bluuebunny/crossref_metadata_2025 huggingface dataset:
Notes on the Mechanism of Leukocytosis
Authors: POLAK H. , NEMEC J. , Zita Z. , Blazková J. , Kucerová M.
Published: October 2019

The authors studied the influence of a six hour infusion of 25 I.U. of ACTH on the contractility and motility of leukocytes and on the absolute number of neutrophils in 10 convalescent patients.

The findings were as follows:

1. A significant increase occurred in leukocyte motility after the ACTH infusion, together with an increase in contractility.

2. The authors assume that leukocytosis following ACTH is due to an increase in the contractility of neutrophil leukocytes.

3. In view of the differences in the bone marrow reserve of mature neutrophils, it is impossible to demonstrate a direct correlation between the increase in motility, contractility and the absolute number of neutrophils.

4. An indirect estimate of the bone marrow granulocyte reserve can be made from the absolute number of neutrophils and the degree of leukocyte motility.
Studies of the Rate of Production and Life Span of Erythrocytes in Acute Leukemia
Authors: NATHAN DAVID G. , BERLIN NATHANIEL I.
Published: October 2019

The rate of red cell formation and the red cell life span were determined in six adult patients with acute myelogenous leukemia by the use of Fe59, Cr51 and glycine-2-C14. One patient with acute monocytic leukemia was studied with Fe59 alone.

Erythropoiesis was normal or increased in two patients, deficient in four patients and absent in one. The data indicate that in the cases of deficient erythropoiesis a decreased number of red cells were produced in the marrow, but that they were released at a rapid rate.

The red cell life span appeared to be normal in one patient, short but finite in four patients, and short owing to random destruction in one patient. One study did not include the measurement of red cell life span.

The liver removed an abnormally large proportion of the plasma iron when marrow erythropoiesis was deficient.

The bone marrow examination may be an unreliable indicator of the rate of erythropoiesis.
The Measurement of Folic Acid Activity in Serum: A Diagnostic Aid in the Differentiation of the Megaloblastic Anemias
Authors: HERBERT VICTOR , BAKER HERMAN , FRANK OSCAR , PASHER INEZ , SOBOTKA HARRY , WASSERMAN LOUIS R. , Weill Hazel , Bandel Lee
Published: October 2019

A modified L. casei microbiologic assay for the "folic acid" content of fasting serum appears to reflect the presence or absence of folic acid deficiency in patients with megaloblastic anemia of various causes.

Advantages of this assay method for fasting serum "folic acid" level over other procedures presently in use for evaluating possible folic acid deficiency are discussed.
Autocannibalism: The Etiology of Nerve-Resection Anemia
Authors: BEUTLER ERNEST , HOFSTRA DIANA
Published: October 2019

1. The finding of Hollán that severe anemia follows nerve resection in rats has been confirmed.

2. By the use of total-body labeling with radioiron, it has been demonstrated that this anemia is due to blood loss.

3. The blood lost by the nerve-sectioned rat is found in the stools, but autopsy reveals no source of gastrointestinal bleeding.

4. Anemia occurs only in animals with excoriation of the denervated foot. Anemia may be precipitated by withdrawing food for 48 hours. Hollán has found that amputation of the denervated limb prevents onset of the anemia.

5. It is concluded that nerve-resection anemia in the rat is due to autocannibalism of the denervated foot.
The Cellular Composition of Inflammatory Exudates in Human Leukemias
Authors: BOGGS DANE R.
Published: October 2019

An induced inflammation in patients with the leukemias was studied with reference to the cellular character of the exudate. Patients with the chronic forms of leukemia generally exhibited a normal cellular response. The granulocytic character of the exudate was proportional to the number of circulating mature neutrophils and metamyelocytes. Immature leukemic cells were not found in the exudates. The patients with acute leukemia with markedly reduced circulating mature granulocytes responded with acellular exudates or with marked qualitative and quantitative alteration in cellular composition. Bacterial infection was most frequent in the patients with few or no cells in the exudate.

The nature of the defect or defects in leukemia relating to increased susceptibility to bacterial infection are reviewed.
In Vitro and in Vivo Assessment of the Viability of Dog Marrow after Storage
Authors: MANNICK JOHN A. , LOCHTE HARRY L. , THOMAS E. DONNALL , FERREBEE JOSEPH W.
Published: October 2019

Assessment has been made of the ability of dog marrow cells to survive storage at 4 C. and at -79 C. Survival has been assessed in vitro by measurements of rates of DNA synthesis and in vivo by ability to restore marrow functions in lethally irradiated recipients.

Dog bone marrow cells synthesize DNA in vitro at values 30 to 80 per cent of normal after storage for 24 hours at 4 C. DNA synthesis is reduced to very low levels by storage for 96 hours at 4 C. Eight lethally irradiated beagle dogs (600 to 1500 r) survived acute irradiation effects and returned to normal health after receiving intravenous infusions of autologous bone marrow that had been stored at 4 C. for 24 hours or less. One dog, similarly irradiated, failed to survive when given marrow stored for 96 hours at 4 C. A tenth dog did survive when given an exceptionally large quantity of marrow stored for 96 hours at 4 C.

Dog marrow cells synthesize DNA in vitro at values 40 to 50 per cent of normal in samples stored at -79 C. in 15 per cent glycerol for periods up to 17 days. Five lethally irradiated beagle dogs (1000 to 1500 r) survived acute irradiation effects and returned to normal health after receiving intravenous infusions of autologous marrow that had been stored at -79 C. in 15 per cent glycerol. One other dog, similarly irradiated and treated, regained marrow function but died of hepatitis. Two other irradiated dogs similarly treated did not regain marrow function and died. These two had received exceptionally small infusions of marrow cells.

The observations demonstrate that dog marrow can be preserved satisfactorily at 4 C. for 24 hours and in glycerol at -79 C. for longer periods. The capacity of the stored marrow to synthesize DNA in vitro has correlated well with its ability to induce recovery in lethally irradiated autologous recipients. DNA synthesis in vitro appears to be a useful index of the ability of marrow cells to proliferate in vivo.
Oxygen Tension Measurements in Bone Marrow Fleck Cultures
Authors: DAVIS J. G. M. , WOODLIFF H. J.
Published: October 2019

An electrochemical method of measuring the oxygen tension in the fluid phase of serum agar cultures of bone marrow flecks is described. The normal pattern of oxygen uptake by the flecks is presented and the possible applications of the technic discussed.
A Simple Method for the Assay of Factor VIII
Authors: BERGNA LUIS JOSÉ
Published: October 2019

A simple method for the assay of factor VIII activity, based on the thromboplastin generation test of Biggs and Douglas, has been described.

Bovine serum is used as a source of factor V and serum factors, and plasma from a hemophiliac is not required. The concentration of factor VIII of the test plasma is compared to that of a standard normal human plasma. The results obtained with the method have been fairly reproducible.
The Kinetics of Intravenously Injected Radioactive Vitamin B12: Studies on Normal Subjects and Patients with Chronic Myelocytic Leukemia and Pernicious Anemia
Authors: BRODY EUGENE A. , ESTREN SOLOMON , WASSERMAN LOUIS R.
Published: October 2019

1. Studies of the fate of intravenously injected radioactive vitamin B12 have been performed in patients with normal, low and high serum concentrations of vitamin B12.

2. Abnormal plasma disappearance curves were noted in chronic myelocytic leukemia, pernicious anemia in relapse and in remission, total gastrectomy and malabsorption syndrome.

3. In chronic myelocytic leukemia, the slow clearance of plasma radioactivity may be explained by the increased binding capacity of the plasma proteins for vitamin B12.

4. Plasma clearance of radioactivity is slower than normal in pernicious anemia, even in remission. The failure of the disappearance curve to return to normal in pernicious anemia in complete remission suggests the existence of a plasma "B12-transferase," whose function is to transfer circulating B12 to the tissues. The disappearance curves suggest that the amount of such "B12-transferase" is diminished in pernicious anemia, total gastrectomy and certain Cases of malabsorption syndrome.

5. A relationship between a hypothetical "B12-transferase" and intrinsic factor is discussed.
Erythrokinetics in the Megaloblastic Anemia of Tropical Sprue
Authors: SHEEHY THOMAS W. , RUBINI MILTON E. , BACO-DAPENA RAUL , PEREZ-SANTIAGO ENRIQUE
Published: October 2019

Blood production and destruction were measured in 10 patients with the megaloblastic anemia of tropical sprue. Methods employed included the determination of the erythroid/myeloid ratio of the marrow, plasma iron turnover, red cell utilization of Fe59 and Cr51 red blood cell survival. Rates of production and destruction were compared to normal.

Patients with the megaloblastic anemia of sprue were usually not iron deficient. Total bone marrow erythroid activity did not approach the maximal response seen in other hemolytic anemias, and there was a marked decrease in the delivery of erythrocytes to the peripheral blood. The rate of red blood cell destruction was increased, but as the red cell volume decreased, the total mass of erythrocytes destroyed per day varied from less than normal to twice normal. Bilirubinemia was not marked, because the amount of hemoglobin destroyed daily was usually not excessive and excretory function was not impaired. The severity of the anemia was largely related to the erythrocyte production defect.
Observations on the Foam Cell in Thalassemia
Authors: GUPTA P. C. SEN , CHATTERJEA J. B. , MUKHERJEE A. M. , CHATTERJI ANJALI
Published: October 2019

Histologic and histochemical study of the foam cell in the spleen in thalassemia has shown that the foamy appearance is due to the accumulation of an acidic mucopolysaccharide of the chondroitin sulfuric acid type in the cytoplasm of this histiocytic cell. This polysaccharide shows intense red coloration with the periodic acid Schiff reaction, which is thus of great value in demonstrating the foam cell in tissue sections. The possible sources of this mucopolysaccharide have been discussed.
Application of Hematopoietic Cell Grafts to the Treatment of Leukemias and Allied Diseases. A Critical Review
Authors: MATHÉ GEORGES
Published: October 2019

A brief summary has been given of the present knowledge concerning transfusion of hematopoietic cells in laboratory animals and also in man.

A survey has been made of the possible application of grafts of hematopoietic cells in the "preventive" treatment of experimental leukemia with emphasis on irradiation-induced and spontaneous leukemias.

Numerous articles have been devoted to describing attempts at curing experimental leukemias, especially the transplantable varieties, by irradiation followed by transfusion of hematopoietic cells. The results vary from one leukemia to the other. Most authors admit the rarity of eradicating leukemia by irradiation with lethal or supralethal doses followed by transfusion of isologous hematopoietic cells. It has been shown that eradication can eventually be obtained when irradiation is followed by transfusion of homologous hematopoietic cells. This, most probably, is due to an immune reaction of those cells against the leukemic cells. Furthermore, even when the leukemia can be eradicated, the animals usually die from the secondary syndrome.

A detailed analysis is given of the reported literature dealing with attempts at treating human leukemia by irradiation followed by transfusion of autologous, isologous or homologous bone marrow.
Humoral Factor(s) in Experimental Hypersplenism
Authors: PÉREZ-TAMAYO RUY , MORA JAIME , MONTFORT IRMGARD
Published: October 2019

A type of experimental hypersplenism characterized by splenomegaly and thrombocytopenia has been produced in the rat by the repeated intraperitoneal injection of methylcellulose. The urine of these animals was collected and given through a gastric tube to another group of normal rats for a period of 4 weeks. The results were a marked and rapidly developing thrombocytopenia, a delayed but definite anemia with mild reticulocytosis and leukocytosis. When the administration of urine was discontinued, the anemia regressed, but the thrombocytopenia persisted unmodified for 2 weeks. When the urine of hypersplenic rats was again given to this group for 6 additional weeks, it failed to induce anemia or to change the persistent thrombocytopenia. Intragastric administration of urine from normal rats, from rats made anemic by total body radiation and from the hypersplenic group after splenectomy to other groups of normal rats, failed to produce the same changes and only induced moderate leukocytosis.

On the basis of these results, it is postulated that in experimental methylcellulose-hypersplenism in the rat there is a humoral factor(s) responsible for the thrombocytopenia, that this humoral factor(s) is eliminated in the urine and that when such urine is given to normal rats, it is responsible for the thrombocytopenia and partially for the anemia that are observed. Such factor(s) are in some important way related to the presence of the spleen.
Studies in Experimental Eosinophilia. I. Repeated Quantitation of Peritoneal Eosinophilia in Guinea Pigs by a Method of Peritoneal Lavage
Authors: LITT MORTIMER
Published: October 2019

A method is described for studying peritoneal cosinophilia quantitatively in guinea pigs. With repeated lavaging of the peritoneal cavity, the total number of eosinophils accumulating locally each day can be precisely measured. This procedure can be repeated indefinitely in individual animals.

Peritoneal eosinophilia was induced by prolonged series of weekly intraperitoneal injections of horse serum, Limulus hemocyanin or human serum albumin. The response was evident during the first three days following reinjection of foreign protein and ceased by the fourth to the twelfth day. The response was specific, occurring only after reinjection of the same protein used to prepare the animals. With continued injections, the magnitude of the eosinophil response became greater. While the total cell values attained varied considerably from animal to animal, the relative responsiveness of an individual guinea pig remained fairly consistent for months.

In the bone marrow, an increased concentration of eosinophils was found in guinea pigs in which peritoneal eosinophilia could be elicited.

In the blood stream, the reinjection of horse serum resulted in a biphasic response: there was an increase in the concentration of eosinophils during the first 12 hours and again at various times during the next seven days.

Peritoneal exudates were obtained frequently in which as many as 40 per cent of the cells were eosinophils; such exudates commonly contained as many as 50 million eosinophils.
Inhibitory Effect of Some Plasma Protein Fractions When Added to Hemostatic Arterial Blood
Authors: CRUZ W. O. , MAGALHAES J. R. , MEIS L.
Published: October 2019

Dog arterial and venous plasma and lymph were fractionated by Cohn method 10 and the fractions tested for inhibitory activity when added to normal arterial blood in the dog hind leg preparation adapted for studies on hemostasis.

Cohn fraction IV from arterial or venous plasma and from lymph was the only fraction, at low concentrations, able to inhibit the hemostatic ability of normal arterial plasma.

Some facts suggest that alpha-lipoproteins are the plasma constituent of fraction IV with inhibitory effect on normal arterial blood. Biochemical changes in blood plasma seem more important or more directly connected with the mechanism of normal hemostasis control than the participation of blood cellular elements.
Quantitative Hemagglutination Studies in the Rh Blood Group System. I. The Assay of the Anti-D (Rho) Agglutinin
Authors: SILBER ROBERT , GIBBS MARY B. , JAHN ELSA F. , AKEROYD JOSEPH H. , Stelter Grant D.
Published: October 2019

The quantitative hemagglutination technic of Wilkie and Becker has been modified for the assay of saline and incomplete anti-D sera. By this method, the relative potencies of anti-D (Rho) sera were determined with an average error of 29 per cent (95 per cent confidence limits). The effect of duration of trypsin treatment upon the cell’s agglutination by incomplete antibody was investigated. The sensitivity of the technic in discerning small changes in agglutination was applied to the characterization of the prozone. The presence of a reversible equilibrium in the D-anti-D system has been established by two independent methods.
Quantitative Hemagglutination Studies in the Rh Blood Group System. II. A Study of the D (Rho) Agglutinogen
Authors: SILBER ROBERT , GIBBS MARY B. , JAHN ELSA F. , AKEROYD JOSEPH H.
Published: October 2019

The reactivity of Rh positive red cells with saline anti-D sera has been investigated by means of quantitative hemagglutination methods. The inhibitory effect of C on the D antigen has been confirmed and the possibility of inhibition by this antigen in the cis position suggested. It is also suggested that the e antigen has suppressive effect on D. The presence of companion antigens results in a -D-> R2 > Ro > R1 progression of decreasing agglutinability. Within families differences in the agglutination behavior between homozygous and heterozygous D positive cells were found. The heterogeneity of this antigen was confirmed.
Protective Effect of Leukapheresis in Man Against Large Dose Antineoplastic Chemotherapy
Authors: BIERMAN H. R. , KELLY K. H. , MARSHALL G. J. , BYRON R. L.
Published: October 2019

Eight patients with widespread metastatic neoplastic diseases following leukopoietic stimulation by leukapheresis were treated on 10 occasions with large doses of HN2, 30 to 280 mg. (0.6 to 4.1 mg./Kg.). Despite severe hematodepression with anemia, leukopenia and thrombocytopenia, hematopoietic recovery occurred in all instances within 16 to 25 days. The recovery from severe hematodepressant doses of HN2 is attributed largely to the previous leukopoietic stimulation. Doses of HN2 at approximately four times the LD50 were unable to eradicate metastatic tissue in Ewings sarcoma and malignant melanoma.

Although hematopoietic protection was evident, the hazard of injuring the next most vulnerable tissues must be considered as larger amounts of cytotoxic agents are employed.
Reciprocal Relationship of Hemoglobins A2 and F in Beta Chain Thalassemias, a Key to the Genetic Control of Hemoglobin F
Authors: ZUELZER WOLF W. , ROBINSON ABNER R. , BOOKER CLIFFORD R.
Published: October 2019

Two pedigrees, each exhibiting the presence of two distinct thalassemia genes are described. Though indistinguishable by their hematologic stigmata the genes in each pedigree differed in their effect on the quantitative behavior of the minor hemoglobin components A2 and F. One gene produced the usual pattern of elevated values for the A2 fraction with minimal if any increases in the proportion of hemoglobin F. Another gene failed to produce increases in the A2 fraction but gave rise to substantial increments in the amounts of fetal hemoglobin. Still another gene produced a similar pattern but with less marked elevations of hemoglobin F though still well above the usual levels for thalassemic heterozygotes. There were intrafamilial similarities with respect to these features. In one family, the combination of two dissimilar genes had produced the picture of thalassemia major in the propositus.

For the particular thalassemia genes observed a reciprocal relationship in the quantitative behavior of the two minor components could be shown on the basis of comparisons including a larger case material studied by the authors. The apparent vagaries in the quantitative behavior of fetal hemoglobin in thalassemic heterozygotes could thus be explained as related to the presence or absence of an elevated A2 fraction. In general, levels of fetal hemoglobin in the former type rarely exceed 3.5 per cent, in the latter they are rarely below 4.0 per cent.

In accordance with other genetic information the findings are compatible with the assumption that both types of thalassemia genes represent mutations of β genes affecting the synthesis of β chains and thus represent a series of multiple alleles at the β chain locus. This interpretation fits the hypothesis of Ingram and Stretton regarding the nature of the defect in thalassemia.

The factor determining whether predominantly δ or γ chains and consequently hemoglobin A2 or hemoglobin F (or still other fractions) are formed appears to be the nature of the particular amino-acid substitutions in the anomalous β chain, resulting in the utilization of one or another metabolic pathway leading to the formation of different by-products of a metabolic block. The genetic implications of this hypothesis are presented with a view to establishing that current genetic theory does not yet fully account for the observations.

The interpretation of γ chains of fetal hemglobin as primitive β chains produced under the control of the same pair of genes which in normal adult life regulate the synthesis of β chains is offered as the basis for a unifying concept concerning the nature and genetic control of fetal hemoglobin. If valid, this concept appears applicable to all conditions thus far known, normal or abnormal, in which fetal hemoglobin occurs.
Unidentified Reticuloendothelial Cell Storage Disease
Authors: MALININ THEODORE I.
Published: October 2019

1. An abnormal cell of probably reticuloendothelial origin with prominent cytoplasmic granules was observed in the bone marrow, liver and a lymph node of an adult white female with incidentally discovered, asymptomatic hepatosplenomegaly.

2. Histochemical studies revealed the granules to consist of a chemical complex which contained bound lipid and protein.

3. The cells differed from those of Gaucher’s disease, Niemann-Pick’s disease and other storage diseases. The significance of these cells remains unknown.
A Review: The Platelet as a Sponge: A Review
Authors: ADELSON EDWARD , RHEINGOLD JACK J. , CROSBY WILLIAM H.
Published: October 2019

This paper summarizes the evidence in favor of the theory that many of the platelet’s factors are adsorbed onto its surface from the plasma. It is suggested that this ability of the platelet is one of its basic functions. The platelet adsorbs coagulation and perhaps vascular factors on its surface and carries them through the circulation to the area where they are needed most—at the site of vessel wall injury. This adsorption by the platelet may be an active rather than a passive process, since it requires the expenditure of energy and since it continues only so long as the platelet is viable. In those diseases in which there is marked abnormality of the plasma proteins, there is evidence to suggest that associated coagulation and hemostatic defects may be due to interference with this "atmosphère plasmatique."
Enzymatic Studies in the Different Types of Normal and Leukemic Human White Cells
Authors: FREI J. , BOREL CL. , HORVATH G. , CULLITY B. , VANNOTTI A.
Published: October 2019

The development of microanalytical methods and the use of technics resulting in leukocyte preparations of satisfactory purity have allowed us to estimate several metabolic functions and to calculate their relative values in different classes of cells. These different categories were analyzed mathematically in the attempt to determine the total enzyme activity of different types of leukocytes.

We have ascertained that the monocyte, derived directly from the reticuloendothelial system, has glycolytic and proteolytic activity, respiration, reducing power, and esterase activity markedly greater than that of the neutrophilic polynuclear. The lymphocyte shows, with exception of the reducing power, low active enzymatic functions in comparison to the neutrophil. The eosinophil, in two pathologic cases, resembles the neutrophil in glycolytic activity, but possesses very low proteolytic capacity and oxygen consumption.

The enzymatic behavior of the leukemic cell shows that the proteolytic power of the myeloblast is diminished while glycolysis and, occasionally, esterase activity, are raised; in the lymphoblast, glycolysis is low, with a slight Pasteur effect. Synthesis of porphobilinogen is intense in the leukocytes, but formation of the porphyrin ring has been observed only in certain cases of leukemia.

A greater number of cases must be examined in order to confirm these preliminary observations on the enzymatic behavior of leukocytes.
The Effect of 6-Mercaptopurine on the Incorporation of Labeled Amino Acids into Cellular Protein of Chronic Granulocytic Leukemia Leukocytes
Authors: NADLER SAMUEL B. , HANSEN HANS J. , SPRAGUE CHARLES C. , SHERMAN HARRY
Published: October 2019

The leukocytes of chronic granulocytic leukemia incorporate labeled valine and leucine at a higher rate than normal leukocytes. 6-mercaptopurine causes significant decrease in the rate of amino acid incorporation into cellular protein of leukemic cells. The onset of a sharp decrease in the amino acid incorporation rate by granulocytic leukemic cells occurs only after several days of therapeutic oral doses of 6-mercaptopurine. The decrease in incorporation rate precedes the decrease in circulating leukocytes by several days, indicating that damage to a vital function of these cells occurs before their disappearance from the blood stream. The decrease in the amino acid incorporation rate persists as long as the leukemia is in remission and even after therapy has been stopped; it exists until exacerbation occurs. Increase in incorporation accompanies exacerbation of the leukemic cell count. A possible action of 6-mercaptopurine is its role in interference with amino acid incorporation into cellular protein of chronic granulocytic leukemia cells.
Hydroxocobalamin. I. Blood Levels and Urinary Excretion of Vitamin B12 in Man After a Single Parenteral Dose of Aqueous Hydroxocobalamin, Aqueous Cyanocobalamin and Cyanocobalamin Zinc-Tannate Complex
Authors: GLASS GEORGE B. JERZY , SKEGGS HELEN R. , LEE DUK HO , JONES E. LINN , HARDY WILLIAM W.
Published: October 2019

A single intramuscular injection of 500 or 1000 µg. of hydroxocobalamin to 17 individuals resulted in a 1.8- to 4.1-times higher mean serum vitamin B12 blood level, respectively, 5 hours after injection; a 4.6- and 12.8-times higher level 24 hours after injection; a 2.4- and 5.2-times higher level 72 hours after injection, and a 1.6- and 2.4-times higher level by the 2nd through the 4th week after injection than identical doses of cyanocobalamin administered to 19 individuals. The vitamin B12 blood levels following i.m. administration of 500 or 1000 µg. of hydroxocobalamin were significantly higher during the first 24 and 48 hours, respectively, than they were after a cyanocobalamin zinc-tannate complex given to 17 individuals at identical doses.

After a single i.m. injection of 500 or 1000 µg. of hydroxocobalamin, an average of only 16 per cent and 27 per cent, respectively, of the vitamin B12 was lost in the 72-hour urines, as compared to 60 per cent and 69 per cent, respectively, after identical doses of cyanocobalamin. These differences, again, were highly significant statistically.

The results of these studies give evidence of a slower rate of urinary excretion of hydroxocobalamin as compared to that of cyanocobalamin, and of its ability to build up consistently higher and more prolonged vitamin B12 levels in the blood.
Erythrokinetic Studies in Severe Bone Marrow Failure of Diverse Etiology
Authors: GEVIRTZ NORMAN R. , BERLIN NATHANIEL I.
Published: October 2019

1. Erythropoiesis was studied in seven patients with refractory anemia.

2. In all seven patients the total red cell volume was low and the plasma volume elevated.

3. The serum iron was elevated and iron binding protein saturated in six of seven patients.

4. The T½ for clearance plasma Fe59 was decreased in one, normal in two, and increased in four patients.

5. The red cell iron turnover was decreased in six of seven patients.

6. Radioiron accumulated in liver and spleen.

7. Red cell life span was difficult to measure but probably shortened.

8. Androgen therapy in two cases was ineffective, and was associated with a slight effect in one patient.
The Plasma Disappearance of Radioactive Vitamin B12 in Myeloproliferative Diseases and Other Blood Disorders
Authors: HALL CHARLES A. , Finkler Alexander E. , Allen Edward S. , Moore Booker T.
Published: October 2019

1. The plasma disappearance of a small intravenous dose of radioactive vitamin B12 was determined in control subjects and in patients with various blood disorders.

2. A delayed, sometimes irregular, disappearance was observed in the majority of patients with acute and chronic myelogenous leukemia, myeloid metaplasia, and polycythemia vera.

3. Disappearance was normal in the lymphogenous leukemias, secondary polycythemia and relative polycythemia.

4. The abnormalities observed are believed to indicate an abnormality of vitamin B12 metabolism common to the diseases of the myeloproliferative group and are further evidence of the close relationship between these diseases.
Studies on the Fate of Lymphocytes. I. Labeling Small Thymic Lymphocytes with Tritiated Thymidine
Authors: MURRAY RAYMOND G. , MURRAY ASSIA
Published: October 2019

A procedure is described whereby 0.5 ml. suspensions containing 3-5 x 108 small lymphocytes per ml., nearly 50 per cent of which were labeled with H3 thymidine, have been prepared from rat thymus. Repeated doses of thymidine totaling 7-8 µc/Gm. and from two to three days were required to produce this percentage, and it is suggested that longer times would not be much more effective. Preliminary results indicate that cells of such suspensions injected in irradiated hosts are widely distributed, do not appear to disintegrate rapidly or to be massively ingested by the macrophages of the reticuloendothelial system, and are still present in good condition one and two days after injection.
Foamy Histiocytes in Spleens Removed for Chronic Idiopathic Thrombocytopenic Purpura
Authors: CZERNOBILSKY BERNARD , FREEDMAN HOWARD H. , FRUMIN ABRAHAM M.
Published: October 2019

1. Foamy histiocytes with mucopolysaccharide granules are reported in 3 of 47 spleens removed from patients with the clinical picture of chronic idiopathic thrombocytopenic purpura (ITP).

2. The absence of lipid in these histiocytes is demonstrated in one case.

3. These cells resemble the foam cells of thalassemia by their mucopolysaccharide content and absence of lipid.

4. The possibility of a histiocytosis manifesting as ITP is suggested.
Marrow Transplants in Lethally Irradiated Dogs Given Methotrexate
Authors: THOMAS E. DONNALL , COLLINS JOHN A. , HERMAN EMERY C. , FERREBEE JOSEPH W.
Published: October 2019

This report describes 41 dogs that received 1200-1600 r of whole body irradiation followed by infusions of homologous marrow. The clinical and hematologic events in these animals are described.

Five dogs given Methotrexate following irradiation lived beyond four months and appeared to have survived the period of secondary syndromes.
Co60 Vitamin B12 Binding Capacity of Human Leukocytes
Authors: MEYER LEO M. , CRONKITE EUGENE P. , MILLER INEZ F. , MULZAC CLAIRE W , JONES IRVING
Published: October 2019

1. Mature neutrophilic leukocytes show the highest Co60B12 binding capacity.

2. Less mature granulocytes, "blast" forms and eosinophils have little or no Co60B12 binding capacity.

3. Disintegrated mature leukocytes from chronic myelocytic leukemia and polycythemia vera show higher B12 binding capacity than intact cells.

4. Mature leukocytes from patients with chronic myelocytic leukemia and polycythemia vera show a two-phase B12 curve suggesting specific and nonspecific binding, similar to that observed in human serum.

5. Disintegration products from mature neutrophilic leukocytes probably contribute largely to increased B12 binding capacity of serum in chronic myelocytic leukemia and polycythemia vera.
The Kinetics of Cell Proliferation in Cultures of Human Peripheral Blood
Authors: MACKINNEY ARCHIE A. , STOHLMAN FREDERICK , BRECHER GEORGE
Published: October 2019

The kinetics of growth of peripheral blood cells in tissue culture are described. There was a rapid increase of cells in DNA synthesis beginning at 24 hours and by 72 hours 40-45 per cent of the cells were in DNA synthesis. Mitotic rates of ∼ 1 per cent/hour were seen after 72 hours in cultures. Studies with tritiated thymidine and colchicine indicated that these cells represent transformed lymphocytes and do not arise from the cells in DNA synthesis at time zero or from any other small population of cells.
The Regenerative Ability of Hemopoietic Tissue Following Lethal X-Irradiation in Dogs
Authors: PERMAN VICTOR , CRONKITE EUGENE P. , BOND VICTOR P. , SORENSEN DALE K.
Published: October 2019

1. Successful treatment of the hemopoietic phase of the acute irradiation syndrome in dogs at the LD100 (400 r) dose is possible on an individual case basis with good nursing care.

2. The onset and rate of regeneration is related to the radiation dose. Partial regeneration with subsequent death occurs with a 550 r dose.

3. The control of infection during the critical period prior to regeneration appeared to be the limiting factor in successful treatment at the dose levels used in this study.
HEMOPHILIA
Authors: CRADDOCK CHARLES G. , LAWRENCE JOHN S.
Published: October 2019

1. Two cases of hemophilia are presented in whom the development of a circulating anticoagulant was detected. This anticoagulant was demonstrated in the whole blood, plasma, and serum of both patients.

2. Both patients became refractory to treatment with either fresh whole blood, plasma, or antihemophilic globulin (Fraction I of Cohn). In fact, the anticoagulant apparently made its appearance as a result of repeated transfusions or injections of antihemophilic globulin.

3. The anticoagulant in each case was shown not to inhibit any of the elements participating in the classical theory of clotting, i.e., prothrombin, thromboplastin, thrombin or fibrinogen. It was also demonstrated that this anticoagulant was not related to heparin in its mechanism of action.

4. Electrophoretic fractionation of the plasma was carried out, and it was found that the anticoagulant was associated with the gamma globulin fraction of plasma.

5. The demonstration of specific precipitin titres in the serum of each of these patients against antihemophilic globulin seemed to indicate that the mechanism of action of the anticoagulant was to inhibit the action of antihemophilic globulin. This was further substantiated by the in vitro inhibition of the ability of antihemophilic globulin to accelerate the coagulation time of ordinary hemophilic blood.

6. A hypothesis is presented to explain the appearance of the anticoagulant. It is believed that these two hemophiliacs are deficient in or lack antihemophilic globulin in their blood, and hence repeated injections of the globulin either in the form of whole blood, plasma, or Fraction I of Cohn results in "isoimmunization" against the injected globulin. The resulting antibodies inhibit any antihemophilic globulin which may then be injected and hence explain the refractory state exhibited by these two cases. Blood from these patients containing these antibodies likewise exerts an anticoagulant influence when added to normal blood by the same mechanism.

7. A discussion of the implications of this phenomenon in the development of a refractory phase in hemophilia is presented.
THROMBOTIC THROMBOCYTOPENIC PURPURA
Authors: SINGER KARL , BORNSTEIN FREDERICK P. , WILE SIMON A.
Published: October 2019

1. "Thrombotic thrombocytopenic purpura" is the name which we propose for a rare but well-defined disorder which manifests itself clinically as an acute febrile illness and which is characterized by (a) petechiae and ecchymoses, thrombocytopenia, prolonged bleeding time and poor clot retraction, (b) by a severe anemia out of proportion to any observed blood loss, (c) by mild acholuric jaundice, hepato-splenomegaly, (d) by bizarre and intermittent mental and neurologic symptoms and signs, and (e) by a transient leukemoid reaction in the peripheral blood.

2. This clinical picture must be correlated with a remarkable histologic pattern, namely the presence of myriads of platelet thrombi in the small arterioles and capillaries of almost all organs of the body.

3. Eleven such cases have been described in the literature. One case of our own is added.

4. The clinical features of this disease are detailed and the differential diagnosis is discussed. It is emphasized that if the physician is familiar with this syndrome a correct clinical diagnosis may become readily possible.
THE CO-EXISTENCE OF CHRONIC LEUKEMIA AND PREGNANCY
Authors: LI JONAH G. , MCBRIDE ALICE , METTIER STACY R.
Published: October 2019

The co-existence of pregnancy in 4 patients with chronic myelogenous leukemia has been reported. One patient was known to have had chronic myelogenous leukemia 3 years prior to her pregnancy. The diagnosis of leukemia was made during the course of pregnancy in the remaining 3 patients; 1 in the first trimester, the other 2 in the third trimester. No specific therapy was required in any of the patients during pregnancy. Their children at birth showed no stigmata of leukemia.

Current literature on the subject has been reviewed. The consensus is that pregnancy does not influence the prognosis of chronic myelogenous leukemia. During the period of gestation, the symptoms can be controlled by administration of a solution of potassium arsenite (Fowler’s solution) and irradiation therapy over long bones, spleen and mediastinum without exposing the fetus.
Production of Macroglobulins in Vitro and a Study of Their Cellular Origin
Authors: ZUCKER-FRANKLIN DOROTHEA , FRANKLIN EDWARD C. , COOPER NORMAN S.
Published: October 2019

Lymph nodes of three patients with macroglobulinemia of Waldenström were studied in tissue culture and shown to synthesize 19S γ-globulin in vitro.

Lymph node imprints, bone marrow, and buffy coat smears of the same patients consisted almost entirely of lymphocytes. When these were stained with fluorescein-conjugated antiserum to macroglobulin, large and medium-sized lymphocytes and lymphoblasts rather than mature lymphocytes or plasma cells were shown to contain the protein.

It is suggested that 19S γ-globulin may also be synthesized by cells belonging to the lymphoid series under normal circumstances.
Clearance Kinetics of Haptoglobin-Hemoglobin Complex in the Human
Authors: FAULSTICK DYREL A. , LOWENSTEIN JEROME , YIENGST MARVIN J.
Published: October 2019

In 15 human Subjects the rate of clearance of haptoglobin-hemoglobin complex was rectilinear with respect to time between plasma levels of 175-20 mg. of bound hemoglobin.
Editorial: Is Hypersplenism a Dead Issue?
Authors: CROSBY WILLIAM H.
Published: October 2019

Evidence favoring the concept of hypersplenic sequestration seems solid indeed, but it does not exclude the possibility that other splenic mechanisms may also cause cytopenic diseases. Although the evidence in favor of inhibitory hypersplenism is fragile and loopholed, there is still reason to suspect the existence of splenic humoral factors; at least there is room for argument.
Detection of Carriers for Factor IX (PTC) Deficiency
Authors: DIDISHEIM PAUL , VANDERVOORT ROBERT L. E.
Published: October 2019

1. A new assay for factor IX (PTC) is described.

2. With the use of this assay, 11 of 14 obligatory carriers of factor IX deficiency were found to have subnormal factor IX activity.

3. One of these carriers has a mild hemorrhagic history.
The Natural History of Iron Deficiency Induced by Phlebotomy
Authors: CONRAD MARCEL E. , CROSBY WILLIAM H. , Benjamin N. R.
Published: October 2019

1. The sequence of characteristic changes of progressive iron deficiency was demonstrated by serial bleeding of normal volunteers and polycythemic patients.

2. After bloodletting, changes occurred in peripheral blood in the following order: a) fall in hemoglobin concentration; b) decreased plasma iron; c) reticulocytosis, increased MCV and MCH; d) diminution of MCV and MCH, increased total iron-binding protein; and e) decreased MCHC.

3. Characteristic changes of iron deficiency returned to prephlebotomy levels in the following sequence: a) hemoglobin concentration; b) cellular indices; c) serum iron; d) serum iron binding protein; and e) bone marrow hemosiderin, and finally the increased gastrointestinal absorption of iron reverted to normal.

4. Accelerated production of red cells continued in polycythemic patients despite the induction of moderate iron deficiency. Quality was sacrificed for quantity, and thereby a more profound microcytosis occurred than in normal subjects with a similar degree of iron deficiency.
Studies on Agranulocytosis. IV. Effects of Chlorpromazine on Nucleic Acid Synthesis of Bone Marrow Cells in Vitro
Authors: PISCIOTTA ANTHONY V. , KALDAHL JOYCE
Published: October 2019

1. When viable marrow cells were incubated with tritiated thymidine and uridine, the cells became radioactive as nucleic acid synthesis proceeded.

2. Excessive concentrations of chlorpromazine (CPZ) partially inhibited the influx of thymidine and uridine into granulocytes of all patients who had had agranulocytosis due to this drug, and of about 75 per cent of random hospital patients. This drug did not effect nucleic acid synthesis in nine individuals who had been treated with a large amount of CPZ, with no alteration in their leukocyte count.

3. A comparison of the effects of dilution of CPZ upon influx of H3 thymidine into granulocytes showed significant dose-dependent depression of granulocyte labeling in CPZ sensitive persons, and no depression in granulocytes of persons on large doses of CPZ who did not develop leukopenia. Random hospital patients not on CPZ showed a degree of depression between these two groups.

4. The number of radioactive normoblasts in the marrow culture preparations diminished slightly, but not significantly, following incubation with CPZ.

5. Non-myelotoxic drugs, such as Phenergan, aspirin, penicillin, and tetracyclene had no significant effect on the degree of influx of tritated thymidine and uridine.

6. There was no effect of CPZ upon incorporation of H3 DL-leucine into marrow cells.
Kinetics of the Alkali Denaturation of Hemoglobin in the Single Erythrocyte
Authors: MATIOLI GASTONE , THORELL BO
Published: October 2019

A microspectrophotometric method was used to record the alkali denaturation kinetics of the hemoglobin in the single erythrocyte. The results showed that differently reacting types of hemoglobin were co-existing in the single cell from human fetal or adult chicken blood.
Association of Radioactive Chromium with Various Components of Hemoglobin
Authors: MALCOLM DANIEL , RANNEY HELEN M. , JACOBS ALAN S.
Published: October 2019

1) When normal hemoglobin was labeled with Cr51 by incubation of whole blood with Na2Cr51O4, or by incubation of hemolysates with either Na2Cr51O4 or Cr51Cl3, most of the Cr51 activity was associated with the electrophoretically rapid hemoglobin A3. The formation of a Cr51 hemoglobin complex with an isoelectric point lower than that of hemoglobin was thought to be the most likely explanation of this finding.4

2) The radioactivity of Cr51-labeled hemolysates containing hemoglobin S, C, and A was found to be associated with the more rapid electrophoretic components. This finding supports the hypothesis of a lower isoelectric point of a Cr-hemoglobin complex.

3) The association of Cr51 activity with the polypeptide chains of hemoglobin was studied by two approaches: 1) determination of the labeling of components in hemolysates containing hemoglobin A (αA2 βA2) and hemoglobin H (βA4), and 2) determination of the labeling of polypeptide chains of Cr51-labeled normal hemoglobin separated by the method of Huehns and co-workers.12 Cr51 activity was found in both the naturally occurring β chain component (hemoglobin H) and in the β chain component prepared by the method of Huehns and co-workers.12 These findings support the hypothesis of others5,6 that β chains of hemoglobin have a greater affinity for chromium than do α chains.
Mitotic Indices of Human Bone Marrow Cells. II. The Use of Mitotic Indices for Estimation of Time Parameters of Proliferation in Serially Connected Multiplicative Cellular Compartments
Authors: KILLMANN SVEN-ÅGE , CRONKITE EUGENE P. , FLIEDNER T. M. , BOND VICTOR P. , BRECHER GEORGE
Published: October 2019

1) The use and restrictions of mitotic indices in computations of time parameters in various types of mitotable cell compartments are discussed. Mitotic time must be known, and any death function in the mitotable pool must be assumed to be negligible.

2) The importance of the position of mitosis with respect to cytologic boundaries in computations of time parameters of mitotable cytologic compartments from mitotic indices is emphasized.

3) For detailed temporal analysis of catenated mitotable compartments, the parameter "turnover time" is shown to be inadequate. A new parameter, mean compartment transit time, is introduced.

4) In a catenated series of multiplicative cell compartments where the exact position of mitoses in the compartments is not known, precise compartment transit times cannot be calculated from mitotic index. However, the maximum mean transit time of each compartment can be computed from the number of cells in the compartment divided by the cell entry rate into the compartment, and the minimum mean transit time can be computed from the number of cells in the compartment divided by the cell exit rate.

5) Generation time can be calculated from mitotic indices only if it is possible to differentiate cell generations cytologically.
Methods of Altering Nitrogen Mustard Toxicity in Dogs. I. Spleen and Mesenteric Artery Exclusion
Authors: LEMPERT NEIL , LEATHER ROBERT P. , SCHARFMAN WILLIAM B.
Published: October 2019

Forty-five dogs have been treated with varying dosages of nitrogen mustard. Nineteen of these dogs were subjected to cross-clamping of the splenic vessels prior to administration of the drug. No appreciable improvement in mortality or degree of marrow depression has been found with this technic.

Exclusion of the spleen and small intestine has been found to be a practical and reliable method for protecting these organs from the effect of intravenous administration of nitrogen mustard.
A Familial Hemorrhagic Diathesis due to an Antithrombin
Authors: BROWN G. MALCOLM , DIAMANT N. E. , GALBRAITH P. R. , WILSON W. E. C.
Published: October 2019

1) A familial hemorrhagic diathesis has been found to be due to an antithrombin.

2) This antithrombin is not fibrinogen, antithrombin II, III, or IV, and is not similar in its characteristics to the antithrombins described in secondary hemorrhagic conditions.

3) The inheritance of this disorder is not sex-linked but is otherwise not clear. The factor may be a dominant, the expression of which is modified by unknown factors.
The Immunologically Competent Cell ("Immunocyte") System—An Attempt at a Delineation of Cellular Relationships
Authors: Berman Lawrence
Published: October 2019

In Dr. Lawrence Berman’s editorial, "The Immunologically Competent Cell ("Immunocyte") System—An Attempt at a Delineation of Cellular Relationships" (February BLOOD, pp. 246-249), the name of R. S. Speirs (reference No. 24 was misspelled. Our apologies to Dr. Speirs.