bluuebunny/crossref_metadata_2025 huggingface dataset:
THE LOCALIZATION OF LIPIDS IN HUMAN BLOOD AND BONE MARROW CELLS
Authors: BLOOM MARVIN L. , WISLOCKI GEORGE B.
Published: October 2019

By Baker’s method for the staining of lipids, various types of cytoplasmic rods and granules in leukocytes give a positive acid hematein test but are negative after the pyridine-extraction test. According to Baker,8 this combination of results indicates the presence of phospholipids. Some of the rods and granules which are stained appear to be mitochondria, judging from their shape, size and distribution. as well as from the fact that they coincide in all respects with mitochondria demonstrable by supravital staining. Baker8 pointed out that in a great variety of cells his method stained mitochondria, although he did not report having examined leukocytes. In addition to mitochondria, Baker’s method stains the specific granules of the three varieties of granular leukocytes. In the neutrophilic leukocytes, the granules appear gray or black; in some of the eosinophilic leukocytes, they are intensely black, while in others they are unstained although surrounded by stained ground substance; and in the basophilic leukocytes, some of the granules of individual cells are stained while others are not. Provided the method is chemically specific, it follows that the specific granules of these leukocytes contain phospholipids. The appearance of the eosinophils indicates that many of them possess granules composed of protein surrounded by phospholipid, although some of them contain granules with lipid in their interiors. These differences in the eosinophils suggest possible functional stages, related perhaps to the age of the cells or some other metabolic factors. In the monocytes, besides a general stippling of the cytoplasm corresponding to mitochondria, the region of the attraction sphere often contains numerous deeply stained granules.

Sudan black B stains both the mitochondria and the specific leukocytic granules in a manner similar to Baker’s method. However, certain slight differences were noticed. Platelets were brought out moderately distinctly by the acid hematein procedure, whereas in sudan black preparations they were barely visible. A variability was noted in the staining of the granules of the eosinophilic leukocytes in Baker’s method, in contrast to the uniformity of their staining with sudan black. This difference should perhaps be interpreted as indicating that the eosinophilic granules contain other lipid substances besides phospholipids. Mitochondnia, in whatsoever type of leukocyte they are observed, appear to stain more deeply and distinctly by Baker’s method than with sudan black, a circumstance suggesting that mitochondria are very rich in phospholipids.
BLOOD EXCHANGE IN REPLACEMENT TRANSFUSIONS
Authors: WASSERMAN L. R. , RASHKOFF I. A. , SHARNEY L. , YOH T. F. , LEAVITT D.
Published: October 2019

Red cells labeled with radioactive phosphorus have been used by us to measure the extent and the rate of the replacement of blood in exchange transfusions. The experimental results confirmed the theoretic formulations developed in the preceding paper. On the basis of the above data, it seems reasonable to introduce these curves and formulae whenever exchange transfusions are to be performed.
THE ELECTRICAL CONDUCTIVITY OF BLOOD
Authors: TEXTER E. CLINTON , HIRSCH FREDERIC G. , HORAN FRANCIS E. , WOOD LLOYD A. , BALLARD WILLIAM C. , WRIGHT IRVING S. , STARR DOROTHY , BLANDIN BENJAMIN P.
Published: October 2019

1. The blood and plasma conductance was measured in 157 blood samples. Of these, 101 were from hospital patients with a variety of clinical conditions, 33 were from normal individuals, and 23 were unclassified.

2. Blood counts were done on the same specimens.

3. An empiric equation, was found to give the red cell count from the conductivity measurements, wherein C1 = 10.49, and g is in millions per cu. mm.

See PDF for Equation

4. A nomograph is presented to simplify the calculations of the red cell count.
TRANSFUSION REACTIONS TO A PLASMA CONSTITUENT OF WHOLE BLOOD
Authors: DAMESHEK WILLIAM , NEBER JACOB
Published: October 2019

1. The clinical histories of 11 patients with a severe and hitherto undescribed type of reaction to in vitro compatible whole blood are presented. These patients all experienced beneficial responses to therapy with washed red blood cell transfusions. The technic of washing the blood is outlined.

2. In 5 of the patients, sensitivity to a heat-labile constituent of fresh normal plasma was demonstrated. In the remaining 6 patients, although actual sensitivity to plasma was not proved, transfusions of washed red blood cells were well tolerated and were therapeutically effective.

3. These uncommon reactions to the plasma in whole blood are differentiated from the usual pyrogenic, allergic or hemolytic plasma reactions by their ease of repetition in the absence of pyrogens, by lack of the usual allergic manifestations, and by the failure to demonstrate hemoglobinemia or hemoglobinuria.

4. A simple diagnostic test ("plasma provocative test") is described which appears to be of specific value in the differentiation of the reaction.

5. It is suggested that in any instance of severe transfusion reaction to apparently compatible whole blood this type of sensitivity to the donated plasma should be borne in mind as a possible cause. The plasma provocative test should then be tried. If positive, the transfusion of well washed red blood cells will probably be effective and in some cases may be of life-saving importance.
THE SPECIFICITY OF 4-AMINOPTEROYLGLUTAMIC ACID (AMINOPTERIN) FOR LEUKEMIC HEMATOPOIETIC TISSUE
Authors: SKIPPER HOWARD E. , RISER WILLIAM H. , NOLAN CONSTANCE W.
Published: October 2019

A study of the effect of aminopterin on the hematopoietic tissue of normal mice and mice with transplanted Ak 4 leukemia is reported.

At less than lethal doses, aminopterin showed a striking inhibition specificity for neoplastic cell production.
MALFORMATION OF THE ERYTHROCYTES IN A CASE OF ATYPICAL RETINITIS PIGMENTOSA
Authors: BASSEN FRANK A. , KORNZWEIG ABRAHAM L.
Published: October 2019

A case is presented of a girl, aged 18, born of parents who were first cousins. She had an atypical retinitis pigmentosa with involvement of the macula. The neurologic examination showed diffuse disease of the central nervous system, as seen in Friedreich’s ataxia. An additional finding (hitherto undescribed) was that of a malformation of the red blood cells. These cells had a peculiar crenated appearance, due to the presence of pseudopods or protoplasmic projections varying in size and shape. They were constantly present in stained blood films taken one year apart. A similar finding in a younger brother, with beginning retinal pigmentary degeneration, added additional proof of the hereditary nature of the condition.
EXPERIMENTAL ANEMIAS IN THE RAT
Authors: KODICEK E. , CARPENTER K. J.
Published: October 2019

1. In agreement with findings by other workers, rats in acute pteroylglutamic acid deficiency showed leukopenia and growth depression followed by death, without any significant change in the red cell picture.

2. In chronic deficiency, however, produced by the addition of small pteroylglutamic acid doses given intermittently, a severe anemia was obtained after seventy days.

3. The anemia was macrocytic and "normochromic." Price-Jones curves showed a preponderance of macrocytes with anisocytosis. This agreed with findings by other workers for other species.

4. The anemia could be cured by single doses of 40 µg. or more of pteroylglutamic acid.

5. There was no significant difference between sexes to pteroylglutamic acid deficiency. Reduction in the protein content of the diets, containing 1 per cent sulfasuxidine, from 18 per cent to 10.5 per cent, produced no significant difference in the time of onset and severity of the blood symptoms.

6. These results were not due to infection with Bartonella muris. This infection produced a macrocytic anemia of a different type, and was curable by treatment with neoarsphenamine.
DANGEROUS UNIVERSAL DONORS
Authors: ERVIN DONALD M. , CHRISTIAN RICHARD M. , YOUNG LAWRENCE E.
Published: October 2019

1. Severe hemolytic reactions were observed in 3 group A (subgroup A1) recipients transfused with group O whole blood or plasma. In one case, 10 ml. of a commerical preparation of soluble A and B factors had been added to 500 ml. of whole blood prior to the transfusion and it is believed that the reaction might have been even more serious had not this material been added.

2. The anti-A antibodies in the serum of the dangerous universal donors causing the hemolytic reactions fixed complement, acted as hemolysins, were difficult to neutralize with soluble A and B factors, were capable of giving positive Coombs tests and their ability to agglutinate A cells was enhanced by the presence of normal human serum. These characteristics were similar to those observed in serum from donors known to be actively immunized against the A factor, but the stimulus for development of "immune" anti-A antibodies in the dangerous group O donors was not apparent.

3. Small amounts of immune A antibody were consistently demonstrated in 12 of 100 random group O sera which, after neutralization, produced indirect Coombs tests with A1 cells and agglutinated A1 cells suspended in compatible normal human serum.

4. Screening procedures for elimination of dangerous group O donors are discussed.
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
Authors: CROSBY WILLIAM H.
Published: October 2019

1. A simple and rapid test for paroxysmal nocturnal hemoglobinuria is described. The test is based upon the activation by thrombin of the hemolytic factor in serum which destroys the red cells of this disease.

2. It is believed that the test is specific for paroxysmal nocturnal hemoglobinuria.
Circulating erythropoietic precursors assessed in culture: characterization in normal men and patients with hemoglobinopathies
Authors: Ogawa M , Grush OC , O'Dell RF , Hara H , MacEachern MD
Published: October 2019

Circulating erythropoietic precursors in normal men and patients with hemoglobinopathies were characterized in culture. Blood mononuclear cells harvested with a modification of the Ficoll-Isopaque technique were cultured in methylcellulose for 14 days. The majority of erythropoietic colonies consisted of several subcolonies assuming the morphology of erythropoietic “bursts” described in murine marrow cultures. Time course studied of colony formation from marrow and blood nucleated cells confirmed that the circulating erythropoietic precursors represented only early stages of development. Peak sedimentation velocity of the circulating precursors analyzed using a Staput apparatus averaged 5.31 mm/hr and corresponded with that of the early erythropoietic precursors in human marrow. One ml of blood yielded an average of 153 colonies in normal men and 785 colonies in patients with hemoglobinopathies. No correlation was observed between colony formation and reticulocyte indices of individual patients. Examination of the proliferative state of the erythropoietic precursors using high specific activity tritium-labeled thymidine revealed that almost none of the cells in normal men or patients with hemoglobinopathies were in the DNA synthetic phase.
Blood Cell Formation in Certain Teleost Fishes
Authors: CATTON W. T.
Published: October 2019

1. The blood cells of trout and roach consist of nucleated erythrocytes and reticulocytes, nucleated thrombocytes, coarse and fine granulocytes, and lymphocytes of varying sizes. It is difficult to distinguish any cells showing characteristics similar to those of the monocytes of mammals. Immature cells occur more frequently in the blood than is the case in mammals.

2. The coarse granulocytes very commonly escape from the blood vessels, and have been observed in large numbers in the intestinal mucosa and submucosa, in the gill epithelia, and in the peritoneum. These cells migrate to the epithelial surface, where they undergo changes in structure leading to the formation of a characteristic discharge pattern of their granules. It is proposed that the "granules" are in reality vesicles with fluid contents, which are ultimately discharged at epithelial surfaces.

3. The hematopoietic organs of these fishes are chiefly the intertubular tissues of the kidneys; in the trout the spleen is also active; in the roach, only the kidney is active; in the perch, only the spleen is active.

4. Two alternative hypotheses of blood cell formation are proposed. On the first hypothesis, the common stem cell is described as a "large lymphoid hemoblast," which gives rise to granulocytes by direct transformation and undergoes mitotic division to give rise to "small lymphoid hemoblasts." From the latter develop the erythrocytes, thrombocytes and blood lymphocytes.

On the second hypothesis, the large lymphoid hemoblast, derived by transformation of reticular cells is the precursor solely of the granulocytes, and the small lymphoid hemoblast is to be derived from endothelial cells and is the precursor of erythrocytes and thrombocytes. In this case the large cell is to be compared with the "primitive white cell" of Doan, Cunningham and Sabin, and the small cell with the "megaloblast" of the same authors. No evidence however is available of the derivation of small hemoblasts from endothelial cell components of the reticulo-endothelium.

5. In the maturation of the erythrocyte in teleost fishes, there is a progressive increase in the size of the cell; in mammals and birds there is a decrease in size. In both cases there is a decrease in size in granulocyte maturation.

6. There are no essential differences between the blood cells and hematopoietic processes of the freshwater and marine teleost fishes examined.
Variation and Error in Eosinophil Counts of Blood and Bone Marrow
Authors: BEST WILLIAM R. , SAMTER MAX
Published: October 2019

1. The literature on eosinophil variations under various stresses is reviewed in the light of recent interest in the adrenal cortex as a regulator of blood eosinophil levels. Chamber eosinophil counts are necessary for accuracy in these studies. Phloxine-propylene glycol or eosin-acetone stains with standard white cell pipets and chambers may be employed for simple and satisfactory chamber counts.

2. Statistical formulae are applied to chamber eosinophil counts and marrow differential counts to delineate the theoretic errors. Actual observations differ slightly from the predicted results but substantiate the appreciable intrinsic errors frequently seen.

3. Studies on physiologic variation are reviewed. There are significant minute-to-minute fluctuations as well as a more marked diurnal trend in eosinophil levels with a mid-morning low and a night-time peak. Comparison of single morning eosinophil levels with single noon specimens may be misleading.

4. Oral ephedrine is a potent eosinopenic agent.

5. Repeated tests of the eosinopenic response to ephedrine or epinephrine frequently show significant variation in the same subject.

6. Many patients with various diseases fail to react adequately to ephedrine or epinephrine.

7. Repeated and controlled observations are necessary before conclusions regarding pituitary-adrenal function can be drawn from eosinophil counts alone.
A Method for Quantitative Estimation of Mast Cells in the Bone Marrow of the Rat
Authors: MOTA IVAN
Published: October 2019

Observations of thick smears of marrow obtained from the femur, tibia, humerus, sternum, and ribs (in rats), showed that in the first three bones, the number of mast cells was much higher than in the latter two bones.

A method for the quantitative estimation of the total number of nucleated cells and of mast cells in the bone marrow of rats is presented. The method involves dilution of the marrow, in a red cell pipet, with a 1:50,000 solution of toluidine blue in 3 per cent acetic acid. This method confirmed the results of mast-cell distribution obtained in the study of marrow smears.
Case Report: Cholelithiasis in Severe Mediterranean (Cooley’s) Anemia
Authors: SMITH CARL H. , MORGENTHAU JOAN E.
Published: October 2019

A case of cholelithiasis is reported in a child with the severe form of Mediterranean anemia. The patient was one of a group of children with this disease but without biliary tract symptoms on whom a roentgenographic survey was carried out. Cholecystitis subsequently occurred in this patient, and a cholecystectomy was performed.

Cholelithiasis occurs as a complication of severe Mediterranean anemia, less frequently than in spherocytic or in sickle cell anemia but on a comparable etiologic basis.
Cerebral Blood Flow and Metabolism in Pernicious Anemia
Authors: SCHEINBERG PERITZ
Published: October 2019

1. Cerebral blood flow and metabolism were measured in 16 patients with pernicious anemia. Seven of the patients were restudied in various stages of therapy.

2. The patients fell into two equal groups, those with severe anemia and those with moderate or no anemia. In the first group, cerebral blood flow was increased and cerebral vascular resistance decreased; in the second group, cerebal blood flow was decreased and vascular resistance increased. In both groups, cerebral oxygen and glucose consumption was decreased, as was cerebral venous oxygen tension .

3. There was a good correlation between the mental status defects and cerebral oxygen consumption and between severity of neurologic involvement and cerebral oxygen consumption. There was no correlation between cerebro-vascular resistance and cerebral oxygen consumption, nor between degree of anemia and cerebral oxygen consumption.

4. Specific therapy resulted in a moderate increase in cerebral oxygen consumption and cerebro-vascular resistance. In no instance did cerebral oxygen consumption become normal.

5. The disparity between the functional ability of the patients and the low values for cerebral metabolism is discussed.

6. It is concluded that pernicious anemia results in specific nervous system involvement not related to the anemia, and that this damage is at least partially irreversible in many patients.
Case Report: Splenectomy in Sickle Cell Anemia: Report of a Case and Review of the Literature
Authors: SHOTTON DONALD , CROCKETT CHARLES L. , LEAVELL BYRD S.
Published: October 2019

1. A case of sickle cell anemia who had numerous hemolytic crises and also hypersplenic effects such as pancytopenia was treated by splenectomy with marked improvement in general condition and in the blood. The literature relating to this subject is reviewed. Those cases with the largest spleens appear to have shown the most striking degrees of improvement.

2. In cases of sickle cell anemia showing various indications of hypersplenism, and excessive hemolysis, splenectomy may be a rational therapeutic procedure.
Observations on the Phosphatase Content of Blood and Bone Marrow Cells in Normal and Pathologic Hemopoiesis
Authors: KERPPOLA WILLIAM
Published: October 2019

The alkaline and acid phosphatase content of blood and bone marrow has been studied by the methods of Gomori-Takamatsu and Gomori in normal individuals and in a great number of different diseases. The presence of a particular phosphatase is related to cellular reaction. Alkaline phosphatase was found in orthochromic normoblasts, polymorphonuclear leukocytes, metamyelocytes and older megakaryocytes. Acid phosphatase was demonstrated in basophilic normoblasts, polymorphonuclear leukocytes and their juvenile forms and in young megakaryocytes. In red blood cells and young megakaryocytes phosphatase was present chiefly in the nuclei, in leukocytes and older megakaryocytes in the cytoplasm.

By studying erythropoiesis, especially during active regeneration of blood, it has been shown that alkaline phosphatase plays a decisive part in the disappearance of the normoblast nucleus. In certain diseases abnormality is observed in the disappearance of the normoblast nucleus (effort syndrome, rheumatoid arthritis). In others acid phosphatase occurs in large amounts in the youngest normoblasts (polycythemia vera, rheumatoid arthritis, nephritis). At the same time phosphatase may also be found in polymorphonuclear leukocytes and their juvenile forms. In rare cases of severe anemia alkaline phosphatase (panmyelophthisis) or acid phosphatase (achrestic anemia) is noted in large amounts in nucleated red cells and in leukocytes.

Only alkaline phosphatase is present in polymorphonuclear leukocytes and metamyelocytes in leukemias, myeloma, Hodgkin’s and Paget’s disease, and in some malignant tumors of the skeleton and the liver.

Several circumstances indicate that phosphatases might destroy cells or their nuclei. In some cases phosphatase activity is physiologic, in others phosphatase concentration is related to accelerated or malignant growth of bone marrow or tissue associated with blood formation. Finally there are cases in which there is as yet no explanation for the appearance of phosphatases.
Tail Blood Eosinophil Levels in Several Inbred Strains of Mice Under Standard Conditions
Authors: HALBERG FRANZ , BITTNER JOHN J. , VISSCHER MAURICE B.
Published: October 2019

1. Data have been presented, showing that it is possible to standardize conditions under which absolute eosinophil levels in the tail blood of mature male mice characteristic for different strains can be obtained.

2. The highest eosinophil levels were found in the strain of mice with the lowest susceptibility to mammary cancer among the stocks tested.

3. The absence of the mouse mammary cancer milk agent did not affect the characteristic eosinophil morning level in A or Z mice.

4. Emphasis is placed upon the necessity of rigid control of the circumstances of observation if reproduceable results are to be obtained in the study of eosinophil levels.
Infectious Mononucleosis: the Prognostic Significance of Various Changes of the Blood Leukocytes
Authors: STEVENS JOHN E. , BAYRD EDWIN D. , HECK FRANK J.
Published: October 2019

Peripheral blood smears were studied in 25 selected cases of infectious mononucleosis. In 7 the onset was acute and the course severe, in 6 the onset was acute and the course mild, in 6 the onset was gradual and the course severe, and in 6 the onset was gradual and the course mild. The predominance of any of the various types of lymphocytes of infectious mononucleosis was not noted to bear any relationship to the clinical course, although type III lymphocytes and granulocytic immaturity may be more frequently seen when the onset is acute. When toxic changes are present in the granulocytes, the clinical course is likely to be severe.
Observations on the Hemolytic Mechanism of Paroxysmal Nocturnal Hemoglobinuria
Authors: CLAPP MARY P. , WILLIAMS MARJORIE J. , MENDEL JULIUS L.
Published: October 2019

1. It has been shown that PNH hemolysis can be inhibited in vitro in the following ways: (a) addition of fluoride, phosphate, citrate, oxalate and calcium ions; (b) inactivation at 56 C.; (c) adsorption of a globulin from serum.

2. The action of at least two serum factors ins PNH hemolysis has been demonstrated. One of these factors is heat labile and magnesium dependent and the other is an adsorbable globulin.

3. It is believed that the heat labile factor must react with the cells prior to the adsorbable factor if hemolysis is to occur.

4. The resemblance of these factors to the components of complement is briefly discussed.
Blood Changes in Hemolytic Anemia under ACTH Therapy
Authors: HANSEN KAI BENT , ANDERSEN JøRGEN
Published: October 2019

A case has been reported of a 76 year old man, who, while in the hospital, developed a rather severe acquired, hemolytic anemia with positive Coombs test. Electrophoresis showed serum protein values within normal limits. ACTH was given for ten days and the reaction followed by electrophoretic tracings. A rather strange elevation of gamma globulins was seen during treatment. Simultaneously the Coombs test became negative. Later in the period of treatment, gamma globulins decreased to normal level and the Coombs test again became positive. These findings and the possibility of viral infection as an etiologic factor in hemolytic anemia are discussed.
The Anticoagulant Effect of Bacterial Polysaccharides in Normal and Thrombocytopenic Plasma of Leukemia
Authors: FREEMAN GUSTAVE
Published: October 2019

Bacterial polysaccharides from cultures of Friedländer’s bacillus and Serratia marcescens (Shear’s P-25) tend to prolong the coagulation time of diluted plasma in vitro. This activity appears to be parallel to, but limited with respect to, that of heparin. The anticoagulant effect of bacterial polysaccharide as well as that of heparin is likely to be enhanced in thrombocytopenic plasma of children with acute leukemia.
The Nutritional Status of Folic Acid in Persons with Leukemia and Its Possible Relation to Effects of Aminopterin Therapy
Authors: SWENDSEID MARIAN E. , SWANSON ANN LOUISE , MEYERS MURIEL C. , BETHELL FRANK H.
Published: October 2019

Folic acid excretion following test doses of the vitamin has been measured in 31 cases of leukemia. Although the percentage excretion values varied widely, the average values were significantly lower in cases of both chronic and acute leukemia than in a series of normal subjects. However, this evidence of depletion of body stores of folic acid occurred more frequently and with a greater degree of severity in cases of chronic leukemia, particularly, those with lymphocytic involvement. This suggests that the degree of folic acid nutritional depletion is related to the varying clinical results obtained with antagonist therapy in chronic and acute leukemia.
Certain Endocrine Influences Governing the Leukocytic Response to Fever
Authors: HUBLER WILLIS L. , HIGGINS GEORGE M. , HERRICK J. F. , WOODS MARY J. , CHRISTENSEN GLEN
Published: October 2019

A study is reported of the influences exerted on the levels of the circulating eosinophils, lymphocytes and neutrophils of rats in which body temperatures have been elevated for one hour to 41.0 or to 41.5 C. by means of the Raytheon microwave diathermy apparatus. Preliminary studies were made to determine the influence exerted on these blood categories by the restrictions imposed on the animals such as confinement in cages and insertion of rectal thermistors: factors incident to the experimental procedure. Data were assembled on intact animals, trained to cage confinement and to thermistor implacement, and on such animals subjected to the elevated temperatures. Data were also assembled on adrenalectomized animals, hypophysectomized animals, hypophysectomized-adrenalectomized animals and adrenal-demedullated animals. These data warrant the following conclusions:

1. Cage restrictions and the insertion of the thermistor into the rectum resulted in a mild form of stress inducing a slight eosinopenia, a lymphopenia and a mild neutrophilia. The energy of the microwaves, applied for one hour, greatly accentuated those changes, resulting in marked eosinopenia and lymphopenia, with a greatly increased neutrophilia. When temperatures ranging from 41.0 to 41.5 C. were induced for one hour in previously trained rats, the total eosinophil tabulation decreased in four hours from a control level of 171 ± 24 cells per cu. mm. of blood to 41 ± 5 cells, a decline of 76 per cent. The total number of mononuclear leukocytes decreased from a control level of 19,940 ± 1,000 cells to 8,330 ± 810 cells immediately after heating, while the total number of neutrophilic leukocytes increased from a control level of 3,580 ± 650 cells per cu. mm. to 8,770 ± 1,920 cells at two hours after heating.

2. Adrenalectomy altered the hemograms of rats subjected to those elevated temperatures, by abolishing the eosinopenic and the lymphopenic trends but it did not alter the neutrophilia.

3. Removal of the pituitary gland from animals prior to the increases in their temperatures resulted in an average decrease in the number of eosinophils, a decrease which was not considered significant. The number of neutrophilic leukocytes remained high.

4. When animals lacking both pituitary gland amid adrenal glands were subjected to the same energy for one hour no significant alterations in the number of eosinophils, of lymphocytes or of neutrophils were recorded.

5. The adrenal medulla did not appear to play a significant role in the chain of events leading to the characteristic hemogram in animals subjected to fever. In adrenal-demedullated animals an eosinopenia, a lymphopenia and a neutrophilia occurred as in normal intact animals.

6. The conclusion seems warranted that hyperpyrexia has produced pituitary and adrenocortical stimulation.
The Blood Picture of Pyridoxine Deficiency in the Monkey
Authors: POPPEN KENNETH J. , GREENBERG L. D. , RINEHART J. F.
Published: October 2019

1. Pyridoxine deficiency in the monkey results in a severe anemia characterized by hypochromia, increase in mean diameter, decrease in mean cell thickness, dehydration, the appearance of "target" cells and increased resistance to hemolysis.

2. The administration of pyridoxine results in restoration of hematologic values to normal, correction of dehydration and disappearance of "target" cells.

3. Further evidence is offered relating "target" cells to dehydration and, in addition, possibly to hepatic damage.

4. A delayed macrocytic anemia which was not corrected by low doses of vitamin B12, folic acid or iron is described in control animals. This anemia occurred chronologically one to two years later than the induced anemia of pyridoxine deficiency and is not necessarily related. The cause of this anemia is unknown.

5. Normal hematologic data on twenty-one M. rhesus monkeys is presented.
Case Report: Erythroblastosis and Leukemia
Authors: VERLOOP M. C. , DEENSTRA H. , VAN DER HOEVEN L. H.
Published: October 2019

The authors report the case of a man, 29 years old, who presented initially a marked erythroblastosis (10,000 to 150,000 erythroblasts per mm.3) in the peripheral blood. Originally, a great hyperplasia of the red system in the bone marrow existed. Gradually this morbid growth of the "red" system was superseded by a proliferation of myeloblasts.

After an illness of about one year’s duration the patient died in a myeloblastic "crisis."

It is pointed out that owing to prolongation of life in this case through repeated blood transfusions and penicillin, the opportunity was presented to observe different hematologic syndromes in the same patient. With the common use of potent therapeutic procedures this situtation is now increasingly present. It may lead to the ultimate recognition that different hematologic syndromes are in reality different manifestations of the same disease.

The various diseases in which an erythroblastosis may occur are discussed.
The Influence of Respiratory Movements upon the Circulating Leukocytes
Authors: BIERMAN H. R. , KELLY K. H. , CORDES F. L. , PETRAKIS N. L. , KASS H. , SHPIL E. L.
Published: October 2019

1. The leukocyte content of venous and arterial blood of 17 subjects was studied repeatedly and frequently during respirations and the Valsalva and Muller maneuvers. The venous and arterial samples were drawn simultaneously and were obtained by direct puncture from freely-flowing peripheral veins or arteries or by catheterization from the right ventricle, pulmonary artery, hepatic vein, left ventricle or aorta.

2. During the Valsalva maneuver, the arterial leukocyte count decreased markedly with relatively little alteration in the simultaneous venous counts; upon release of the forced expiration both counts promptly regained the control level.

3. During the Muller maneuver, increases in both arterial and venous leukocyte counts occurred in one patient, while no significant effect was observed in venous samples in a second subject.

4. During inspiration the arterial leukocyte count fell and the simultaneous venous count rose with reciprocal changes upon expiration. These changes occurred whether the initial counts were elevated, normal or leukopenic.

5. The changes in leukocyte number of both arterial and venous blood during respiratory movements are not due to hemoconcentration or hemodilution and suggest a tidal ebb and flow of leukocytes into and from the pulmonary circulation of a significant degree.
The Principles of Eosinophil Diluents
Authors: SPEIRS R. S.
Published: October 2019

The various eosinophil diluents have been outlined and the action of each component discussed. A chart of difficulties often experienced with acetone diluents has been presented along with possible causes and cures.
Treatment of Paroxysmal Nocturnal Hemoglobinuria with ACTH
Authors: KALANT NORMAN , CYR DONAT P.
Published: October 2019

A proven case of paroxysmal nocturnal hemoglobinuria is reported in which the patient was treated with ACTH on three occasions. Following an initial failure, the second course of ACTH resulted in a dramatic deceleration of hemolysis which, however, lasted only a short time after the cessation of treatment. A third attempt was again of no avail in relieving the condition. Treatment with dicumarol coincided with a remission of the hemolysis which has lasted, so far, for five weeks.
The Clinical Use of Triethylene Melamine
Authors: KRAVITZ SHELDON C. , DIAMOND HENRY D. , CRAVER LLOYD F.
Published: October 2019

Triethylene melamine (TEM), a nitrogen mustard-like compound, which can be administered orally and intravenously, has been found to be of considerable clinical use in the palliative treatment of the lymphomas and leukemias. This drug is indicated when a patient presents generalized disease and constitutional symptoms such as fever and pruritus. The incidence of nausea and vomiting following TEM administration is significantly less than that following HN2. The other toxic effects of the two agents are comparable. TEM may be used in conjunction with roentgen therapy. Patients may be maintained om small oral doses of TEM for long periods of time, but extreme caution must be exercised in the oral use of TEM since its tolerance varies considerably with each individual.
The Effect of Sublingual Administration of Crystalline Vitamin B12 in Tropical Sprue
Authors: SUÁREZ RAMÓN M. , SABATER JUAN , SUÁREZ RAMÓN M. , BUSO ROBERTO
Published: October 2019

Sublingual administration of crystalline vitamin B12 in daily doses of 25 µg for ten consecutive days failed to induce clinical or hematologic remissions in 5 patients with tropical sprue.
Activation of Plasminogen by Trypsin and Plasmin
Authors: KOCHOLATY WALTER , ELLIS WILLIAM W. , JENSEN H.
Published: October 2019

Incubation of human or bovine plasminogen with trypsin or bovine plasmin resulted in the production of increased fibrinolytic activity, indicating that plasminogen is converted into plasmin under these conditions. Chymotrypsin under idential conditions was found not to possess this property.
Separation and Purification of Leukocytes and Platelets
Authors: TULLIS JAMES L.
Published: October 2019

Methods and equipment for the separation of the formed elements of the blood are outlined and discussed. Selection of any given method should be predicated on the purposes for which the isolated cells are to be used. The technics vary from simple fractional sedimentation requiring no equipment (when viable cells are not necessary) to complex, refrigerated, centrifuge equipment when cells in their true state in nature are desired. An apparatus for the rapid separation of blood in a continuous, closed-system is described and discussed.
Case Report: The Detection of Malignant Melanoma by Bone Marrow Aspiration A Report of Two Cases
Authors: FRANKLIN JOHN W. , ZAVALA DONALD C. , RADCLIFFE C. E.
Published: October 2019

We have presented 2 cases of disseminated malignant melanoma with bone marrow metastases which are, so far as we have been able to find, the ninth and tenth cases reported in the literature. In Case 1 the cytoplasm of the tumor cells contained abundant dark pigment, whereas in Case 2 the pigment deposits were rare. A study of the morphology of the bone marrow smears reveals that the melanoma cell usually differs from other tumor cells by the presence of deposits of dark pigment in the cytoplasm. The amelanotic type would not be easily identifiable since it is without pigment. Caution is needed not to confuse the melanoma cell with the reticulo-endothelial cell. A study of other patients with malignant melanoma is now in progress.
c-fms expression is a molecular marker of human acute myeloid leukemias
Authors: Dubreuil P , Torres H , Courcoul MA , Birg F , Mannoni P
Published: October 2019

The c-fms protooncogene product was identified as the CSF-1 or M-CSF receptor, a polypeptide growth factor that plays a major role in myelomonocytic differentiation. This led us to look for expression of c- fms in fresh acute myeloid leukemia (AML) cells, using Northern blot analysis. c-fms expression was found in the leukemic cells of 28 AML patients, regardless of their stage of differentiation, which was assessed in the French-American-British (FAB) classification. However, the level of c-fms expression was especially high in AML of the M5 stage. High levels of expression were not accompanied by either amplification or rearrangements of the c-fms gene in AML cell DNAs. In contrast, c-fms expression was not found in acute lymphoid leukemias, whether of T or B origin. Thus, c-fms expression appears as a specific molecular marker of leukemogenesis in the myeloid lineage.
Transformation of lymphocytes from immunized Rh(D)-negative subjects by Rh(D) isoantigen
Authors: Varvarigou-Frima A , Mantagos S , Beratis NG
Published: October 2019

Since immune memory in Rh(D)-negative isoimmunized subjects remains through life, even in the absence of measurable anti-Rh(D), we investigated the transformation of lymphocytes from such donors by Rh(D) antigen. The time lapse from the last stimulus was up to 13 years. Mononuclear cells from immunized women were stimulated by Rh(D)- positive erythrocyte stroma. Maximum transformation was observed on the sixth day of culture, with a stroma protein concentration of 8 micrograms/mL of culture medium. The stimulation index (SI) in cells from 11 immunized women was 6.8 +/- 3.1 (mean +/- SD), with a range from 3.1 to 15.0. In five different sets of control cultures, the SI ranged from 0.9 +/- 0.2 to 1.3 +/- 0.4. There was no overlap between stimulated and control cultures. No anti-D could be demonstrated in the serum of four of the 11 immunized cases studied. Also, transformation was observed in mononuclear cells from Rh(D)-negative immunized women with Rh(D)-positive erythrocytes. The findings demonstrate that lymphocytes from isoimmunized Rh(D)-negative subjects maintain the immune memory and are transformed in vitro by the Rh(D) isoantigen.
Clonal analysis of bcr-abl rearrangement in T lymphocytes from patients with chronic myelogenous leukemia
Authors: Jonas D , Lubbert M , Kawasaki ES , Henke M , Bross KJ , Mertelsmann R , Herrmann F
Published: October 2019

The cytogenetic hallmark of chronic myelogenous leukemia (CML) is the Philadelphia chromosome (Ph1), which reflects a chromosomal translocation t(9;22) and a rearrangement of the ABL and bcr genes. This marker is found in all cells arising from the same malignant precursor cell and can be detected in CML cells of the myeloid, monocytic, erythroid, and B-lymphocyte lineage. It is, however, controversial as to whether T lymphocytes of CML patients carry this gene rearrangement. An answer to this question would clarify whether the translocation in CML occurs in a pluripotent hematopoietic stem cell or in a precursor cell already committed to certain lineages, but not the T-cell lineage. To address this question, we established T-cell clones from peripheral venous blood cells of four patients with CML and screened these clones for bcr-abl fusion transcripts by means of polymerase chain reaction and Southern blot analysis. In four T-cell clones of three of these patients, the bcr-abl transcript could be detected. None of 12 T-cell clones of the fourth patient disclosed detectable bcr-abl amplification product. Both CD4+ as well as CD8+ clones displayed fused bcr-abl sequences. These data imply that in CML some but not all T lymphocytes may originate from the Ph1-positive stem cell.
Complications and outcome in childhood acute lymphoblastic leukemia with hyperleukocytosis
Authors: Eguiguren JM , Schell MJ , Crist WM , Kunkel K , Rivera GK
Published: October 2019

Hyperleukocytosis (greater than or equal to 100 x 10(9) leukocytes/L) was identified at diagnosis of acute lymphoblastic leukemia in 64 of 358 patients enrolled on St Jude Total Therapy Study XI from February 1984 to September 1988. These children received a seven-drug induction regimen followed by high-dose methotrexate, cranial irradiation at 1 year of remission, and 120 weeks of continuation therapy with rotational administration of four drug pairs. The 27 patients with leukocyte counts greater than or equal to 200 x 10(9)/L underwent initial cytoreduction via leukapheresis or exchange transfusions. The complete remission rate for patients with hyperleukocytosis (94%) was similar to that for the overall series (96%). Stepwise regression analysis showed that hyperleukocytosis was significantly associated with age less than 1 year at diagnosis, T-cell immunophenotype, leukemic cell ploidy less than or equal to 50 chromosomes, organomegaly, and elevated lactic dehydrogenase. The 27 patients with extreme hyperleukocytosis (greater than 200 x 10(9)/L) different from the other 37 children only in a higher frequency of French-American- British (FAB) L2 morphology. Estimated 4-year event-free survival (EFS) was 52% +/- 8% (SE) for patients with hyperleukocytosis versus 79% +/- 4% for patients with leukemic counts less than 100 x 10(9)/L (P less than .0001). Patients with leukocyte counts of 100 to 200 x 10(9)/L had a significantly better EFS than those with counts greater than 200 x 10(9)/L (64% +/- 10% v 34% +/- 14%; P = .04). Thus, the therapy in this trial proved satisfactory for children with leukocyte counts of 100 to 200 x 10(9)/L; further study is needed to improve the outlook for children with counts greater than 200 x 10(9)/L.
Rapid recovery from cytopenia in hairy cell leukemia after treatment with 2-chloro-2'-deoxyadenosine (CdA): relation to opportunistic infections
Authors: Juliusson G , Liliemark J
Published: October 2019

Sixteen patients with symptomatic hairy cell leukemia were treated with a single course of 2-chloro-2′-deoxyadenosine (CdA), 0.7 mg/kg total dose. Twelve patients achieved complete remission (CR). One patient with a CD19+/CD5+/CD25- phenotype and one with a pentostatin-treated CD19+/CD25- variant form had minor responses. Two patients with advanced disease and poor performance status died early from invasive mycosis. Three patients recovered from infections caused by cytomegalovirus and by candida. No patient had infections caused by bacteria or by unknown organisms. The median time to full recovery from anemia and thrombocytopenia was 6 and 2 weeks from start of therapy, respectively. Patients with infections, however, recovered at 13 and 5 weeks, respectively. Neutrophil, monocyte, and lymphocyte counts returned to normal at a median of 5, 5, and 10 weeks, respectively. Infections developed more frequently in pancytopenic patients than in those with one or more blood cell count within the normal range (P less than .01). All patients with one or no previous therapy had a CR, whereas those with more than one previous regimen had a lower CR rate (P less than .01). Thus, 1 week of CdA therapy frequently induced CR also in patients resistant to interferon. Toxicity was limited, and recovery from cytopenia was faster than what is reported during interferon therapy.
Functional expression of the macrophage colony-stimulating factor receptor in human THP-1 monocytic leukemia cells
Authors: Datta R , Imamura K , Goldman SJ , Dianoux AC , Kufe DW , Sherman ML
Published: October 2019

Macrophage colony-stimulating factor (M-CSF) is required for the proliferation, differentiation, and activation of monocytes. High- affinity receptors for M-CSF are encoded by the c-fms proto-oncogene. In the present study, we show that c-fms transcripts are detectable in human THP-1 myeloid leukemia cells. Furthermore, radiolabeled 125I-M- CSF is rapidly internalized into THP-1 cells and then degraded intracellularly. The results also show that treatment of THP-1 cells with M-CSF is associated with the activation of protein kinase C (PKC) and the induction of tumor necrosis factor (TNF) gene expression. TNF transcript levels were low to undetectable in uninduced THP-1 cells, reached maximal levels by 1 hour of exposure to M-CSF, and returned to those of control cells by 24 hours. Transcriptional run-on analysis showed that a low level of TNF transcription is detectable in untreated THP-1 cells, and M-CSF treatment increased the rate of TNF transcription. Pretreatment of THP-1 cells with pertussis toxin inhibited the increase in PKC activity but not the induction of TNF transcripts by M-CSF. Moreover, exposure of THP-1 cells to inhibitors of protein kinase activity blocked the increase in TNF messenger RNA. These findings suggest that at least two M-CSF-mediated signaling pathways exist in THP-1 cells and that the induction of TNF may be regulated by a protein kinase-dependent mechanism distinct from PKC.
Stem cell factor increases colony-forming unit-spleen number in vitro in synergy with interleukin-6, and in vivo in Sl/Sld mice as a single factor
Authors: Bodine DM , Orlic D , Birkett NC , Seidel NE , Zsebo KM
Published: October 2019

Hematopoiesis is thought to be modulated by interactions of progenitor cells with hematopoietic growth factors. We have shown that colony- forming units-spleen (CFU-S) and repopulating stem cells require interleukin-3 (IL-3) to survive in vitro, and that CFU-S number and long-term repopulating ability can be increased by culture in the combination of IL-3 and IL-6. In this report, we describe the effects of stem cell factor (SCF) on CFU-S and repopulating stem cells. Injection of SCF into anemic Sl/Sld mice caused a twofold and 20-fold increase in CFU-S number in the bone marrow and spleen of treated animals, respectively. After 6 days in suspension culture, CFU-S number increased threefold in cultures supplemented with SCF and IL-6, or SCF, IL-3, and IL-6 relative to the number at day 0. The long-term repopulating ability of cells cultured in SCF, IL-3, and IL-6 was approximately sevenfold better than that of cells cultured in IL-3 or SCF. Similar experiments were performed on populations of bone marrow cells enriched for, or depleted of, CFU-S by elutriation and lineage subtraction. The combination of SCF and IL-6 increased CFU-S number approximately fourfold to eightfold in the CFU-S-enriched fraction, but had no effect on the CFU-S-depleted cells. These results show that SCF alone can increase CFU-S number in vivo, and in combination with other growth factors increases CFU-S numbers in vitro.
The c-kit receptor ligand functions as a mast cell chemoattractant
Authors: Meininger CJ , Yano H , Rottapel R , Bernstein A , Zsebo KM , Zetter BR
Published: October 2019

Mast cells accumulate at sites of neovascularization, solid tumors, and many immune reactions. Such accumulation requires directed migration of mature mast cells or their precursors. The nature of the chemoattractants that regulate mast cell motility and the identity of the receptors that mediate the chemotactic response are poorly understood. We have tested the ability of stem cell factor (SCF), a mast cell growth factor, to stimulate mast cell migration. Our results show that SCF is a potent mast cell attractant that stimulates directional motility of both mucosal and connective tissue-type mast cells. The activity is potentiated by costimulation with interleukin-3 (IL-3), another mast cell chemoattractant. SCF, a known ligand for the c-kit tyrosine kinase receptor, was unable to stimulate motility in W42 mutant mast cells, which have a defective c-kit tyrosine kinase. However, W42 mast cells were still able to migrate in response to IL-3. These results show that SCF is a chemotactic factor as well as a growth factor and that the c-kit receptor can transduce signals leading to both cell proliferation and increased directional cell motility.