bluuebunny/crossref_metadata_2025 huggingface dataset:
Leukocyte Counts of Germ-Free Neonatally Thymectomized CFW Mice
Authors: BEALMEAR PATRICIA M. , WILSON RAPHAEL
Published: October 2019

Examination of hematologic data from germ-free, germ-free thymectomized, conventional, and conventional thymectomized CFW mice revealed few statistically significant differences in hematocrit values or total leukocyte counts. Germ-free thymectomized and conventional thymectomized mice had significantly higher counts than their controls on 8 and 9 days out of the first 2 weeks following thymectomy, but not after 2 weeks. A slight decrease in agranulocytes was noted in both groups of thymectomized mice only during the first 2 weeks postthymectomy. With the onset of wasting disease both granulocyte and agranulocyte counts increased in the conventional thymectomized mice.
Histochemical Demonstration of 5-Hydroxytryptamine in Platelets and Megakaryocytes
Authors: TANAKA CHIKAKO , KURUMA ISAMI , KURAMOTO ATSUSHI
Published: October 2019

A histochemical fluorescence method for the demonstration of biogenic monoamines was applied to the smear preparation of peripheral blood platelets and bone marrow megakaryocytes of rabbits and humans. The fluorescence obtained was identified as 5-HT by histochemical and pharmacologic criteria. With this technic, the following results were obtained: (1) A large amount of 5-HT was present in platelets and in mature platelet-forming megakaryocytes. (2) Only a small amount of 5-HT was demonstrable in the intermediate maturation forms of megakaryocytes with lack of platelet budding.

The possibility that the 5-HT detected was derived from (a) transport of 5-HT formed elsewhere, and/or (b) 5-HT formation from 5-HTP in the megakaryocytes themselves during their maturation was discussed.
Energy Metabolism of Human Leukemic Lymphocytes and Granulocytes
Authors: LASZLO JOHN , Ellis Clarence
Published: October 2019

1. Leukocytes taken from patients having acute lymphocytic leukemia and chronic lymphocytic leukemia are characterized by high respiratory rates and low to absent aerobic glycolysis. Leukemic granulocytes have low respiratory rates and high aerobic glycolysis.

2. Lymphocytes and granulocytes have the capacity for high glycolytic rates under anaerobic conditions.

3. Lymphocyte respiration is independent of glucose concentration in contrast to granulocyte respiration.

4. High energy phosphate levels of lymphocytes and granulocytes are unchanged if these cells are incubated aerobically, either with or without glucose, or anaerobically in the presence of glucose.

5. Aerobic glycolysis can be induced in lymphocytes by the addition of foreign plasma. Foreign plasma may also alter granulocyte metabolism.
Prediction of in Vivo Cytotoxicity of Chemotherapeutic Agents by Their Effect on Malignant Leukocytes in Vitro
Authors: CLINE MARTIN J.
Published: October 2019

In order to develop a test system for predicting the response to chemotherapeutic agents, leukocytes from patients with leukemia and leukolymphosarcoma were cultured in vitro and the effect of several drugs on the incorporation of H3-uridine into ribonucleic acid was measured. Cortisol, vincristine and cytosine arabinoside at concentrations near the therapeutic range produced inhibition of H3-uridine incorporation in sensitive leukocytes. The in vitro effects of 6-mercaptopurine and methotrexate were variable. In 39 trials on 25 patients with leukemia or lymphosarcoma, the in vitro test was used successfully to predict the response to treatment with prednisone and vincristine. It was concluded that the in vitro test system can predict the in vivo cytotoxicity of certain drugs for malignant cells, although it cannot be used to predict the likelihood of the induction of remissions with these drugs.
Defective ADP-Induced Platelet Factor 3 Activation in Uremia
Authors: HOROWITZ HERBERT I. , COHEN BURTON D. , MARTINEZ PABLO , PAPAYOANOU MITSU F.
Published: October 2019

A test for platelet thromboplastic function measuring the activation of platelet factor 3 on incubation of ADP with citrated platelet-rich plasma has been standardized in terms of ADP and platelet concentrations, and amount of agitation, to give sensitive and reproducible results. Abnormal results have been found in patients with elevated blood urea nitrogen; the abnormality is due to a plasma inhibitor and is reversible on the addition of small amounts of calcium. Guanidinosuccinic acid, a newly described metabolite found in the urine of patients with azotemia, also inhibits ADP-induced platelet factor 3 activation. The properties of guanidinosuccinic acid and the uremic inhibitor so far studied suggest that they may be identical.
Differences in Distribution of Erythropoietic and Reticuloendothelial Marrow in Hematologic Disease
Authors: VAN DYKE D. , SHKURKIN C. , PRICE D. , YANO Y. , ANGER H. O.
Published: October 2019

Although reticuloendothelial cells are an invariable component of normal marrow, the distribution of phagocytic acitivity may or may not correspond to the distribution of erythropoietic activity in the presence of disease affecting the marrow. A direct comparison of the distributions of reticuloendothelial marrow (using Tc99m-sulfur colloid) and erythropoietic marrow (using Fe52) in patients receiving treatment for various diseases affecting the bone marrow has been made. In the presence of hematologic disease, the correlation between the distributions of these two marrow functions has varied from identical to totally dissimilar.

Unless one is studying normal subjects, knows a priori that marrow composition is normal, or is specifically studying the reticuloendothelial component of the marrow, one must be cautious in equating marrow distributions obtained with colloidal material with erythropoietic marrow distribution.
Hypothesis: "Immunologic" Oncogenesis
Authors: FIALKOW PHILIP J.
Published: October 2019

The evidence that immunologic mechanisms may predispose to malignancy is reviewed, and an attempt is made to relate neoplasia possibly induced by immunologic or other reactions involving the recognition of self and not-self to known oncogenic mechanisms. It is suggested that "immunologic" oncogenesis as well as malignant transformation induced by known oncogenic agents may be mediated at least in part by chromosomal aberrations. These could act directly to promote neoplasia, or the cell death and proliferation consequent to them could promote other mutational events. Alternatively, the chromosomal changes themselves may not be sufficient for oncogenesis, but they may potentiate malignant transformation by other agents such as viruses.
Granulocytes and Red Cell Lysis
Authors: WALKER RICHARD I. , HERION J. C. , SMITH S. W.
Published: October 2019

Intact granulocytes from man and rabbit hemolyze red cells in vitro. The hemolytic activity is related to the lysosomes. A highly-basic protein fraction from the lysosomes and lysosomal membrane material produce hemolysis in isosmotic buffered saline and increase the osmotic fragility of red cells. Sucrose does not inhibit this hemolytic activity but low temperature incubation and heparin do.
The Relative Osmotic Resistance of Chronic Lymphocytic Leukemia Lymphocytes
Authors: WESTRING DAVID W. , BRITTIN SUZANNE B.
Published: October 2019

Lymphocytes from healthy subjects and patients with chronic lymphocytic leukemia were exposed to graded hypotonic salt solutions and to distilled water. Nucleoproteins released into the media from 5x106 cells were measured spectrophotometrically at 260 mµ as an estimate of cell fragility.

Leukemic lymphocytes were relatively more resistant to hypotonic stress than normal cells. Cell volume and extractable nucleoproteins were shown to be the same for both groups of cells. While nucleoproteins released from the healthy cells underwent a greater optical density increase in distilled water than anticipated, the leukemic cell products exhibited no significant color change in distilled water environment for periods up to 3 hours.
BRIEF REPORT: Appearance of Platelet-Clumping Substance in Plasma of Rabbits after Intravenous Injection of Agar-Solution, Bacterial Endotoxin or Adrenaline
Authors: YAMAZAKI HIROH , SHIMAMOTO TATSUO , MURASE HIROSHI , SHIMAMOTO TAKIO
Published: October 2019

The platelet-clumping substance appeared statistically significant (p < 0.01 ∼ 0.05) in the heparinized plasma of 29 rabbits collected 5 minutes, 30 minutes, and 1 and 2 hours after the intravenous injection of either 5 ml./Kg. of 0.5 per cent agar-saline solution, 100 µg./Kg. of bacterial endotoxin derived from Escherichia coli, or 10 µg./Kg. of adrenaline, as compared with that in the platelet-saline suspension from the other 36 rabbits. At the same time, the circulating platelet count decreased significantly (p<0.01 ∼0.05). Twenty-four hours after the injection these changes disappeared. The platelet-clumping substance was detected only in heparinized plasma, and not in citrated, oxalated, and EDTA-plasma or serum. The addition or removal of calcium or magnesium ions did not affect the appearance of clumping of platelets. It is stable for storage at 4 C. and is not dialyzable. It induced clumping of platelets not only in the platelet-saline suspension, but also in the platelet-rich plasma, while ADP, serotonin, catecholamine or thrombin (0.001 ∼ 100µg./ml. or units/ml.) did not induce clumping of washed rabbit platelets even under the presence of the normal platelet-free heparinized plasma.
Marrow Engraftment by Allogeneic Leukocytes in Lethally Irradiated Dogs
Authors: STORB R. , EPSTEIN R. B. , RAGDE H. , BRYANT J. , THOMAS E. D.
Published: October 2019

Infusion of white blood cells separated from peripheral blood produced allogeneic bone marrow engraftment in lethally irradiated dogs. Approximately 100 x 109 leukocytes obtained from a single donor over an 8-day period were adequate to establish marrow repopulation. Marrow engraftment was indicated by rising blood count, marrow histology, and, in one instance, cytogenetic studies. Marrow grafts were associated with a severe secondary syndrome. Survival was prolonged with methotrexate.
The Use of Bovine Albumin in the Examination of Bone Marrow Obtained at Autopsy
Authors: RICKERT ROBERT R. , VIDONE ROMEO A.
Published: October 2019

This report presents the findings using a minor modification of Berenbaum’s albumin method of preparing bone marrow smears on post-mortem material. The method was used in 50 cases ranging in time from two to 23 hours after death and in the majority of cases (72 per cent) produced specimens of the superior cytologic quality to direct bone marrow smears obtained at the same time. This technique is especially valuable when used in conjunction with tissue sections and bone marrow cell blocks obtained at autopsy. This method has been successfully used with two histochemical techniques suggesting its usefulness in the application of other histochemical procedures in the study of autopsy marrows. The simplicity of this technique lends itself readily to routine use on a general autopsy service and should certainly be employed where hematologic disorders are suspected, especially when clinical bone marrow material is inadequate or not available.
Coexistence of Polycythemia Vera and Biclonal Gammopathy (γGK and γAL) with Two Bence Jones Proteins (BJK and BJL)
Authors: DITTMAR KLAUS , KOCHWA SHAUL , ZUCKER-FRANKLIN DOROTHEA , WASSERMAN LOUIS R.
Published: October 2019

A patient with long standing polycythemia vera, who was treated with P32, chemotherapy and phlebotomies recently developed a myeloma-like disease picture. Two paraproteins (γG type K and γA type L) were found in the serum together with two Bence Jones-like proteins in the urine (kappa and lambda). γM was increased to twice the normal value.

Immunofluorescence studies of the bone marrow showed two clones of plasma cells each of which produced only one type of heavy chain. No cells with double fluorescence were seen. The two types of immunologically different plasma cells were morphologically indistinguishable from one another.
Effect of Phytohemagglutinin in Cultures on the Lactate Dehydrogenases of Lymphocytes from Chronic Lymphatic Leukemia
Authors: RABINOWITZ YALE , DIETZ ALBERT A. , Lubrano Tina , Schimo Inge , Wilhite Betty A.
Published: October 2019

1. Normal lymphocytes show significant increases in their total LDH content and proportion of M-LDH during the first 24 hours of culture with PHA, while most of them undergo blast-cell formation in three days. The changes in LDH occur before mitosis is a factor in altering the cell population and apparently is the result of PHA action at the genetic loci controlling the synthesis of M- and H-LDH polypeptide subunits.

2. The capacity of lymphocytes from patients with CLL to produce blast-cells and to increase their total LDH activity and M-LDH content varied inversely with the height of the peripheral WBC counts. Sometimes prolongation of incubation to five days permitted LDH and blast-cell changes to become discernible. This perhaps resulted from increase by mitosis in the numbers of cells capable of reacting to PHA.

3. Increase in total LDH and proportion of M-LDH promotes glycolysis which may be needed to supply increased energy requirements for both blast-cell formation and mitosis.
Tissue Culture of Primitive Human Myeloid Cells for the Study of Cellular Proliferation
Authors: SHOHET STEPHEN B. , GARDNER FRANK H.
Published: October 2019

Sera from two patients with chronic myelogenous leukemia obtained within one hour after irradiation of the spleen inhibited the growth of a stable cell line derived from the blood of a patient with acute myelogenous leukemia. This inhibitory factor was stable in vitro for one half hour at 55 C. and for 3 days at -80 C.

Serum from a patient with metastatic carcinoma of the breast following thoracic irradiation did not have a similar effect.
Formation of Cytoplasmic Granules in Human Eosinophilic Myelocytes: An Electron Microscope Autoradiographic Study
Authors: FEDORKO MARTHA E.
Published: October 2019

The intracellular flow of tritiated lysine in human eosinophilic myelocytes was studied by electron microscope autoradiography so that information could be obtained on the formation of eosinophil granules. Bone marrow particles obtained from a patient with a marked increase in the number of bone marrow eosinophils were incubated in vitro for periods up to 150 minutes. The percentage of cytoplasmic grains over the Golgi complex rose from 11 percent at 5 minutes to 28 percent by 30 minutes and fell to 15 percent at 150 minutes. Grains over cytoplasmic granules steadily rose to 37 percent by 150 minutes. These results are statistically significant and demonstrate that: human eosinophilic myelocytes are able to form cytoplasmic granules under the in vitro conditions employed, and that intracellular amino acids or proteins flow through the Golgi complex before incorporation into granules.
Granulocyte Transit from Bone Marrow to Blood
Authors: MALONEY MARY A. , PATT HARVEY M.
Published: October 2019

The release of granulocytes from marrow to blood was studied in the dog by hourly sampling of the peripheral blood from 48 to 143 hours after injection of tritiated thymidine. Labeled granulocytes were classified by grain count and cells with 30 or more grains were considered to represent the progeny of a single generation. The blood curve for the most heavily labeled cells was corrected for exponential cell loss with a T½ of 6 hours. It was possible in this way to determine that granulocyte release from bone marrow was normally distributed with a mean time from labeling as a myelocyte to appearance in blood of 102 ± 13.8 hours. The mean transit time of segmented granulocytes in marrow is about 50 hours, which is indicative of a much larger pool of mature cells than formerly thought.
Chromosomal Studies in Erythroleukemia and Chronic Erythremic Myelosis
Authors: CASTOLDI GIANLUIGI , YAM LUNG T. , MITUS W. J. , CROSBY WILLIAM H.
Published: October 2019

Chromosome studies were performed in four cases of erythroleukemia, in one case of acute erythremic myelosis and in one case of chronic erythremic myelosis. Abnormalities were encountered in all of these cases. No consistent patterns were found although clonal lines could be detected in three cases. A common feature in five of the cases was a variable degree of involvement of the chromosomes of the G group (presence of G monosomy in two cases, Ph1-like chromosome in two cases, and a slight reduction in size of a small acrocentric chromosome in 40 per cent of the metaphases in the case of chronic erythremic myelosis). C trisomy was present in one case. These findings indicate that the involvement of groups G and C may represent an important feature of the Di Guglielmo syndrome and suggest a close relationship of this disorder with other myeloproliferative diseases.
In Vitro Measurements of the Effects of Anticoagulants on the Flow Properties of Blood: The Relationship of these Effects to Red Cell Shrinkage
Authors: ROSENBLUM WILLIAM I.
Published: October 2019

Citrate and oxalate increased the viscosity of blood as measured in a capillary viscosimeter. The elevated viscosity was accompanied by erytrhocyte shrinkage, manifest by the decreased hematocrit of blood anticoagulated with either of these agents. Plasma viscosity was not affected. EDTA, which does not alter cell size or shape, also failed to alter blood viscosity, while citrate no longer affected viscosity, if utilized in ACD solution, a milieu which prevents cell shrinkage. When erythrocytes were suspended in hypertonic NaCl, "blood" viscosity was also elevated in comparison to that of suspensions in lower concentrations of NaCl. The data indicate that blood viscosity will be elevated by anticoagulants which are permitted to shrink erythrocytes.
Brief Report: Presence of Erythropoietin in the Plasma of One Anephric Patient
Authors: NAETS J. P. , WITTEK M.
Published: October 2019

Thirty-seven plasma samples from eleven anemic anephric patients have been assayed for erythropoietin determination. In one case, a high titer of the hormone was observed after a severe hemorrhage. The significance of this finding is discussed.
Brief Report: Vitamin B12 and Folate Activity in Normal Human Platelets
Authors: WEISS HARVEY J. , KELLY ALAN , HERBERT VICTOR
Published: October 2019

The vitamin B12 and folate content of human platelets have been determined. The B12 concentration was sixfold that in red cells and one-sixth that in leukocytes. In normal whole blood, with a platelet count of 300,000 per cu. mm., the B12 activity contributed by platelets would be 6-21 pg. per ml. The contribution of platelets to the folate activity of normal whole blood averaged 0.4-1.7 ng. per ml. The folate activity in platelets was one-fifth that in an equal volume of red cells, but unlike red cell folate, was not increased by incubating platelet extracts with plasma.
Characterization and Measurement of Heme Synthetase in Normal Human Bone Marrow
Authors: BOTTOMLEY SYLVIA S.
Published: October 2019

The heme synthetase step in human bone marrow has been characterized in a crude lysate as an enzymatic reaction in that it has a pH optimum of 7.4, is heat labile, and at optimum substrate concentrations is linear with time and enzyme concentration over the first 30 minutes. The Km of iron was found to be 1.7 x 10-5M and for protoporphyrin 1.8 x 10-6M.

High iron concentrations do not affect the enzyme but ascorbic acid and glutathione were found to augment the activity of the enzyme. Pyridoxine and high protoporphyrin concentrations inhibit heme synthetase activity. A negative feedback control of heme synthetase by heme is present in human red cell precursors.
Thrombocytopenic Effect of Ethanol Infusion
Authors: POST ROBERT M. , DESFORGES JANE F.
Published: October 2019

Transient thrombocytopenia was induced by ethanol infusion in an alcoholic patient with transient thrombocytopenia. A fall in activity of Cr51 labeled platelets paralleled the fall in platelet count, but no hepatic or splenic sequestration could be demonstrated. It is postulated that ethanol produced a metabolic alteration in the platelets which led to aggregation and temporary sequestration at an unknown site.
The Effects of Varying Concentrations of Phytohemagglutinin and Conditions of Incubation on the Enhanced Survival of Human Peripheral Lymphocytes in Vitro
Authors: RICHTER MAXWELL , NASPITZ CHARLES K.
Published: October 2019

1. Various concentrations of PHA were utilized to determine the optimal subthreshold concentration of PHA for the maintenance of lymphocytes in vitro. Although 0.1, 0.3 and 0.6 ml. of PHA (diluted one hundred-fold) appeared to be similar in effectiveness during the initial 35 days of culture, 0.1 or 0.3 ml. of PHA were more effective over longer periods of time.

2. Whether the culture medium was changed at weekly intervals or not had little effect on the culture during the initial 35 days. Over the long run, however, changing the culture medium every week resulted in a larger number of surviving lymphocytes.

3. Many phagocytic cells could be observed during the entire period of cultare. Most conspicuous were clumps of cells consisting of a central macrophage surrounded by blasts and a few small and medium-sized lymphocytes.
Absorption of Liver-bound Vitamin B12 in Relation to Intrinsic Factor
Authors: OKUDA KUNIO , TAKARA ISAO , FUJII TERUMI
Published: October 2019

Rat liver containing radioactive native B12 was prepared by repeated injections of 57Co-OH-B12, and absorption of liver B12 was measured in patients with pernicious anemia and in subjects without stomach, using physiologic doses. It was found that absorption of liver B12 was very poor, not superior to that of free OH-B12, and coadministration of IFC markedly enhanced absorption.

In vitro digestion of rat liver with several enzymes, as determined from liberation of dialyzable radioactivity, suggested its easy digestibility. Biochemical studies of the dialyzable products of liver containing 57Co-B12 failed to demonstrate any detectable quantities of radioactivity other than free 57Co-OH-B12. A study in which cow liver powder mixed with a small quantity of 57Co-CN-B12 was fed to humans and digestion of liver was estimated from the reduction in absorption of radioactivity, indicated that most of the extractable liver B12 was liberated free in the intestine. Thus, no evidence has been obtained for the production of B12-peptide complexes from liver by digestion that require no IF for absorption.
Hemoglobin Gun Hill: An Unstable Protein Associated with Chronic Hemolysis
Authors: RIEDER RONALD F. , BRADLEY THOMAS B.
Published: October 2019

A new unstable hemoglobin variant, hemoglobin Gun Hill, is reported. Two members of a Caucasian family were found to be heterozygous for the abnormal hemoglobin. Evidence of mild chronic hemolysis was found in both individuals.

Heinz-Ehrlich bodies were absent from the peripheral blood of the patients with hemoglobin Gun Hill, but Heinz-like inclusions were readily produced in their red cells upon in vitro incubation with the redox dyes brilliant cresyl blue or new methylene blue. Precipitation of hemoglobin occurred when solutions of hemoglobin Gun Hill were exposed to the dyes or were heated to 50 C. Previous studies have shown that there is a deletion of five amino acids in the β chains of hemoglobin Gun Hill. This results in impaired heme binding, and the abnormal molecule lacks half the expected number of heme groups. These structural alterations are probably responsible for the instability of the abnormal hemoglobin.

Studies of the relative rates of synthesis of hemoglobins A and Gun Hill, using in vitro and in vivo technics, indicated an increased turnover rate for the variant protein. The evidence also suggested that hemoglobin Gun Hill is synthesized more rapidly than hemoglobin A.
Effect of Streptokinase on Hemostasis
Authors: HIRSH JACK , BUCHANAN MICHAEL , GLYNN MICHAEL F. , MUSTARD JAMES F.
Published: October 2019

The effect of streptokinase on hemostasis was studied by direct observation of hemostatic plugs in the rabbit mesentery. Infusion of streptokinase did not produce dissolution of hemostatic plugs which were already formed. It did cause a delay in the formation of a platelet mass capable of arresting bleeding from injured vessels. In contrast to systemic infusion, topical application of streptokinase did produce disruption of hemostatic plugs which were already formed. Comparison of the electronmicroscopic appearances of plugs from the control and streptokinase infused animals revealed a lack of fibrin around the plugs in the streptokinase treated animals but no significant difference in platelet morphology. In vitro tests with ADP, thrombin and collagen on platelet-rich plasma from the streptokinase infused animals did not show any difference in platelet aggregation between the pre-and postinfusion samples, even though streptokinase infusion produced a marked increase in plasma fibrinolytic activity. It is suggested that streptokinase infusions, which produce only a slight fall in the plasma fibrinogen level, impair hemostatic plug formation by digestion of fibrin as it is formed around the aggregated platelets.
Leukocyte Labeling with 51Chromium
Authors: MCMILLAN ROBERT , SCOTT JAMES L.
Published: October 2019

A method for labeling concentrated leukocytes in vitro with radioactive chromium is described. Intravascular survival data and organ distribution of the 51Cr-labeled leukocytes of ten hematologically normal subjects are presented and compared with the results of sequential or simultaneous granulocyte survival determinations using 32DFP. Both granulocytes and lymphocytes are labeled by 51Cr. No evidence of diminished cell viability or significant elution or reutilization of the label could be demonstrated by in vitro studies. Curves of both 51Cr and 32DFP leukocyte radioactivity in the circulation were exponential, with average T 1/2 values of 10.5 and 10.3 hours respectively, reflecting the random departure of labeled granulocytes from the circulation. An early rapid phase of label disappearance was noted in the 51Cr studies, attributable to label elution or the disappearance of labeled non-granulocytic leukocytes. Body counting rate curves during the first 12 hours parallel the disappearance of leukocyte and plasma radioactivity; a later plateau reflects radioactivity in RBC contaminating the concentrated leukocyte suspensions. No evidence of pulmonary or splenic sequestration was noted. Estimations of granulocytic pool sizes from the 51Cr data compared poorly with data derived using 32DFP, probably as a result of the early elution of a portion of the radiochromate from the labeled cells or from the more rapid disappearance of 51Cr-labeled mononuclear cells. Epinephrine infusion after injection of labeled leukocytes produced peripheral leukocytosis, increased counting rates over the lungs, liver and heart and a marked diminution in counting rates over the spleen suggesting that a significant portion of the marginal granulocytic pool is located in the spleen.

We conclude that the 51Cr labeling technic will be useful in the study of the intravascular survival and tissue distribution of cells not labeled with 32DFP, and that its use will supplement the study of granulocytes labeled with 32DFP.
Monoclonal Gammopathy in a Child with Leukemia
Authors: STOOP JAN W. , ZEGERS BEN J. M. , VAN DER HEIDEN CEES , BALLIEUX RUDY E.
Published: October 2019

This paper describes the case history of a boy found to suffer from acute blastic leukemia at the age of two years. Manifestations of an intracranial localization of the leukemic process occurred several times in the course of the next 18 months; a generalized relapse responded well to therapy.

The boy subsequently developed a severe refractory virus infection of the skin and suffered a few other virus infections, without any of the usual changes in the morphology of the blood. A few weeks later he developed a monoclonal gammopathy of the IgG class type L with Bence Jones proteinuria, likewise of type L.

The possible causes of this clinical course and of the paraproteinemia are discussed.
Megakaryocyte Maturation Rate in Thrombocytopenic Rats
Authors: EBBE SHIRLEY , STOHLMAN FREDERICK , DONOVAN JANET , OVERCASH JOAN
Published: October 2019

Increased production of platelets was apparent during recovery from acute thrombocytopenia in rats. Preceding this there was acceleration of maturation of megakaryocytes as determined from the pattern of labeling with 3HTdR. Turnover of an increased number of megakaryocytes was indicated by maintenance of normal megakaryocyte differential counts in the presence of accelerated maturation.
Brief Report: Quantitative Studies on the Flicker Phenomenon in the Erythrocytes
Authors: BURTON ALEXIS L. , ANDERSON WALLACE L. , ANDREWS ROBERT V.
Published: October 2019

A technic has been described which allows one to analyze the vibratory variation of density which is visible inside the cytoplasm of the erythrocytes and has been termed "flicker." Further investigations will be performed, dealing with variations of physical conditions and with the action of various chemicals in order to determine whether or not this phenomenon is related to a metabolic activity.
The Genetic Basis of Hereditary Elliptocytosis With Hemolysis
Authors: PEARSON HOWARD A.
Published: October 2019

Two pedigrees containing cases of hemolytic elliptocytosis provide insight into the genetic basis of hemolytic elliptocytosis. One demonstrates non-interaction of genes for G6PD elliptocytosis. In the second, a woman with benign elliptocytosis, had children with hemolytic elliptocytosis by two unrelated fathers. Variable expression of a dominant gene is supported as the most likely explanation for the variability of spectrum of clinical severity in the hereditary elliptocytic syndromes.
Leukemia in a Rhesus Monkey (Macaca Mulatta) Following Exposure to Whole-Body Proton Irradiation
Authors: SIEGAL ALAN M. , CASEY HAROLD W. , BOWMAN ROBERT W. , TRAYNOR JOSEPH E.
Published: October 2019

A rhesus monkey (Macaca mulatta) developed acute granulocytic leukemia 2½ years after whole-body irradiation with protons. This is the third reported case of primate leukemia following irradiation.
Euchrysine, A Supravital Fluorescent Lysosomal Stain: Technic and Application for Hematologic Investigation
Authors: BLUME R. S. , GLADE P. R. , CHESSIN L. N.
Published: October 2019

Euchrysine, a fluorescent aminoacridine dye which is selectively accumulated in lysosomes, has been used in an investigation of cells of hematopoietic origin. The technics for its preparation and use are described as well as the characteristics and patterns of lysosomal fluorescence for 1) primary lysosomes in peripheral blood and bone marrow cells; 2) secondary lysosomes; and 3) lysosomes and lysosomal aggregates in states of altered lymphoid proliferation. Euchrysine fluorescent staining appears to be a convenient and reliable technic for the identification of lysosomes in hematologic investigation.
Abnormal Nucleic Acid Metabolism of Lymphocytes in Plasma Cell Myeloma and Macroglobulinemia
Authors: SALMON SYDNEY E. , FUDENBERG H. HUGH
Published: October 2019

Twenty-six patients with multiple myeloma and macroglobulinemia of Waldenström were studied clinically and immunologically with characterization of their paraproteins and normal immunoglobulins, as well as by in vitro culture of their peripheral lymphocytes for evaluation of DNA and RNA synthesis after phytohemagglutinin stimulation. The lymphocytes of the patients were found to be significantly deficient in response to PHA as compared to normals and patients with benign hypergammaglobulinemia. Levels of normal immunoglobulins were reduced in almost all of the paraproteinemic patients, but there was not a direct correlation between lymphocyte unresponsiveness and immunoglobulin deficiency. The defect in lymphocyte function appeared to be cellular inasmuch as normal lymphocytes had normal DNA synthesis when cultured in myeloma plasma. The decrease in lymphocyte nucleic acid synthesis appeared to be unrelated to immunoglobulin class, quantitative levels or antigenic characteristics of the patients’ paraproteins. Untreated myeloma patients with a past history of infection had lower levels of lymphocyte DNA synthesis than those patients who lacked such a history, suggesting a relationship between the in vitro lymphocyte response to PHA and the in vivo response to the antigenic challenge of bacterial infection.
Combination Chemotherapy in Lymphosarcoma and Reticulum Cell Sarcoma
Authors: HOOGSTRATEN BARTH , OWENS ALBERT H. , LENHARD RAYMOND E. , GLIDEWELL OLIVER J. , LEONE LOUIS A. , OLSON KENNETH B. , HARLEY JOHN B. , TOWNSEND STUART R. , MILLER SHERWOOD P. , SPURR CHARLES L.
Published: October 2019

Patients with lymphosarcoma and reticulum cell sarcoma were randomly allocated to treatment with cyclophosphamide alone or to two dosage levels of combinations of cyclophosphamide, vincristine and prednisone. Remission induction was significantly better for the combinations with lymphosarcoma patients and for the high dose combination with reticulum cell sarcoma patients. Toxicity, more pronounced with high combination, was tolerable. Remissions as measured by decrease in tumor size were associated with improvement in hemoglobin, performance, food intake, weight and fever. The study provides impetus for further trial with other drug combinations and schedules.
Release of Folate by Rat Liver and Spleen Slices
Authors: MAGNUS ERIK M. , DEMPSEY HUGH , BUTTERWORTH C. E.
Published: October 2019

1. The effects of rat plasma and chicken pancreas have been appraised concerning their role in releasing bound folate from rat liver and spleen slices in vitro. Net changes in folate concentration of the bathing solution have been determined by bacteriologic assay employing L. casei as the test organism.

2. Both rat plasma and chicken pancreas extract enhance the release of folate from liver slices in comparison with saline controls. Rat plasma was as effective in liberating bound folate from liver as a 1:25 dilution of conventionally-prepared chicken pancreas extract. The evidence suggests that a considerable portion of liver folate exists in an insoluble form which is bound to cellular structures.

3. Mature red cells appeared to be impermeable to high concentrations of natural folate released from liver.

4. Spleen slices released folate to the supernatant fluid when incubated with chicken pancreas extract, although at levels approximately one-tenth as great as liver slices. When spleen slices were incubated for short periods with plasma, evidence was obtained favoring a flux of folate into surviving cells.
The Elution of 51Cr from Labelled Leukocytes —a New Theory
Authors: RONAI PETER M.
Published: October 2019

Chromium-51 elutes rapidly from labelled leukocytes and tumor cells both in vitro and in vivo. Eluted 51Cr is dialysable and is not precipitated with trichloracetic acid and it has therefore been assumed to be free chromium which has dissociated from the labelled cellular protein. In vitro studies with 51Cr-labelled albumin have, however, demonstrated the extreme stability of the covalent bond between chromium and protein.

Paper electrophoresis experiments are here described which show that the 51Cr which elutes from labelled mouse peritoneal cells behaves electrophoretically like 51Cr-labelled peptides and not at all like free 51Cr in either hexavalent or trivalent forms, or 51Cr-labelled lysine and arginine.

Whole body counting studies after the intravenous injection of the various 51Cr preparations into mice indicate that eluted 51Cr and 51Cr-labelled peptides also have similar biologic behavior.

Together, the electrophoretic and whole body counting studies exclude the presence of significant amounts of free 51Cr (either hexavalent or trivalent) in the 51Cr that elutes from labelled cells and supports the hypothesis that 51Cr elution results from turnover of labelled protein within the cell and loss of non-reutilisable labelled protein fragments.

Confirmation of this theory would provide a powerful technic for the study of intra and extracellular protein metabolism.
Fine Structural Studies of Leukocytes from Patients and Heterozygotes with the Chediak-Higashi Syndrome
Authors: DOUGLAS STEVEN D. , BLUME RALPH S. , WOLFF SHELDON M.
Published: October 2019

Fine structural studies of leukocytes from four patients with the Chediak-Higashi syndrome, including two in the accelerated phase, demonstrate a pleomorphism of substructure of the giant lysosome-like organelles pathognomonic of this syndrome. These organelles differ in composition in relationship to the cell type in which they occur. Many circulating lymphoid cells have altered nuclear chromatin and a diminution in cytoplasmic constituents. Virus-like particles are not seen and there is no evidence of abnormal cytoplasmic sequestration. Large abnormal lysosome-like organelles are present in a small percentage of lymphoid cells from the six parents of these patients, demonstrating that heterozygotes exhibit a cellular abnormality in vivo.
Brief Report: On a Regulatory System of the Adenine Level in the Plasma Connected with Red Cell Maturation and its Effect on the Adenine Nucleotides of the Circulating Erythrocyte. Lack of Relation Between ATP-Level and Life Span of the Erythrocyte
Authors: SYLLM-RAPOPORT I. , JACOBASCH G. , PREHN S. , RAPOPORT S.
Published: October 2019

In 3 cases of Erythrogenesis imperfecta (Diamond-Blackfan) the concentration of adenine nucleotides in the red cells from normal donors was found to rise to twice the normal level. A factor in the plasma of the patients was postulated and proved to be an adenine compound. The concentration was 2-3 times as high in the plasma of patients as compared with normals and the excretion in the urine was likewise several fold higher. From these data it is deduced that the plasma adenine level is regulated by a hormonal interplay between the bone marrow and the liver. It is hypothesized that the bone marrow secretes an inhibitor of adenine production in the liver, which is connected with a maturation stage beyond the proerythroblast.

The life expectancy of the donor cells was not prolonged despite their high ATP level. It is concluded that factors other than ATP are limiting for the survival of the red cell.
Studies of Iron Transport in Portal and Systemic Circulation
Authors: KAJANI M. K. , DE LEEUW N. K. M.
Published: October 2019

Simultaneous 59Fe absorption curves in portal and systemic venous blood showed different rates of entry of the isotope into the portal (and systemic) circulation: the most rapid entry was seen in two patients with decreased iron stores, whereas negligible counts were obtained in two patients with increased iron stores. These data, combined with 59Fe excretion data, indicate a barrier function of the intestinal mucosa for the passage of iron in two iron-sufficient patients, with evidence of prolonged excretion of 59Fe into the bowel in one of these. The data support a two-step mechanism of absorption of inorganic ferrous iron in humans, the first step being uptake of iron by the intestinal mucosa; the second step transfer of mucosal iron to the portal circulation.

In the two patients with decreased iron stores the shape of the absorption curves ruled out significant hepatic deposition of isotope; the amount of isotope transported in the systemic circulation correlated closely with that utilized for hemoglobin synthesis.

Different rates of absorption of inorganic ferrous iron and folic acid were demonstrated in one patient.
Destruction of Immature Erythrocytes Measured by Bilirubin Excretion
Authors: NAGAI KIYOYASU , KAKISHITA EIZO
Published: October 2019

The change in radioactivity of bilirubin with time was measured after injection of glycine 2-14C into rats with a bile fistula. The total radioactivity and specific activity of bilirubin were abnormally high in rats of which erythropoiesis was increased following hemorrhage.

When the newly formed erythrocytes labeled with glycine 2-14C in the peak of reticulocytosis were transfused into rats with a bile fistula, the excretion of labeled bilirubin increased rapidly.

The amount of newly formed erythrocytes destroyed within 7 days after transfusion into normal animals was calculated as 4.4 per cent of the total erythrocytes formed during maximum reticulocytosis and 1.1 per cent of those formed in the normal state in Sprague Dawley rats, while in the Wistar strain, the values were 13.4 per cent and 2.2 per cent, respectively.

These results provide direct evidence for increased production of short-lived erythrocytes during enhanced erythropoiesis, and the hemolysis of newly formed erythrocytes soon after they reach the general circulation may contribute to the production of shunt bilirubin.
The Action of Phytohemagglutinin in Rabbits. V. Morphological Changes Following Previous Immunization with and Daily Injections of Phytohemagglutinin
Authors: BLENNERHASSETT J. B. , NASPITZ C. K. , RICHTER M.
Published: October 2019

The administration of a series of four or eight daily injections of PHA neither diminished nor enhanced the peripheral and parenchymal changes observed after a single injection of PHA. These changes include the peripheral leukopenia followed by a leukocytosis, the hyperplasia of the splenic white pulp, and the myeloid metaplasia or infiltration in the splenic red pulp.

The circulating leukocytes appear to become resistant to the leukopenic action of PHA following a series of injections of PHA. However, this stage of refractoriness lasts only one to two weeks in the absence of any further injection of PHA.

Immunization with PHA with formation of antibodies capable of neutralizing the mitogenic factor(s) in PHA did not affect the capacity of a subsequent challenge injection of PHA to induce the characteristic morphologic changes which follow a single injection of PHA. Thus, the presence of circulating antibodies does not invalidate the use of PHA as a chemotherapeutic agent.
Thymidine Salvage Pathway in Normal and Leukemic Leukocytes with Effects of ATP on Enzyme Control
Authors: RABINOWITZ YALE , WILHITE BETTY A.
Published: October 2019

The enzymes of the "salvage" pathway for thymidine in normal and leukemic leukocytes separated on glass-bead-columns were studied. Levels of thymidine kinase activity in blast cells were high, but were low in granulocytes, normal and leukemic lymphocytes, and in RBC. Phosphatase and thymidine phosphorylase activity was high in granulocytes and in normal and leukemic lymphocytes, but became apparent in blast cells only in the absence of ATP. All the cells studied could phosphorylate TMP to some extent, but the amount of TTP formed depended greatly on the presence of an optimum ATP concentration. Without added ATP breakdown to thymine was at its peak, while phosphorylation of TMP was negligible. Excess ATP reduced or inhibited the activity of most of the enzymes, preventing both phosphorylation and breakdown. Concentrations of Mg equimolar with the ATP gave maximum TTP production, while inhibition by high ATP concentrations occurred despite equimolar Mg concentrations. Both TTP and thymine production ceased in the absence of Mg. Changes in ATP levels in cell loci may function in regulating thymidine metabolism.
Leukocyte Kinetics in Chronic Myeloid Leukemia: I. DNA Synthesis Time in Blood and Marrow Myelocytes
Authors: VINCENT P. C. , CRONKITE E. P. , GREENBERG M. L. , KIRSTEN C. , SCHIFFER L. M. , STRYCKMANS P. A.
Published: October 2019

Using a double labeling technic the DNA synthesis time of CML blood myelocytes was found to be 14.2 ± 0.8 hours if all myelocytes were considered, and 13.6 ± 0.6 hours for large myelocytes only.

The DNA synthesis time of CML marrow myelocytes did not differ significantly from that for blood myelocytes.

These values are indistinguishable from previous estimates of DNA synthesis time in normal granulopoietic precursors.
Prolonged Survival in Paroxysmal Nocturnal Hemoglobinuria
Authors: CHARACHE SAMUEL
Published: October 2019

Some patients with paroxysmal nocturnal hemoglobinuria survive for many years. Three such patients are reported with survivals of 43, 29, and 27 years. Their histories, and those of 14 other patients who survived for more than 20 years, suggest that prolonged survival is not necessarily related to amelioration of the disease. In some patients with apparent "remission" of the disease, laboratory abnormalities persisted for many years.
Studies on Red Cell Aplasia. II. Report of a Second Patient with an Antibody to Erythroblast Nuclei and a Remission After Immunosuppressive Therapy
Authors: KRANTZ SANFORD B. , KAO VINCENT
Published: October 2019

When the marrow from a patient with red cell aplasia was incubated in vitro a marked increase in heme synthesis occurred. Heme synthesis was further increased by the addition of erythropoietin. The patient’s plasma contained both a γG-antibody to erythroblast nuclei and a γG-fraction that inhibited heme synthesis. After the patient was treated with cyclophosphamide, the antinuclear antibody and the inhibitor to heme synthesis disappeared and erythropoiesis was normal. These experiments confirm our previous study and indicate that red cell aplasia may be due to an antibody to marrow erythroblasts.
Cytochemical and Immunohistologic Investigations on the Source and the Functional Changes of Mononuclear Cells in Skin Window Exudates
Authors: SCHMALZL F. , HUBER H. , ASAMER H. , ABBREDERIS K. , BRAUNSTEINER H.
Published: October 2019

The cellular exudates in skin windows of 10 normal controls, 3 patients with myeloblastic leukemia, 3 patients with acute monocytic leukemia and 4 patients with symptomatic monocytosis were evaluated by cytochemical methods (naphthol-AS-esterase, acid phosphatase, naphthylamidase, sudan-black B) and by immunofluorescence using a specific antiserum against human lysozyme. Monocytes and derived cells were identified by their content of characteristic NaF (1.5 mg./ml.) -sensitive naphthol-AS-esterase, whose presence was demonstrated by a double incubation method. After an initial decrease, corresponding to degranulation, the acid hydrolases appeared again in the Golgi zone. Macrophages with NaF-sensitive esterase and strong lysosomal enzyme activities became apparent after 12-16 hours, and there was no indication of a development of these cells from lymphocytes. In myeloblastic leukemia and symptomatic monocytosis the cellular exudate was comparable to that of normal humans. In monocytic leukemia an early exudation, predominantly of monocytoid cells, (instead of granulocytes) was a consistent finding. The transformation of monocytoid cells to typical macrophages with an increase of the lysosomal enzymes occurred with enzyme activities remaining lower than in normals.