bluuebunny/crossref_metadata_2025 huggingface dataset:
Reticulum Cell Sarcoma Terminating in Acute Leukemia
Authors: ZEFFREN J. LESTER , ULTMANN JOHN E.
Published: October 2019

The records of 113 patients dying at the Francis Delafield Hospital with documented reticulum cell sarcoma revealed six cases whose course terminated in a syndrome resembling acute leukemia. Their course was characterized by weakness, pallor, petechiae, hemorrhages and hepatosplenomegaly. The blood showed anemia, leukocytosis (white blood cell count 20,000 to 80,000/ cu.mm.) and thrombocytopenia (platelet count [unknown] 100,000/cu.mm.). Differential count in the blood and the bone marrow revealed a high percentage of immature cells (35 to 96 per cent). These were identified as reticulum cells in three patients, as myeloblasts in two and as monocytoid granulocytes in one. In all six patients, this explosive illness terminated in systemic infection or hemorrhage within two months. Therapy with 6-mercaptopurine, adrenal steroids, or both, gave no benefit.
Pyrimidine Metabolism in Man. II. Studies of Leukemic Cells
Authors: SMITH LLOYD H. , BAKER FAITH A. , SULLIVAN MARGARET
Published: October 2019

1. The activities of three enzymes involved in pyrimidine synthesis— aspartate carbamyltransferase, dihydro-orotase and dihydro-orotic dehydrogenase—were studied in sonicates of circulating leukocytes from 5 patients with myelocytic leukemia, 2 with lymphocytic leukemia, 2 with myeloproliferative disorders and 5 with infection. The erythrocytes from one patient with the Di Guglielmo syndrome were studied.

2. Neoplastic cells showed increased activities of all three enzymes tending to parallel the cytologic evidence of immaturity. The increase of dihydroorotic dehydrogenase was the most striking abnormality. Leukocytes from patients with infection or with myeloproliferative disorders showed similar but much less marked alterations in the enzyme pattern.

3. Dihydro-orotic dehydrogenase, absent from mature erythrocytes, was present in the nucleated erythrocytes in the Di Guglielmo syndrome.

4. The enzyme 5 carboxymethylhydantoinase, previously found in some bacteria, was absent from normal and abnormal hemic cells.
The Preparation of Plasma Thromboplastin Antecedent (PTA) and its Assay with Purified Clotting Components
Authors: GALLICK HAROLD , HYNDMAN L. A. , MCCALL K. B.
Published: October 2019

By replacing the three crude reagents commonly used in thromboplastin generation tests—washed platelets, barium sulfate- or alumina-adsorbed plasma, and serum—with purified clotting factors, many variables and uncertainties were eliminated. It was demonstrated that plasma thromboplastin antecedent (PTA) was required for the generation of thromboplastic activity.

A method was developed for the preparation of purified PTA from fraction IV-1 of human plasma. Its identity was established by its ability to correct, in vitro, the defect in the plasma of a PTA-deficient patient. Thus, further evidence in support of the belief that PTA is a discrete component, essential for blood coagulation, was obtained. More specifically, it was found to be essential in the generation of thromboplastic activity in plasma.

A test system for thromboplastin generation was described which was used to assay PTA in vitro and which did not require the use of PTA-deficient plasma or serum. Omission of any one of the components of this system resulted in a marked loss of thromboplastic activity; restoration of activity was proportional to the amount of the component that was added. Thus, with this system of purified components, it was possible to assay any one of them without the use of, or requirement for, plasma or serum specimens from patients with specific coagulation deficiencies.
An Electron Microscope Study of the Source and Distribution of Ferritin in Hepatic Parenchymal Cells of the Newborn Rabbit
Authors: HAMPTON JAMES C.
Published: October 2019

Evidence that erythrocytes are phagocytized and dismantled by hepatic parenchymal cells in the newborn rabbit is presented. It is concluded that in these cells iron is recovered from disintegrating erythrocytes, synthesized into ferritin and released into the hepatic cell cytoplasm and into the biliary passages. These conclusions are based upon observations on the distribution of material giving the Prussian blue reaction in sections of liver as revealed by the light microscope and upon electron microscopic images of particles displaying the size, density and configuration of the ferritin molecule.
The Hemoglobin E Syndromes. II. Sickle-Cell—Hemoglobin E Disease
Authors: AKSOY MUZAFFER
Published: October 2019

1. A clinical and hematologic description is presented of a patient with sickle-cell-hemoglobin E disease in a new family. In contrast to the mild hematologic and clinical changes observed in the patients described by the author previously, the clinical and hematologic manifestations in the new patient were moderate in degree. The anemia was normocytic in type. Variation in the clinical and hematologic picture of sickle cell-hemoglobin E disease has been noted.

2. Genetic studies of two families with sickle-cell-hemoglobin E disease have been presented. According to the genetic data obtained by evaluation of the genealogies of these two families, it is strongly suggested that the genes responsible for hemoglobins S, E and A are allelomorphs or linked.
Chronic Lymphocytic Leukemia, Hypogammaglobulinemia and Autoimmune Hemolytic Anemia— An Experiment of Nature
Authors: PISCIOTTA ANTHONY V. , JERMAIN LOUIS F. , HINZ JEAN E.
Published: October 2019

1. The case study is presented of a 75 year old man who had chronic lymphatic leukemia, autoimmune hemolytic anemia and hypogammaglobulinemia. The positive antiglobulin reaction with serum made from gamma globulin and the neutralization of the antiglobulin reaction with human gamma globulin demonstrated that this patient’s erythrocytes were coated with gamma globulin.

2. There was a normal survival time of I131-labeled normal human gamma globulin, suggesting defective synthesis of gamma globulin. Failure to demonstrate radioactivity on the patient’s erythrocytes when I131-labeled normal gamma globulin was given signified that normal human gamma globulin has no affinity in vivo for the patient’s red cells and that the erythrocyte-coating protein was derived from a source endogenous to the patient.

3. These relationships favor an immunologic mechanism in the development of an antiglobulin reaction in this patient.
Radioactive Iron Studies in Patients with Iron Deficiency Anemia with Concurrent Abnormal Hemolysis
Authors: VERLOOP M. C. , VAN DER WOLK M. , HEIER A. J.
Published: October 2019

A report is presented on two women suffering from severe iron deficiency anemia, concomitant with abnormal hemolysis. The life span of the patients’ red cells was shortened; transfused normal red cells were more rapidly broken down. Extracorpuscular factors seem to be responsible for the pathologic hemolysis. There was no pathologic sequestration of red cells labeled with Cr51 in the spleen.

After incorporation of radioactive iron into the red cells, the utilization percentage of Fe59 under iron therapy fell to about 15 per cent within a few weeks. This, too, indicates that the pathologic hemolysis was to be ascribed to extracorpuscular factors. The Fe59 was apparently not sufficiently reutilized. The constantly decreased serum iron concentration might also indicate a disturbance in the reutilization of iron liberated during red cell breakdown.

Six other patients with less severe iron deficiency anemia and an insufficient response to iron therapy were examined in addition. In 5 of these patients, the life span of red cells labeled with radioactive chromium was found shorter than normal. An insufficient response to iron therapy in patients with chronic iron deficiency anemia may be ascribable, in some instances, to concomitant pathologic hemolysis.
Evaluation of Marrow Granulocytic Reserves in Normal and Disease States
Authors: CRADDOCK CHARLES G. , PERRY SEYMOUR , VENTZKE LUTZ E. , LAWRENCE JOHN S. , Baker Mary H. , Paul Gloria
Published: October 2019

Recent concepts of the relationship of the blood granulocyte mass to the marrow reserve of granulocytes have been reviewed. Evidence has been presented to show that the marrow is the chief area of granulocyte "reserves" or "stores." The development of acute leukocytosis in response to a stimulus such as the intravenous injection of bacterial endotoxin depends upon release of cells from the intramedullary pool of granulocytes.

The turnover of the marrow granulocyte reserve (MGR) is an orderly process in the steady state, and determines the form of the curve of DNA-labeled granulocytes in the peripheral blood. From estimates of the turnover time of the MGR it appears that the granulocyte spends an average time of about 10 hours in the peripheral blood. Granulocytes do not appear to recirculate once they have left the peripheral blood and have entered the tissues. However, granulocytes may be sequestered within capillary beds for variable periods, and may re-enter the circulating blood from such areas. Such cells are not to be considered as having re-entered the blood from the tissues.

The intravenous injection of a purified bacterial lipopolysaccharide as a stimulus to acute leukocytosis is described. The possbile usefulness of this procedure in assessing the MGR is discussed.
Hemoglobin H Associated with an Uncommon Variant of Thalassemia Trait
Authors: DITTMAN W. A. , HAUT A. , WINTROBE M. M. , CARTWRIGHT G. E.
Published: October 2019

A 26 year old American housewife of Sardinian extraction with chronic hypochromic anemia was found to have a hemoglobin component identical to hemoglobin H. The A2 hemoglobin fraction was decreased. Relatives were found to exhibit the hematologic features of thalassemia trait. In this pedigree, in contrast to the usual finding in the "thalassemia trait," the A2 values were not increased. The same observation had been made in the only other comparable report.
Is There an "Embryonic" or "Primitive" Human Hemoglobin?
Authors: MATSUDA G. , SCHROEDER W. A. , JONES RICHARD T. , WELIKY NORMAN
Published: October 2019

An attempt has been made to detect the "embryonic" or "primitive" human hemoglobin that has been reported by other authors. Chromatographic comparisons have detected no significant differences in the hemoglobin components of fetuses in age from 15 weeks to term. The method of alkali denaturation has been applied in conjunction with the chromatographic comparisons, but it also has detected no significant differences in the various samples.

All samples that have been investigated contain a hemoglobin component termed FI. It is present to the extent of about 10 per cent in all samples and presumably is a normal constituent. Its rate of denaturation by alkali is essentially indistinguishable from that of the main component in cord blood and so FI is included in all determinations of hemoglobin F by alkali denaturation.

The results of this investigation lead to the conclusion that there is no "embryonic" human hemoglobin that precedes hemoglobin F in the way the hemoglobin F precedes hemoglobin A in the life of the individual.
Brief Note: Erythroid Hypoplasia Associated with Chloramphenicol Therapy
Authors: OZER FARUK L. , TRUAX WAYNE E. , LEVIN WILLIAM C.
Published: October 2019

1. A case of transient erythroid hypoplasia with maturation arrest and thrombocytopenia probably due to a large dose of chloramphenicol is reported.

2. The literature is briefly surveyed.
Radioautographic Investigations on DNA and Protein Metabolism in 2 Cases of Di Guglielmo’s Disease
Authors: GAVOSTO FELICE , MARAINI GIOVANNI , PILERI ALESSANDRO
Published: October 2019

H3-thymidine and H3-DL-leucine incorporation in the erythroblasts of the bone marrow from a case of acute and one of chronic Di Guglielmo’s disease was studied. A similar investigation was also carried out with bone marrow from 4 normal subjects. The high resolution of the radioautographic technic employed allowed a comparative study at the cellular and subcellular level.

A definitely lowered thymidine uptake was observed in the cells of acute erythremic myelosis, while increased incorporation of DL-leucine was detected in both the acute and the chronic form of this disease.
Microspectrophotometric Determination of Nonheme Iron in Maturing Erythroblasts and its Relationship to the Endocellular Hemoglobin Formation
Authors: SONDHAUS C. A. , THORELL BO
Published: October 2019

The strong near-UV absorption of inorganic iron makes possible the microspectrophotometric determination of nonheme intracellular iron as distinct from hemoglobin-bound iron. Erythroid cells of Salamandra Maculosa were therefore studied microspectrophotometrically in the near ultraviolet and visible region. Absorption curves from cytoplasmic areas in living and dried cells were obtained from 310 to 700 mµ., and two component analyses were made to determine the presence and amount of hemoglobin and nonhemoglobin absorption. Under the experimental conditions, intracellular hemoglobin was present largely as the carbon monoxide derivative, a stable form which provided a well defined standard to correct for nonspecific absorption and other spectral distortion due to the optical properties of single cells.

Absorption curves from the youngest cells measured were found to differ from those of mature cells, the difference curve agreeing most closely with that of inorganic iron or ferritin in solution. In the youngest cells, nonheme iron appeared to exceed 6 per cent by weight of hemoglobin, or over 20 times molar hemoglobin concentration, dropping and remaining at about twice the hemoglobin molarity from the time hemoglobin synthesis was one-third complete until maturity. Allowing for the increase of total cell mass with growth, the data suggest that although young erythroblasts may already have enough Fe for subsequent Hb synthesis, they continue to incorporate excess Fe throughout maturation and may thus contain a reserve pool of nonheme iron.
Electron Microscopic Localization of Russell Bodies in the Human Plasma Cell
Authors: WELSH RONALD A.
Published: October 2019

The location of Russell bodies in the human plasma cell was shown by electron microscopy to be within the intracisternal space of the endoplasmic reticulum. The significance of this finding was discussed from the standpoint of possible intracellular function of the endoplasmic reticulum. The appearance of the affected plasma cells tended to negate a degenerative process, and the suggestion was offered that the Russell body results from a condensation of intracisternal secretion.
Heparin Precipitability of the Macroglobulin in a Patient with Waldenström's Macroglobulinemia
Authors: MULLER DAVID
Published: October 2019

The macroglobulin isolated from a patient with macroglobulinemia was shown to be specifically precipitable by heparin. Maximal precipitation occurred at relatively low (by weight) concentrations of heparin and persisted over a broad range of heparin concentration. The possible clinical significance of the finding has been briefly discussed.
Nonspherocytic Congenital Hemolytic Anemia
Authors: DE GRUCHY G. C. , SANTAMARIA J. N. , PARSONS I. C. , CRAWFORD HAL
Published: October 2019

1. The clinical and hematological features of seven cases of nonspherocytic congenital hemolytic anemia occurring in four different families are presented, together with family studies. Four cases resemble Selwyn and Dacie’s Type I and three cases their Type II. Cases in the literature similar to our cases are reviewed.

2. The Type I cases showed the following features: normocytic or slightly macrocytic anemia with mild hypochromia and some stippling; a decreased or normal osmotic fragility of fresh blood and a decreased fragility of incubated blood; a slightly increased autohemolysis corrected by glucose and by ATP. The family history was positive and clinical onset was usually in adult life. Survival studies suggest that splenectomy may result in partial remission.

3. The Type II cases showed the following features: a marked uniform macrocytosis with numerous Pappenheimer bodies (postsplenectomy); a normal osmotic fragility of fresh blood and an increased fragility of incubated blood; an increased autohemolysis uncorrected by glucose but corrected by ATP. The family history was often negative and clinical onset was usually in infancy. Splenectomy in general appeared to produce no benefit.

4. The classification and pathogenesis of these anemias is discussed. It is pointed out that Type I is not a homogeneous group, and that our cases simply represent one subgroup of this type. Type II appears to be a more homogeneous group. Preliminary biochemical studies suggest the difference in clinical types may be determined by differences in biochemical defects.
A Cooperative Assay of a Sample with Erythropoietic Stimulating Activity
Authors: KEIGHLEY GEOFFREY , LOWY PETER H. , BORSOOK HENRY , GOLDWASSER EUGENE , GORDON ALBERT S. , PRENTICE THEODORE C. , RAMBACH WALTER A. , STOHLMAN FREDERICK , VAN DYKE DONALD C.
Published: October 2019

A batch of erythropoietically active material made from the plasma of phenylhydrazine treated rabbits was distributed to seven laboratories in this country for the purpose of comparing assay methods. The results of the assays using 10 different methods or major variations are presented.

Most of the assay methods being employed were represented so that other laboratories should be able to compare their results to those obtained in this study.

The importance of obtaining some uniform basis for comparison of activity of erythrocyte stimulating factor between laboratories has been emphasized and a tentative unit has been proposed based on a net incorporation into rat red cells of 20 per cent of injected Fe59, using a standardized assay procedure.
Platelets and Platelet Phosphatides in Uremia
Authors: ALTSCHULER GERALD , MARCUS AARON J. , ULLMAN HARRIS L.
Published: October 2019

1. The platelets of 20 uremic subjects were studied, utilizing the following procedures; phase platelet count, serum prothrombin time, thromboplastin generation test with evaluation of plasma, serum, and platelet reagents.

2. Platelet phospholipids from these subjects were used as reagents in the thromboplastin generation test and examined by means of silicic acid paper and column chromatography.

3. Thrombocytopenia was the most common abnormality encountered and was associated with either normal or abnormal prothrombin consumption. Some patients demonstrated defective prothrombin utilization despite normal platelet counts, but their platelets had normal thromboplastic activity, as did those of all patients studied.

4. The paper chromatographic pattern of the phosphatides in all subjects was the same as that reported for normal platelets. Similar results were obtained on column chromatographic analysis of a pooled extract from nine of the uremic patients.

5. On the basis of these studies it was not possible to demonstrate a qualitative platelet defect in uremia.
Studies on the Dynamics of the Reaction Between Rh Antibody and Antigen
Authors: EVANS ROBERT S. , MEBUST WINSTON K. , HICKEY MARY T.
Published: October 2019

The anti-D antibody of two human sera was found to be transferred in part from sensitized group A Rh (D)-positive cells to normal group B Rh (D)-positive cells when the cell suspensions were mixed and incubated in a saline medium.

The amount of anti-D antibody transferred from sensitized to normal cells in a given period of time was found to be directly related to the concentration of antibody to which the group A donor cells were originally exposed. It is concluded that the amount of antibody transferred to recipient cells under standard conditions is related to the concentration of antibody on the surface of the donor cells.
Serum Protein Changes in Malignant Diseases. I. The Acute Leukemias
Authors: FAHEY JOHN L. , BOGGS DANE R.
Published: October 2019

A study of the serum protein changes and clinical events in acute myeloblastic and acute lymphoblastic leukemia was undertaken as a part of investigations on the effects of malignancies in man. In order to appraise the effects of the leukemic processes, an evaluation of the effects of disease type, activity, complications and therapy was also undertaken. Over a five-year period, clinical appraisal and electrophoretic serum protein analyses were compared 171 times in 82 patients with acute lymphoblastic leukemia and 64 times in 28 patients with acute myeloblastic leukemia.

Serum electrophoretic evaluation showed characteristic patterns in the two types of acute leukemia studied. Analyses conducted in the absence of fever, infection or liver disease typically revealed elevation of the gamma globulins in myeloblastic but not in lymphoblastic leukemia. Alpha-2 globulin elevation, however, was representative of active lymphoblastic leukemia. Serum albumin was significantly lowered, and the beta globulins component remained essentially normal in both myeloblastic and lymphoblastic leukemia. Alpha-1 and alpha-2 globulin values were notable for the wide range of values obtained.

Hematologic remission in some patients with acute lymphoblastic leukemia was associated with a return of albumin and alpha globulin values toward normal, but the total experience indicated a general persistence during remission of the abnormalities seen in active diseases.

Fever, in the absence of infection, was associated with elevation of the alpha-1 globulin component. Bacterial infection was associated with similar elevation of the alpha-1 globulin fraction and, in addition, a further fall in serum albumin levels.

Marked depression of the gamma globulins was unusual. The mild decreases encountered in lymphoblastic leukemia could not be related to the frequency of bacterial infection. Administration of antimetabolites or adrenal corticosteroids could not be shown to produce any direct effect on the serum electrophoretic components.
The Body Hematocrit/Venous Hematocrit Ratio and the "Splenic Reservoir"
Authors: FUDENBERG HUGH , BALDINI MARIO , MAHONEY JOHN P. , DAMESHEK WILLIAM
Published: October 2019

1. Red cell volume and plasma volume were measured by the radioactive sodium chromate and the chromic chloride method respectively in 37 patients.

2. The body hematocrit/venous hematocrit (BH/VH) ratio was found to be constant in normal subjects and in patients in whom there was neither splenomegaly nor edema. The ratio was 0.896 ± 0.039.

3. In splenectomized patients the BH/VH ratio was normal indicating that in man, in normal conditions, the spleen does not have the function of a significant blood reservoir with raised cell/plasma ratio.

4. In patients with splenomegaly the BH/VH ratio was found to be significantly increased in direct proportion to the degree of splenic enlargement, indicating an increased concentration of erythrocytes in the enlarged spleen.

5. In the presence of extravascular fluid retention caused by prolonged prednisone treatment the BH/VH ratio was lower than normal.

6. It was concluded that in patients with splenomegaly or edema measurement of either red cell volume or plasma volume alone in conjunction with the "corrected" venous hematocrit does not permit valid assessment of the non-measured parameter nor of the total blood volume.
A Study of Prednisone Therapy in Chronic Lymphocytic Leukemia
Authors: SHAW RICHARD K. , BOGGS DANE R. , SILBERMAN HAROLD R. , FREI EMIL
Published: October 2019

A study of prednisone therapy in 18 patients with chronic lymphocytic leukemia is reported.

1. Antileukemic effects consisting of subjective improvement, decrease in organ infiltration, improvement in hemoglobulin and absolute neutrophil count occurred.

2. These effects were transient.

3. An increase, often marked, in the number of circulating lymphocytes occurred in 16 of the 18 patients.

4. The administration of prednisone was attended by an increase in the severity of infections. Some increase in the frequency of infections was also observed, but this was not statistically significant (p > 0.05).

It is concluded that corticosteroids should not be used electively in patients with chronic lymphocytic leukemia except in the presence of hemolytic anemia, significant thrombocytopenia or in the presence of advanced disease associated with bone marrow failure.
A Histochemical Method for Sulfatase Activity in Hemic Cells and Organ Imprints
Authors: AUSTIN JAMES H. , BISCHEL MARGARET
Published: October 2019

1. A new histochemical method is described for arylsulfatase activity (ASA) in hemic cells and organ imprints. Some common limitations in histochemical technics have been tested and appear to be minimized in this method.

2. With the present method, a wide series of hemic cells may be identified, and their ASA separately graded from 0-4.

3. A study has been made of normal ASA values in all series of human hematopoietic cells and of neutrophilic granulocyte ASA in common laboratory animals. Eosinophils, megakaryocytes, and neutrophils have the highest ASA. Increases in ASA occur early during cell maturation in neutrophils and eosinophils.

4. Humans have a higher ASA than the laboratory animals tested. Within certain species, there is some general correlation between neutrophilic granulocyte ASA and ASA of other organs. Under these conditions, leukocyte ASA is a potentially useful general screening method for ASA.

5. Some factors which enhance or inhibit leukocyte ASA have been tested.
The Morphology of Glucose 6 Phosphate Dehydrogenase Deficient Erythrocytes: Electron-microscopic Studies
Authors: DANON D. , SHEBA CH. , RAMOT B.
Published: October 2019

The conclusion that may be drawn is that though under normal conditions the survival time of enzyme deficient red blood cells is not too far from normal, the ageing of these cells from a morphological point of view occurs at a much faster rate; in other words, one could speak of "progeria" of the enzyme deficient red blood cells.
Leukemia and Lymphoma Mortality in Relation to Cosmic Radiation
Authors: CRAIG LEONARD , SEIDMAN HERBERT
Published: October 2019

The 1949-1951 leukemia and lymphoma mortality rates for the 163 metropolitan areas in the United States were compared to the corresponding elevations of the areas, taken as an approximate measure of the intensity of cosmic radiation. No increase in mortality rates with rise in elevation was apparent. From this it is concluded that at usual habitation levels in the United States variation in cosmic ray intensity either has no effect upon leukemia and lymphoma mortality rates, or has very small effect as compared to other factors.

The same procedure was applied to congenital malformation mortality rates. In this instance, there appears to be a distinct increase in this condition between the lowest elevation zone and all others.

If we assume a positive relationship between the intensity of cosmic radiation and the rate of congenital malformations, it is reasonable to expect a progressive increase in congenital malformations as elevation (and hence cosmic radiation) increases. However, according to table 6, the rate of congenital malformation mortality remains fairly constant over the three highest elevation zones. From this it is concluded that the variation in the intensity of cosmic radiation does not play an important part in the mortality from this disease. It is possible that some factor not considered by us accounts for the difference in congenital malformation mortality between the lowest elevation zone and the other zones.
Fumarase Activity of Human Leukocytes and Erythrocytes
Authors: TANAKA KOUICHI R. , VALENTINE WILLIAM N.
Published: October 2019

1. The results of over 400 assays of fumarase activity in separated leukocytes and erythrocytes in a variety of hematologic and nonhematologic diseases are presented.

2. The highest mean leukocyte fumarase values occurred in acute monocytic leukemia and acute granulocytic leukemia. Blast cells have greater fumarase activity than more mature forms of the same cell type.

3. Fumarase appears to be distributed ubiquitously among the various leukocytes. Cell populations which contained predominantly neutrophils, lymphocytes, monocytes, blasts, eosinophils, and basophils, all exhibited appreciable enzyme activity.

4. Assays of erythrocyte fumarase activity did not reveal a pattern with the exception of elevated values in macrocytic anemias and in some, but not all, cases of hemolytic anemia.
Cytoplasmic Inclusions in Acute Hemocytoblastic Leukemia: Case Report
Authors: SARAIVA L. G. , BOURROUL G. P. , SILVEIRA M. , PROSPERO J. D. , ANGULO J. J.
Published: October 2019

A case of hemocytoblastic leukemia in a 56 year old white man is reported which was characterized by cytoplasmic inclusions in some of the hemocytoblasts, reticulum cells and macrophages of the bone marrow as well as in some of the hemocytoblasts of the circulating blood. Phase and electron microscopic studies confirmed the corpuscular nature of the inclusions. Cytochemical stains gave negative results when tested for the presence of mucoproteins, lipids, phospholipids. neutral fat, desoxyribonucleic acid, peroxidase and phosphatases. The test for polysaccharides was slightly positive. Preliminary studies underway with electron microscopy suggest the possibility of a viral nature of the inclusion bodies.
Megaloblastic Erythropoiesis in Acquired Hemolytic Anemia
Authors: WILLOUGHBY M. L. N. , PEARS M. A. , SHARP A. A. , SHIELDS M. J.
Published: October 2019

1. A case of auto-immune hemolytic anemia complicated by megaloblastic erythropoiesis is described. The possible mechanism is discussed.

2. The direct Coombs test is a useful adjunct in the diagnosis of megaloblastic anemias.
Studies on the Formation of Heinz Bodies. II. The Nature and Significance of Heinz Bodies
Authors: HARLEY JOHN D. , MAUER ALVIN M.
Published: October 2019

Simultaneous studies were made as to the degrees of Heinz body formation, of change in hemoglobin and of change in osmotic fragility in erythrocytes incubated with certain drugs which are known to produce Heinz bodies in vivo. Certain factors that modify the pattern of effect of drugs on normal adult erythrocytes were also studied.

A close relationship was found between the degrees of Heinz body production and "intact" hemoglobin destruction. Factors that caused variation in the degree of "intact" hemoglobin destruction caused similar variation in the degree of Heinz body production. Staining studies suggested that Heinz bodies are protein in nature and derived from hemoglobin. These observations were taken to indicate that Heinz bodies probably result from the direct effect of certain drugs on intra-erythrocytic hemoglobin.

β-naphthol and primaquine were found to cause marked increase in osmotic fragility relative to the degrees of Heinz body production and of "intact" hemoglobin destruction, whereas acetyl phenylhydrazine produced marked Heinz body production and "intact" hemoglobin destruction with relatively little increase in osmotic fragility. These observations were regarded as evidence that Heinz body production is not the sole determinant of instability of erythrocytes exposed to these various drugs.

Under no experimental conditions was Heinz body production or "intact" hemoglobin destruction found without methemoglobin formation. Evidence was presented to indicate that Heinz body production could be inhibited by trapping methemoglobin as methemoglobin cyanide or methemoglobin azide. The suggestion was advanced that methemoglobin is in fact an essential stage in the destruction of "intact" hemoglobin and the formation of Heinz bodies.
Studies on Erythropoiesis. XVII. Some Quantitative Aspects of the Erythropoietic Response to Erythropoietin
Authors: GURNEY CLIFFORD W. , WACKMAN NANCY , FILMANOWICZ EDWARD
Published: October 2019

The transfusion-induced polycythemic mouse is an excellent subject in which to study the physiology of erythropoiesis because endogenous erythropoiesis is reduced in a manner that does not appear to impair, to any recognizable degree, the animal’s ability to respond to an erythropoietic stimulus.

Using a purified glycoprotein, erythropoietin, obtained from the plasma of anemic sheep, a number of experiments was carried out on polycythemic mice. Morphological evidence of erythropoiesis in the spleen was observed following a single subcutaneous injection of erythropoietin. A cumulative response to multiple injections was noted. For a given total dose of erythropoietin, a greater response was produced when this amount was fractioned than when it was administered as a single dose. Animals made polycythemic by transfusion were maintained in a polycythemic state by daily injections of erythropoietin. Finally, a true erythrocytosis was produced by a prolonged course of injections of erythropoietin in normal mice.
The Mechanism of the Development of Anemia in Untreated Chronic Lymphatic Leukemia
Authors: WASI PRAWASE , BLOCK MATTHEW
Published: October 2019

The following conclusions can be made concerning the cause of anemia in patients with untreated chronic lymphatic leukemia excluding the rare case with an autoimmune hemolytic anemia:

1. Early in the natural history of the disease there is a normal amount of erythroblastic tissue which produces red cells at a normal rate. The rate of red cell destruction is also normal.

2. With progression of the disease the erythroblastic tissue is gradually replaced by lymphatic tissue, leading to a decrease in red cell production. The rate of red cell destruction is still normal.

3. Only late in the disease may decreased rate of red cell production be aggravated by an increased rate of red cell destruction.
Supravital Blood Studies, Using Acridine Orange Fluorescence
Authors: JACKSON JOHN F.
Published: October 2019

A simple method for supravital fluorochroming of blood with acridine orange has been described. The supravital method is of value in distinguishing nucleated cellular elements, reticulocytes and erythrocytic inclusions. Preliminary studies of peripheral blood in leukemia indicate that it may be helpful in differentiating certain abnormal cellular elements. The chemistry of acridine orange with respect to metachromatic color differentiation of DNA and RNA has been discussed. Based on supravital observations of the L. E. cell phenomenon, speculation has been offered as to the site of interaction of the L.E. factor with DNA.
Thalassemia Minor Associated with Hemoglobin-B2 Heterozygosity. A Family Report
Authors: HUISMAN TITUS H. J. , PUNT K. , SCHAAD J. D. G.
Published: October 2019

1. In 14 members of 26 cases of a family originating from Surinam a double heterozygosity (for thalassemia and for the abnormal minor component Hb-B2) was demonstrated. Thalassemia heterozygous carriers or individuals heterozygous for the Hb-B2 abnormality alone were not encountered.

2. The diagnosis of thalassemia minor was based on hematologic data. The abnormal minor Hb-component present in these cases was identified using the conventional electrophoretic and chromatographic technics and the fingerprinting method as being Hb-B2 (an abnormal Hb-A2). The percentages of the two minor Hb-fractions (Hb-A2 and Hb-B2) in these thalassemia heterozygous carriers are doubled, their sum being similar to the high level of Hb-A2 typical for most cases of thalassemia trait.

3. The genetic relationship between thalassemia minor (genotype: tT) and Hb-B2 heterozygosity (genotype: A2/B2) is discussed. The data on this pedigree are suggestive of a close linkage of the t-T and A2/B2-loci.
A Note on Mortality from Lymphatic Leukemia in Oriental Populations of the United States
Authors: SHIMKIN MICHAEL B. , LOVELAND DONALD B.
Published: October 2019

Leukemia mortality data by race for the decade 1949-1958 were examined to ascertain whether chronic lymphatic leukemia occurs infrequently, as has been reported for Singapore and Japan, among Chinese and Japanese in the United States. It was found that mortality ascribed to lymphatic leukemia in adult Chinese and Japanese in the United States was only 40 to 45 per cent of that reported in the white population.
Studies of the Irradiation Protection Effect of Fetal Liver in Mice. I. Influence of the Gestational Age of the Donor Tissue
Authors: TSCHETTER PAUL N. , GITHENS JOHN H. , MOSCOVICI M. GIOVANNELLA
Published: October 2019

1. The gestational age of donor hematopoietic tissue appeared to have no influence on the 30-day mortality following homologous transplants in irradiated mice.

2. Recipients of second trimester homologous donor tissue had a late (90-day) mortality that was 16 per cent lower than that observed in animals receiving tissue from third trimester and neonatal donors, but statistical analysis showed a low level of significance.

3. Irradiation alone appeared to cause a late mortality in non-injected irradiated animals and in isologously transplanted irradiated animals.
The Transfusion Behavior of Avian Erythrocytes: The Lack of Functional Transplantation Antigens in a Nucleated Cell
Authors: SILBER ROBERT , HEDBERG STEPHEN E. , AKEROYD JOSEPH H. , FELDMAN DONALD
Published: October 2019

1. Autotransfusion and cross-transfusion experiments in the turkey reveal that the avian erythrocyte, despite the presence of a nucleus, survives normally in homologous recipients of compatible blood groups.

2. Skin homografts were rejected without apparent relationship to blood group compatibility.

3. Evidence for blood groups in the turkey is presented. While no naturally occurring iso-agglutinins were found, stimulation led to the appearance of incomplete antibodies.
Pyridoxine-Responsive Anemia
Authors: RAAB SPENCER O. , HAUT ARTHUR , CARTWRIGHT GEORGE E. , WINTROBE MAXWELL M.
Published: October 2019

1. Two patients with microcytic hypochromic anemia, hyperferremia, and hemosiderosis have been described .A partial hematologic remission was observed in both patients following the administration of pyridoxine.

2. Interruption of pyridoxine therapy resulted in reticulocytopenia, a decline in the concentration of hemoglobin and a decrease in free erythrocyte protoporphyrin. Increased excretion of kynurenine and kynurenic acid, but not xanthurenic acid, was observed in the urine of one of the patients following administration of tryptophane. The excretion of tryptophane metabolites was within normal limits in the second patient.

3. Reinstitution of pyridoxine therapy was followed by reticulocytosis, an increase in free erythrocyte protoporphyrin and an increase in the concentration of hemoglobin. The excretion of tryptophane metabolites in the urine following the administration of tryptophane was within normal limits in both patients. However, microcytosis, hypochromia, anemia and hyperferremia persisted.

4. The administration of brewer’s yeast, Valentine’s liver extract, calcium disodium ethylenediamine tetra-acetic acid, ethinyl estradiol, pantothenic acid, pyridoxal, pyridoxamine, ascorbic acid, niacin, riboflavin, glutamic acid and tryptophane failed to elicit a further hematologic response.

5. These patients have been compared with the seven other reported cases of "pyridoxine-responsive" anemia.
Studies of the Irradiation Protection Effect of Fetal Liver in Mice. II. Storage by Freezing
Authors: GITHENS JOHN H. , TSCHETTER PAUL N. , MOSCOVICI M. GIOVANNELLA , HATHAWAY WILLIAM E.
Published: October 2019

Various methods of freezing have been evaluated for the preservation of the radiation protection effect in fetal mouse liver. The best results were obtained with tissue frozen slowly in glycerol to -80 C., stored at -50 C. or lower, and thawed rapidly. Other variables such as the size of the tissue particles, the amount of serum in the freezing mixture, and the method of dilution did not influence the results.
The Effect of Sodium Nitrite and Para-Aminopropriophenone Administration on Blood Methemoglobin Levels and Red Blood Cell Survival
Authors: BEUTLER ERNEST , MIKUS BARBARA J.
Published: October 2019

1. The administration of sodium nitrite or para-aminopropriophenone (PAPP) to rats caused a rise in the methemoglobin level with maximum concentrations of methemoglobin occurring generally after one-half to one hour. The level of methemoglobinemia gradually declined thereafter. No significant difference was observed between intragastric and subcutaneous administration either in the time-course or in the maximum level of methemoglobinemia achieved. When adminisitered at separate sites by the subcutaneous route, sodium nitrite and para-aminopropriophenone exert an additive effect in forming methemoglobin.

2. The concentration of PAPP in propylene glycol affected appreciably the course of methemoglobinemia. More concentrated solutions of PAPP caused greater methemoglobin formation, even when the total amount given was identical.

3. The dosage response curve for PAPP and sodium nitrite in rats has been defined.

4. Limited data have been obtained on the dosage response curves of human subjects without hematologic disease after the administration of sodium nitrite and PAPP.

5. No effect of red cell age on methemoglobin content of erythrocytes could be discerned using the method of differential osmotic hemolysis.

6. Stable concentrations of methemoglobin in the blood of human subjects could be achieved by chronic administration of drug every four hours.

7. The administration of 5 mgs. PAPP/Kg. body weight to rats resulted in accelerated destruction of red cells. In contrast, the administration of propylene glycol alone or the administration of 50 mgs. sodium nitrite/Kg. body weight, a quantity inducing tile same degree of methemoglobinemia, failed to accelerate red cell destruction.
An Unidentified Erythropoietic Substance in Liver
Authors: HORRIGAN DANIEL L.
Published: October 2019

Hematologic observations on a patient with hypochromic anemia and hyperferremia indicate (1) the presence in oral crude liver extract of an unidentified erythropoietic substance, and (2) an apparent metabolic relationship of this liver factor with pyridoxine and tryptophane.
Further Observations on Polycythemia in Hepatocellular Carcinoma
Authors: KAN Y. W. , MCFADZEAN A. J. S. , TODD D. , TSO S. C.
Published: October 2019

Direct measurement of the red cell mass has confirmed a previous report of the occurrence of polycythemia in patients with hepatocellular carcinoma. Twenty patients (17 males and 3 females) have been investigated. The red cell mass was increased in 11, normal in 8 and reduced in one. Because of hypervolemia, present in 15 of the 20 patients investigated and attributable to the associated cirrhosis of the liver, the hematocrit might be normal in the presence of an increased red cell mass. A venous hematocrit of 48 per cent and above was found invariably to be associated with an increase in the red cell mass. Using this criterion, 17 of 145 patients with hepatocellular carcinoma were found to be polycythemic, an incidence of 11.7 per cent.

Plasma erythropoietic stimulating factor determined by Fe59 incorporation into red cells of fasted rats was not increased in 4 patients with hepatocarcinoma and polycythemia.

These findings are briefly discussed.
Blood Coagulation Factors in Total Body Irradiation
Authors: SISE HERBERT S. , GAUTHIER JACQUES , BECKER ROBERT , BOLGER JOHN
Published: October 2019

Investigation of the clotting factors in five humans accidentally exposed to total body irradiation disclosed no deficiencies. There was no evidence of a circulating anticoagulant in any case. Moderate fibrinolysis was seen in two instances in the same individual but was not evident in the others. At the eleventh day there was uniformly a moderate increase in the levels of fibrinogen. At the twenty-ninth day there was observed an increase in the levels of factors V and VIII coincidental with thrombocytopenia. This change reversed itself with recovery. A similar increase in the levels of factor VIII and less so of factor V was seen in cases of idiopathic thrombocytopenic purpura and secondary thrombocytopenia. An increase in level of factor VIII was observed in patients on oral coumarin anticoagulation. It is concluded that the supernormal levels of factors V and VIII are secondary to lowered thrombin levels in the circulating plasma as a result of the thrombocytopenia and not due directly to the effect of irradiation.
A Study of Fibrinogen Turnover in Classical Hemophilia and Congenital Afibrinogenemia
Authors: RAUSEN AARON R. , CRUCHAUD ANDRE , McMILLAN CAMPBELL W. , GITLIN DAVID
Published: October 2019

The rate of disappearance from the plasma of intravenously administered I131-labeled fibrinogen was studied in six patients with classical hemophilia and in one patient with congenital afibrinogenemia.

The six patients with hemophilia had radioiodinated fibrinogen half-lives ranging from 2.8 to 3.6 days, while the patient with congenital afibrinogenemia had a labeled fibrinogen half-life of 3.0 days. These results compare favorably with fibrinogen turnover rates measured in normal adults by others and were similar to the normal fibrinogen turnover rate determined in the patient with congenital afibrinogenemia in a previous study. This failure to demonstrate a prolongation of survival of fibrinogen in patients with hemophilia suggests that in vivo clotting, if it occurs at all normally, is not a major factor in the turnover of fibrinogen.
A New Technic for Separation of Human Leukocytes
Authors: LALEZARI PARVIZ
Published: October 2019

A simple technic for separation of human leukocytes is described. It utilizes differential sedimentation following red cell and platelet agglutination induced by Polybrene. In this technic, lymphocytes are partially removed and over 50 per cent of polymorphonuclears are recovered. The leukocyte/red cell ratio is about 5, if blood samples with normal leukocyte counts are used. By use of blood samples containing higher white cell counts this ratio may be increased. The separated cells proved to be highly viable as tested by phase microscopy, supravital staining and phagocytosis. There was no significant change in oxygen uptake of leukemic cells in the presence of a relatively large Polybrene concentration.
Fluorescence Microscopy with Acridine Orange: A Study of Hemopoietic Cells in Fixed Preparations
Authors: SCHIFFER LEWIS M.
Published: October 2019

1. A technic for the study of fixed preparations of blood and bone marrow by means of fluorescence microscopy with acridine orange is presented.

2. The distribution of RNA and DNA within the blood cells can be demonstrated cytochemically.

3. The RNA content of the erythroid and myeloid cells decreases with maturation. Mature plasma cells contain large quantities of RNA.

4. It is possible to demonstrate cytoplasmic metachromasia between the AO-RNA complexes of the erythroid, myeloid, and plasmacytic cells.
The Morphologic Responses of the Lymphoid System to Homografts. II. The Effects of Antimetabolites
Authors: ANDRÉ JANINE A. , SCHWARTZ ROBERT S. , MITUS W. J. , DAMESHEK WILLIAM
Published: October 2019

The effects of 6-mercaptopurine and thioguanine on the morphologic responses of lymph nodes and spleen were studied in the rabbit. The main effect of these drugs was to inhibit the proliferation of hemocytoblasts, cells considered to be immunologically competent. Homograft rejection did not occur as long as these cells were suppressed. Rabbits which rejected their grafts in spite of continued 6-mercaptopurine treatment developed large numbers of hemocytoblasts in their lymphoid apparatus. These cells were thought to be drug resistant and analogous to resistant leukemic cells.