bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Sulfinpyrazone on Platelet Economy and Thrombus Formation in Rabbits
Authors: MUSTARD J. F. , ROWSELL H. C. , SMYTHE H. A. , SENYI A. , MURPHY E. A.
Published: October 2019

Platelet survival was prolonged in rabbits which had been on sulfinpyrazone for 30 days or more. This was not accompanied by changes in tests of blood coagulation in vitro. Thrombus formation in flowing blood was on the average less, but not significantly so.

The mechanism of the change in platelet economy is unknown. It does not appear to depend on blood coagulation and cannot be explained by serum uric acid which does not occur in the rabbit. It may be attributable to changes in the platelet membrane which may also account for the increase in serotonin uptake.
Hemoglobin Polymorphism in White-Tailed Deer: Subunit Basis
Authors: KITCHEN HYRAM , PUTNAM FRANK W. , TAYLOR W. JAPE
Published: October 2019

A variety of aberrant erythrocyte forms have been related to seven adult and two fetal hemoglobins in white-tailed deer. While sickling of the erythrocyte was not associated with a single hemoglobin type, it was precluded by hemoglobin V or VII, even when in combination with other hemoglobin types normally associated with sickling. The subunit basis of the hemoglobin polymorphism was presented. Two kinds of α subunits, six kinds of β subunits and one γ subunit were related to the whole hemoglobin molecule. The heterogeneity of the deer hemoglobins was based upon a variety of combinations of these numerous polypeptide chains. It was concluded from the results of limited structural studies that there were multiple peptide differences upon comparison of three non-α polypeptide chains.
Neutrophilic Function in Animals with the Chediak-Higashi Syndrome
Authors: PADGETT GEORGE A.
Published: October 2019

Peritoneal exudate neutrophils collected from mink and cattle with and without the Chediak-Higashi syndrome were compared using various criteria. No significant differences were found in the motility, phagocytic capacity, or bactericidal action of C-HS neutrophils when compared to those from normal animals.

There was no significant difference in the amount of bactericidal cationic proteins, acid phosphatase, cathepsin and β-glucuronidase in leukocytes from C-HS and normal mink and cattle.

The abnormally enlarged granules in neutrophils from C-HS animals did not lyse following phagocytosis of bacteria.

The amount of lysozyme present was the same in C-HS and normal mink polymorphonuclear leukocytes. No lysozyme was detectable in cattle neutrophils, but they killed bacteria as well as mink neutrophils.
IN VITRO STUDY OF BONE MARROW. III. ERYTHROPOIESIS IN VITRO OF STERNAL MARROW FROM CASES OF PERNICIOUS ANEMIA AND LYMPHATIC LEUKOSIS UNDER THERAPY
Authors: CLEMMESEN JOHANNES , ESPERSEN TAGE , PLUM CLAUS MUNK
Published: October 2019

Experiments have been performed on sternal marrow kept alive in vitro with serum as a nutritional medium.

Cross experiments with marrow and serum from two normal persons show roughly identical values for erythropoiesis. The same applies to marrows and sera from cases of mild simple anemia.

Marrow from a patient with pernicious anemia showed increased erythropoiesis in vitro if nourished on normal serum, whereas serum from the same case lowered the erythropoiesis of normal marrow. After treatment with liver extract, conditions tended to return to normal.

Marrow from 2 cases of lymphatic leukosis displayed corresponding phenomena, and showed a tendency to return to normal after treatment with urethane and folic acid.

Further investigations along these lines are in progress.
ELECTRON MICROSCOPE STUDIES OF BLOOD CELLS
Authors: REBUCK JOHN W. , WOODS HELEN L.
Published: October 2019

Several technics were employed for the application of the electron microscope to the study of the blood cells. First; lymphocytes, macrophages, and neutrophilic leukocytes of acute inflammatory lesions in man were prepared by imbedding formvar-covered screens in the corium of the forearm. Exudative cells which migrated to the undersurfaces of the specimen screens were quick-frozen and dehydrated in vacuo, according to a modified Altmann-Gersh technic. In some cases formvar-covered glass cover slips were substituted for the screens in the lesions, in which case an extra step was needed to transfer the preparations to specimen screens.

In a further technic, blood cells of lymph nodes, spleen and bone marrow of man were imprinted upon glass slides covered with formvar. These preparations were also frozen and dehydrated in vacuo. The films were then transferred to screens by a direct method in which the cells were retained intact.

Neutrophil granules, seen only as irregular, indistinct granules with the optical microscope, are actually round, oval, or rod-shaped structures measuring from 70 by 85 millimicrons up to as much as 465 by 650 millimicrons.

Immature blood cell precursors were found to possess fine chromatin patterns with distinct chromatin-parachromatin distinction and well-demarcated nucleoli.

At the higher magnifications made possible by electron microscopy, a new level of cytostructural organization appeared in the mononuclear phagocytes or macrophages. Individual fibrillar structural units can be made out in both the nuclear and cytoplasmic protoplasm which can be measured in Angstrom units. The nuclear protoplasmic interstices so formed are smaller than the corresponding cytoplasmic areas. The nuclear membrane is actually an anchoring structure for both nuclear and cytoplasmic fibrillar cross-pieces. Phagocytosis is depicted and the wall of the phagocytic vacuole is described. Finally, the observed cyto-structural features of the blood cells are discussed in the light of newer concepts of the finer structure of protoplasm.
AUTOHEMAGGLUTININS AND HEMOLYSINS WITH HEMOGLOBINURIA AND ACUTE HEMOLYTIC ANEMIA, IN AN ILLNESS RESEMBLING INFECTIOUS MONONUCLEOSIS
Authors: ELLIS LAURENCE B. , WOLLENMAN OSCAR J. , STETSON RICHARD P.
Published: October 2019

A case is reported of a young man with acute hemolytic anemia and hemoglobinuria who presented: an initial blood picture consistent with infectious mononucleosis, associated with a heterophile agglutination test positive in high dilution; auto-hemagglutinins, active in the cold, at room temperature and at 37 Centigrade; a hemolysin active at 37 C. after chilling, requiring the presence of a thermolabile component of serum for hemolysis; a positive Donath-Landsteiner test but no evidence of syphilis. In addition there was clubbing of the digits with certain other roentgenologic changes in the bones; absence of any other etiologic factors known to be concerned with such anemia; uneventful improvement under massive transfusion therapy, with apparent recovery from his hematologic disorder when studied two years later.
The Pattern of Platelet Disappearance
Authors: MURPHY E. A. , ROBINSON G. A. , ROWSELL H. C. , MUSTARD J. F.
Published: October 2019

In pigs and in dogs simultaneous tagging of platelets with cohort and population labels suggests that platelet destruction is largely independent of platelet age. No evidence of endogenous platelet aging has been encountered. The implications of these findings are discussed. It seems reasonable for the time being to use the "exponential half-life" as an index of platelet survival without committing oneself to the view that the exponential model adequately represents the phenomenon.
Studies on the Energy Metabolism of Human Leukocytes
Authors: FOSTER JOHN M. , TERRY MARY L. , Gunther Harriet
Published: October 2019

1. Oxidative phosphorylation has been studied in mitochondrial preparations from human leukocytes, using recently developed methods for homogenization, measuring respiration, and assaying for ATP.

2. Appreciable stimulation of both respiration and phosphorylation was limited to 3 substrates: succinate, malate, and α-glycerophosphate. The effects of other substrates were minimal.

3. The stimulating effects of these 3 substrates responded to inhibitors in a manner typical of mitochondrial oxidative phosphorylation. There was also considerable endogenous activity which, however, was insensitive to inhibitors. It is concluded the endogenous respiration and phosphorylation are not associated with electron transport. Subtracting their values from the data, P/O ratios consistent with good phosphorylation with the 3 substrates are obtained.

4. Studies with oligomycin and dinitrophenol suggest the presence of respiratory control. This indicates the mitochondria are intact. It is concluded that in the intact leukocyte the mitochondria are a major source of ATP.
Hypothesis: The Leukemias—Proliferative or Accumulative?
Authors: BIERMAN HOWARD R.
Published: October 2019

Contrary to the traditional concept, in many instances the leukemias are characterized by an essentially normal or slower individual leukocyte generation time, impaired maturation, altered cell release into the circulation, and prolonged survival of the "leukemic" cell, resulting in a progressive accretion of the potentially divisible cell population arrested in intermediary phases of development.

We have come to a critical reorientation in our thinking of the leukemias and neoplasia in general. Continued expansion along conventional lines might be profitably complemented by another program aimed at correction of the leukemic process by encouraging maturation without cellular destruction.

The significance of this moment is the inevitable realization that the dream of a cell specific "magic bullet" which would jam the metabolic machinery of the "leukemic cell" may instead correct that defective mechanism by aiding the leukocyte to mature properly. Efforts to accelerate or correct the altered maturation may offer additional approaches to the treatment of the leukemias with or without conventional chemotherapy. A reevaluation of the leukemias and possibly other neoplasms as disorders primarily of accumulation rather than proliferation may be a useful working hypothesis to encourage newer therapeutic approaches.
A Comparison of Normal Red Cell ATP Levels as Measured by the Firefly System and the Hexokinase System
Authors: BEUTLER ERNEST , MATHAI CLARAMMA K.
Published: October 2019

Widely divergent normal red cell ATP levels have been reported by investigators using different methods. In order to clarify the cause of these discrepancies and to establish correct normal values for red cell ATP, the firefly technic for measuring ATP levels was compared with other methods. The ATP content of TCA filtrates of red cells was the same when determined by the firefly method as by the hexokinase-linked technic. Relatively low concentrations of protein were found to stimulate light output when lyophilyzed firefly extract, but not freshly prepared firefly extract, was used. Thus, falsely, high values were obtained when red cell extracts were examined, unless protein was also added to the standard. Storage of heparinized blood for as little as 1 hour resulted in a substantial decrease in red cell ATP levels. The loss with ACD blood was less, and could be obviated entirely by using an ACD solution with a pH adjusted to between 3.5 and 4.0. Removing the buffy coat or washing cells in saline resulted in no further loss of red cell ATP. Extraction of washed red cells with TCA resulted in an average loss of 4.6 per cent of ATP, while extraction of whole blood with TCA resulted in a 14 per cent loss of ATP. In contrast, perchloric acid extraction resulted in no ATP loss. If ATP determinations are carried out using the firefly method, protein should be added to the standard. If red cells must be stored for any period of time prior to extraction of ATP, an ACD solution with a pH of 3.5 to 4.0 should be used. If extracts of red cells are made, perchloric acid appears significantly superior to trichloroacetic acid.
Malabsorption of Folic Acid due to Diphenylhydantoin
Authors: DAHLKE MIRIAM B. , MERTENS-ROESLER ELIZABETH
Published: October 2019

A high incidence of subnormal serum folate levels in pediatric subjects receiving diphenylhydantoin is reported. The effect is observed shortly after the onset of therapy and is not related to dosage of drug. An adult epileptic, who presented with a megaloblastic anemia secondary to a diphenylhydantoin-induced folate deficiency, demonstrated normal serum and erythrocyte folate levels only after folic acid was administered orally in amounts of 600 µg. per day. The folate deficiency was due to malabsorption of folic acid induced by diphenylhydantoin. Folic acid tolerance tests performed at 0, 4, 12, 16 and 20 hours after diphenylhydantoin showed a progressive rise in serum levels as diphenylhydantoin was withheld for longer periods prior to the test dose of folic acid. Further evidence of improved absorption was an associated rise in urinary folates.

In addition, the patient demonstrated a convincing hematologic response to ingested conjugase, in the form of chick pancreas. The hematologic response was observed, despite prior demonstration of conjugase activity in the patient’s intestinal secretions. Attempts to show inhibition of chick pancreas conjugase activity by diphenylhydantoin in vitro were unsuccessful. Several explanations for these conflicting observations are offered.
Reduction of in Vitro Autohemolysis in Hereditary Spherocytosis by Impermeant Molecules
Authors: MOHLER DANIEL N. , Eby Norman
Published: October 2019

It has been shown that a variety of compounds will reduce the abnormal autohemolysis which occurs after 48 hours of incubation of HS erythrocytes. These compounds either provide energy in the form of ATP, as is the case with glucose and adenosine, or provide an external osmotic force by virtue of their inability to cross the red cell membrane, as is the case with phosphorylated compounds, glutathione and sucrose. None of these latter compounds caused a significant preservation of erythrocyte ATP content. In assessing the effect of added compounds in the autohemolysis test, their osmotic behavior should be taken into account.
Brief Report: The Exacerbation of Hemolysis in Paroxysmal Nocturnal Hemoglobinuria by Strenuous Exercise
Authors: BLUM STUART F. , SULLIVAN JAY M. , GARDNER FRANK H.
Published: October 2019

Muscular exercise in patients with paroxysmal nocturnal hemoglobinuria has been shown to result in systemic acidosis with lacticacidemia and exacerbation of in vivo hemolysis. It is suggested on the basis of this study that patients with PNH be advised to avoid severe muscular exercise.

The acid hemolysis test should be performed in all patients that are suspected of having March hemoglobinuria.
Case Report: Autoimmune Hemolytic Anemia in Chronic Granulocytic Leukemia
Authors: MALDONADO NORMAN I. , HADDOCK JENARO , PÉREZ-SANTIAGO ENRIQUE
Published: October 2019

A patient with chronic granulocytic leukemia developed autoimmune hemolytic anemia. He was found to have a cold agglutinin and a nonspecific warm panagglutinin. Therapy with prednisone appeared to control the hemolytic crisis and did not affect the granulocytic process. The patient died of bronchopneumonia, and at autopsy no other neoplasm was found.
Leukemia in Offspring of Atomic Bomb Survivors
Authors: HOSHINO TAKASHI , KATO HIROO , FINCH STUART C. , HRUBEC ZDENEK
Published: October 2019

In a survey having a 90 percent chance of detecting a quadrupling of risk, no significant increase in leukemia has been observed in the offspring of persons exposed to atomic bomb radiation in Hiroshima and Nagasaki.

In the children with leukemia who were born to previously irradiated parents, there was no unusual finding in regard to the interval from parental exposure to onset, age at onset, or type of leukemia.

Failure to demonstrate a radiation effect does not mean that there is no such effect. It merely means that within the experience thus far open to observation, no effect is to be seen. There now is sufficient experience to justify a long period of observation of the F1 and subsequent generations for a possible increase of leukemia.
Transplacentally Acquired Antibody to Intrinsic Factor with Vitamin B12 Deficiency
Authors: BAR-SHANY SHULAMITH , HERBERT VICTOR
Published: October 2019

A newborn infant was found to have circulating maternal intrinsic factor antibody in the same titer as his 41 year old mother, who had had known pernicious anemia since age 33. At 11 days of age, no intrinsic factor was demonstrable in the infant’s gastric juice; whether this was related to the presence of serum IF antibody or was a variant of normal is not certain. At three months of age, the infant had B12 deficiency, manifested by a low serum B12 level and hypersegmentation of the nuclei of the neutrophilic leukocytes, but the gastric biopsy was normal, as was the intrinsic factor secretion. Maternal antibody to intrinsic factor was no longer present.

These findings support the concepts that:

(1) Intrinsic factor antibody may accelerate the development of B12 deficiency;

(2) The antibody may not, of itself, produce any permanent gastric damage.
Brief Report: Infusion of Isologous Immune Plasma in Chronic Lymphocytic Leukemia
Authors: LASZLO JOHN , BUCKLEY C. E. , AMOS D. BERNARD
Published: October 2019

This report describes the results obtained by the infusion of cytotoxic isoantibodies into patients having chronic lymphocytic leukemia. Each study was followed by transient lymphopenia and decrease in lymph node size. The fractional catabolic rate of large amounts of labeled isoantibody (IgG) was more rapid than of normal IgG.
Prolonged and Massive Administration of Iron-Dextran Complex Resulting in Selective Glomerular Iron Deposition in the Kidneys
Authors: ROSS LIVIA , FREMLAND HARRIET
Published: October 2019

A case with massive long-standing iron-dextran administration is reported. Selective glomerular iron deposition is the outstanding feature of the generalized hemosiderosis. Similar glomerular iron deposits have been described in experimental animals.
The Maturation and Fate of Reticulocytes after In Vitro Labeling with Tritiated Amino Acids
Authors: STRYCKMANS P. A. , CRONKITE E. P. , GIACOMELLI G. , SCHIFFER L. M. , SCHNAPPAUF HP.
Published: October 2019

1. Tritiated histidine and leucine are incorporated into hemoglobin by rat and dog reticulocytes and fulfill the conditions of a good red cell label for autoradiographic studies.

2. After mild erythropoietic stimulation, all reticulocytes appear to mature into normal red cells with expected lifespans.

3. After marked erythropoietic stimulation, the reticulocytes mature into red cells with normal potential lifespans but decreased mean lifespans.

4. In one animal studied, macrocytes produced by increased erythropoietic stimulation were found to have the same magnitude of shrinkage as do normal red cells.

5. The normal maturation time of the rat reticulocyte in the blood is about 33 hours in vivo and is increased following erythropoietic stimulation.
A Radioassay for Serum B12 Using Unsaturated Transcobalamin I as the B12 Binding Protein
Authors: ROTHENBERG SHELDON P.
Published: October 2019

A radioisotopic assay for serum vitamin B12 is described based on the fact the unlabeled B12 will competitively inhibit the binding of Co57B12 to a specific B12 binding protein, transcobalamin I. This protein is stable in dilute solution and at the concentration of Co57B12 used for the assay, its binding capacity increases much less than IF or normal serum as the concentration of B12 increases in the reaction mixture. Because of the stability of the binding capacity of stored frozen TC-I containing serum, only a single standard curve need be established with each lot of binding protein. When a limited quantity of TC-I is incubated with 60 pg of CO57B12 and crystalline B12 concentrations ranging from 10 to 160 pg/ml, a linear standard curve is obtained when the reciprocal of the fraction of Co57B12 bound to TC-I is plotted as a function of unlabeled B12 concentration. This permits use of a simple arithmetic expression to determine the B12 concentration of unknown extracts after experimentally determining the fraction of Co57B12 bound to TC-I. The serum B12 concentration of 25 normal subjects ranged from 154 to 674 pg/ml while the range in 15 B12 deficient patients was 0-126 pg/ml. The B12 concentration in 4 patients with chronic myelogenous leukemia was greater than 1000 pg/ml. The mean variance of 15 serum extracts frozen and reassayed several weeks later was 7.4 per cent. The range of recovery of B12 added to serum extracts was 84-118 per cent.
Sternberg-Reed Cells in the Thoracic Duct Lymph of Patients with Hodgkin’s Disease
Authors: ENGESET A. , BRENNHOVD I. O. , CHRISTENSEN I. , HAGEN S. , HØEG K. , HØST H. , LIVERUD K. , NESHEIM A.
Published: October 2019

Typical Sternberg-Reed cells were found in the thoracic duct lymph in three of four patients with a histologically proven diagnosis of Hodgkin’s disease, but in none of the patients were these cells demonstrated in the peripheral blood. The findings are discussed.
Relationships between Spleen, Platelets and Factor VIII Levels
Authors: LIBRE EUGENE P. , COWAN DALE H. , WATKINS STANLEY P. , SHULMAN N. RAPHAEL
Published: October 2019

(1) The spleen is essential for the Factor VIII elevations observed after adrenalin infusion and other acutely stressful stimuli. The spleen appears to be capable of either storing and releasing Factor VIII, or of effecting release of Factor VIII from some other site.

(2) The Factor VIII elevations do not appear to be dependent on the concomitant platelet rises that occur after adrenalin.

(3) An inverse relationship between platelet and Factor VIII levels is frequently found in pathological states associated with chronic thrombocytopenia or thrombocytosis.

(4) Platelet transfusions do not appear to influence Factor VIII levels.

(5) In vitro attempts to demontrate adsorption of Factor VIII by platelets or elution of Factor VIII from platelets in the presence and absence of adrenalin were not successful.
Characteristics of Vitamin B12 Correction of The Abnormal Erythropoiesis of Pernicious Anemia
Authors: HILLMAN ROBERT S. , ADAMSON JOHN , BURKA EDWARD
Published: October 2019

Nine comparable patients with vitamin B12 deficiency were studied during therapy by iron kinetic technic with special attention to the earliest phase of reticulocyte response, in order to define the fate of a megaloblast population and to explain the very high reticulocytosis typical of the pernicious anemia response.

After B12 therapy, there is a 2-2.5 day lag before reticulocytosis, during which ineffective erythropoiesis of the megaloblasts continues and repopulation by an entirely new normoblast series from the stem cell level occurs. Once reticulocytosis begins, it is characterized by delivery of very young reticulocytes from the bone marrow. These cells demonstrate a prolonged maturation phase, resulting in cumulative counting over several days and an apparent greater than expected reticulocyte level. If the reticulocyte peak is corrected for this maturation delay, a reticulocyte production index is obtained which correlates well with the measured plasma iron turnover production indices.
The Effect of Testosterone on Erythropoietin Levels in Anemic Patients
Authors: RISHPON-MEYERSTEIN N. , KILBRIDGE T. , SIMONE J. , FRIED W.
Published: October 2019

Studies in five patients with various types of anemias have shown that testosterone can increase plasma erythropoietin levels in humans. We suggest that testosterone stimulates erythropoiesis in some anemic patients by this mechanism.
The Fine Structure of Sickled Hemoglobin in Situ
Authors: WHITE JAMES G.
Published: October 2019

The sickling of susceptible erythrocytes from patients with sickle cell anemia has been related in previous studies to the intracellular precipitation of reduced sickle hemoglobin (Hb S). Though this knowledge has been available for many years, the form assumed by insoluble reduced Hb S in intact sickled cells has not been previously demonstrated. In the present study, glutaraldehyde incubated with susceptible cells at 37 C. was found to promote the sickling phenomenon as well as preserve the structural form assumed by Hb S after polymerization. Sickled erythrocytes were filled with filaments and rods. The severity of erythrocyte distortion was closely related to the amount of Hb S converted to the rod form and the extent of parallel association of the rods. Cytoplasmic organization in cells sickled by reduced oxygen tension or sodium bisulfite prior to aldehyde fixation was identical to that observed in cells exposed to glutaraldehyde alone. The rods formed by polymerization of Hb S in situ are not morphologically identical to microtubules, but their response to physical and chemical agents suggests that the two types of protein polymers are markedly similar.
A Tetrazolium-Linked Cytochemical Method for Estimation of Glucose-6-Phosphate Dehydrogenase Activity in Individual Erythrocytes: Applications in the Study of Heterozygotes for Glucose-6-Phosphate Dehydrogenase Deficiency
Authors: FAIRBANKS VIRGIL F. , LAMPE LINDA T.
Published: October 2019

A new method is described for the graded estimation of G6PD activity in individual erythrocytes. The method appears to offer some technical advantages over other methods. It requires reagents that are neither hazardous nor unstable and such equipment as might be found in the usual hematology laboratory. It appears to be more sensitive than conventional methods for identification of women heterozygous for G6PD deficiency and further substantiates the existence of erythrocyte mosaicism in such individuals.
Peripheral Leukocyte Kinetic Studies of Acute Leukemia in Relapse and Remission and Chronic Myelocytic Leukemia in Blastic Crisis
Authors: GODWIN HERMAN A. , ZIMMERMAN THEODORE S. , PERRY SEYMOUR
Published: October 2019

Peripheral blood leukocyte dynamics were investigated in a group of patients with acute leukemia both in relapse and remission and in chronic granulocytic leukemia in blastic crisis. In acute leukemia in relapse and in chronic granulocytic leukemia in blastic crisis, labeled blast cells appeared promptly with a peak at one to two days. Secondary peaks occurred 40-70 hours following the first peaks with labeled blasts usually the predominant labeled cell in both peaks. The time interval between these successive waves of labeled blasts could represent a generation time. The leukocyte specific activity patterns obtained in patients in blastic crisis resembled some of the patterns of patients with acute leukemia.

The leukocyte kinetic patterns in patients with acute leukemia considered to be in complete remission were usually normal. However, in some patients in bone marrow remission only, an abnormal early peak was present usually composed of labeled abnormal cells released early into the peripheral circulation. In the presence of a known leukemic infiltrate, alteration of the normal leukocyte kinetic curve apparently depended upon release of these leukemic cells into the circulating blood.
Mitochondrial Electron Transport Enzymes in Normal and Leukemic Human Leukocytes
Authors: EVANS AUDREY E. , GETZ GODFREY S.
Published: October 2019

Assays of TD transhydrogenase and succinate cytochrome C reductase carried out on the homogenate of normal and leukemic human leukocytes and on the 1.5 M. fraction (fraction 3) of a continuous sucrose density gradient analysis of a crude mitochondrial fraction, provided strong evidence for the mitochondrial location of TD transhydrogenase. A slightly higher activity of these enzymes was found in the homogenate of cells from chronic lymphocytic and acute leukemia compared to those of normal polymorphonuclear leukocytes, normal lymphocytes, and cells from chronic myeloid leukemia. These differences were very much more marked when purified mitochondrial fractions from these cells were examined. The significance of these findings is discussed.
The Effect of N Acetyl D-Galactosamine and Other Sugars on the Mitogenic Activity and Attachment of PHA to Tonsil Cells
Authors: BORBERG H. , YESNER I. , GESNER B. , SILBER R.
Published: October 2019

The effect of several simple sugars on the mitogenic and binding properties of PHA has been investigated. N acetyl D-galactosamine in concentration of 3-10 mg./ml. inhibited the incorporation of uridine-2-C14 and thymidine-2-C14 into the acid precipitable fraction of human tonsil cells stimulated by phytohemagglutinin. No inhibition, or a significantly lesser degree of inhibition was observed with N acetyl D-glucosamine or glucose. The binding of I131 labeled PHA to cells was decreased by NAGAL or EDTA. The EDTA inhibition, unlike the NAGAL inhibition was overcome by magnesium.
Erythrocyte Pyruvate Kinase Deficiency in Non-spherocytic Hemolytic Anemia: A System of Multiple Genetic Markers?
Authors: ZUELZER WOLF W. , ROBINSON ABNER R. , HSU THERESA H. J.
Published: October 2019

Extreme intrafamilial differences between PK-deficient phenotypes regarding hemolysis, ATP stability, and glucose consumption were observed in two pedigrees in which the index cases had severe nonspherocytic hemolytic anemia. Genetic analysis was consistent with heterozygosity for two distinct interacting mutants in minimally affected relatives of severely anemic homozygotes. Neither the mature erythrocytes of the former nor the reticulocyte-rich cell populations of the latter showed accumulation of glycolytic intermediates, but 2,3-DPG was elevated in both. Despite severe PK deficiency, red cell survival in the minimal type was near normal, glucose consumption was unaffected in three of four subjects tested, and ATP maintenance in vitro was adequate, in contrast to the severe type in which these parameters were grossly depressed.

The genetic and pathophysiologic implications of these findings are discussed. The possibility is considered that defective glycolysis may play a subordinate role in the hemolytic process associated with PK deficiency and that the enzyme defect may be a genetic marker for as yet unknown erythrocytic abnormalities involving an increase of 2,3-DPG and possibly primary membrane lesions creating excessive demands on the energy metabolism of the erythrocytes. Regardless of the mode of gene action, it is concluded that the nonspherocytic hemolytic anemias associated with PK deficiency are genetically and phenotypically heterogeneous, and that the genetic diagnosis cannot rest on PK assay alone.
Studies of Plasma Protein Synthesis by Peripheral Cells from Normal Persons and Patients with Infectious Mononucleosis
Authors: MACKINNEY ARCHIE A.
Published: October 2019

Tissue culture of peripheral blood leukocytes with 14C leucine resulted in radioactive proteins identified as immunoglobulins by immunoelectrophoresis, gel filtration, and immunoprecipitation. Radioactive heterophile antibody was detected by precipitin reaction with heterophile antigen. It was found in significant concentration in infectious mononucleosis cultures but not in normal controls. Apparent synthesis of heterophile antibody and active cell division are two parameters which distinguish infectious mononucleosis cells from normals in vitro.
The Transformed Cell in Thymus-PHA Cultures: Blood or Tissue Origin?
Authors: SCHWARZ M. ROY
Published: October 2019

The present study demonstrated that of the 18 million thymus, lymph node, or spleen cells in cultures containing PHA, on the average only 540, 990, and 6,170 small lymphocytes, respectively, were located in the blood vessels of these organs when the cell suspensions were prepared. Even if all of these cells transformed in response to PHA, it is unlikely that they could account for the transformation observed. Therefore, it was concluded that the lymphocytes of the parenchyma possessed the ability to transform in response to mitogenic agents.
Hemoglobin D Los Angeles in Two Caucasian Families: Hemoglobin SD Disease and Hemoglobin D Thalassemia
Authors: SCHNEIDER ROSE G. , UEDA SATOSHI , ALPERIN JACK B. , LEVIN WILLIAM C. , JONES RICHARD T. , BRIMHALL BERNADINE
Published: October 2019

Data are presented on two Caucasian families with hemoglobin D Los Angeles, (α2β2121gln) In one family, the mother, of Spanish origin, has sickle cell trait and the father, of Mexican origin, has hemoglobin D trait. One child has sickle cell hemoglobin D disease and suffers from a moderately severe hemolytic anemia. In the other family, of English, Scotch, and Irish ancestry, one member has the hemoglobin DAF pattern of hemoglobin D β-thalassemia disease and suffers from moderate hemolytic disease.
Polycythemia and Increased Erythropoietin Production in a Patient with Hypertrophy of the Juxta-Glomerular Appartus
Authors: JEPSON J. , MCGARRY E. E.
Published: October 2019

A patient with proven hypertrophy of the juxtaglomerular apparatus was found to be polycythemic and hypervolemic. Increased levels of erythropoietin were present in the urine and plasma collected from the patient. The associated increase in aldosterone secretion rate, elevated blood renin and angiotensin levels suggest the juxtaglomerular apparatus may directly or indirectly play a role in the production of erythropoietin.
Regulation of Erythropoiesis XXII. Erythropoietin Production in the Newborn Animal
Authors: CARMENA ALBERTO O. , HOWARD DONALD , STOHLMAN FREDERICK
Published: October 2019

Erythropoietin production was examined in the newborn rat. Even though there was significant anemia present during the early neonatal phase of life in the rat, erythropoietin could not be demonstrated in the plasma. Exposure to simulated levels of altitude of 23,000 feet for a period of 18 hr. resulted in the production of demonstrable levels of erythropoietin in the plasma. The amount of erythropoietic activity which could be demonstrated in the plasma of hypoxic animals increased with age from values of 0.76 units/ml. in the 1 day old animal to normal adult values of approximately 8 units/ml. by the thirtieth day of life. Bilateral nephrectomy prior to exposure to hypoxia in the 5 day old and 15 day old rat reduced the amount of erythropoietin to values of 50 per cent and 25 per cent of those observed in the intact hypoxic animal. By the thirtieth day of life, erythropoietin could no longer be demonstrated in anephric animals exposed to hypoxia.

It is concluded that there is a gradual increase in the capacity of the rat to produce erythropoietin in response to an hypoxic stimulus, and that in significant measure during the early neonatal phase, erythropoietin production is accomplished by extrarenal sources.
Satisfactory Red Cell Viability with Slight Excess of Acid Citrate Dextrose
Authors: MAYER KLAUS , D'AMARO JOSEPH
Published: October 2019

Platelet suspensions obtained from blood donors are improved by increased acidification. The simplest way to accomplish this is to collect less blood into the standard quantity of ACD. Since we have previously reported an impairment in red cell viability when blood is collected in a great excess of ACD, it became pertinent to test the survival of stored red cells collected in a "slight" excess of ACD.

The volume of the blood collected was lowered to 375 ml. in 75 ml. ACD (N. I. H. formula A). At this ratio the pH. was 6.5 which is sufficiently low to minimize platelet clumping. The red cells were separated, stored for 21 days at 4 C., and viability was tested by the 51Chromate method. The results showed adequate red cell survival for blood collected and stored in this manner.
Brief Note: Marrow Repopulating Ability of Peripheral Blood Cells Compared to Thoracic Duct Cells
Authors: STORB R. , EPSTEIN R. B. , THOMAS E. D.
Published: October 2019

Ten dogs were exposed to 1200 r. of whole body irradiation at a dose rate of 9.2 r./min. Five of these dogs were then given infusions of 21 to 74 x 109 autologous peripheral blood cells which had been previously stored at -80 C. 4.0 to 19.4 x 109 of these cells were lymphocytes, 0.4 to 4.9 x 109 were monocytes and 16.4 to 50.3 x 109 were granulocytes. All five dogs showed clinical or histologic evidence of bone marrow repopulation. The remaining 5 dogs were given 7 to 22 x 109 autologous thoracic duct lymphocytes. In none of these dogs was marrow repopulation observed.

It was concluded that hemopoietic stem cells are not present in the thoracic duct lymph of the dog in any appreciable number.
Clinical Implications of Cytogenetic Variants in Chronic Myelocytic Leukemia (CML)
Authors: WHANG-PENG JACQUELINE , CANELLOS GEORGE P. , CARBONE PAUL P. , TJIO J. H.
Published: October 2019

Serial cytogenetic studies were performed on 179 chronic myelocytic leukemia patients (CML) at the Clinical Center of the National Institutes of Health. Patients were divided into 6 groups according to cytogenetic findings: Ph1 negative (18 patients), Ph1 negative with other chromosomal abnormalities (3 patients), Ph1 positive (116 patients), Ph1 positive and negative (10 patients), Ph1 positive with other chromosomal abnormalities (24 patients), and Ph1 positive which turned to other chromosomal abnormalities (8 patients). Patients who were Ph1 negative and negative with other chromosomal abnormalities (11.8 per cent of total) had the shortest median survival, 12 to 15 months. In contrast, the median survival of patients in the Ph1 positive groups was 31 to 40 months. The development of other chromosomal abnormalities in Ph1 positive patients presaged the terminal stage of the disease.
The Significance of Bone Marrow Lymphocytosis of Acute Leukemia Patients in Remission
Authors: SKEEL ROLAND T. , HENDERSON EDWARD S. , BENNETT JOHN M.
Published: October 2019

Bone marrow lymphocytosis (BML) 20 per cent or greater occurring during remission of acute leukemia has been looked upon in the past as an unfavorable sign that may presage early subsequent relapse. Seventy-four patients with acute lymphocytic leukemia were studied to evaluate the significance of BML in remission. It was found that 14 patients with less than 20 per cent bone marrow lymphocytes at any time in remission had a median remission duration of 3 months and a median survival of 21 months, while 60 patients with 20 per cent or more bone marrow lymphocytes at any time in remission had a median remission duration of 14 months and a median survival time of 34 months. Patients with AGL and lymphocytosis had remissions and survivals not significantly longer than those without lymphocytosis It is concluded that there is no justification for excluding a patient from complete remission status because of bone marrow lymphocytosis.
Immunochemical Quantitation of Proteins in Single Cells
Authors: GITLIN DAVID , SASAKI TERUO , VUOPIO PEKKA
Published: October 2019

An immunochemical method for the quantitative determination of specific soluble proteins in individual erythrocytes has been described. Application of the method revealed:

1. From 0.5 to 0.9 per cent of the normal adult erythrocytes studied contained small amounts of γ-chains, from 2.5 to 12.5 µµg. as hemoglobin per cell.

2. In cord blood of normal infants of 38 weeks’ gestation, significant numbers of erythrocytes were found which contained either γ-chains or β-chains or both, independently of carbonic anhydrase B.

3. Once initiated within a given erythrocyte, β-chain synthesis in that cell rapidly approached adult rates. Derepression of carbonic anhydrase B synthesis was independent of derepression of hemoglobin synthesis, and in fetal cells which contained carbonic anhydrase B the amount found was well below that of most adult erythrocytes.

4. In 4 patients homozygous for hemoglobin S and in 2 persons heterozygous for thalassemia, an increase in F hemoglobin was associated with an increase in γ-chain content of individual erythrocytes as well as an increase in the number of erythrocytes containing γ-chains; in 2 patients homozygous for thalassemia, an unusual distribution of cells with increased γ-chain content was observed.
Brief Report: Decreased Hemolytic Capacity of Sera From Patients With Paroxysmal Nocturnal Hemoglobinuria
Authors: BLUM STUART F. , GARDNER FRANK H.
Published: October 2019

The sera of patients with Paroxysmal Nocturnal Hemoglobinuria have been shown, in vitro and in vivo, to be less hemolytic for PNH erythrocytes than are normal sera. This defect may result from the liver disfunction encountered in many of the patients although the exact defect has not been defined.

The necessity for using normal sera when performing the acid hemolysis test is emphasized.
Physical Properties of Red Cells as Related to Effects in Vivo. II. Effect of Thermal Treatment on Rigidity of Red Cells, Stroma and the Sickle Cell
Authors: HAM THOMAS HALE , SAYRE RICHARD W. , DUNN REBECCA F. , MURPHY JOHN R.
Published: October 2019

Heating of human or dog red cells at 49 C. for 15 minutes or 60 minutes increased resistance to packing by a centrifugal force, increased viscosity and deformed them. After 15 minutes of heating, osmotic fragility was usually normal but was elevated after 60 minutes with the formation of spheroidal cells.

The increase in viscosity caused by heating red cells at 49 C. for 60 minutes did not appear to result from the effect of heat on the hemoglobin or the hemolysis products of red cells disrupted by sonic treatment. The heating of intact human or dog red cell stroma in serum, or stroma washed multiple times in physiologic saline however, regularly increased their viscosity and produced buds and microstroma. The rigidity of stroma was increased by heating, probably accounting for the increased viscosity of heated intact red cells.

The rigidity of heated stroma of red cells was further demonstrated by showing that the shape changes of the sickling process could be prevented in large part by the heating of sickle cells. Heating did not, however, prevent tactoid formation in stroma-free sickle-cell hemoglobin solutions.
Phagocytosis by Human Eosinophils
Authors: CLINE MARTIN J. , HANIFIN JON , LEHRER ROBERT I.
Published: October 2019

Eosinophils were isolated from the blood of patients with eosinophilia and tested for phagocytic ability. Eosinophils ingested inert polystyrene particles, Escherichia coli, Staphylococcus aureus 502A and Candida albicans, but did so less efficiently than neutrophils. They did not phagocytize antibody-coated red cells. Phagocytosis occurred over a broad pH range and in the presence of inhibitors of oxidative metabolism. Inhibitors of glycolysis, puromycin and colchicine inhibited particle ingestion to a variable extent.

Metabolic concomitants of phagocytosis, including enhanced incorporation of uridine into RNA, stimulation of glucose oxidation and degranulation and loss of lysosomal enzymes were similar in neutrophils and eosinophils. Endotoxin had similar effects on glucose oxidation by eosinophils and neutrophils in vitro.
Brief Report: Ultrastructural Localization of Myeloperoxidase in Human Neutrophil and Rabbit Heterophil and Eosinophil Leukocytes
Authors: DUNN W. B. , HARDIN J. H. , SPICER S. S.
Published: October 2019

Ultrastructural cytochemical observations revealed peroxidase reactivity in primary (azurophil) granules, but not in secondary (specific) granules, of rabbit and human polymorphonuclear leukocytes. Peroxidase reactivity was also observed in the rough endoplasmic reticulum and granules of rabbit eosinophils and in granules of human monocytes.
The May-Hegglin Anomaly: Platelet Function, Ultrastructure and Chromosome Studies
Authors: LUSHER JEANNE M. , SCHNEIDER JOHN , MIZUKAMI I. , EVANS RUTH K.
Published: October 2019

A father and son with the May-Hegglin anomaly were studied. Both were asymptomatic, although the father had a mild thrombocytopenia and a probable platelet thromboplastic function defect. Possible mechanisms for the bleeding tendency observed in approximately one-fourth of the persons with this anomaly are discussed. The autosomal dominant mode of inheritance is again demonstrated, and both father and son were found to have normal chromosomes.
Immunologic Studies of Antihemophilic Factor (AHF, Factor VIII): Cross-Reacting Material in a Genetic Variant of Hemophilia A
Authors: HOYER LEON W. , BRECKENRIDGE ROBERT T.
Published: October 2019

Immunologic studies have identified two genetically distinct types of hemophilia A. While a majority of patients apparently fail to synthesize AHF, a variant has been recognized in which a nonfunctional but antigenically cross-reacting AHF-like protein is present. Plasmas from two of twenty-seven families with hemophilia A have a cross-reacting material which inactivates an anticoagulant to AHF. Nonfunctional cross-reacting material was not present in plasmas from six patients with von Willebrand’s disease.
Deficiency of Vitamin B12-Binding Alpha Globulin in Two Brothers
Authors: CARMEL RALPH , HERBERT VICTOR
Published: October 2019

Persistent deficiency of serum B12-binding alpha-1 globulin was demonstrated in two brothers, manifesting primarily as low serum B12 levels. Despite the inability of one subject to maintain normal levels of B12 in the blood, as shown by persistently low serum values despite monthly injections of B12, no evidence of metabolic B12 deficiency could be found. Tissue B12-storing ability appeared to be intact. His brother exhibited only minimal hypersegmentation of neutrophil nuclei; otherwise, he too presented a completely normal picture.

The normally present alpha globulin B12-binder was virtually absent from saliva and peripheral leukocyte extracts of both subjects.

Current indirect evidence favors neutrophils as at least a partial source of the serum globulin.33 The cause of the possibly hereditary defect in the 2 subjects is unknown. Neither excessive B12-binding protein excretion34 nor a destructive factor in their serum or leukocytes was found.
Brief Report: On the Chemical Abnormality of Hb "Alexandra," a Fetal Hemoglobin Variant
Authors: LOUKOPOULOS DIMITRIS , KALTSOYA ANASTASIA , FESSAS PHAEDON
Published: October 2019

The original fetal hemoglobin variant "Alexandra" has been fingerprinted; the interpretation of the fingerprint is compatible with the substitution of threonine by lysine in the twelfth position of the γ-chain.
The Effect of Bleeding on the Proportion of Red Fluorescing Forms among the Total Normoblasts of Bovine Porphyric Bone Marrow
Authors: RUNGE WALTER , WATSON C. J.
Published: October 2019

The percentage of fluorescing, porphyrin rich normoblasts in the bone marrow of five bovine porphyrics increased after bleeding to a range of 66-91 per cent, as contrasted with 26-50 per cent in the same animals before bleeding. This is believed to be more in accord with a uni- than a bimodal distribution of normoblasts in respect to the genetic abnormality and the resultant overproduction of porphyrin.
Mobility of Human Red Blood Cells of Different Age Groups in an Electric Field
Authors: YAARI A.
Published: October 2019

Using citrated blood of eleven healthy donors the density distribution of red blood cells (D.D.C.) was determined and eight fractions from each sample separated. Separated red cells were resuspended in their own plasma and employed for the electric mobility measurements.

The Ruhenstroth-Bauer Cytopherometer was used at a current of 5 ma. at 24 C. The range of migration of red cells was found to be 0.855 to 1.47 x 10-4cm.2v-1sec.-1. In separated fractions the older the cells the slower they migrated in the electric field.
Brief Report: Hemozygous Erythrocyte Glutathione-Peroxidase Deficiency: Clinical and Biochemical Studies
Authors: NECHELES T. F. , MALDONADO NORMAN , BARQUET-CHEDIAK ANTONIO , ALLEN D. M.
Published: October 2019

An adult Puerto Rican male is described who developed an acute hemolytic episode following the infusion of three units of stored autologous red cells. The acute episode was associated with the presence of numerous red cells containing Heinz bodies. Investigation of his red cells revealed a markedly decreased level of the enzyme glutathione peroxidase. Examination of family members revealed moderately decreased levels of red cell glutathione peroxidase activity in both parents and in a sibling suggesting an autosomal recessive mode of inheritance. Metabolic studies on the erythrocytes from this patient revealed a normal level of hexose monophosphate shunt activity under basal conditions but a lack of normal activation of this pathway in the presence of hydrogen peroxide. The results of these studies support the concept that this enzyme, glutathione peroxidase, plays a major role in mediating the normal red cell response to the presence of peroxides.