achieved by filtration of chylomicronpoor human plasma through columns of agarose. The final product contained, on the average, 67 units of antihemophilic activity per mg of protein, and was 3360-fold purified compared with the filtered plasma. The molecular weight of antihemophilic factor appeared to be at least two million. Preparations separated by gel filtration were contaminated with appreciable amounts of plasma thromboplastin antecedent (PTA), and traces of Christmas factor and Hageman factor, but no detectable fibrinogen was present. Similar fractions of plasma prepared from the blood of patients with classic hemophilia, von Willebrand's disease, or a circulating anticoagulant directed against antihemophilic factor contained, on the average, somewhat less protein than normal plasma; whether this difference was significant is not yet known. The purified fractions were partially stabilized by the addition of 1% gelatin. Adaptation of the technique of gel filtration to purification of antihemophilic factor for clinical use remains to be explored.

Authors

Oscar D. Ratnoff, Lawrence Kass, P. Dieter Lang

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